Annual Meeting of the Canadian Association for the Study of the Liver (CASL), the Canadian Network on Hepatitis C (CANHEPC) and the Canadian Association of Hepatology Nurses (CAHN) 2024 Abstracts

doi:10.3138/canlivj-7.1-abst

. 2024 Feb 26;7(1):72–253. doi: 10.3138/canlivj-7.1-abst

Annual Meeting of the Canadian Association for the Study of the Liver (CASL), the Canadian Network on Hepatitis C (CANHEPC) and the Canadian Association of Hepatology Nurses (CAHN) 2024 Abstracts

PMCID: PMC10946187 PMID: 38505785

The Canadian Liver Meeting is a collaborative effort of the Canadian Association for the Study of the Liver (CASL), the Canadian Network on Hepatitis C (CanHepC), the Canadian Association of Hepatology Nurses (CAHN), and the Canadian NASH Network (CanNASH). The meeting program offers a forum for presentation and discussion of basic science, and translational and clinical aspects of liver disease. This is a unique opportunity to exchange ideas, promote collaboration, and foster knowledge translation among Canadian researchers, health care practitioners, and community-based groups with an interest in Hepatology.

ORAL PRESENTATIONS

February 2024

CLM-O01 Risk environments and binge drug injection in a cohort of people who inject drugs in Montreal

CLM-O02 Epidemiology of hepatitis C over 28 years of monitoring in nine provinces: Blood donors lend insight into the low-risk undiagnosed population

CLM-O03 Impact of sex and type 2 diabetes mellitus on quality of life among non-alcoholic fatty liver disease patients: A large Canadian cohort study

CLM-O04 Estimating the prevalence and undiagnosed proportion of chronic hepatitis C infection among immigrants in Quebec using mathematical modelling and health administrative data

CLM-O05 Impact of the COVID-19 pandemic on hepatitis C virus (HCV) screening in provincial prisons in Quebec, Canada

CLM-O06 Comparative efficacy of fibrosis-4, liver stiffness measurement, and fibroscan-ast score to predict major liver-related outcomes in metabolic associated steatotic liver disease: An international multicenter study

CLM-O07 Steatotic liver disease in people living with hepatitis C virus following viral eradication with direct-acting antiviral therapy: a pilot study

CLM-O08 Sofosbuvir/Velpatasvir (S/V) for the treatment of HCV infection among vulnerable inner-city residents

CLM-O09 Prevalence of, and effect of semaglutide on, features of non-alcoholic steatohepatitis in patients with obesity with and without type 2 diabetes: analysis of data from two randomised placebo-controlled trials using somasignal tests

CLM-O10 Hedgehog signalling and metabolic responses drive CD8 T cell hyperfunction in advanced liver diseases

CLM-O11 Lack of protective immunity against hepatitis C virus reinfection post antiviral therapy

CLM-O12 Evaluating the cost-effectiveness of prison needle and syringe programs in preventing hepatitis C infection among people who inject drugs in Canadian Federal prisons

CLM-O13 Ethnic disparity in mortality related to extrahepatic manifestations among people with chronic HCV infection: a large, linked administrative population-based study in British Columbia, Canada

CLM-O14 mTORC1 activation promotes systemic and hepatic M1 macrophage polarity in viral and diet-induced advanced liver fibrosis

CLM-O15 Efficacy and safety of maralixibat in patients with progressive familial intrahepatic cholestasis (MARCH): A randomized placebo-controlled phase 3 study

CLM-O16 IL-16, IL-10 and subpopulations of effector and regulatory CD4 T cells as biomarkers of disease activity and response to treatment in patients with autoimmune hepatitis

CLM-O17 Single cell atlas reveals hepato-inflammatory gene activation and recruitment of myeloid-t cell axis specific to the neurologically deceased donor liver in comparison to the living donor liver

CLM-O18 Single-cell atlas of human pediatric livers reveals a macrophage specific inflammatory signature

CLM-P001 Disengagement from clinical care among people co-infected with hiv and hepatitis C (HCV): a scoping review

CLM-P002 “I’d prefer to go to the pharmacy. There's a couple procedures there eliminated right from the get go“ - characteristics of pharmacy-based hepatitis C testing of importance to people who inject drugs

CLM-P003 Collaborating with prison to test and treat people who use drugs in Victoria, British Columbia

CLM-P004 Providing cell phones and peer support is effective at engaging people released from incarceration or experiencing unstable housing in to hepatitis C care

CLM-P005 Integrating a novel model of care for the screening and treatment of hepatitis C for clients enrolled in an opioid agonist management (OAT) program

CLM-P006 Community pop-up clinic: cascade of care and HCV treatment of Vancouver's inner-city PWID populations

CLM-P007 Tackling hepatitis C disparities: Pasan's prison educational initiatives

CLM-P008 Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with liver fibrosis in people with Hepatitis C

CLM-P009 Comparison of hepatitis C virus screening strategies in community and clinical settings in Ontario

CLM-P010 Positive hepatitis B core antibody is associated with liver fibrosis in people with HIV independently of metabolic dysfunction-associated steatotic liver disease (MASLD)

CLM-P011 An evolutionary concept analysis: stigma among women in the context of hepatitis C

CLM-P012 Development of a support tool for HCV treatment decision-making

CLM-P013 Raising awareness about HCV and offering access to rapid testing for migrant communities in Montreal with a culturally and linguistically tailored approach

CLM-P014 Validation of an alternative, potentially portable, approach to APRI and FIB4 testing

CLM-P015 Prevalence and clinical characteristics of hepatitis delta virus (HDV) infected individuals in British Columbia

CLM-P016 MECHANISTIC ANALYSIS OF ARGONAUTE 2 AND MIR-122 PROMOTION OF HEPATITIS C VIRUS REPLICATION

CLM-P017 Elucidating the role of an RNA guanine-quadruplex in hepatitis C virus replication

CLM-P018 Breaking down barriers in hepatitis B virus diagnostics and antiviral screening: development of low cost quantitative assays for HBSAG, HBEAG, and HBV DNA

CLM-P019 Regulation of protein kinase R by HCV NS5A is genotype-dependent and does not require cyclophilin A

CLM-P020 Evaluation of hepatitis C virus transmitted/founder variants obtained from observed HCV infection through lung transplantation from HCV-infected donors to uninfected recipients

CLM-P021 Elucidating the role of nonstructural protein 5A in regulating endoplasmic reticulum stress during hepatitis C virus infection

CLM-P022 Bystander CD8 T cell activation is associated with liver damage in chronic hepatitis B

CLM-P023 Elucidating the switch from translation to replication in the HCV life cycle

CLM-P024 Targeting hepatitis b virus (HBV) by pretending to be hepatitis delta virus (HDV): investigating the interaction between HDV proteins and HBV RNA

CLM-P025 Activation of interferon regulatory factor 1 by cyclosporine a contributes to its antiviral activity against hcv and other RNA viruses

CLM-P026 G4Q-binding ligands: a starting point for potential cure therapies for chronic hepatitis B infections

CLM-P027 Development of a community informed and PEER-led public health promotion campaign using graffiti street art to increase hepatitis C awareness in the downtown eastside of Vancouver, BC

CLM-P028 Predicting 6-month drug poisoning (overdose) mortality among people living with HIV-HCV CO-infection

CLM-P029 HCV reinfection among people who use drugs (PWUD) treated for HCV infection: a long-term view

CLM-P030 A comparison of sofosbuvir/velpatasvir (S/V) and glecaprevir/pibrentasvir (G/P) for the treatment of hcv infection among HCV-infected people who use drugs (PWUD)

CLM-P031 HBV care cascade in Rwanda: a population based-study from 2016 to 2023

CLM-P032 In-person interactions impact on HCV, HIV, and Syphilis rates in at risk populations

CLM-P033 The impact of new DAA therapy on the prevalence and undiagnosed proportion of chronic hepatitis C infection in Alberta: a model-based analysis

CLM-P034 Testing patterns for hepatitis C virus in infants born between 2010-2019 in British Columbia

CLM-P035 Hepatitis C treatment challenges for individuals incarcerated in Alberta provincial correctional facilities: can we do better?

CLM-P036 Mixed-genotype HCV direct acting antiviral outcomes: a CANUHC analysis

CLM-P037 A descriptive analysis of CanHepC participants and HCV direct acting antiviral outcomes

CLM-P038 A descriptive analysis of canuhc participants and hepatitis C virus (HCV) direct acting antiviral outcomes

CLM-P039 The impact of the COVID-19 pandemic and related measures on the delivery of HCV-related care and services and preferred solutions for improving access to care: a survey of health care providers in Canada

CLM-P040 The impact of COVID-19 on access to HCV-related care and services, and preferred solutions: a survey of people disproportionately affected by incarceration, under-housing and/or substance use in Canada

CLM-P041 The perspectives of Canadian healthcare providers on hepatitis C care and services during the COVID-19 pandemic: a qualitative study

CLM-P042 Understanding perceptions of hepatitis C and its management among people with experience of incarceration in Quebec, Canada: a qualitative study guided by the common-sense self regulation model

CLM-P043 Impact of COVID-19 pandemic on treatment for hepatitis B in British Columbia, Canada: An interrupted time series analysis

CLM-P044 Understanding the factors that impact access to screening and treatment for hepatitis C among immigrants – an implementation science-informed qualitative study

CLM-P045 Joining forces to advocate for the right to provide easy access to community-based screening in Québec

CLM-P046 Epidemiology, treatment pattern, and survival in Canadian patients with chronic hepatitis B-related hepatocellular carcinoma

CLM-P047 Preliminary insights on the interplay between oat, chronic pain, and pain dimensions among people who inject drugs in Montreal, Canada

CLM-P048 The impact of first-wave COVID-19 restrictions on HCV testing trends among the birth cohort in Alberta

CLM-P049 Progress towards HCV elimination among people living with HIV-hepatitis C virus (HCV) co-infection

CLM-P050 Estimating hepatitis D virus prevalence among Canadian immigrants

CLM-P051 Serum fibrosis and steatosis biomarkers for the prediction of mortality in liver transplant recipients

CLM-P052 Validation of FIB-4 for the diagnosis of liver cirrhosis in metabolic dysfunction-associated steatotic liver disease

CLM-P053 Discrete choice experiments to elicit the preferences of people living with diabetes for health screening: a scoping review

CLM-P054 Validation of AGILE 3+ for MASLD advanced fibrosis in a Canadian cohort

CLM-P055 Prevalence of metabolic associated steatotic liver disease (MAFLD) by transient elastography in patients with cardiovascular and chronic kidney disease: a cross-sectional study

CLM-P056 Assessing the utilization and perspectives of weight loss medications in pediatric gastroenterology and hepatology when managing metabolic dysfunction-associated steatotic liver disease: current practices, barriers, and future implications

CLM-P057 Breaking boundaries: unraveling metabolic dysfunction-associated steatotic liver disease in children of India and Canada

CLM-P058 Fecal micrornas as predictors of persistent non-alcoholic steatohepatitis in patients with obesity who underwent bariatric surgery

CLM-P059 Non-invasive biomarkers predicting the progression of MASLD to advanced fibrosis: a prospective cohort study based in southwestern Ontario

CLM-P060 Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with impaired health-related quality of life in people with HIV

CLM-P061 Liver fibrosis is associated with cardiovascular disease burden amongst patients with non-alcoholic steatohepatitis: the uncover-nash longitudinal cohort study

CLM-P062 Autoantibodies in non-alcoholic fatty liver disease: implications for early intervention

CLM-P063 Probe to capsule distance measured during point of care liver assessment

CLM-P064 Age-dependent differences in FIB-4 predictions of fibrosis in patients with nafld referred from primary care

CLM-P065 Efficacy of GLP-1 receptor agonists and SGLT-2 inhibitors for the treatment of diabetes mellitus in liver transplant recipients

CLM-P066 Loss of hepatic BRCA1 protects against fatty liver and tumourigenesis

CLM-P067 IRP1 deficiency triggers metabolic reprograming, increases insulin sensitivity and protects mice against liver steatosis

CLM-P068 Evaluating the liver immune environment in a preclinical model of pathobiont accelerated metabolic dysfunction associated steatotic liver disease

CLM-P069 The protective mechanism of the A165T variant of MTARC1 on the development of metabolic dysfunction-associated steatotic liver disease (MASLD)

CLM-P070 Hedgehog signalling and metabolic responses drive CD8 T cell hyperfunction in advanced liver diseases

CLM-P071 Severe metabolic dysfunction-associated steatotic liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota in people with HIV

CLM-P072 The rise of metabolic dysfunction-associated steatotic liver disease (MASLD) among adults in Canada between 2012 and 2018

CLM-P073 Material deprivation is associated with liver stiffness measurement and liver-related events in people with HIV

CLM-P074 Projected healthcare system cost burden of metabolic dysfunction-associated steatotic liver disease in Canada

CLM-P075 Nutritional management is an urgent need in patients on the waiting list for liver transplantation!

CLM-P076 “YOUR LIVER, YOUR HEALTH”: an innovative approach to improve public health awareness of metabolic dysfunction-associated steatotic liver disease (MASLD)

CLM-P077 Low skeletal muscle index is a predictor of liver-related events and mortality in patients with cirrhosis independently of portal hypertension

CLM-P078 Low subcutaneous adipose tissue index is a predictor of mortality in female patients with cirrhosis, independently of portal hypertension

CLM-P079 Serial MELD and prognosis in alcohol-associated hepatitis: opportunities for trial design

CLM-P080 The neutrophil-lymphocyte ratio improves prediction of liver-transplant-free survival beyond risk factors in existing prognostic scores for patients with PBC: a machine learning study

CLM-P081 A dedicated automatic recall hepatocellular cancer surveillance program improves retention rates: a population based cohort study

CLM-P082 A mixed methods process evaluation of a consultative, collaborative outpatient palliative care clinic for patients with end-stage liver disease

CLM-P083 Harnessing the synergy of add-on FXR and PPAR agonism in patients with primary biliary cholangitis: the Toronto centre for liver disease experience of ‘Triple’ therapy

CLM-P084 Evaluation of APOBEC3 expression in patients with inflammatory bowel disease: a similar pattern between Crohn's disease and primary biliary cholangitis

CLM-P085 Patient, caregiver and provider perspectives on the transition from pediatric to adult care in liver diesase: reducing the trauma of transition and transfer of care

CLM-P086 Prediction of survival benefit of living donor liver transplant versus deceased donor liver transplant for waitlisted patients with decompensated liver disease using deep learning

CLM-P087 Evaluation the 6 month abstinence rule prior to liver transplant: a clinical practice guideline

CLM-P088 Dynameld: a nonlinear, dynamic model of end-stage liver disease for accurate and fair risk assessment

CLM-P089 OPAL: online prehabilitation for patients awaiting liver transplantation - a multicenter randomized controlled trial to reduce physical frailty and improve health outcomes

CLM-P090 Fosfomycin-induced liver injury: a case report and literature review

CLM-P091 The new paradigm in HCV treatment in Alberta provincial corrections – review of the first year

CLM-P092 Impact of an interdisciplinary alcohol-associated liver disease clinic on alcohol use disorder treatment and patient engagement

CLM-P093 Impact of maralixibat on cholestatic pruritus in young adults aged 16 years and older with alagille syndrome

CLM-P094 The impact of scalable mind-body internet and mobile-based interventions on depression and anxiety in adults living with chronic physical conditions: a systematic review and meta-analysis of randomized controlled trials

CLM-P095 Evaluation of a nurse-led paracentesis model for patients with decompensated liver disease in ambulatory care: a retrospective review

CLM-P096 The rate and risk factors for postoperative mortality in patients with cirrhosis undergoing surgery: a longitudinal cohort study

CLM-P097 Hepatosplenic T-cell lymphoma diagnosed on liver explant in a patient with ulcerative colitis

CLM-P098 Phenotype and long-term outcome in recurrent pediatric acute liver failure secondary to NBAS, RINT1, LARS1, and SCYL1 mutations: a review and individual participant data analysis

CLM-P099 Evaluation of a nutritional education guide developed for patients with cirrhosis: impact of hepatic encephalopathy

CLM-P100 Children with aih receiving standard-of-care therapy demonstrate long-term excess weight gain and obesity: an under-recognized complication of pediatric AIH therapy

CLM-P101 Long-term prevalence of malnutrition, sarcopenia, and frailty after liver transplantation: impact of hepatic encephalopathy

CLM-P102 Real-world study of transient elastography with liver stiffness measurement and spleen stiffness measurement in a tertiary center

CLM-P103 The role of HBRV infection in CD and UC

CLM-P104 Clinical impact of clinically significant portal hypertension among primary biliary cholangitis patients

CLM-P105 Leveraging machine learning to improve the diagnostic accuracy of ultrasound screening for hepatocellular carcinoma

CLM-P106 Clinical presentation of patients with autoimmune hepatitis stratified by immunoglobulin G levels

CLM-P107 Reduced inflammatory potential of tumor associated macrophages promotes t cell tolerance and exhaustion in human hepatocellular carcinoma

CLM-P108 Intestinal retoxification of bile acids by the beta-glucuronidase enzymes from the mictobiota: a potential novel target for the treatment ofcholestatic autoimmune liver diseases

CLM-P109 HCV-specific CD4+ T-cells are targeted by HIV-1 infection and viral reservoir persistence

CLM-P110 Protectin dx improves the response to obeticholic acid in liver cells

CLM-P111 Uric acid in chronic liver disease and its cognitive complications: lessons from a rat model

CLM-P112 The association of body cell mass with bedside body composition tools and frailty in patients with liver cirrhosis

CLM-P113 Establishing a viable in vitro platform to culture primary murine hepatic myeloid cells

CLM-P114 Diagnostic, prognostic, and therapeutic implications of glutamine metabolism reprogramming in hepatocellular carcinoma

CLM-P115 Targeting glutamine consumption: insights on ASCT2 and SNAT2 as putative major glutamine transporters in hepatocellular carcinoma

CLM-P116 Impact of the COVID-19 pandemic on temporal trends in alcohol-related and non-alcohol-related cirrhosis hospitalizations: a Canadian population-based study

CLM-P117 Developing and validating novel coding algorithms to improve case identification accuracy for alcohol- and non-alcohol-related cirrhosis in administrative databases

CLM-P118 COVID pandemic impact on care delivery and quality of life among patients with primary biliary cholangitis: a large Canadian study

CLM-P119 “The times have changed. HEP C treatment is readily available so why isn’t Hep C testing readily available” - Perceptions and experiences of people who inject drugs surrounding testing for Hepatitis C virus infection

CLM-P120 HBV care cascade in Rwanda: the impact of integration and decentralization of HBV services on enhancing the HBV care continuum

CLM-P121 The impact of COVID-19-related public health measures on hepatocellular carcinoma screening in British Columbia, Canada: an interrupted time series study

CLM-P122 The changing landscape of cirrhosis: impact on young adults and females

CLM-P123 Predicting future decompensation in patients with cirrhosis: a machine learning approach to risk stratification at the first patient visit

CLM-P124 Evaluating the non-viral liver disease burden in people living with HIV and abnormal liver enzymes

CLM-P125 Access to systemic therapy in hepatocellular carcinoma in Canada is variable

CLM-P126 Validation of hepatorenal syndrome diagnostic code in hospitalized patients at the university health network

POSTER PRESENTATIONS

February 2024

CONTROL ID: 3991170 AI in hepatology: A comparative analysis of CHATGPT-4, BING, and BARD at answering clinical questions

CONTROL ID: 3995455 Geographic and socioeconomic disparities in cirrhosis incidence and prevalence: A population-based study in Manitoba, Canada

CONTROL ID: 3999950 Immune checkpoint inhibitor liver-related adverse events: A case series

CONTROL ID: 4000412 Real-world performance of vibration-controlled transient elastography with liver stiffness measurement and spleen stiffness measurement in a tertiary center

CONTROL ID: 4003416 Biliary atresia in pediatric patients with concurrent complete situs inversus and pathogenic variants in ciliary genes

Can Liver J. 2024 Feb 26;7(1):78–79.

CLM-O01 Risk environments and binge drug injection in a cohort of people who inject drugs in Montreal

N Minoyan ^1,², S H⊘j ², S Larney ^2,³, D Jutras-Aswad ^2,⁴, V Martel-Laferrière ^2,⁵, M-P Sylvestre ^1,², J Bruneau ^2,³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: High-intensity episodes of drug injection, or ‘binges’, may be important yet overlooked drivers of HCV transmission among people who inject drugs (PWID). It is acknowledged that drug-related risk behaviours are strongly influenced by broader ‘risk environments’ – the social and structural forces that constrain individual-level agency. In many urban settings, PWID either live in or visit central geographic areas to acquire and use drugs, as well as to meet survival-related needs by i) accessing harm reduction and health & social service sites, and ii) leveraging street-level economies and peer networks. Factors present in these areas (e.g. drug markets, perceived norms, harm reduction) might affect their propensity to engage in high-risk behaviours.

Purpose: We sought to examine whether exposure to the central borough of Ville-Marie (VM) is associated with binge drug injection among PWID in Montreal, Quebec.

Method: Data were drawn from HEPCO, a longitudinal cohort study involving three-monthly interviews with active PWID (eligibility: past-6-month injection, age ≥18). At each visit (2010–2020), participants reported whether they had injected large quantities of drugs over sustained periods until unable to continue (‘binged’) in the last 3 months. The ‘risk environment’ exposure variable was a four-category indicator based on recently dwelling (y/n) and/or injecting most often (y/n) in the VM borough. VM contains the most identifiable open drug scene in the city as well as a high density of services for vulnerable populations. GEE models estimated the odds of binge as a function of the exposure. Models were adjusted for age, gender and recent: incarceration (y/n), housing type (street/unstable/stable), ‘survival’ income (y/n), psychological distress (K10 score), and sex with an injection partner (y/n).

Result (s): 805 participants (82% male, median age 41) provided 8158 observations. At the first included study visit, about one third dwelled & injected in VM; a similar proportion dwelled & injected outside the borough. 21% dwelled outside but injected in VM. 7% lived in VM but injected outside. The three groups exposed to VM exhibited heightened odds of binge compared to those dwelling & injecting outside (Fig.1). However, after multivariable adjustment, the heightened odds of binge only persisted in the group dwelling outside VM but injecting in the borough (aOR: 1.50 [95% CI 1.11-2.02]). Members of this group were younger, more stably housed and more likely to report past-month opioid injection than other groups.

graphic file with name canlivj-7.1-abst_fig1.jpg — Image:

Conclusion(s): The heightened risk of binge among those dwelling in VM may be attributable to individual-level vulnerability-related factors. Less entrenched PWID may, in contrast, be travelling to the borough to engage with the local drug scene, and bingeing due to factors present in the environment (e.g. drug types, social networks, policing). Safer environment interventions may play a role in preventing binge and its long-term consequences, including HCV infection and overdose.

References: 1. Rezaei, O., Ghiasvand, H., Higgs, P., Noroozi, A., Noroozi, M., Rezaei, F., Armoon, B., & Bayani, A. (2020). Factors associated with injecting-related risk behaviors among people who inject drugs: A systematic review and meta-analysis study. Journal of Addictive Diseases, 38(4), Article 4. https://doi.org/10.1080/10550887.2020.1781346

2. Rhodes T. The ‘risk environment’: a framework for understanding and reducing drug-related harm. International Journal of Drug Policy. 2002 Jun 1;13(2):85–94.

Disclosure of Interest: N. Minoyan: None Declared, S. H⊘j: None Declared, S. Larney Consultant of: Advisory board fees from Gilead Sciences, unrelated to the current work, D. Jutras-Aswad Grant / Research support from: Received study materials from Cardiol Therapeutics for a publicly funded clinical trial not related to this manuscript's theme, V. Martel-Laferrière: None Declared, M.-P. Sylvestre: None Declared, J. Bruneau Grant / Research support from: Funding from Gilead Sciences, outside the scope of the current work, Consultant of: Advisory board fees from Gilead Sciences, AbbVie and Cepheid Sciences, outside the scope of this work.

Can Liver J. 2024 Feb 26;7(1):79–80.

CLM-O02 Epidemiology of hepatitis C over 28 years of monitoring in nine provinces: Blood donors lend insight into the low-risk undiagnosed population

SF O’Brien ^1,², B Ehsani-Moghaddam ^1,³, M Goldman ^4,⁵, SJ Drews ^6,⁷

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Hepatitis C is a blood-borne infection caused by the hepatitis C virus (HCV) that can progress to cirrhosis and liver cancer. About 70% of infections become chronic (detectable HCV NAT for more than 6 months). For donors who are both anti-HCV and HCV NAT positive the most likely clinical scenario is chronic infection although late acute infection cannot be ruled out. Direct acting antiviral treatment was available since 2014 initially based on disease stage, and in 2018 for all infected; clinical screening is risk-based. About 1% of Canadians have had hepatitis C, with 0.5% chronically infected (about 25% unaware). Higher chronic infection prevalence is associated with birth between 1945 and 1964, intravenous drug use and foreign birth. Blood donors are in good general health and deferred for risks such as intravenous drug use and sexual risks. Blood donor data can provide insight into the low-risk undiagnosed population.

Purpose: We aimed to describe HCV epidemiology in first-time blood donors over 28 years of monitoring.

Method: All first-time blood donors in all provinces except Quebec (1993 to 2021) were included. All donors were tested for anti-HCV. Since late 1999 all were also tested for HCV NAT. Donors both anti-HCV and HCV NAT positive were assumed to have chronic hepatitis C. The Pampalon Material Deprivation and the CanMarg Ethnocultural indices were based on the donor's residential postal code. Separate logistic regression models were fitted with anti-HCV positivity and chronic hepatitis C as the dependent variables. Independent variables were year, age cohort (born before 1945, 1945-1964, 1965 or later), sex, region, material deprivation and ethnocultural quintiles. The quarterly percentages of HCV positive donations also HCV NAT positive were calculated. An ARIMA model was fitted with interruption in 2014.

Result(s): There were 2,334,238 donations from 1993 to 2021. Prevalence for anti-HCV 0.33% (0.30,0.37) in 1993 and 0.07% (0.05,0.09) in 2021. In 2021 0.03% (0.01,0.04) had chronic HCV. Predictors for both anti-HCV positivity and chronic HCV were similar. For chronic HCV were male sex (OR 1.8, 1.6,1.9), birth between 1945 and 1964 (OR 7.0, 6.2,7.8), living in the western provinces and living in material deprived (OR 2.7, 2.2,3.2) and more ethnocultural concentrated neighbourhoods (OR 1.7, 1.4,2.1). The ARIMA model showed modest decline prior to 2014, with greater decline afterwards (p<0.01).

Conclusion(s): Chronic HCV infections have declined in blood donors. Blood donors have 16 times lower chronic HCV prevalence than the general population in keeping with deferral for risk factors. The decline in the proportion of anti-HCV positive donors with chronic infections after 2014 may be related to introduction of direct acting antivirals. Donors largely mirror population trends and highlight the ongoing prevalence of untreated infections in groups without obvious risk factors missed by risk-based clinical screening.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):80–81.

CLM-O03 Impact of sex and type 2 diabetes mellitus on quality of life among non-alcoholic fatty liver disease patients: A large Canadian cohort study

E Baguley ¹, M Knaub ², W Schaufert ³, MG Swain ¹, A-A Shaheen ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Non-alcoholic fatty liver disease (NAFLD) is a growing epidemic worldwide. A NAFLD diagnosis can significantly impact quality of life (QoL).

Purpose: We described QoL among NAFLD patients at risk of advanced liver fibrosis. We evaluated associations between sex and type 2 diabetes mellitus (T2DM) status on QoL domains.

Method: In this prospective study, the Patient Reported Outcomes Measurement Instrument Survey (PROMIS-29), a 29-item validated survey with seven health domains (pain interference, depression, physical function, ability to participate in social roles/activities, fatigue, anxiety and sleep disturbance, and a single pain intensity item) was administered to patients identified in primary care through the Calgary NAFLD pathway with either an inconclusive or elevated (≥8kPa) shearwave elastography (n=812) between March 2017 and March 2023. Patients completed the PROMIS-29 survey before assessments with transient elastography (Fibroscan®) and hepatologist discussion. PROMIS-29 scores were compared between our NAFLD cohort and a general reference 2000 General US Census population. PROMIS-29 scores of our cohort were compared based on sex (female vs. male) and T2DM status (yes vs. no). A T2DM diagnosis was confirmed in patients with hemoglobin A1c ≥6.5%, or a previous T2DM diagnosis and treatment with T2DM medications.

Result(s): Participants had a median age of 58 years (IQR: 48.3-66.0). Over half of the participants were female (57.4%), and 41.0% had T2DM. Compared to the reference population, our cohort scored worse in the physical function, sleep disturbance, anxiety, and pain interference domains (p<0.001); however, our cohort showed a better score for participation in social roles and activities (p=0.001). Females experienced worse (p<0.001) QoL compared to men across all PROMIS-29 domains (Table 1). Participants with T2DM experienced greater issues with physical functioning (p<0.001), more fatigue (p=0.004), increased depression (p=0.044), more sleep disturbances (p<0.001), reduced ability to participate in social roles and activities (p=0.003), higher pain interference (p<0.001), and increased overall pain intensity (p<0.001), when compared to participants without T2DM (Table 1).

graphic file with name canlivj-7.1-abst_fig2.jpg — Image:

Conclusion(s): Among NAFLD patients identified in primary care at risk for significant liver fibrosis, females and patients with T2DM had reduced QoL. Further, NAFLD patients have reduced QoL across many health domains compared to the general population.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):82–83.

CLM-O04 Estimating the prevalence and undiagnosed proportion of chronic hepatitis C infection among immigrants in Quebec using mathematical modelling and health administrative data

F Forouzannia ¹, AM Passos-Castilho ², N Janjua ³, B Sander ⁴, C Greenaway ², WWL Wong ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: According to the Canadian census, 23% of the population were foreign born (i.e., immigrants). Many immigrants came from countries where hepatitis C virus is highly or moderately endemic. Thus, a proportion of the chronic hepatitis C (CHC) population in Canada is comprised of immigrants. In Canada, data on CHC prevalence among immigrants are very limited. CHC can remain clinically asymptomatic until the late stages of the disease and many infections are undiagnosed. The prevalence and undiagnosed proportion of CHC are important factors in planning screening and treatment interventions to achieve the World Health Organization's (WHO) 2030 hepatitis C elimination targets.

Purpose: Our objective is to estimate the CHC prevalence and undiagnosed proportion among immigrants in Quebec using a model-based approach informed by provincial population-level health administrative data.

Method: This study has two components. First, a population-based retrospective analysis based on Immigration, Refugees and Citizenship Canada data linked with health administrative data for Quebec (2000-2016) was conducted to generate the annual incidence of newly diagnosed CHC cases, decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and HCV-related treatment cases for three birth cohorts among the immigrant population: individuals born before 1945, individuals born between 1945 and 1965 and individuals born after 1965. Second, we used a back-calculation modeling approach to estimate the historical prevalence of CHC for each cohort through a calibration process based on a Bayesian Markov chain Monte Carlo (MCMC) algorithm. The algorithm constructs the historical prevalence of CHC for each cohort by comparing the model-generated predictions of the annual incidence of the CHC-related health events against the observed incidence generated in the retrospective analysis.

Result(s): CHC prevalence among immigrants in 2016 was estimated to be 1.27% (95% CI: 0.98% - 1.6%) for individuals born prior to 1945, 4.36% (95% CI: 2.76% - 6.03%) among individuals born between 1945 and 1965, and 1.22% (95% CI: 0.61% - 2.25%) among individuals born after 1965. In 2016, the undiagnosed CHC proportion was 50.67% (95% CI: 39.39% -61.76%) among individuals born prior to 1945, 76.95% (95% CI: 66.76% - 84.12%) among individuals born between 1945 and 1965, and 43.04% (95% CI: 22.67% - 80.70%) among individuals born after 1965. Overall, the mean prevalence and undiagnosed CHC proportion estimates among immigrants in Quebec over all birth cohorts were assessed to be 2.03% (95% CI: 1.44%-2.8%) and 52.51% (95% CI: 39.21%-76.75%) in 2016, respectively (Figure 1).

graphic file with name canlivj-7.1-abst_fig3.jpg — Image:

Conclusion(s): The estimated CHC prevalence among immigrants in our study is at least 3 times higher than that among the general population. Furthermore, the undiagnosed proportion is high (>50%), indicating an enormous diagnostic gap among immigrants. Hepatitis C elimination will not be achieved without increasing diagnosis among immigrants.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):83–84.

CLM-O05 Impact of the COVID-19 pandemic on hepatitis C virus (HCV) screening in provincial prisons in Quebec, Canada

N Kronfli ^1,^2,³, F Leone ¹, C Dussault ¹, M Maheu-Giroux ³, G Miliani ⁴, E Gallant ⁵, J Cox ^1,^2,³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: The COVID-19 pandemic placed unprecedented strain on healthcare systems, diverting human and financial resources away from national hepatitis C virus (HCV) elimination efforts. However, little is known about the impact of the COVID-19 pandemic on HCV screening efforts in Canadian carceral settings.

Purpose: To explore the impact of the COVID-19 pandemic on HCV screening in two of Quebec's largest provincial prisons.

Method: Retrospective data of all HCV-related laboratory tests (antibody and RNA) performed on incarcerated individuals between July 2018 and February 2022 at l’Établissement de détention de Montréal (EDM; on-demand HCV screening) and l’Établissement de détention de Rivière-des-Prairies (EDRDP; risk-based HCV screening) were obtained. Duplicate (n=127) and repeat HCV-antibody (HCV-Ab) tests within 90 days of the first test (n=151) were excluded. To examine the association between the pandemic and the number of HCV-Ab screening tests, a three-level time period variable was created (pre-outbreak, outbreak and post-outbreak). Locally estimated scatterplot smoothing (LOESS) was performed to trend monthly prison admissions. Negative binomial regression (with monthly admissions as an offset) was used to assess the change in HCV-Ab tests across time periods and by prisons. Adjusted odd ratios (aOR) with 95% confidence intervals (95% CI) were calculated.

Result(s): Overall, 1,639 individuals were screened for HCV (1,079 at EDM and 560 at EDRDP). Among the 56 (3.4%) who tested HCV-Ab positive, 44 (79%) had confirmatory HCV testing (30/35 (86%) at EDM and 14/21 (67%) at EDRDP). Of these, 23 (52%) screened HCV RNA positive (18 (78%) at EDM and 5 (22%) at EDRDP). EDM experienced two outbreaks (April-July 2020 and December 2020-June 2021) while EDRDP experienced one outbreak (December 2020-April 2021); 266 and 32 incarcerated individuals tested positive for SARS-CoV-2, respectively. There was a significant decrease in HCV-Ab screening at EDM during the outbreak (aOR 0.32; 95% CI 0.18-0.58) and post-outbreak (aOR 0.44; 95% CI 0.31-0.63) periods compared to the pre-outbreak period. There was no change in HCV-Ab screening at EDRDP during the outbreak (aOR 1.03; 95%CI 0.55-1.90) or post-outbreak (aOR 1.66; 95% CI 0.83-3.26) periods compared to the pre-outbreak period.

Conclusion(s): The COVID-19 pandemic negatively affected HCV screening in the largest provincial prison in Quebec (EDM) but had minimal impact at EDRDP. Additional research is needed to understand these differences, but reprioritization of human resources was likely an important factor. To eliminate HCV from carceral settings, attempts to minimize screening interruptions during future outbreaks should be prioritized, and combined screening for HCV and SARS-CoV-2 should be considered.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):84–85.

CLM-O06 Comparative efficacy of fibrosis-4, liver stiffness measurement, and fibroscan-ast score to predict major liver-related outcomes in metabolic associated steatotic liver disease: An international multicenter study

YJ Wong ^1,², YH Chan ³, V Chen ⁴

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Non-invasive tests (NITs) such as Fibrosis-4 (FIB-4), liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE), and FibroscanAST (FAST) are frequently used for risk stratification in metabolic-associated steatotic liver disease (MASLD). However, when NITs yield discordant results, it remains unclear as to how such discrepancies should be interpreted, especially when the comparative performance of NITs is unclear.

Purpose: We aim to evaluate the comparative performance of FIB-4, LSM and FAST scores to predict clinical outcomes in MASLD patients.

Method: We include consecutive adult MASLD patients with transient elastography performed between 2015-2022 from USA and Singapore. MASLD patients stratified based on baseline FIB-4, LSM and FAST score were followed up until clinical outcomes such as major liver-related outcomes, (MALO, defined as liver-related events and death), death and major adverse cardiac events (MACE).

Result(s): A total of 1,837 MASLD patients (63% with obesity and 39% with diabetes) with VCTE were followed up for a median 3.5 years. The overall incidence rate per 1000 person-years for MALO, death and MACE was 6.3, 4.9, and 1.8, respectively. FIB-4 stratified MASLD patients into low-risk (<1.3), intermediate-risk (1.3-2.67) and high-risk (>2.67) in 58.8%, 31.7% and 9.5%, respectively.

No MALO occurred with baseline FIB-4<1.3, regardless of LSM and FAST score (10% of low-risk MASLD patients by FIB-4 were misclassified as “high-risk” by VCTE). Higher FIB-4 was associated with a higher risk of MALOs within each LSM category. FIB-4 was more accurate to predict the occurrence of MALO than LSM (tAUC at 3 years: FIB4: 0.90 vs 0.79, p=0.023; 5 years: FIB4: 0.89 vs 0.80 p=0.035) or FAST score (tAUC at 3 years: FIB4: 0.90 vs 0.78, p=0.014; 5 years: FIB4: 0.89 vs 0.72 p<0.001). All 3 scores had limited ability to predict MACE (tAUC: 0.58-0.68).

When using NITs to identify low-risk MASLD patients to be discharged to primary care, sequential testing of FIB-4 and LSM identified 77.5% of the low-risk MASLD patients at the expense of missing out 11.8% of MALO. The combination of FIB and LSM for all patients reduces the missed MALO to 0%, but also substantially reduces the proportion of low-risk MASLD patients identified to 41.3%.

Conclusion(s): In this multicenter international study, FIB-4 has good negative predictive value in identifying low-risk MAFLD patients to be monitored in primary care settings. In moderate/high-risk MASLD patients, FIB-4 and LSM synergistically predicted the risk of MALO. FIB-4 should be incorporated into risk stratification in MASLD even among patients who underwent VCTE. Our findings support the sequential approach of FIB-4 followed by VCTE as recommended by most international guidelines and highlight the disadvantages of routine VCTE in low-risk MASLD patients.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):85–86.

CLM-O07 Steatotic liver disease in people living with hepatitis C virus following viral eradication with direct-acting antiviral therapy: a pilot study

M Shengir ¹, W Elgretli ¹, F Cinque ^2,^3,⁴, R Lombardi ^2,³, A Cespiati ^2,³, A Fracanzani ^2,³, LE Ramos Ballesteros ⁴, M Deschenes ⁴, P Wong ⁴, T Chen ⁴, G Sebastiani ^1,⁴

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: Yes

Background: Recently, the nomenclature of fatty liver disease has been updated and steatotic liver disease (SLD) was proposed as an overarching term that encompasses several causes of hepatic steatosis (HS). Under the SLD umbrella, nonalcoholic fatty liver disease has been replaced by the new term “metabolic dysfunction-associated steatotic liver disease” (MASLD)(1). Given the fact that HCV is also a well-known cause of HS and both conditions may coexist(2), the potential effect of sustained virologic response (SVR) on HS in HCV patients within the framework of MASLD remains uncertain.

Purpose: To estimate the effect of SVR on SLD and significant liver fibrosis, as well as ascertaining the occurrence of SLD in individuals who do not have HS at baseline.

Method: This is a retrospective pilot study of people with HCV evaluated between 2016 and 2019 at two clinical centers for HS and liver fibrosis using transient elastography (TE) and controlled attenuation parameter (CAP) before receiving direct-acting antivirals (DAA) and 6 months after SVR. Eligible participants were aged ≥18 years, had received DAA therapy, and achieved SVR. MASLD was defined by the coexistence of HS and ≥1 cardiometabolic risk factors, including increased body mass index (BMI) and/or waist circumference, prediabetes or diabetes, hypertension, hypertriglyceridemia, and low serum high-density lipoprotein cholesterol. The presence of HS and MASLD was used to stratify participants into 3 groups: HCV without HS, HCV with MASLD, and HCV without MASLD. A CAP cut-off of ≥248 dB/m was utilized to define HS and TE of ≥8 and ≥13 kPa served as thresholds to identify significant liver fibrosis and cirrhosis, respectively. We employed a multivariate logistic regression analysis to determine the effect of SVR on the presence of HS and significant liver fibrosis while accounting for potential confounders.

Result(s): We included 89 HCV mono-infected patients (mean age 65 yrs, 49% male). The percentage of individuals with SLD was 50% at baseline and 65% 6 months after SVR (p=0.043). While MASLD remained unchanged from 56% at baseline to 51% after SVR, there was an increase in post-SVR SLD (not meeting MASLD criteria) from 0% to 7% (p=0.010). Significant liver fibrosis and cirrhosis declined after SVR, from 27% to 16% (p=0.074) and from 18% to 3% (p=0.001), respectively (see Figure). Furthermore, in 65% of patients, TE decreased to a level below the threshold of significant liver fibrosis. In the multivariate model, SVR was associated with a higher odd of post-SVR SLD (adjusted odds ratio (aOR) 2.7, 95% confidence interval (CI) 1.38 – 5.52) and a decline in significant liver fibrosis by 80% (aOR 0.20, 95% CI 0.09 – 0.42). Moreover, SVR showed no impact on MASLD (aOR 1.87, 95% CI 0.95 – 3.68).

graphic file with name canlivj-7.1-abst_fig4.jpg — Image:

Conclusion(s): Our pilot results suggest that SVR nearly tripled the likelihood of post-SVR SLD, but not MASLD. Moreover, the effect of SVR on liver fibrosis was consistent with previous research.

References: 1. Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023.

2. Elgretli W, Chen T, Kronfli N, Sebastiani G. Hepatitis C Virus-Lipid Interplay: Pathogenesis and Clinical Impact. Biomedicines. 2023;11(2).

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):86–87.

CLM-O08 Sofosbuvir/Velpatasvir (S/V) for the treatment of HCV infection among vulnerable inner-city residents

B Conway ^1,², S Beitari ¹, R Yung ¹, S Yi ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: The combination of Sofosbuvir/Velpatasvir(S/V) is approved for the treatment of chronic HCV infection. In registrational trials, cure rates of 95% were achieved when administered as one pill/day for a period of 12 weeks regardless of genotype or disease stage. IN the SIMPLIFY study of HCV-infected injection drug users, 97/103 (94%) participants were cured with S/V, with no demonstrated cases of virologic failure. There is a need to extend these results to other groups, including more vulnerable inner-city residents in areas with a high prevalence of HCV infection.

Purpose: To evaluate the safety and efficacy of S/V in a prospective study of HCV-infected inner-city residents enriched for risk behaviors for non-adherence to therapy, including ongoing fentanyl use and unstable housing.

Method: Through dedicated outreach events, we identified HCV-infected patients who were not currently engaged in health care and who were eligible to receive government-funded antiviral treatment for HCV infection. We offered the opportunity to enroll in a multidisciplinary program of care to address medical, psychological, social, and addiction-related needs, and provide S/V therapy in this context, with enhanced supervision of adherence. The endpoint of this analysis was the efficacy of S/V therapy and its correlates.

Result(s): In this ongoing study, we have identified 251 eligible subjects, 28.3% female, 18.7% identifying as indigenous, median age of 46 (20-81) years. The most common genotypes were 3A/1A being 3A followed by 1A (46.2%/43.8%), 22.7% with F3-F4 fibrosis, 70.1% with unstable housing, 97.6% active drug users, mainly fentanyl or amphetamines (98%/74.3%). Of the 251, HCV therapy has been started in 219 cases (within a median 6 weeks of engagement in care), with 30 awaiting treatment and 2 drug related deaths before treatment initiation. Of 219, 192 have completed treatment, 13 are currently on treatment, 3 died after initiating treatment due to drug overdoses, 6 discontinued prematurely and 5 documented virologic relapse. All 6 who discontinued prematurely did so within the first week of treatment. Of the 192 completing treatment, final outcomes are available in 181 cases, with 176 confirmed as cured (mITT SVR rate 97.2%).

Conclusion(s): Our data support the use of S/V for the treatment of less stable HCV-infected PWUD. When this is done within the context of multidisciplinary programs such as ours, the rate of loss to follow up is only 2% and the cure rate exceeds 97%.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):87–89.

CLM-O09 Prevalence of, and effect of semaglutide on, features of non-alcoholic steatohepatitis in patients with obesity with and without type 2 diabetes: analysis of data from two randomised placebo-controlled trials using somasignal tests

JP Arab ¹, JM Schattenberg ², H Gr⊘nbæk ³, I Kliers ⁴, S Ladelund ⁴, MT Long ⁴, SB Nygård ⁴, AJ Sanyal ⁵, M Davies ⁶

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Novel, non-invasive biomarkers to grade and stage non-alcoholic fatty liver disease (NAFLD) and its progressed form, non-alcoholic steatohepatitis (NASH), are urgently needed. A targeted proteomics signature derived from patients with histologically-defined NASH has been developed collaboratively with the NASH Clinical Research Network (SomaSignal tests) to relate to the presence and severity of NASH components and changes over time.

Purpose: In this analysis, SomaSignal tests were applied to proteomics data generated from two weight-loss trials in order to characterize the prevalence of NASH components at baseline and investigate the effect of semaglutide.

Method: STEP 1 (NCT03548935) and STEP 2 (NCT03552757) were phase 3a, randomised, placebo-controlled trials of once-weekly subcutaneous semaglutide (2.4 mg in STEP 1; 1.0 mg and 2.4 mg in STEP 2) vs placebo for weight reduction in adults with overweight/obesity without (STEP 1) or with (STEP 2) type 2 diabetes (T2D). Patients received treatment for 68 weeks. Prediction probabilities (PP) for NASH components at baseline were derived using SomaSignal models. The efficacy of semaglutide vs placebo was analyzed as presence or absence of NASH components using a binary classifier derived from the PP (PP ≥ 0.5) at the end of the trial (EOT) and as odds ratios at EOT based on PPs directly. The SomaSignal categories included: steatosis grade 1–3 vs 0; lobular inflammation grade 2–3 vs 0–1; hepatocyte ballooning grade 1–2 vs 0; and fibrosis stage 2–4 vs 0–1. Based on the SomaSignal classifiers, patients were characterised into NAFLD stages: NAFL if steatosis was present but with no other NASH components; indeterminate if some, but not all, NASH components or fibrosis were present; and NASH if steatosis, inflammation and ballooning (with or without fibrosis) were present.

Result(s): Proteomics data were available for 1307/1961 and 643/1210 randomised patients in STEP 1 and 2; these patients were representative of the full study populations in each trial. At baseline, steatosis was present in 43% of patients in STEP 1, and the prevalence of the other components was 5% or less. In STEP 2, steatosis was present in 72% of patients, 15% had NASH and 12% had NASH with fibrosis. The odds of having each NASH component were significantly lower at EOT for patients who received semaglutide vs placebo, with a dose-dependency trend in STEP 2, using both PP and binary classification (Figure). Further, semaglutide was associated with significantly lower odds of having a more severe NAFLD stage after treatment vs placebo.

graphic file with name canlivj-7.1-abst_fig5.jpg — Image:

Conclusion(s): Steatosis is highly prevalent in people with overweight/obesity, with NASH likely present in 15% of patients with overweight/obesity and T2D (STEP 2). Semaglutide had a favourable effect on NASH components in the current analysis in populations with overweight/obesity, with and without T2D, as measured by SomaSignal models.

Disclosure of Interest: J. P. Arab: None Declared, J. Schattenberg Grant / Research support from: Boehringer Ingelheim, Gilead Sciences, Histoindex Siemens Healthcare GmbH, Consultant of: AGED Diagnostic, Apollo Endosurgery, Bayer, Boehringer Ingelheim, Gilead Sciences, GSK, Intercept Pharmaceuticals, Inventiva Pharma, Ipsen, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Siemens Healthineers; and speaker honorarium from Boehringer Ingelheim, Echosens, MedPublico GmbH, Histoindex, Madrigal Pharmaceuticals and Novo Nordisk., H. Gr⊘nbæk Grant / Research support from: Abbvie, ADS AIPHIA Development Services AG, ARLA Food for Health, and Intercept, Consultant of: Ipsen, Novo Nordisk and Pfizer, Paid Instructor of: AstraZeneca and EISAI; and is part of the data monitoring committee IQVIA, I. Kliers Employee of: Novo Nordisk, S. Ladelund Shareholder of: Novo Nordisk, Employee of: Novo Nordisk, M. Long Shareholder of: Novo Nordisk, Employee of: Novo Nordisk, S. Nygård Employee of: Novo Nordisk, A. Sanyal Shareholder of: Akarna, Durect, Galmed, Genfit, Indalo, Inversago and Tiziana;, Grant / Research support from: Astra Zeneca, Bristol Myers Squibb, Cumberland, Echosens, Gilead, Intercept, Mallinckrodt, Merck, Novartis, Salix, Shire and Tobira and receives royalties from Elsevier and UptoDate., Consultant of: 89 Bio, Alnylam, Amgen, Astra Zeneca, Birdrock, Boehringer Ingelheim, Bristol Myers Squibb, Conatus, Eli Lilly, Enyo, Exhalenz, Genfit, Gilead, Hemoshear, Inventiva, Janssen, Mallinckrodt, Merck, Nimbus, Nitto Denko, Northsea Pharmaceuticals, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche, Sagimet, Salix, Siemens, Takeda, Terns, Tobira and Valeant, M. Davies Grant / Research support from: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk and Sanofi-Aventis. She is co-funded by the NIHR Leicester Biomedical Research Centre., Consultant of: acted as a consultant, advisory board member and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi-Aventis, as an advisory board member and speaker for AstraZeneca, as an advisory board member for Gilead Sciences Ltd, Janssen and Lexicon, and as a speaker for Napp Pharmaceuticals, Novartis and Takeda Pharmaceuticals International Inc.

Can Liver J. 2024 Feb 26;7(1):89–91.

CLM-O10 Hedgehog signalling and metabolic responses drive CD8 T cell hyperfunction in advanced liver diseases

J Li ^1,^2,³, K Jorritsma ^1,^2,³, A Vranjkovic ², KR Levesque ^1,², J Madani ^1,², D Read ^1,², WL Stanford ^3,^4,^5,⁶, AC Cheung ^3,⁷, CL Cooper ^3,^8,^9,¹⁰, M Ardolino ^1,^3,¹¹, AM Crawley ^1,^2,^3,¹²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: Prolonged liver insult in chronic HCV infection (cHCV) and metabolic dysfunction-associated liver disease (MASLD) results in progressive liver damage and increased risk for hepatocellular carcinoma. CD8 T cell function is altered in infectious and non-infectious liver diseases regardless of antigen-specificity. We previously reported long-lasting bulk CD8 T cell hyperfunction in cHCV associating with fibrosis severity, yet specific underlying mechanisms remain elusive.

Purpose: To investigate mechanisms of generalized CD8 T cell dysfunction in advanced liver disease.

Method: We isolated blood CD8 T cells from cHCV or MASLD patients with varying degrees of liver damage. Gene Set Enrichment and Gene Ontology analyses of RNA-seq data were performed on stimulated cells from cHCV, which lead to flow cytometry probing of Hedgehog (Hh) signalling using pathway inhibitors, and cell death assessment. We established mouse models of T cell hyperfunction in liver disease by exposure to hepatotoxin carbon tetrachloride (CCl₄), or high-fat, methionine-choline deficient diet (HFMCDD), the latter mirroring human MASLD pathophysiology. T cell function and metabolic activity in these models were assessed by flow cytometry and Seahorse XF Mito Stress test.

Result(s): RNA-seq identified 362 differential genes in CD8 T cells from cHCV patients with cirrhosis vs minimal fibrosis, highlighting genes associated with T cell metabolism and function, including Hh signalling, apoptosis, glycolysis, oxidative phosphorylation, cytoskeletal regulation, inflammatory processes, and cell cycle regulation. RT-qPCR confirmed increased Hh pathway gene expression (PTCH1, GLI1) in cHCV patients with cirrhosis. Hh signalling inhibition in hyperfunctional CD8 T cells from cHCV patients with cirrhosis restored T cell function to healthy control levels, while functional cells also express higher cell death markers. Hyperfunction was also observed in HCV⁻ MASLD patients with biopsy-proven advanced fibrosis/cirrhosis. In CCl₄-treated mice, CD8 T cell hyperfunction was coupled to impaired responses to ectopic tumour growth and immunotherapy. In HFMCDD-treated mice, cells also exhibited hyperfunction, coupled with increased glycolytic activity and mitochondrial respiration. HFMCDD-treated mice also exhibited increased metabolic activity in CD4 T cells and elevated inflammatory profiles in systemic and hepatic macrophages (see abstracts: N. Campeau, D. Lawton).

Conclusion(s): In advanced liver disease, CD8 T cell hyperfunction appears driven by an overall disruption in inflammatory and metabolic processes upon activation, which may involve dysfunctional Hh signalling and a greater propensity for apoptosis. In mice, CD8 T cell hyperfunction is coupled to host and cellular metabolic disruptions, which may contribute to impaired anti-tumour and immunotherapy responses. Understanding mechanisms of chronic immune dysfunction may translate to therapeutic strategies to improve clinical outcomes for individuals living with advanced liver diseases.

References: (1) Vranjkovic, A., F. Deonarine, S. Kaka, J. B. Angel, C. L. Cooper, and A. M. Crawley. 2019. Direct-Acting Antiviral Treatment of HCV Infection Does Not Resolve the Dysfunction of Circulating CD8+ T-Cells in Advanced Liver Disease. Front Immunol 10:1926. (2) Li, J., A. Vranjkovic, D. Read, S. P. Delaney, W. L. Stanford, C. L. Cooper, and A. M. Crawley. 2023. Differential and lasting gene expression changes in circulating CD8 T cells in chronic HCV infection with cirrhosis and related insights on the role of Hedgehog signaling. BioRxiv (Pre-print) BIORXIV/2023/557725. (3) Madani, J., J. Li, A. Vranjkovic, K. Jorritsma, M. S. Hasim, M. Daneshmand, A. C. Cheung, A. M. E. Ching, J. E. Bruin, M. Ardolino, and A. M. Crawley. 2023. CD8 T cell hyperfunction and reduced tumour control in models of advanced liver fibrosis. BioRxiv (Pre-print) BIORXIV/2023/557752.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):91–92.

CLM-O11 Lack of protective immunity against hepatitis C virus reinfection post antiviral therapy

E Gomez Escobar ^1,², A Fieffé-Bédard ¹, NF Abdeltawab ^1,³, N Bédard ¹, M Eisa ¹, N Flores ^1,², J Bruneau ^1,⁴, A Grakoui ⁵, NH Shoukry ^1,⁶

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: Around 30% of subjects acutely infected with hepatitis C virus (HCV) spontaneously clear the infection with long-lived memory T and B cell responses. We and others have demonstrated that these memory responses expand rapidly upon reinfection leading to higher rates of spontaneous clearance (50-80%) [1,2]. In contrast, most acute infections become chronic with dysfunctional immune responses. Direct-acting antiviral (DAA) leads to sustained virologic response (SVR) in >95% of persistently infected subjects. However, recent studies showed that immune responses are not fully restored after cure and maintain an immunological scar [3]. This suggests that restored immune responses will not be functional in reinfection/vaccination of high-risk individuals like people who inject drugs (PWID). PWID reinfected with HCV after cure represent a natural rechallenge experiment to identify correlates of protective immunity mimicking vaccination post cure.

Purpose: We aimed to determine whether T cell and antibody responses in cured PWID protect upon HCV reinfection following viral elimination by DAA or IFN-based therapy.

Method: We examined the proportion of participants (n=74) from the Montreal Hepatitis C cohort that spontaneously cleared the first episode of HCV reinfection post spontaneous clearance, IFN or DAA therapy. We evaluated the longitudinal immune response in a subset of PWID reinfected post DAA- (n=5) or IFN- (n=11) cure. We studied key time points: pre-treatment, SVR/pre-reinfection (<2 years pre-reinfection), early acute (<3 months post estimated date of reinfection (EDI)), late acute (3-7 months post-EDI) and follow-up (>7 months post-EDI). We evaluated T cell response by IFNg ELISpot against overlapping peptide pools of HCV polyprotein, and HCV antibodies by ELISA and neutralization assays (HCV pseudoparticles). We compared results to those of PWID who cleared HCV reinfection post spontaneous clearance (SR/SR, n=14).

Result(s): The proportion of participants that spontaneously cleared post-DAA reinfection was 0% as compared to 28% post-IFN and 68% post-SR. The magnitude of HCV-specific T cell response at early reinfection post therapy was lower than SR/SR (p=0.1135). The T cell response to nonstructural proteins was predominant in all groups but some SR/SR (n=6) showed early strong response to structural ones, not observed in reinfection post cure. HCV antibodies were high after DAA-cure and remained stable upon reinfection. In contrast, antibody levels dropped post IFN-cure and increased progressively during reinfection. Despite significantly higher plasma neutralizing breadth and potency post DAA-cure than post IFN-cure (p=0.0035, p=0.0251) and SR/SR (p=0.004, p=0.0007), subjects were not protected and became chronic upon reinfection.

Conclusion(s): Restored HCV-specific immune responses post DAA-cure do not protect against chronic infection upon re-exposure and reinfection suggesting customized vaccination strategies will be required in this group.

References:

1. Osburn et al, Gastroenterology 2010

2. Abdel-Hakeem et al, Gastroenterology 2014

3. Hensel et al, Nat Immunol 2021

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):92–93.

CLM-O12 Evaluating the cost-effectiveness of prison needle and syringe programs in preventing hepatitis C infection among people who inject drugs in Canadian Federal prisons

F Houdroge ¹, N Kronfli ^2,^3,⁴, M Stoove ^1,⁵, N Scott ^1,⁵

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Prison needle and syringe programs (PNSPs) are evidence-based prevention strategies that reduce the transmission of bloodborne viruses including hepatitis C virus (HCV) among incarcerated populations. PNSPs were introduced in Canadian federal prisons in 2018, but are only available in nine of 43 prisons. PNSPs have been shown to be cost-effective in the community but have yet to be assessed in carceral settings.

Purpose: To assess the return-on-investment of existing PNSPs in nine federal prisons and project the benefit-cost ratio (BCR) of scaling-up PNSPs to all 43 federal carceral settings.

Method: A stochastic compartmental model was developed, incorporating the entire incarcerated population housed in federal prisons, to estimate the number of HCV infections and injecting-related infections (IRIs) prevented under different PNSP scenarios over 2018-2030 and compared with a counterfactual scenario without PNSPs. The first scenario was status quo, reflecting current PSNP coverage observed between 2018-2022 and future coverage assumed to remain at 2022 levels. The second scenario was PNSP scale-up, with PNSPS implemented in all 43 federal prisons over 2024-2026, and coverage increased to reach 50% of people who inject drugs (PWID) in prison by 2030. The primary outcome of each scenario was the projected number of new HCV infections and IRIs occurring among PWID in prison. Costs are reported in 2023 Canadian dollars and discounted at 3.5% per annum. The BCR was calculated as total benefits divided by total costs.

Result(s): In 2022, PNSP coverage across the nine federal prisons was estimated at approximately 10% of PWID. Compared to no PNEP, this was estimated to cost CAD $0.48 million [$0.36 – $0.69 million] and avert 9 [95% confidence interval -308 – 316] HCV infections and 30 [-2,049 – 2,099] IRIs over 2018-2030, with an estimated BCR of 1.4 [-20.5 – 22.3]. Compared to maintaining current coverage, expanding PNSPs to reach 50% of PWID across all federal prisons from 2024 to 2030 was estimated to cost an additional $2.1 million [$1.5 – $3.3 million], avert an additional 45 [-132 – 177] HCV infections and 462 [-617 – 1,537] IRIs, and save $7.2 million [-$1.1 – $15.7 million] in HCV and IRI treatment costs. This scale-up scenario had an estimated BCR of 3.4 [-0.1 – 6.9].

Conclusion(s): This study demonstrates that while the current modest coverage is cost-saving, scaling-up PNSPs to all Canadian federal prisons could amplify these savings due to even more averted HCV and IRI treatment costs. While the current program has had modest health benefits due to low uptake, a comprehensive scale-up could lead to additional health and economic returns.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):93–94.

CLM-O13 Ethnic disparity in mortality related to extrahepatic manifestations among people with chronic HCV infection: a large, linked administrative population-based study in British Columbia, Canada

D Jeong ¹, S Wong ², JD Makuza ¹, HA Velásquez García ², PA Adu ², SR Bartlett ^1,², EM Yoshida ³, A Ramji ³, ME Karim ^1,⁴, AR Manges ^1,², M Binka ², A Yu ², M Alvarez ², G Cua ², M Krajden ^2,³, NZ Janjua ^1,²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: HCV infection is the leading cause of liver-related death and is associated with increased risk of non-liver-related mortality due to extrahepatic manifestations (EHM).^1,2 Previous studies suggested ethnic disparities in HCV-related clinical outcomes.^3,4 Currently, research regarding ethnic disparities in EHM-related mortality is limited.

Purpose: We aimed to assess the ethnic disparity in EHM-related mortality in a population-based cohort in British Columbia (BC), Canada.

Method: We used the BC Hepatitis Testers Cohort (BC-HTC) to identify all individuals diagnosed with HCV from 1990-2015, linked with administrative health datasets. We defined EHM-related deaths as causes of death from cardiovascular and cerebrovascular diseases, chronic kidney disease (CKD), and diabetes mellitus. Individuals were followed from the date of their first HCV diagnosis until the earliest of the following: 1) EHM-related death, 2) other death, or 3) end of study (2021/12/31). EHM mortality rates were generated for each ethnic group (East Asian, South Asian, and Other) and by HCV treatment status (treated, untreated). We used multivariable subdistribution hazards models to account for competing risks and confounders.

Result(s): Study population included 1,399 East Asian, 1,522 South Asian and 37,890 Other people diagnosed with chronic HCV in the BC-HTC. East Asian and South Asian were older compared to Other (45.4% vs 43.0% vs 25.9% ≥ 50 years of age, respectively), had a greater prevalence of diabetes (7.4% vs 12.8% vs 4.3%), end-stage renal disease (1.1% vs 2.4% vs 0.6%), and hypertension (15.7% vs 17.5% vs 8.4%), with greater material deprivation (28.6% vs 44.2% vs 23.6%), respectively. However, East and South Asian, compared to Other, had a lower prevalence of alcohol use disorder (2.6% vs 8.3% vs 17.8%) and injection drug use (5.5% vs 7.1% vs 20.9%). The overall EHM-related mortality rate was the highest among untreated South Asian (14.26 per 1,000 PYs) followed by untreated East Asian (13.25 per 1,000 PYs) and untreated Other (10.44 per 1,000 PYs). The mortality rates were considerably lower for all individuals who were treated (2.52, 3.06, 2.87 per 1,000 PYs, for East Asian, South Asian and Other, respectively). Among untreated people, East Asian had a lower risk of overall EHM-related death (adjusted subdistribution hazard ratio [asHR] 0.79 95%CI 0.63-0.98) compared to Other; South Asian had a higher risk of CKD-related mortality compared to Other (asHR 1.61 95%CI 1.15-2.25). Among those who were treated, the risk of EHM-related death did not statistically differ for East and South Asians compared to Other.

graphic file with name canlivj-7.1-abst_fig6.jpg — Image:

Conclusion(s): EHM-related mortality was higher among East and South Asians diagnosed with HCV, especially for those who didn’t receive treatment. HCV treatment reduced the risk of EHM-related death across all ethnicities and reduced disparities in EHM-related mortality. Continued provider and patient engagement efforts for HCV treatment could significantly reduce the burden of HCV-related mortality.

References:

1. Blach S et al. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol. 2017 Mar 1;2(3):161–76.

2. Negro F et al. Extrahepatic Morbidity and Mortality of Chronic Hepatitis C. Gastroenterology. 2015 Nov 1;149(6):1345–60.

3. Emmanuel B et al. Racial disparity in all-cause mortality among hepatitis C virus-infected individuals in a general US population, NHANES III. J Viral Hepat. 2017;24(5):380–8.

4. Jeong D et al. Impact of HCV infection and ethnicity on incident type 2 diabetes: findings from a large population-based cohort in British Columbia. BMJ Open Diabetes Research and Care. 2021 Jun 1;9(1):e002145.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):94–95.

CLM-O14 mTORC1 activation promotes systemic and hepatic M1 macrophage polarity in viral and diet-induced advanced liver fibrosis

D Lawton ^1,^2,³, K Jorritsma ^1,², A Cheung ^3,⁴, CL Cooper ^3,^5,^6,⁷, AM Crawley ^1,^2,^3,⁸

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: Monocyte-derived macrophages (MoMϕs) infiltrate in large quantities to augment the resident liver Kupffer cells (KC) and play a central role in maintaining the homeostasis of the liver and mediating the development of fibrosis and liver healing. mTORC1 activation promotes inflammatory M1 macrophage phenotypes in systemic and hepatic niches in several chronic diseases. We have previously identified M1 macrophages as key producers of IFN-γ and this was amplified in HCV infection with cirrhosis, however, it remains unclear if mTORC1 is promoting M1 dysfunction in chronic advanced liver diseases.

Purpose: Identify the mechanism promoting M1 dysfunction in chronic HCV and diet-induced advanced liver fibrosis

Method: Macrophage subsets were differentiated in vitro with M-CSF, polarized and stimulated with lipopolysaccharide (LPS) from blood monocytes of healthy and treatment-naïve HCV+ individuals with minimal or advanced fibrosis (< 9 KPa or > 12.5 KPa). Male C57BL/6 mice were fed a high-fat methionine and choline-deficient diet (HFMCDD) ad libitum for 16 weeks to induce advanced liver fibrosis. Tibia and femurs were collected to generate bone marrow-derived macrophages (BMDMs) and livers homogenized for Kupffer cell analysis. To impair M1 macrophage development, mTORC1 inhibitor (rapamycin) was added in conjunction with polarizing cytokines. Cell phenotype and function were assessed by flow cytometry.

Result(s): Inhibition of mTORC1 with FDA-approved rapamycin during polarization of MDMs impairs M1 differentiation, including IFN-γ secretion. Inhibition of mTORC1 via rapamycin treatments was confirmed by a reduction of phosphorylated S6 protein. Untreated, HCV-derived advanced fibrosis-derived macrophages appeared to prefer an M2-like phenotype (CD80-CD163+) while producing high amounts of IFN-γ compared to healthy controls. M1 polarization and LPS activation induced increased CD80 expression with advanced fibrosis than in minimal fibrosis. HFMCD mice exhibited significant F4 fibrosis post-16 weeks of diet when compared to regular chow controls. Both male and female mice showed elevated inflammatory markers including IFN-γ in polarized macrophages in both BMDMs and KCs, which may be reversed with mTORC1 inhibition.

Conclusion(s): We have identified significant systemic dysfunction of monocyte-derived macrophages in cHCV infection with advanced fibrosis and this was replicated in BMDMs and KC in an animal model of diet-induced liver fibrosis. Enhanced inflammatory macrophage activity, characterized by elevated IFN-γ, predominates systemically and in the liver in advanced liver fibrosis. These findings suggest rapamycin may be a therapeutic target to restore systemic and hepatic macrophage polarity. Identify the mechanism promoting M1 dysfunction in chronic HCV and diet-induced advanced liver fibrosis.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):95–97.

CLM-O15 Efficacy and safety of maralixibat in patients with progressive familial intrahepatic cholestasis (MARCH): A randomized placebo-controlled phase 3 study

AG Miethke ¹, A Moukarzel ², G Porta ³, JC Esquer ⁴, P Czubkowski ⁵, F Ordonez ⁶, M Candusso ⁷, AA Aqul ⁸, RH Squires ⁹, E Sokal ¹⁰, D D’Agostino ¹¹, U Baumann ¹², L D’Antiga ¹³, N Kasi ¹⁴, N Laborde ¹⁵, C Arikan ¹⁶, C-H Lin ¹⁷, N Mittal ¹⁹, S Gilmour ¹⁸, FK Chiou ²⁰, SP Horslen ⁹, W-D Huber ²¹, A Van Leerberghe ²², S Weber R⊘nn ²², T Nunes ²², A Lascau ²², L Longpre ²², DB Mogul ²², W Garner ²², P Vig ²², VF Hupertz ²³, RP Gonzalez-Peralta ²⁴, U Ekong ²⁵, J Hartley ²⁶, N Laverdure ²⁷, N Ovchinsky ²⁸, RJ Thompson ²⁹

^¹Cincinnati Children's Hospital Medical Center, Cincinnati, United States,

^²Hotel Dieu De France Saint Joseph University Hospital, Beirut, Lebanon,

^³Hospital Sirio Libanes, Sao Paulo, Brazil,

^⁴Nois De Mexico SA De CV, Jalisco, Mexico,

^⁵The Children's Memorial Health Institute, Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, Warsaw, Poland,

^⁶Cardioinfantil Foundation - Lacardio, Bogota, Colombia,

^⁷Ospedale Pediatrico Bambino Gesu Irccs, Lazio, Italy,

^⁸University of Texas Southwestern Medical Center, Dallas, Texas, United States,

^⁹UPMC Children's Hospital of Pittsburgh, Pediatrics, Pittsburgh, United States,

^¹⁰Pediatric Hepatology, Uclouvian, Cliniques Universitaires St Luc, Belgium,

^¹¹Hospital Italiano De Buenos Aires, Buenos Aires, Argentina,

^¹²Hannover Medical School, Pediatric Gastroenterology and Hepatology, Hannover, Germany,

^¹³Hospital Papa Giovanni XXIII, Paediatric Hepatology, Gastroenterology and Transplantation, Bergamo, Italy,

^¹⁴Medical University of South Carolina, Charleston, United States,

^¹⁵Hôpital Des Enfants – CHU Toulouse, Toulouse, France,

^¹⁶Koc University School of Medicine, Istanbul, Türkiye,

^¹⁷Children's Hospital Los Angeles, Los Angeles, United States,

^¹⁸Pediatrics, University of Alberta, Alberta, Canada,

^¹⁹University of Texas Health Science Center at San Antonio, San Antonio, United States,

^²⁰Kk Women's and Children's Hospital, Singapore, Singapore,

^²¹Medical University of Vienna, Vienna, Austria,

^²²Mirum Pharmaceuticals, Foster City, California, United States,

^²³Cleveland Clinic Children's, Cleveland, Ohio, United States,

^²⁴AdventHealth for Children and AdventHealth Transplant Institute, Pediatric Gastroenterology, Hepatology, and Liver Transplant, Orlando, Florida, Canada,

^²⁵Medstar Georgetown University Hospital, Medstar Georgetown Transplant Institute, Washington, DC, United States,

^²⁶Birmingham Women and Children's Hospital, Birmingham, United States,

^²⁷Hopital Femme Mere Enfant, Hospices Civils De Lyon, Pediatric Hepato Gastroenterology and Nutrition Unit, Lyon, France,

^²⁸New York University Grossman School of Medicine, New York, United States,

^²⁹King's College London, Institute of Liver Studies, London, United Kingdom

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Progressive familial intrahepatic cholestasis (PFIC) is a group of genetic disorders resulting in disrupted bile composition, cholestasis, and pruritus.

Purpose: We evaluated maralixibat, an ileal bile acid transporter inhibitor, in a Phase 3 placebo-controlled study open to participants of all PFIC types at higher doses than previously studied.

Method: Participants aged 1-18 years with moderate-severe pruritus and elevated serum bile acid (sBA) levels were randomized 1:1 to maralixibat 570 μg/kg BID or placebo for 26 weeks. Primary and key secondary endpoints were mean change from Baseline in pruritus (0-4 ItchRO scale) and sBA, in the BSEP cohort. Mean change in pruritus and sBA were also analyzed in All-PFIC cohort.

Result(s): 93 participants were enrolled (maralixibat=47, placebo=46): 31 in BSEP cohort, 64 in All-PFIC cohort (31 BSEP, 13 FIC1, 9 MDR3, 7 TJP2, 4 MYO5B), 29 in exploratory cohort. Mean Baseline age, sBA, pruritus, and liver biochemistries were balanced. Mean reduction in pruritus for maralixibat vs placebo was -1.7 vs -0.6 (p=0.0098) in BSEP cohort and -1.8 vs -0.6 (p<0.0001) in All-PFIC cohort. 64% (maralixibat) vs 26% (placebo) of participants achieved clinically meaningful 1-point pruritus reduction (p=0.0023). Mean reduction in sBA for maralixibat vs placebo was -176 vs. 11 μmol/L (p=0.0013) in BSEP cohort and -157.5 vs. 2.9 (p<0.0001) in All-PFIC cohort. In All-PFIC cohort, total and direct bilirubin, and weight significantly improved under maralixibat. The most common adverse event, diarrhea, was mild and transient.

Conclusion(s): In the largest clinical study in PFIC, maralixibat significantly improved pruritus, sBA, bilirubin, and growth, and was well-tolerated.

Disclosure of Interest: A. Miethke Grant / Research support from: Mirum Pharmaceuticals, A. Moukarzel: None Declared, G. Porta: None Declared, J. Esquer: None Declared, P. Czubkowski: None Declared, F. Ordonez Speakers bureau of: Alexion Pharmaceuticals, Valentech Pharma, M. Candusso: None Declared, A. Aqul Consultant of: Mirum Pharmaceuticals, Albireo, Vivet Pharmaceuticals, R. Squires: None Declared, E. Sokal Shareholder of: Cellaion, Grant / Research support from: Mirum Pharmaceuticals, Albireo, Intercept, Consultant of: Albireo, D. D’Agostino: None Declared, U. Baumann Consultant of: Mirum Pharmaceuticals, Albireo, Vivet Therapeutics, L. D’Antiga Consultant of: Mirum Pharmaceuticals, Albireo, Selecta, Vivet Pharmaceuticals, Tome, Spark, Genespire, and Alexion, N. Kasi Consultant of: Mirum Pharmaceuticals, N. Laborde: None Declared, C. Arikan: None Declared, C.-H. Lin: None Declared, N. Mittal Grant / Research support from: Mirum Pharmaceuticals, S. Gilmour: None Declared, F. K. Chiou: None Declared, S. Horslen Grant / Research support from: Mirum Pharmaceuticals, Consultant of: Albireo, W.-D. Huber: None Declared, A. Van Leerberghe Shareholder of: Mirum Pharmaceuticals, Employee of: Mirum Pharmaceuticals, S. Weber R⊘nn Shareholder of: Mirum Pharmaceuticals, Employee of: Mirum Pharmaceuticals, T. Nunes Shareholder of: Mirum Pharmaceuticals, Employee of: Mirum Pharmaceuticals, A. Lascau Shareholder of: Mirum Pharmaceuticals, Employee of: Mirum Pharmaceuticals, L. Longpre Shareholder of: Mirum Pharmaceuticals, Employee of: Mirum Pharmaceuticals, D. Mogul Shareholder of: Mirum Pharmaceuticals, Employee of: Mirum Pharmaceuticals, W. Garner Shareholder of: Mirum Pharmaceuticals, Employee of: Mirum Pharmaceuticals, P. Vig Shareholder of: Mirum Pharmaceuticals, Employee of: Mirum Pharmaceuticals, V. Hupertz: None Declared, R. Gonzalez-Peralta Grant / Research support from: Mirum Pharmaceuticals, Consultant of: Mirum Pharmaceuticals, Albireo, U. Ekong Consultant of: Mirum Pharmaceuticals, J. Hartley: None Declared, N. Laverdure: None Declared, N. Ovchinsky Grant / Research support from: Mirum Pharmaceuticals, Albireo, Travere, Consultant of: Albireo, R. Thompson Shareholder of: Generation Bio, Rectify Therapeutics, Consultant of: Mirum Pharmaceuticals, Albireo, Generation Bio, Rectify Therapeutics, Alnylam

Can Liver J. 2024 Feb 26;7(1):97–98.

CLM-O16 IL-16, IL-10 and subpopulations of effector and regulatory CD4 T cells as biomarkers of disease activity and response to treatment in patients with autoimmune hepatitis

V Navalhas Cipriano ¹, F Dilauro ¹, V-A Raymond ¹, C Vincent ², F Alvarez ³, M Bilodeau ^1,², P Lapierre ^1,²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: First-line treatment achieves adequate response in 80-90% of patients with autoimmune hepatitis (AIH). However, if liver inflammation is not controlled, 10-20% of patients may progress to cirrhosis or liver transplantation. Currently, no clinical, biological, or histological parameters can predict the initial response to treatment or long-term remission. Therefore, there is a crying need for reliable biomarkers to predict disease activity and response to treatment.

Purpose: This study aimed to identify biomarker(s) of disease activity and treatment response in AIH patients.

Method: Using our biobank of biological samples and clinical data of AIH patients, a cross-sectional immunological profiling of cytokines linked to subtypes of CD4 T cells and flow cytometry analysis of CD4 T cells was performed on biological samples at the time of diagnosis and during treatment.

Result(s): IL-10 expression by PBMCs increased significantly after treatment in AIH patients that responded to treatment (13.64±2.84 Fold vs. 3.36±3.1, n=9, p=0.017) while plasma levels of IL-16 decreased (542.3±107.2 vs. 338.7±22.7 pg/mL, n=116, p=0.0099). Patients with elevated ALT levels (>40 IU/L) had significantly higher plasmatic levels of IL-16 (393.7±14.64 vs. 465.1±32.94, n=243, p=0.0359) that correlated with their level of activated CD4 but not activated CD8 T cells (r²=0.2720, n=20, p=0.0184). Patients that responded to treatment had higher CD3⁺CD4⁺FoxP3⁺CD25_highCD127_low regulatory T cells (Tregs) levels after treatment (5.38%±0.42%, n=6), similar to that of healthy controls (4.93%±0.55%, n=5), compared to patients before treatment (4.06%± 0.24%, n=3, p=0.038) and these levels correlated with IL-10 expression (r²=0.6484, n=9, p=0.0088) and plasmatic levels of IL-16 (r²= 0.1658, n=44, p=0.0061). Interestingly, plasmatic levels of IL-2 correlated with IL-16 levels suggesting a possible link between Treg and IL-16 (r²=0.1475, n=302, p<0.0001). PCA Analysis showed that CD4+ CXCR3+, CD8+ T cells, and Treg levels were responsible for most of the ALT variance (n=40). In vitro, IL-16 promoted the migration of CD4+ but not CD8+ T cells from AIH patients, and elevated plasmatic levels of IL-16 were associated with increased migration of CD4+ T cells (r²=0.7977, n=9, p=0.0012). Interestingly, patients treated with prednisone only had significantly lower levels of IL-16 and IL-2 compared to patients treated with azathioprine only (n=78, p=0.0304 and n=91 p=0.0071, respectively).

Conclusion(s): IL-10 and CD4 regulatory T cells are increased in patients that respond to treatment while IL-16 levels are decreased suggesting that these could be biomarkers of disease activity and treatment response in AIH patients. The identification of reliable biomarkers could allow for the prediction of treatment response in treatment-naïve patients and the development of effective personalized therapy and could be a milestone achievement for the clinical management of difficult-to-treat AIH patients.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):98–99.

CLM-O17 Single cell atlas reveals hepato-inflammatory gene activation and recruitment of myeloid-t cell axis specific to the neurologically deceased donor liver in comparison to the living donor liver

D Nakib ^1,², CT Perciani ¹, S Chung ^1,², D Camat ^1,², L Liu ^1,², XZ Ma ¹, J Manuel ¹, B Sayed ¹, M Cattral ¹, G Sapisochin ¹, A Ghanekar ¹, M Selzner ¹, N Selzner ¹, ID McGilvray ¹, SA MacParland ^1,²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Living donor (LD) liver transplantation represents 1 in 8 liver transplantations in Canada and has led to successful outcomes for patients on waitlists for neurologically-deceased donor (NDD) livers. Although short term recipient outcomes are similar between LD and NDD liver transplantation, it is unclear whether there are fundamental differences in the donor tissue types that influence long term outcomes¹. For example, hepatocyte stress, immune infiltration, and inflammation may differ. Studies have demonstrated an upregulation of inflammatory genes during the preparation, preservation and reperfusion of LD and NDD transplanted livers^2,3, which could have important impacts on transplant success.

Purpose: To better understand the underlying transcriptomic differences between the LD and NDD liver and how they may impact recipient outcomes, we generated an integrated single cell RNA-sequencing (scRNA-seq) map of both tissue types.

Method: We employed 10x Genomics 5’ scRNA-seq with T cell receptor (TCR) and B cell receptor (BCR) sequencing to examine the cellular landscapes of NDD liver caudates (n=10) and LD liver biopsies (n=10) collected immediately after laparotomy. In addition to LD liver biopsies, we collected matched blood (n=10).

Result(s): Our atlas demonstrates the presence of expected human hepatic cell populations in both the NDD and LD liver. We confirm the increased expression of pro-inflammatory genes in NDD-specific hepatocyte populations, examples include TGM2, NAMPT and SERPINE1, which are involved in myeloid polarization, recruitment and activation. We observe several NDD-specific myeloid populations. These include a recently-recruited neutrophil population enriched in inflammatory genes (S100A8/9), chemokine receptors (CXCR1/2), and CXCL8, a gene involved in T cell and myeloid recruitment to the liver. Through gene set enrichment analysis, we observe that the NDD-specific myeloid populations, as well as NDD-specific neutrophils, are enriched in pathways related to leukocyte activation, responses to inflammation and stress, in addition to the regulation and activation of T cells. After excluding any lymphocytes sharing gene expression profiles with circulating PBMCs, TCR sequencing reveals a significant increase in the clonotypic diversity of both naive CD4+ and effector memory CD8+ T cells in NDD livers in comparison to LD livers. However, BCR sequencing reveals similar clonotypic diversity of mature and antibody-secreting B cells in the NDD and LD liver. This suggests increased T cell-specific recruitment and infiltration of the NDD liver that is not observed in the LD liver.

graphic file with name canlivj-7.1-abst_fig7.jpg — Image:

Conclusion(s): Our results reveal that the NDD liver experiences an upregulation of hepato-inflammatory genes across cell types that is associated with the recruitment of a neutrophil-T-cell axis not observed in the LD liver.

References:

1. Goto, T. et al. Superior Long-Term Outcomes of Adult Living Donor Liver Transplantation: A Cumulative Single-Center Cohort Study With 20 Years of Follow-Up. Liver Transpl. 28, 834–842 (2022).

2. MacParland, S. A. et al. Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations. Nat. Commun. 9, 4383 (2018).

3. Borozan, I. et al. Gene expression profiling of acute liver stress during living donor liver transplantation. Am. J. Transplant. 6, 806–824 (2006).

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):100.

CLM-O18 Single-cell atlas of human pediatric livers reveals a macrophage specific inflammatory signature

RD Edgar ¹, D Nakib ^1,², D Camat ^1,², J Atif ^1,², S Chung ^1,², C Perciani ¹, L Liu ^1,², XZ Ma ¹, N Selvakumaran ³, J Manuel ¹, B Sayed ^1,³, I McGilvray ¹, K Huysentruyt ³, A Ricciuto ³, Y Avitzur ³, G Bader ^2,⁴, SA MacParland ^1,²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: Yes

Background: The liver is vital for metabolism and immune function. Although it is known that the liver is composed of a heterogeneous mix of cell types, how these cell types contribute individually, and in concert, toward liver function remains poorly understood. What is known about healthy liver function, cellular heterogeneity and cell structures is primarily based on studies of the adult liver. Comparatively little is known about the pediatric liver.

Purpose: To better understand cellular drivers of childhood liver diseases, including many rare metabolic and immune disorders, we generated single-cell RNA-seq (scRNA-seq) maps of the normal pediatric liver and employed this map to examine disease-specific populations in biopsies from pediatric patients with Intestinal Failure-Associated Liver Disease (IFALD).

Method: Here we integrated 10x Genomics scRNA-seq from adult normal, pediatric normal and pediatric IFALD livers for a total of 17 profiled livers.

Result(s): The pediatric liver map consists of 31,806 cells from caudate liver lobes of 7 pediatric transplant donors aged 2-17 years. In comparison to an adult map (25,428 cells; age 26-69) we observed differences in myeloid populations in the pediatric liver. Specifically, pediatric Kupffer-like cells (MARCO+C1QA+VSIG4+) exhibited higher expression of inflammatory cytokines and chemokines than adults (CCL4, CCL3 and IL1-β). Using the normal pediatric liver map as a comparator for three IFALD biopsies (12,018 cells; age 4 months-9 years) we were able to identify myeloid cell populations specific to IFALD as well as higher expression of profibrotic genes (LY96) in IFALD Kupffer-like cells.

Conclusion(s): The normal pediatric liver map will allow for further comparison of adult and pediatric livers, which could establish commonalities and pediatric-specific differences—an important issue as there are clear differences in pediatric and adult liver function. In addition the map will serve as an important comparator for the study of pediatric liver diseases.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):100–102.

CLM-P001 Disengagement from clinical care among people co-infected with hiv and hepatitis C (HCV): a scoping review

DA Dinh ¹, Y Tan ², S Saeed ³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: The “cascade of care” captures cross-sectional snapshots describing critical clinical care milestones. People living with HIV (PLWH) and Hepatitis C (HCV) co-infection follow two nested care cascades each presenting unique challenges. Disengagement from care (or losses along the cascade) has been shown to increase the risk of negative health outcomes and pose significant barriers to achieving the 95-95-95 HIV treatment targets and the WHO's viral hepatitis elimination goals.

Purpose: Given the paucity of synthesized information on the co-infected population, we conducted a scoping review to highlight the gaps in the literature related to the definition and conceptualization of disengagement from clinical care.

Method: The scoping review was conducted in accordance with the Joanna Briggs Institute framework. With the assistance of a health sciences librarian, a comprehensive search strategy was developed using 46 relevant keywords, including “HIV”, “HCV”, “co-infection”, and “disengagement”. An electronic search of 8 databases, reference screening of eligible studies, and cited reference searching via Google Scholar was conducted. Two reviewers screened for eligible studies: original, peer-reviewed or grey-literature articles from high-income countries published before May 2023. Only studies targeting cohorts of PLWH and HCV were included. Studies were classified as defining disengagement as the outcome, the exposure, and/or interventions related to disengagement.

Result(s): The search yielded 4462 non-duplicated studies, which were scoped to 27 (19 peer-reviewed and 8 grey literature sources). Most of the studies (n=22, 81%) focused on the HCV care cascade, two on the HIV care cascade, and three were not specific to either cascade. There was significant heterogeneity in the definitions of disengagement (Figure 1), and nine studies did not state the definition. Disengagement from clinical care was most commonly defined as an outcome of the included studies. Studies identified predictors of disengagement to be related to drug and substance use (n=5 articles), social and welfare (n=4), clinical factors (n=3), treatment setting (n=3), and demographic characteristics (n=2). When disengagement was defined as an exposure, it was associated with reduced odds of HCV treatment initiation (n=3), achieving sustained virological response (n=2), and maintaining HIV viral suppression (n=1). Interventions to improve care engagement among PLWH and HCV were limited to five studies, which used cash incentives (n=1), individual case management facilitated by pharmacists (n=1), nurses (n=1), social workers (n=1), or a multidisciplinary team (n=1) to mitigate disengagement.

graphic file with name canlivj-7.1-abst_fig8.jpg — Image:

Conclusion(s): Disengagement from clinical care cannot be compared between studies nor meta-analysed, due inconsistent definitions. To synthesize published literature, it will be imperative to establish a standardized definition of disengagement from care.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):102.

CLM-P002 “I’d prefer to go to the pharmacy. There's a couple procedures there eliminated right from the get go“ - characteristics of pharmacy-based hepatitis C testing of importance to people who inject drugs

C Balsom ¹, D Kelly ¹, S Bugden ¹, L Jackson ²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: There are barriers to the multi-step process of accessing standard Hepatitis C (HCV) testing for people who inject drugs (PWID). A pharmacy-based testing model has been proposed to improve access to testing for sexually transmitted and blood-borne infections (STBBI). Pharmacies are ideally positioned to offer point-of-care testing for STBBI because of their accessibility and widespread availability in most communities. Pharmacists can increase awareness of HCV risk by providing education and advice to those who receive injection supplies and opioid agonist therapy. Pharmacist testing models include providing education about the infection and treatment options, in addition to offering testing, interpreting/explaining results and linking people with reactive screening test results to confirmatory testing, care and treatment. Since pharmacies provide care for a variety of reasons there may be a sense of discretion from getting tested in pharmacies that is different from accessing testing through a needle syringe program or addictions center. However, whether pharmacies are seen favourably and are an attractive venue for testing among PWID is uncertain.

Purpose: This qualitative study aimed to determine what features of a pharmacy-based testing program for HCV would be important to people who inject drugs.

Method: Between June and August 2022, eleven PWID were interviewed using semi-structured interviews. Data were transcribed verbatim and reflective thematic analysis was performed.

Result(s): Five themes representing aspects of pharmacy-based testing that were appealing or of concern are presented: Ease of pharmacy testing, Confidentiality is important to attract people to testing, A fast result is often valuable, Less invasive testing is appealing to some, and the Relationship with the pharmacy and pharmacist affects willingness to be tested.

Conclusion(s): This study describes factors that are important in developing screening programs for PWID and reasons why they may or may not be interested in receiving HCV testing at a community pharmacy. To make progress towards HCV elimination efforts it will be important to address these factors to improve access and uptake of HCV testing programs for PWID, to increase case-finding and connect people with care and treatment.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):102–103.

CLM-P003 Collaborating with prison to test and treat people who use drugs in Victoria, British Columbia

T Barnett ¹, M Selfridge ^1,², L Munro ³, S Johnson ³, A Drost ¹, K Guarasci ¹, K Lundgren ¹, C Fraser ^1,⁴

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Canada is currently on target to reach the 2030 WHO goal of hepatitis C (HCV) elimination. Continued high rates of treatment initiation are required to meet this goal. People who use drugs (PWUD), account for the majority of new HCV cases in BC and continue to have many barriers to accessing DAA therapies, despite demonstrated high SVR rates in clinical trials. Prisons have a high level of HCV worldwide and HCV micro-elimination in prisons is an effective strategy to treat PWUD.

Prior to the partnership between Cool Aid Community Health Centre (CACHC) and the local prison there was a lack of communication in the community that led to HCV RNA positive individuals being lost to follow up. Provincially incarcerated individuals are sentenced to 2 years less a day. Limited blood draws done once a week in 4 hours block done by the local lab has been a barrier to accessing HCV treatment as clients are prioritized for phlebotomy based on severity of health conditions. The local lab requires clients be brought from their unit to the health centre which takes 25 minutes to move through the prison. There is over 200 people in the prison and the lab does 4-6 blood draws a week.

Purpose: The Prison HCV testing project seeks to determine whether testing in a Provincial prison in Victoria BC can be successful in finding populations who use drugs still living with HCV.

Method: Preceptorships and long-term relationship building with prison medical staff has allowed CACHC's HCV treatment nurse to get security clearance to enter the prison. The HCV treatment nurse along with the prison nurse hold HCV testing ‘blitzes’ on the prison units once a month and offer phlebotomy for screening and HCV pretreatment bloodwork. Candy bag incentives are offered at testing events. The HCV treatment nurse draws the bloodwork. The HCV treatment nurse follows up on HCV RNA positive results, does the treatment applications, case management, and follow up required. The prison nurse follows up on any abnormal results. Clients who test HCV RNA positive start on HCV treatment and if discharged from prison before completion of HCV treatment the HCV treatment nurse will follow the client in the community.

Result(s): Within the first 7 months of the project, nursing staff tested 111 people at the prison: To date 29 people have tested HCV antibody positive, 7 people tested RNA+ and 5 people have been started on treatment.

Conclusion(s): This innovative and novel approach to HCV therapy in PWUD in prisons was able to sucessfully test and treat HCV. CACHC and prison staff have an established relationship, reduced barriers, and have reached PWUD and others who remian untreated.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):103–105.

CLM-P004 Providing cell phones and peer support is effective at engaging people released from incarceration or experiencing unstable housing in to hepatitis C care

S Bartlett ^1,², N Gale ^1,³, M Korchinski ⁴, A Tiwana ^1,⁵, P Young ⁴, D Schmitz ⁶

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: People who experience criminalization (PWEC), including people who use drugs or who are incarcerated, have high prevalence of hepatitis C virus (HCV) infection. PWEC are often unsuccessfully reached by care providers, resulting in low HCV treatment uptake. A key reason for this is PWEC frequently do not have stable a contact number. Strategies to address this and enhance engagement in HCV care among PWEC are needed.

Purpose: ‘Test Link Call’ (TLC) was launched as a continuous quality improvement project in British Columbia (BC) in October 2021 to support engagement in HCV care among PWEC.

Method: TLC provides PWEC living with HCV a free cell phone and 6 month plan, plus connection to a Peer Health Mentor (PHM) to support engagement in HCV care. PHMs receive referrals from correctional centres and meet clients at release to provide phone and connect to care. A network of 16 services across BC identify additional PWEC in the community through outreach or among those that present for care. Services have cell phones on site to provide immediately to enrolled clients. We conducted a mixed methods evaluation of the first 15 months of TLC project to determine it's effectiveness and impact.

Result(s): Over 15 months, a total of 205 PWEC enrolled in TLC. Semi-structured interviews conducted with clients (n=10), PHMs (n=3) and care providers (n=5) described TLC as highly effective at increasing engagement in HCV care among PWEC. Five themes emerged to explain why and how TLC is effective:

1)
sense of personal value;
2)
convenience in accessing care;
3)
communication and trust;
4)
social connection; and
5)
motivation to change.

In-depth quantitative data collection was conducted in October 2022. Data were analysed to create an HCV care cascade (Figure 1). Overall, 49% (74/151) of clients had no fixed address and 38% (58/151) were on opioid agonist therapy (OAT). Among clients who received a prescription, 81% (58/72) started HCV treatment.

graphic file with name canlivj-7.1-abst_fig9.jpg — Image:

Conclusion(s): TLC effectively engages PWEC in HCV care. We haveexpanded eligibility of TLC to including supporting engagement in care among PWEC for HIV and hepatitis B virus as well now. Enrollment, monitoring and evaluation of TLC project is on-going.

Disclosure of Interest: S. Bartlett Grant / Research support from: AbbVie Corp., Gilead Sciences Inc., Consultant of: AbbVie Corp., Gilead Sciences Inc., Cepheid Canada, Speakers bureau of: AbbVie Corp., Gilead Sciences Inc., N. Gale: None Declared, M. Korchinski: None Declared, A. Tiwana: None Declared, P. Young: None Declared, D. Schmitz: None Declared

Can Liver J. 2024 Feb 26;7(1):105–106.

CLM-P005 Integrating a novel model of care for the screening and treatment of hepatitis C for clients enrolled in an opioid agonist management (OAT) program

LC Abraham ¹, B Dewdeny ¹, C Pinczak ¹, H O’Reilly ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: People on OAT are more likely to have HCV than the general population but less likely to travel to a lab for venipuncture. PATHOntario has developed a virtual self-screening model of care where clients self-screen for HCV while waiting for their OAT appointment. This model was tested as a method to increase HCV screening rates in people on OAT.

Purpose: Using a standard model of care, people on OAT are less likely to travel to a lab for venipuncture thus missing opportunities to be tested, diagnosed, and treated for HCV. PATHOntario developed a virtual self-screening model to give clients the opportunity to self-screen for HCV while waiting for their OAT appointment at any PATH site across Ontario. This model was tested in real time as a method to increase HCV engagement, screening, and treatment rates in people on OAT.

Method:

•
Clients on OAT due HCV screening are flagged via alert on their electronic medical record (EMR).
•
Clients present to their local clinic for their virtual OAT appointment. The EMR alert informs the virtual administrator that the client requires HCV screening. Point-of-care antibody tests and dried blood spot testing supplies are provided to the client, who is then connected virtually with an HCV nurse.
•
The HCV nurse guides the client to self-screen using the POC kit. If positive, DBS is completed. Clients are notified of results by the HCV RN and enrolled into care if indicated

Result(s):

From August 2022 to September 2023 1680 charts have been reviewed. 36.2% were AB-, 30.6% had no results on file, 19.4% were previously treated, 34.5% were RNA+ with no history of treatment, 3.4% were AB+ with no history of RNA testing and 4.5% were RNA+ with no history of treatment. See Figure 4.

Clients were flagged for HCV virtual screening or linkage to care. The results of the virtual POC and DBS screening and linkage to care element were: AB Screened 557, AB + 304, RNA Screened 254, RNA + 206, Initial Appt 124, Started Tx 108, SVR 4 23, SVR 12 23. See Figure 5.

This virtual HCV screening and treatment model has shown to be effective in both identifying clients in need of HCV treatment and linking them successfully to care. Adding and intensifying the retrospective review to eventually review all TrueNorth sites has also provided the opportunity to not only substantially increase numbers across all variables, but also provides the opportunity to add Alerts to any chart from Screening to any point in the Cascade of Care that necessitates the RN connecting with the patient.

Conclusion(s): Through the integration of HCV self-screening with Opioid Agonist Therapy (OAT), this model enables a single registered nurse (RN) to conduct POC screening, DBS screening and treatment consultations from various locations within a single day. This approach ensures equitable access to care for clients in remote communities and can be successfully implemented in any virtual OAT environment, effectively removing geographical and resource-based obstacles to care.

References: Lourenço, L., Kelly, M., Tarasuk, J., Stairs, K., Bryson, M., Popovic, N., & Aho, J. (2021). The hepatitis C epidemic in Canada: An overview of recent trends in surveillance, injection drug use, harm reduction and treatment. Canada communicable disease report = Releve des maladies transmissibles au Canada, 47(12), 561–570. https://doi.org/10.14745/ccdr.v47i12a01

Grebely, J., Tran, L., Degenhardt, L., Dowell-Day, A., Santo, T., Larney, S., Hickman, M., Vickerman, P., French, C., Butler, K., Gibbs, D., Valerio, H., Read, P., Dore, G. J., & Hajarizadeh, B. (2021). Association Between Opioid Agonist Therapy and Testing, Treatment Uptake, and Treatment Outcomes for Hepatitis C Infection Among People Who Inject Drugs: A Systematic Review and Meta-analysis. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 73(1), e107–e118. https://doi.org/10.1093/cid/ciaa612

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):106–107.

CLM-P006 Community pop-up clinic: cascade of care and HCV treatment of Vancouver's inner-city PWID populations

B Conway ^1,², S Yi ¹, S Beitari ¹, R Yung ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Several strategies have been proposed to identify HCV-infected inner-city residents, engage them in care, provide them with antiviral therapy, establish conditions to maximize treatment completion and its success. Elimination of HCV infection as a public health concern by the end of this decade will require a concerted effort to accomplish this in all target populations, including vulnerable inner-city populations, many of whom are actively using drugs and are facing other issues more challenging that HCV infection: housing and financial insecurity, untreated mental illness, and active untreated addiction.

Purpose: This study aims to assess the effectiveness of a multidisciplinary care approach in delivering HCV treatment to people who inject drugs (PWID) within Vancouver's inner city.

Method: We have evaluated a novel approach of Community Pop-Up Clinics, held on a weekly basis at single-room occupancy buildings in Vancouver's inner city. At each event, up to 30 individuals are offered point-of-care testing for HCV infection. If positive, an offer of integration into multidisciplinary care is made, including antiviral therapy if required, with such therapy delivered daily or weekly as required to maximize adherence. All participants are maintained in care to ascertain treatment outcome. This analysis was undertaken to evaluate the number of individuals who could be identified with this programmatic approach as well as treatment outcomes

Result(s): From 01/21 – 08/23 (32 months), we conducted 112 CPCs and evaluated 1968 individuals, of whom 620 (31.5%) were found to carry HCV antibodies, with 474 (76.5%) being viremic. Engagement in care was secured in 387 (81.6%) cases, with 326 (84.2%) individuals have started treatment and 60 in care but still in the pre-treatment phase, and 1 overdose death. The median time from CPC attendance to HCV treatment initiation was 6 weeks. Of 326, 302 have completed treatment, 18 are currently on treatment, 1 died of an overdose during treatment and 5 discontinued treatment within the first week and were lost to follow up (LTFU). Of the 302, 284 are confirmed as cured (SVR 12), 16 are awaiting SVR 4, and 2 had a documented virologic relapse. By mITT, the cure rate is 284/286 (99.3%). Loss to follow up rate is 5/387 (1.3%). We only documented 2 overdose deaths over 326 PY of overall follow-up.

Conclusion(s): For each hour of operation, the CPC program has identified at least one person requiring HCV therapy and engagement in care. Once engagement has been secured, the LTFU rate is extremely low and the rate of successful completion of treatment is 99% or more. An additional benefit my be a reduction in opioid overdose deaths. Taken together, the data we present validates the development of multidisciplinary programs such as ours aimed at treating HCV in vulnerable inner-city populations that must be engaged in care for HCV elimination to become a reality.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):107.

CLM-P007 Tackling hepatitis C disparities: Pasan's prison educational initiatives

C Cordon ¹, J Porter ², J Rowe ³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Hepatitis C Virus (HCV) remains a significant public health concern in Canada, disproportionately affecting incarcerated individuals. Moreover in Ontario, prisoners exhibit a higher prevalence of HCV, primarily due to injection drug use, tattooing, and other risky behaviors. PASAN, a non-profit organization in Ontario dedicated to delivering initiatives focusing on education and harm reduction, recognize that informed individuals are more likely to make safer choices. By conducting seminars tailored to the unique needs of incarcerated populations, PASAN equips prisoners with essential knowledge about HCV transmission, prevention, and treatment.

Purpose: PASAN's educational seminars employ evidence-based strategies, including interactive workshops, peer-led discussions, and the distribution of easy-to-read informational materials. By engaging with prisoners, PASAN fosters a safe and supportive environment for discussions about HCV. This collaborative approach is essential, as many prisoners have limited access to healthcare services and are often unaware of their HCV status.

Method: PASAN's impact is substantial, with reach extending to numerous provincial prisons and hundreds of incarcerated individuals across Ontario. PASAN's work not only contributes to reducing the spread of HCV within correctional facilities but also promotes healthier behaviors post-release, benefiting the broader community. Therefore, PASAN's work with incarcerated individuals has implications to Public Health.

PASAN also collaborates with other healthcare providers and government agencies to advocate for improved access to HCV testing, treatment, and harm reduction services within the prison system. PASAN emphasizes the importance of testing and early diagnosis to link infected individuals with appropriate care, ultimately reducing the long-term burden of liver disease.

Result(s): PASAN's innovative approach to educating prisoners about HCV plays a pivotal role in reducing the disproportionate impact of the virus on incarcerated populations. Their efforts exemplify the power of targeted education, peer support, and advocacy in addressing HCV disparities.

Conclusion(s): In this presentation, our objectives are to (1) underscore the unique care needs of incarcerated individuals living with HCV in Ontario prisons, (2) describe PASAN's innovative initiatives to decrease HCV transmission within the prison system and larger community, and (3) discuss our key learnings to date and encourage further collaboration, partnership, and support for this vital work with one of Canada's most vulnerable population.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):107–109.

CLM-P008 Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with liver fibrosis in people with Hepatitis C

W Elgretli ¹, M Shengir ¹, LE Ramos Ballestreros ², M Deschenes ³, P Wong ³, T Chen ³, A Keeshan ⁴, S Tandon ⁴, C Cooper ⁴, G Sebastiani ^1,^2,³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: Yes

Background: Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide leading to liver fibrosis, cirrhosis, and hepatocellular carcinoma. The development of significant liver fibrosis (stage ≥2) is associated with an increased risk for adverse hepatic outcomes. 45-55% of HCV patients can develop hepatic steatosis. A pan-national Delphi consensus has recently introduced the term steatotic liver disease (SLD) as an umbrella term and replaced the term “nonalcoholic fatty liver disease” to overcome its exclusionary and stigmatizing nature. SLD with cardiometabolic conditions is defined as “metabolic dysfunction-associated steatotic liver disease (MASLD)”. MASLD emphasizes the metabolic nature of hepatic steatosis and acknowledges its common coexistence with conditions such as alcohol consumption and HCV. However, the effect of this coexistence on liver fibrosis is unknown.

Purpose: To investigate the effect of the coexistence of MASLD and HCV on liver fibrosis.

Method: This was a retrospective, cross-sectional study including people with HCV monoinfection. Participants aged ≥18 years without HIV co-infection or other chronic liver diseases were included from 2 centers: McGill University Health Center (MUHC) and The Ottawa Hospital between the year 2014 and 2023. MASLD was defined as the presence of hepatic steatotis by controlled attenuation parameter (CAP) ≥275 dB/m plus one of the following cardiometabolic conditions: increased body mass index (BMI) and waist circumference; prediabetes or diabetes; hypertension; hypertriglyceridemia; low high-density lipoprotein. Liver fibrosis was defined as a liver stiffness measurement (LSM) of ≥7.1 kPa. The prevalence of liver fibrosis was estimated after stratifying our patients according to their steatosis and MASLD statuses. Cofactors of liver fibrosis were investigated in multivariable analysis by logistic regression.

Result(s): We included 590 people with HCV monoinfection (mean age 51±12, 39% females, mean BMI 28±6, 25% with diabetes or prediabetes, 17% with genotype 3, 74% with detectable HCV RNA). SLD was found in 36% of patients, and distributed as follows: MASLD 31% and SLD without cardiometabolic conditions 5%. The prevalence of liver fibrosis was 57%, 48% 38% in MASLD, SLD without cardiometabolic conditions, and no steatosis group, respectively (see Figure). After adjusting for age, sex, HCV RNA positivity, HCV genotype, and duration of diagnosis of HCV infection, cofactors of liver fibrosis were MASLD with prediabetes or diabetes (adjusted odds ratio [aOR] 4.92, 95% confidence interval [CI] 1.89-12.77; p=0.001) and MASLD with hypertension (aOR 2.25, 95% CI 1.18-4.29; p=0.01).

graphic file with name canlivj-7.1-abst_fig10.jpg — Image:

Conclusion(s): MASLD is associated with higher prevalence of fibrosis in people with HCV. Beyond pursuing virological cure, healthcare practitioners should target metabolic conditions. Longitudinal studies are needed to define the effect of the newly MASLD definition and enhance preventive and management strategies within this at-risk population.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):109–110.

CLM-P009 Comparison of hepatitis C virus screening strategies in community and clinical settings in Ontario

G Hirode ¹, B Wolfson-Stofko ¹, A Vanderhoff ¹, C Capraru ¹, J Karkada ¹, D Smookler ¹, SM Friedman ², K Bates ³, T Mazzulli ^4,⁵, JV Juan ⁶, HA Shah ¹, BE Hansen ⁷, HL Janssen ⁷, M Biondi ^1,⁸, JJ Feld ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Hepatitis C virus (HCV) screening and linkage to care with ongoing patient engagement is crucial to prevent transmission and progression to advanced liver disease. Existing strategies largely focus on risk-based and population-based screening instead of method of testing.

Purpose: This purpose of this study was to evaluate the effectiveness of different modalities of HCV antibody (Ab) testing including point-of-care tests (POC), dried blood spot collection cards (DBS), and phlebotomy-based serologic tests (ST) conducted in a large, real-world cohort across various clinical and community settings in Ontario.

Method: This is a cross-sectional study of individuals who completed HCV Ab testing at centers in partnership with the Viral Hepatitis Care Network (VIRCAN) (n=26,478). HCV RNA testing used DBS for POC and DBS Ab, and phlebotomy-based tests for ST (no reflex testing). Turnaround time was similar across all testing modalities; approximately two weeks for Ab and RNA. Test settings included primary care or HIV pre-exposure prophylaxis clinics (PC/PrEP), emergency department or walk-in clinics (ED/walk-in), one-time screening events (SE), community outreach programs (CO), and drug treatment centres (DC).

Result(s): Among the HCV Ab tested individuals, 36% were POC, 9% were DBS, and 55% were ST (figure). SE, CO, and DC largely used POC (≥95%), PC/PrEP used ST (92%), and ED/walk-in used a combination of POC (38%) and DBS (62%). Overall HCV Ab prevalence was 5.4% (n=1,431); 13% among POC, 3% among DBS, and 0.9% among ST. Among HCV Ab positives, 62% were newly identified infections of which 79% were POC (n=708), 7% were DBS (n=58), and 14% were ST (n=122). POC and DBS had higher proportions of RNA tests completed compared to ST after an HCV Ab positive test result. After an HCV RNA positive test result, POC had better engagement in the care cascade compared to DBS, particularly in setting the first appointment across all settings. No linkage to care data was available for ST.

graphic file with name canlivj-7.1-abst_fig11.jpg — Image:

Conclusion(s): Compared to conventional screening, POC and DBS are more effective and improve linkage to care. While POC Ab testing identified a higher proportion of new HCV Ab infections, POC and DBS both improved HCV RNA testing compared to ST. Quicker turnaround using POC likely increased patient engagement by efficiently setting up the first appointment after an RNA positive result. Given that the type of Ab test was closely related to setting and available resources, matching the optimal Ab screening modality to the test setting will be vital to reach elimination targets.

Disclosure of Interest: G. Hirode: None Declared, B. Wolfson-Stofko: None Declared, A. Vanderhoff: None Declared, C. Capraru: None Declared, J. Karkada: None Declared, D. Smookler: None Declared, S. Friedman: None Declared, K. Bates: None Declared, T. Mazzulli: None Declared, J. Juan: None Declared, H. Shah: None Declared, B. Hansen Grant / Research support from: Intercept, CymaBay, Albireo, Mirum, Calliditas, Gliad, Consultant of: Intercept, CymaBay, Albireo, Mirum, Genfit, Calliditas, Eiger, ChemomAb, H. Janssen Grant / Research support from: AbbVie, Gilead Sciences, Janssen, Roche, Consultant of: AbbVie, Bristol Myers Squibb, Gilead Sciences, Janssen, Merck, Roche, Arbutus, Vir Biotechnology Inc, M. Biondi: None Declared, J. Feld Grant / Research support from: Abbvie, Gilead, Janssen, Enanta, Eiger, Consultant of: Abbvie, Gilead, Finch, Arbutus, GlaxoSmithKline

Can Liver J. 2024 Feb 26;7(1):110–111.

CLM-P010 Positive hepatitis B core antibody is associated with liver fibrosis in people with HIV independently of metabolic dysfunction-associated steatotic liver disease (MASLD)

DH Kim ¹, F Cinque ¹, D Kablawi ¹, TF Tadjo ¹, M Nudo ¹, C Long ¹, A Lupu ¹, G Sebastiani ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: People with HIV (PWH) are at high risk for liver fibrosis and MASLD, and they also have high prevalence of positive hepatitis B virus (HBV) markers. Previous exposure to HBV may increase the risk of liver fibrosis and clinical outcomes in patients with chronic hepatitis C and MASLD, but this is unknown in PWH.

Purpose: We aimed to study the effect of previous HBV infection on liver fibrosis and clinical outcomes in PWH.

Method: This was a single centre cohort study of PWH from the LIVEr disease in HIV (LIVEHIV) Cohort. Consecutive patients with available transient elastography with controlled attenuation parameter and at least 1 year follow-up were included. Anti-Hepatitis B core antibody (anti-HBc) was used to detect the previous HBV infection. We excluded patients with chronic hepatitis C and B. MASLD was defined as the presence of hepatic steatosis, diagnosed as CAP≥248 dB/m, plus any among type 2 diabetes, overweight (BMI>25 Kg/m²) or two other metabolic risk abnormalities. The outcome of interest was significant liver fibrosis, defined as liver stiffness ≥8 kPa. Logistic regression was used to assess cofactors of liver fibrosis. We explored association with clinical outcomes (all-cause mortality, liver-related or cardiovascular events).

Result(s): We included 706 PWH. Prevalence of MASLD and liver fibrosis were 36% and 21%, respectively. Significant liver fibrosis was more prevalent in PWH with positive anti-HBc compared to negative (25% vs. 17%, p=0.01) while no difference in MASLD prevalence was observed. After adjustments, positive anti-HBc was independently associated with significant liver fibrosis (adjusted odds ratio 1.54, 95% CI 1.01-2.69) (see Table 1). At a mean follow-up of 2.5 years, patients with positive anti-HBc had a higher incidence of all-cause mortality (1% vs 0.2%; p=0.04), cardiovascular events (8 vs 5%; p=0.02) but not of liver-related events.

graphic file with name canlivj-7.1-abst_fig12.jpg — Image:

Conclusion(s): Positive anti-HBc predicts liver fibrosis in PWH, independently of MASLD. PWH with positive anti-HBc may also have higher incidence of all-cause mortality and cardiovascular events.

References: Maurice JB et al. Prevalence and risk factors of nonalcoholic fatty liver disease in HIV-mono infection. AIDS. 2017 Jul 17;31(11):1621-1632.

Jung J, Nguyen MH. Liver-Related Mortality in Hepatitis B Virus Core Antibody+/Hepatitis B Virus Surface Antigen- Patients: Occult Hepatitis B Virus, Hepatitis B Virus Reactivation, and Hepatocellular Carcinoma Development. Am J Gastroenterol. 2023 Jan 1;118(1):24-25.

Zhang P et al. Positive hepatitis B core antibody is associated with advanced fibrosis and mortality in nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol. 2023 Mar 1;35(3):294-301

Cervo A et al. Prevalence, Predictors, and Severity of Lean Nonalcoholic Fatty Liver Disease in Patients Living With Human Immunodeficiency Virus. Clin Infect Dis. 2020 Dec 17;71(10)

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):111–113.

CLM-P011 An evolutionary concept analysis: stigma among women in the context of hepatitis C

C Masterman ¹, A Mendlowitz ^2,³, C Capraru ⁴, K Campbell ⁵, G Eastabrook ⁶, M Yudin ⁷, T Kushner ⁸, J Flemming ⁹, J Feld ^2,³, Y Babenko-Mould ¹, P Tryphonopoulos ¹, M Biondi ^2,^3,¹⁰

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: Yes

Background: Stigma is a complex social phenomenon that marginalizes individuals and influences the course of illness. In the context of hepatitis C virus (HCV), stigma is a well-documented barrier to accessing HCV care and treatment. The Blueprint for informing hepatitis C elimination efforts in Canada emphasizes the need for additional actions to address stigma and its harmful effects. It also highlights the importance of healthcare professionals in providing destigmatizing approaches to care.

Purpose: A formal concept analysis is a strategy for examining concepts for their semantic structure, refining and clarifying concepts for use in theory, practice, and research by arriving at precise theoretical and operational definitions. This concept analysis investigated stigma in the context of women living with HCV and was informed by Rodgers’ evolutionary method. Analyzing stigma within the context of women living with HCV is critical for developing models of care that support women's physical and emotional well-being.

Method: PubMed, CINAHL and Google Scholar databases were searched to identify articles that evaluate HCV in women. The combination of subject headings ’hepatitis C AND stigma AND women’ were utilized for the search criteria. Articles from peer-reviewed journals from all disciplines and geographic locations were included in the analysis, published between 2002-2022. As specified in Rodgers’ evolutionary method, articles were analyzed with a focus on the concept's context, surrogate and related terms, antecedents, attributes, examples, and consequences.

Result(s): Following screening protocols, 17 articles were selected for inclusion in the analysis. Surrogate and related terms to stigma identified in the literature were discrimination and marginalization. The antecedents of stigma for women living with HCV were identified as lack of education, receiving a diagnosis, and disclosure. Prevalent attributes of stigma in the literature were feelings of decreased self-worth, negative stereotyping, and fear of transmission. Stigmatization of women living with HCV resulted in negative consequences to relationships and healthcare access due to decreased health-seeking behaviours.

Conclusion(s): The analysis identified that stigma associated with HCV in women stands apart from other forms of infectious disease-related stigma, primarily due to its associations with injection drug use and transactional intercourse. This enhanced understanding of stigma among women living with HCV can, in turn, inform healthcare professionals on more effective approaches when interacting with this demographic, address stigma in the healthcare system, and contribute to the overarching goals of HCV elimination.

References: Aronsohn, A. (2022). Identifying Stigma as a Key Initial Step to Equitable Hepatitis C Virus Care. JAMA Network Open, 5(12), e2246610-e2246610. https://doi.org/10.1001/jamanetworkopen.2022.46610

The Canadian Network on Hepatitis C. (2019). Blueprint to inform hepatitis C elimination efforts in Canada. https://www.canhepc.ca/sites/default/files/media/documents/blueprint_hcv_2019_05.pdf

Butt, G. (2008). Stigma in the context of hepatitis C: concept analysis [https://doi.org/10.1111/j.1365-2648.2008.04641.x]. Journal of Advanced Nursing, 62(6), 712-724. https://doi.org/https://doi.org/10.1111/j.1365-2648.2008.04641.x

Rodgers, B., & Knafl, K. (2000). Concept Development in Nursing. Foundation, Techniques and Applications. (In Concept Development in Nursing: Foundations, Techniques and Applications, 2nd edn ed.). Saunders, Philadelphia.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):113–114.

CLM-P012 Development of a support tool for HCV treatment decision-making

C Masterman ¹, M Biondi ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: Yes

Background: Decision support tools provide patients with information to guide, identify and clarify their values around a decision and have been shown to improve patient knowledge and preparation for treatment decisions. Additionally, treatment decision support tools are unique in their ability to foster shared decision-making between clinicians and patients. Research around patient decision support tools is relatively new in chronic disease management, and there are few if any, HCV treatment tools created with provider and patient input.

Purpose: The decision to prepare for and initiate HCV treatment is essential to mitigating HCV transmission and reducing long-term complications. Currently, there are no support tools for HCV decision-making for treatment initiation. Developing HCV decision support tools for HCV treatment initiation is vital to engaging patients fully in their care.

Method: This study invited 12 nurse providers specializing in HCV (RPNs, RNs, and NPs) from varying geographic locations across Ontario to participate in three virtual small group semi-structured focus group sessions. The first group session focused on initial thoughts, feedback, and ideas for the tool. In the second focus group session, participants reviewed emerging themes. In the final focus group session, providers reviewed a preliminary draft of the tool. In the subsequent phase, the drafted tool will be reviewed by patient participants.

Result(s): As an initial theme, all providers advised that a tool for HCV treatment initiation would be helpful. The strong consensus was that it needed to be quick and efficient, focus on graphics over words, incorporate storytelling elements, and fit in a pocket or wallet. Key themes that emerged in focus group discussion included incorporating treatment readiness, emphasizing patient choice, food security, housing, and protecting health information.

Conclusion(s): This study has demonstrated that the development of a decision support tool for HCV treatment initiation is important for empowering patients to make informed decisions about their treatment. By leveraging the insights from both healthcare providers and patients, we can develop a highly effective tool that reflects the specific needs of the end-users.

References: Matlock, D. D., and E. S. Spatz (2014). ”Design and Testing of Tools for Shared Decision Making.“ Circulation: Cardiovascular Quality and Outcomes 7(3): 487-492.

Austin, C.A., et al., Tools to Promote Shared Decision Making in Serious Illness: A Systematic Review. JAMA Intern Med, 2015. 175(7): p. 1213-21.

Mills, R. and S.B. Haga, Qualitative user evaluation of a revised pharmacogenetic educational toolkit. Pharmgenomics Pers Med, 2018. 11: p. 139-146.

Nota, I., et al., Development of a web-based patient decision aid for initiating disease-modifying anti-rheumatic drugs using user-centred design methods. BMC Med Inform Decis Mak, 2017. 17(1): p. 51.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):114–115.

CLM-P013 Raising awareness about HCV and offering access to rapid testing for migrant communities in Montreal with a culturally and linguistically tailored approach

M Pruvost ¹, F Oliveira ¹, L Mersilian ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Immigrants and newcomers account for a third of HCV cases in Canada, yet HCV testing is not included in the immigration medical exam requirements. Navigating the healthcare system in Quebec can be complicated for newcomers, especially those who don’t speak French.

This presentation describes the model developed by CAPAHC to raise awareness and increase access to screening for immigrant communities in Montreal.

Purpose: Through this project, we aim to raise HCV awareness among immigrant communities, provide information in a linguistically and culturally adapted manner, and offer HCV rapid testing on the spot to those who would not otherwise be able to access these services.

Method: In March 2022, we hired a community facilitator and a nurse from the Latinx community. The team offered hepatitis C workshops in Spanish —tailored for the Latin American community— and the option for participants to get a free Oraquick HCV rapid test. To reduce barriers further, participants were only asked to provide their name and phone number. In the case of a positive test result, their last name and phone number would be used to connect them with the support needed to undergo an RNA test.

Result(s): 83 people attended the 7 hepatitis C workshops and indicated a high level of satisfaction. While participation rates fluctuated, they were higher if the workshops took place in a community organisation with which people were familiar, and where they were accessing other services, such as language courses.

Misconceptions were identified among the participants, including that there is a vaccine available to prevent hepatitis C or that the virus can be transmitted through kissing.

Most participants requested an HCV rapid test. We even saw that people who did not attend our workshops —workers from organisations, for example— also wanted to be screened. Some participants called friends and family to come to get tested. 80 people got tested for HCV antibodies following the workshops, all the test results were negative.

Conclusion(s): In conclusion, facilitating culturally and linguistically adapted workshops increases trust between organisations and participants. People are willing to get screened when they have information and access to testing. Providing rapid testing immediately after offering information about HCV leads to a high opt-in rate.

As we continue to roll this project in different communities, we believe it provides a tangible example of the WHO recommendation to decentralise services, especially screening, in order to reach communities that may not access services otherwise.

References: The Canadian Network on Hepatitis C Blueprint Writing Committee and Working Groups. Blueprint to inform hepatitis C elimination efforts in Canada. Montreal, QC: Available at: canhepc.ca/sites/default/ files/media/documents/blueprint_hcv_2019_05.pdf

Greenaway, C., Azoulay, L., Allard, R. et al. A population-based study of chronic hepatitis C in immigrants and non-immigrants in Quebec, Canada. BMC Infect Dis 17, 140 (2017). https://doi.org/10.1186/s12879-017-2242-y

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):115–116.

CLM-P014 Validation of an alternative, potentially portable, approach to APRI and FIB4 testing

D Smookler ¹, S Tran ¹, M Kuczynski ², A Saunthar ², A Mendlowitz ¹, B Barber ¹, A Vanderhoff ¹, M Biondi ², C Capraru ¹, J Feld ²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Decentralizing and simplifying HCV treatment will greatly assist in the goal of eliminating viral hepatitis by 2030. The ideal “one-stop-shop” model, where testing, work-up, and treatment are done at one time, is particularly useful for marginalized and hard to reach populations. Important to the work-up is identifying liver cirrhosis. Two accepted blood tests for ruling out cirrhosis are the APRI (AST-platelet ratio index) and the FIB4 test, comparing AST, ALT, age, & platelets. This usually requires patients coming to a lab or hospital, which can be a serious hurdle.

Purpose: Validation of APRI and FIB4 testing using finger-prick blood and two small blood analyzers, the OLO and the Piccolo.

Method: OLO furnishes a complete blood count; Piccolo quantifies AST & ALT. Participants provided finger-prick blood, analyzed by the OLO and Piccolo (FP-OLO/P); and venipuncture blood, analyzed by our local core lab. The calculated APRI and FIB4 scores from both methods were compared. Cut-offs for APRI used were: <1.0 to indicate low risk of cirrhotic; >2 to indicate high risk; 1.0-2.0 was considered indeterminate. For FIB4, <1.45 was considered low risk; >3.25 cirrhotic; and 1.45-3.25 as indeterminate of cirrhosis. Participants were patients arriving for their scheduled hepatology visit. Each patient either had a transient elastography test that day (TE), or had been previously established to have liver cirrhosis.

Result(s): 60 participants (32F, 28M, mean age 56) provided samples for both the core lab and the FP-OLO/P APRI and FIB4 scores.

APRI:

Low TE (<8 kPa) n=25. Core lab: 25/25 <1. FP-OLO/P: 23/25 <1; 2/25 mid risk.

Indeterminate TE (8-12.5kPa) n=11. Core lab: 9/11 <1; 2/11 mid-risk. FP-OLO/P: 8/11 <1; 3/11 mid-risk.

High TE (>12.5) n=16. Core lab: 7/16 <1; 4/16 mid-risk; 5/16 >2. FP-OLO/P: 7/16 <1; 4/16 mid-risk; 5/16 >2.

Clin. determined cirrhosis n=8. Core lab: 2/8 <1; 5/8 mid-risk; 1/8 >2. FP-OLO/P: 2/8 <1; 4/8 mid-risk; 2/8 >2.

FIB4:

Low TE (<8 kPa) n=25. Core lab: 18/25 <1.45; 6/25 mid-risk; 1/25 >3.25. FP-OLO/P: 11/25 <1.45; 12/25 mid risk; 2/25 >3.25.

Indeterminate TE (8-12.5kPa) n=11. Core lab: 5/11 <1.45; 4/11 mid-risk; 2/11 >3.25. FP-OLO/P: 2/11 <1.45; 6/11 mid-risk; 3/11 >3.25.

High TE (>12.5) n=16. Core lab: 2/16 <1.45; 3/16 mid-risk; 11/16 >3.25. FP-OLO/P: 2/16 <1.45; 3/16 mid-risk; 11/16 >3.25.

Clin. determined cirrhosis n=8. Core lab: 8/8 >3.25. FP-OLO/P: 8/8 >3.25.

Conclusion(s): FP-OLO/P was as sensitive as the core lab at predicting cirrhosis at all levels, for both FIB4 and APRI. APRI results closely matched throughout. For FIB4, the FP-OLO/P often had higher estimates than the core lab, suggesting less specificity than core lab readings. However, as the goal in testing people for cirrhosis during an HCV work-up is to ensure no one is missed who might have serious liver disease, this appears to be a reliable method for obtaining an APRI or FIB4 score, and could widely expand HCV care beyond the hospital setting.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):116–118.

CLM-P015 Prevalence and clinical characteristics of hepatitis delta virus (HDV) infected individuals in British Columbia

VO Zaborska ¹, A Ramji ^2,³, HH Ko ^2,³, E Tam ²

What is your preferred presentation method?: Poster Only

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: HDV is a virus that requires HBV to complete its replication cycle (1). Globally, HDV is reported in 4.5-13% of chronic hepatitis B (CHB) patients (1). HDV and HBV co-infection is associated with progression to cirrhosis and higher risk of hepatocellular carcinoma (HCC) (2-4). HDV prevalence in Canada is not fully elucidated.

Purpose: The purpose of the study was to describe the prevalence and clinical characteristics of HDV infection in CHB patients in a tertiary care centre.

Method: Retrospective study of HBsAg-positive patients >18 years of age tested for HDV Ab between April 2013 and October 2022. Data collected included HDV Ab status, patient demographics, comorbidities, alcohol use, fibrosis stage, and therapies utilized.

Result(s): Among 663 HBsAg-positive patients tested for HDV Ab,10/663 (1.5%, 95% CI 0.58-2.44) were HDV-Ab (+), with 8/10 (80%, 95% CI 0.55-1.05) of those confirmed HDV RNA(+). Average age of HDV patients was 57.8 (95% CI 52.7- 62.9) years, similar to HBV patients. Compared to HBV monoinfected patients, HBV-HDV co-infected patients were more likely to be male (90.0% vs 57.6%; p=0.04), have decompensated liver disease (30.0% vs 1.4%; p< 0.0001) and less likely to be Asian (50.0% vs 80.9%; p =0.014). One HBV-HDV co-infected patient was also HIV/HCV co-infected, and two had cleared HCV. One HDV patient had a known history of IVDU (10%, 95% CI 0.09 – 0.28). Mean ALT in HDV patients was 55.9, vs. 34.3 in HBV mono group (p=0.0508). 50% of HDV patients consumed any lifetime alcohol compared to 31.9% of HBV mono-infected patients (p=0.22). HDV patients were more likely to have liver stiffness measurements >9.0 kPa 30% vs 8.9%, p=0.02), and equally likely to have HCC 10% vs 2.5% (p=0.13).

graphic file with name canlivj-7.1-abst_fig13.jpg — Image:

Conclusion(s): The prevalence of HDV positivity in CHB patients in this tertiary care centre was 1.5%. This was similar to 1.6% previously reported in Western Canada (5). This was less than a previously noted 4.8% prevalence of HDV positivity amongst HBsAg-positive patients enrolled in in the Canadian HBV Network between 2011-2019. Persons with HDV were more likely to be male, and have decompensated liver disease and less likely to be Asian than those with HBV mono-infection. Further studies to understand the burden of disease in other regions are needed.

References: [1] Carla Osiowy et al. Molecular epidemiology and clinical characteristics of hepatitis D virus infection in Canada, JHEP Reports, Volume 4, Issue 5, 2022,100461.

[2] Rizetto M, Hamid S. The medical impact of hepatitis D virus infection in Asia and Africa; time for a reappraisal. Liver Int 2021;41:16-19.

[3] Da BL et al. Risk factors for Delta hepatitis in a North American cohort: who should be screened? Am J Gastroenterol 2021;116:206–209.

[4] Alfaiate D et al. Chronic hepatitis D and hepatocellular carcinoma: a systematic review and meta-analysis of observational studies. J Hepatol 2020; 73:533–539.

[5] Cheng HH et al. The prevalence of antibody to delta virus in western Canada. Clin Invest Med. 1986;9(3):156-9. PMID: 3757321.

Disclosure of Interest: V. Zaborska: None Declared, A. Ramji Grant / Research support from: Abbvie, Gilead, Intercept, Novo-Nordisc, Pfizer, Janssen, Novartis, Speakers bureau of: Abbvie, Amgen, Gilead, Intercept, Novo-Nordisc, H. H. Ko Consultant of: Abbvie, Gilead, Intercept, Ipsen, Lupin, Merck, Sanofi, Speakers bureau of: Abbvie, Gilead, Intercept, Lupin, Merck, Sanofi, E. Tam Consultant of: Advanz, Speakers bureau of: Abbvie, Gilead, Intercept

Can Liver J. 2024 Feb 26;7(1):118–119.

CLM-P016 Mechanistic Analysis of Argonaute 2 and MIR-122 Promotion of Hepatitis C Virus Replication

M A Palmer ¹, Y Amador-Cañizares ¹, J A Wilson ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: Yes

Background: The Hepatitis C virus (HCV) genome consists of positive-sense, single-stranded RNA approximately 9.6 kb in length with a single ORF, flanked by structured 5’ and 3’ untranslated regions (UTRs). Interestingly, HCV relies on liver-specific microRNA miR-122 to promote viral replication. miRNAs typically bind the 3’ UTR of an mRNA transcript, leading to translational regulation. By contrast, miR-122 binds two sites within the HCV 5’ UTR, promoting replication. The mechanism of miR-122-directed replication is suggested to involve modification of 5’ UTR structure induced by miR-122 annealing. Argonaute proteins (Ago1-4) play a role in delivering miR-122, though the involvement of each unique function is unknown. In canonical miRNA suppression, Ago interacts with TNRC6, localizing mRNA to P-bodies (PBs) and stress granules (SGs). While all Ago isoforms undergo post-translational modification (PTM) and have unwinding activity, possibly involved in miRNA processing, cleavage of target mRNA is unique to Ago2.

Purpose: We will determine the precise role of Ago proteins in HCV replication promotion by identifying both required biochemical functions and pro-viral PTMs. These data will aid in further characterization of the viral life cycle and could uncover potential therapeutic options for the treatment and prevention of HCV.

Method: Ago2 functional domains and PTMs that play a role in HCV replication promotion will be identified using a previously established Ago2 complementation system. In Ago1/Ago2 double-knockout Huh-7.5 cells, HCV replication is severely impaired but can be rescued by transfection of exogenous Ago2 mRNA. This allows us to assay Ago2 mutants deficient in specific functions to determine if they are required for promotion of HCV replication. Further, phospho-mimetic and phospho-null mutations of phosphorylation sites allows for the determination of pro-viral phosphorylation events. The biological relevance of these PTMs will be determined by mass spectrometry of endogenous Ago2, which will show if HCV induces specific phosphorylation.

Result(s): Mutations affecting Ago2:TNRC6 complex formation attenuate viral replication, while inhibition of unwinding activity or other host interactions results in a less severe but still noticeable decrease. As expected, cleavage deficiency showed no significant impact on viral replication. Further, the effects of various phosphorylation mutations are diverse, indicating a likely role for phosphorylation in the HCV life cycle, potentially induced by the virus itself.

Conclusion(s): HCV miR-122-dependent replication promotion relies on interaction of Ago2 with specific pro-viral host proteins, suggesting a more complex role for this protein beyond simply delivering miR-122 to the viral 5’ UTR. While the data indicate a role for phosphorylation in HCV replication, the mechanism of this process requires further study. As certain phosphorylation states appear pro-viral in nature, it is possible HCV influences the cellular environment, inducing these PTMs.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):119–120.

CLM-P017 Elucidating the role of an RNA guanine-quadruplex in hepatitis C virus replication

S D'souza ^1,², MD Badmalia ², G Balderas-Figueroa ², TR Patel ^1,², C Coffin ^1,³

What is your preferred presentation method?: Poster Only

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: Nucleic acids rich in guanine nucleotides can form a secondary structure known as a Guanine-quadruplexes (G-quadruplex or G4). These G-quadruplex structures are formed through Hoogsteen hydrogen bonded guanine bases which stack to create a stable structure. G4 structures are conserved across all three domains of life and have roles in transcription, translation, and replication. More recently, these G-quadruplexes have also been identified in viruses; however, their functional role is yet to be deciphered. Using prediction algorithms, a highly conserved G-quadruplex sequence was identified in the 3’ untranslated region (UTR) of the negative strand in the hepatitis C virus (HCV). The location of this G-quadruplex on the stem-loop IIy’ region is within the 1-154 nt sequence which is identified as the minimal region required for efficient HCV replication.

Purpose: We hypothesize that stem-loop IIy’ is flexible during HCV replication and can adopt a G-quadruplex structure to aid in efficient viral replication.

Method: Using G4-hunter, we have designed wild-type/mutant RNA oligos of the putative G-quadruplex forming sequence in the negative-strand 3’UTR of HCV. These oligos were folded into G-quadruplexes and purified using size exclusion chromatography. The G-quadruplex structure was characterized using circular dichroism spectroscopy and confirmed using MicroScale Thermophoresis (MST) binding experiments with a commercially available antibody (BG4), which binds exclusively to G-quadruplexes. We have also performed Small Angle X-ray Scattering (SAXS) of wild-type and mutant HCV G-quadruplexes to see if mutations disrupt these structural features. We will subsequently perform replication assays using a luciferase reporter-based HCV replicon system to investigate the functionality of these wild-type and mutant G-quadruplexes in viral replication. We will also perform viral RNA pull-down assays to determine if a functional HCV G-quadruplex exists.

Result(s): CD spectroscopy experiments demonstrated that all oligos form G-quadruplexes and structure stability is buffer-dependent KCl>NaCl>LiCl. The wild-type G4 appears to have the most quartets intact when compared to the single-mutant and double-mutant G4s. MST experiments showed that BG4 can recognize all four HCV constructs – indicating that they all form G-quadruplexes. MST experiments were consistent with CD spectroscopy where G4s are most stable in KCl and less stable in NaCl buffer. Through SAXS we were able to determine the size of WT and mutant G4s and show that quartet disruption occurs with the introduction of single nucleotide mutations.

Conclusion(s): Biophysical studies indicate that a 22nt HCV oligo can form a G-quadruplex structure. The identification of a functional role of these G-quadruplexes in HCV can give us insight into how nucleic acid sequence and structure can impact viral replication.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):120–121.

CLM-P018 Breaking down barriers in hepatitis B virus diagnostics and antiviral screening: development of low cost quantitative assays for HBSAG, HBEAG, and HBV DNA

S D'souza ^1,², L Al-Yasiri ¹, A Chen ¹, DT Boghici ¹, G van Marle ¹, JA Corcoran ¹, TR Patel ^1,², C Coffin ^1,³

What is your preferred presentation method?: Poster Only

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: The hepatitis B virus (HBV) is an enveloped, partially double-stranded, blood-borne DNA virus that belongs to the Hepadnaviridae family. Despite the availability of an effective HBV vaccine, global estimates are that over 296 million people globally are living with chronic hepatitis B virus (CHB) infection with only 10.5% of the population aware of their infection. 880,000 deaths per year are directly attributed to HBV infection; as individuals living with CHB are at high risk of developing cirrhosis, liver cancer, and liver failure. The World Health Organization has set ambitious goals to eliminate viral hepatitis by 2030 by reducing HBV chronic infection by 90% and mortality by 65%, which requires investment and scaling up of programs for HBV birth dose vaccination, testing, and treatment to achieve these targets. A major impediment to this goal is the inaccessibility of diagnostic tests that provide rapid and accessible means to identify asymptomatic HBV carriers.

Purpose: We aim to develop a low-cost quantitative assay for the detection of HBV markers (HBsAg, HBeAg, and HBV DNA) from patient plasma and cell culture.

Method: Patient plasma (genotypes A-F) and HBV-positive HepAD38 cells/supernatant were used as samples to optimize our in-house assays for the detection of HBsAg, HBeAg, and HBV DNA. For patient samples, results from our in-house detection assays were compared to those obtained from the Abbott Architect-based system. To detect HBsAg and HBeAg, we developed and optimized a quantitative sandwich enzyme-linked immunosorbent assay (qELISA). For DNA isolation, we compared the use of a silica-based column to a column-free DNA isolation method and performed HBV DNA quantification using an in-house SYBR-green-based qPCR.

Result(s): In-house qHBsAg and qHBeAg sandwich ELISAs can recognize HBV genotypes A-F and have a lower limit of detection (LLOD) of 0.78 IU/mL and 0.39 ng/mL respectively, with a cost of $0.11-$0.13 per sample tested. In-house HBV qPCR ($0.4/sample) when paired with DNA isolation using a silica-based column ($4.1/extraction) provided comparable HBV DNA loads from patient plasma to the Abbott Architect platform. Comparatively, when the column-free DNA isolation method ($0.1/extraction) was used, a 1 log reduction in assay detection sensitivity was observed. Despite the reduction in assay sensitivity with DNA prepared from the column-free DNA isolation method, in HepAD38 cells treated with Tenofovir we show comparable EC₅₀ values from the column and column-free DNA isolation methods.

Conclusion(s): In summary, our in-house ELISAs and qPCR assays provide a low-cost alternative to the commercially available gold-standard diagnostic assays for evaluating HBV markers in patient plasma and cell culture. These assays may provide additional tools to improve HBV diagnosis and for HBV cure research including antiviral screening in resource-limited settings.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):121–122.

CLM-P019 Regulation of protein kinase R by HCV NS5A is genotype-dependent and does not require cyclophilin A

CE Gallardo Flores ¹, J Cho ¹, C Colpitts ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: Chronic hepatitis C virus (HCV) infection affects 71 million people worldwide and increases the risk of developing hepatocellular carcinoma (HCC). HCV is genetically diverse, with 6 genotypes reported to date that differ in their severity and pathogenicity. Although direct-acting antivirals against HCV can cure the infection, they do not eliminate the risk of developing HCC. Protein kinase R (PKR), a multifaceted kinase, is implicated in liver disease and cancer, but its regulation in the context of chronic HCV infection and HCC is poorly understood. Interestingly, PKR has been reported to interact with HCV non-structural protein 5A (NS5A)¹, and mutations in the PKR-binding domain of NS5A have been associated with HCC.²

Purpose: We sought to better understand how HCV NS5A regulates PKR function.

Method: We infected Huh7.5 cells with HCVcc (JFH-1) or transfected 293T/17 cells with mammalian expression constructs for HCV-NS5A from two different genotypes: HCV-NS5A genotype 1b (J4; HCV-gt1b-NS5A) or HCV-NS5A genotype 2a (JFH-1; HCV-gt2a-NS5A). We evaluated PKR activation by western blot for phosphorylated PKR and assessed downstream effects of PKR activation, including translation shutdown and SG formation. To assess protein translation, we used luciferase reporter assays, while SG formation was visualized by immunofluorescence to evaluate the localization of G3BP1, a well-reported SG marker.

Result(s): Our results show that PKR is activated in Huh7.5 cells infected with HCV JFH-1. To investigate the mechanism of PKR activation and the role of NS5A, we ectopically expressed NS5A in 293T/17 cells and similarly observed PKR activation and corresponding SG formation. Furthermore, NS5A expression decreased the translation of luciferase in a constitutive luciferase reporter assay, indicating translation shutdown. Interestingly, HCV-gt1b-NS5A more potently induced PKR activation, inhibition of protein synthesis, and SG formation than HCV-gt2a-NS5A, suggesting that genotype differences may affect the ability of NS5A to modulate PKR activation. The use of an NS5A inhibitor, daclatasvir, did not affect PKR activation by NS5A. Furthermore, PKR activation by NS5A does not require cyclophilin A, a known interaction partner of both NS5A and PKR, as the cyclophilin inhibitor cyclosporin A had no effect on NS5A-mediated PKR activation. Through mutational studies and immunoprecipitation experiments, we are currently evaluating the NS5A determinants that impact PKR activation and underlie the genotypic differences that we observed.

Conclusion(s): Our findings show that HCV-gt1b-NS5A and HCV-gt2a-NS5A differentially activate PKR, restrict protein translation, and induce SG formation. We speculate that these differences may contribute to different pathogenicity of HCV gt1b relative to 2a. Overall, these findings contribute to understanding the regulation of PKR during HCV infection that may aid in understanding HCC progression.

References: ¹Gale et al. (1998) Mol Cell Biol. 18:5208

²Paolucci et al. (2020) Viruses 12:255

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):122–123.

CLM-P020 Evaluation of hepatitis C virus transmitted/founder variants obtained from observed HCV infection through lung transplantation from HCV-infected donors to uninfected recipients

N Fadlelmawla ¹, MA Zahoor ², A Mosa ², A Chowdhury ², A Gehring ^2,³, J Feld ^1,²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: Yes

Background: In contrast to the large diversity seen in chronic hepatitis C virus (HCV) infection, samples taken from acute HCV infection have shown only a small number of viral lineages, suggesting the presence of a limited number of Transmitted/Founder (T/F) variants that are able to efficiently expand and establish infection. Characterization of T/F variants has been limited due to the difficulty of obtaining samples from early HCV infection and in identification of the donor virus. Using samples from lung transplant recipients who received organs from HCV-infected donors, we evaluated the presence of T/F variants in observed HCV infection.

Purpose: Using our confirmed donor/recipient pairs of HCV infection, we will tackle the limitations in founder variant characterization. Identifying founders may inform new strategies for vaccine development.

Method: Using Illumina MiSeq (2x250bp) we obtained the sequences of donors and their respective recipients. The recipients’ timepoints were chosen according to the viral load (higher than log 10^5 IU/ml). ShoRAH, a bioinformatics tool used for haplotype reconstruction, was used to identify unique haplotypes in the Core-E2 region and estimate their frequencies. Focusing on HVR1 in E2, we used maximum likelihood phylogenetic trees (PhyML) to identify founders and non-founders and cross-referenced identified non-founder sequence with previously reported functional analyses of HVR1.

Result(s): We analyzed HVR1 sequence in 5 donor/recipient pairs to identify founders and non-founders. In figure 1, four recipient donor pairs demonstrated donor variants that were not transmitted to recipient (all except Recipient B/ Donor B). By analyzing the synonymous and non-synonymous mutations of donor/recipient pairs we noticed in 3 out of 5 donor/ recipient pairs (RA/DA, RC/DC, RE/DE), only HVR1 donor variants with positively charged residues (R,H,K) in one of the 3 positions (3,11,25) were found in recipients while donor variants with Q residues (uncharged) where not transmitted (Figure 2). HVR1 positions 3,11 and 25 are dominantly occupied with positively charged residues (R,H,K) to ensure efficient entry to the cells through interaction with negatively charged cell receptors such as LDL-R and SR-BI.

graphic file with name canlivj-7.1-abst_fig14.jpg — Image:

Conclusion(s): Our preliminary data show that at the time of HCV transmission in organ transplant patients, we identified non-transmitted variants which possessed uncharged residues in HVR1 in positions 3, 11 or 25 compared to transmitted founder variants which possessed positively charged residues in at least 1 of these positions. These sites in HVR1 are known to be occupied by positively charged residues to ensure efficient interaction with cell receptors and viral entry. This suggests selection of founder variants for their enhanced infectivity and absence of non-founder variants that may be less fit at establishing infection. More analysis is in progress to track founder evolution in longitudinal recipient samples and assess functional characteristics in vitro.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):123–124.

CLM-P021 Elucidating the role of nonstructural protein 5A in regulating endoplasmic reticulum stress during hepatitis C virus infection

TH Tooley ¹, CC Colpitts ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: Chronic HCV infection has long-term consequences, including the development of hepatocellular carcinoma (HCC). During infection, the HCV ribonucleoprotein complex forms replication organelles (RO) derived from endoplasmic reticulum (ER) membranes to facilitate viral replication. RO formation, as well as the burden of viral protein production on the cell, leads to the induction of ER stress. During HCV infection, the complexity of ER stress responses has led to conflicting results in literature. As such, the potential mechanisms through which HCV modulates ER stress responses remain elusive. Given the role of the HCV non-structural protein 5A (NS5A) in RO formation and its localization to the ER, we hypothesize that NS5A plays a role in modulating ER stress during HCV infection. Furthermore, it has been reported that HCV NS5A may enhance Toll-like receptor 4 (TLR) expression. TLR4 has been shown to independently activate ER stress via XBP1, leading to the production of proinflammatory cytokines. Interestingly, TLR4 expression is enhanced in patients with HCC, and cancerous cells often display increased ER stress.

Purpose: We aim to characterize the regulation of ER stress and TLR4 expression during HCV infection to identify potential mechanisms contributing to HCC.

Method: We infected Huh7.5 human hepatoma cells with HCV JFH-1_T, or transfected human embryonic kidney 293T cells with NS3-5A of genotype 2a (JFH-1) and NS5A of genotype 1b (J4), and harvested RNA 24, 48- and 72 hours post infection or transfection. We evaluated induction of ER stress using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) or semi-quantitative RT-PCR to assess the splicing of XBP1.

Result(s): We show that HCV infection differentially increases steady state transcriptional levels of ER stress-associated genes over time. We observe increases in BiP, CHOP and HERPUD1 gene expression at 48 and 72 hours post infection. Surprisingly, we observe no significant increase in PERK, ATF4, and Xbp1 transcripts or canonical Xbp1s-responsive genes, and there is no significant splicing of Xbp1 during infection. The lack of induction of the IRE1-XBP1 and PERK ER stress response pathways during infection suggests that HCV may counteract these pathways, or selectively activate the ATF6 response pathway. Similar modulation of ER stress responses is observed in cells ectopically expressing NS3-5B or NS5A, highlighting a role for NS5A in the ER stress response during HCV infection. However, we do not observe a significant increase in TLR4 mRNA expression in HCV-infected cells, suggesting that modulation of TLR4 expression does not underlie the observed ER stress response.

Conclusion(s): The long-term risks and consequences of HCV infection are not eliminated despite the development of direct acting antivirals. These findings lay the groundwork for further studies to understand the role of ER stress in HCV pathogenesis and liver disease progression.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):124–125.

CLM-P022 Bystander CD8 T cell activation is associated with liver damage in chronic hepatitis B

J Lin ^1,², Y Ghosheh ¹, E Winter ¹, S Nkongolo ³, J Feld ¹, A Gehring ^1,²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Persistent liver damage is the driver of disease progression in chronic hepatitis B. Οur previous work defined an auto-aggressive CXCR6⁺ CD8 T cell population (CD8 T_AGR) driving antigen-independent, Fas ligand (FasL)-mediated hepatocyte killing in human livers. IL-2 and IL-12 could induce the CD8 T_AGR phenotype in the presence of total liver immune cells, but not in isolated CD8 T cells. This indicated that additional factors may be required for CD8 T_AGR induction. The critical roles of cytokines, particularly IL-15 and IL-18, in the pathogenesis of both viral (PMID: 36594467) and non-viral (PMID: 33762736, 9378984) forms of hepatitis have been previously documented. Furthermore, intercellular communication may also contribute to the progression of chronic diseases (PMID: 21059892).

Purpose: We hypothesize that liver immune cells provide additional soluble factors and/or intercellular communication required for CD8 T_AGR induction. This project aims to investigate the soluble factors and/or intercellular communication required for CD8 T_AGR activation and differentiation.

Method: Liver immune cells were acquired by perfusing healthy donor livers prior to living donor liver transplant. CXCR6⁺ CD8 T cells, CD14⁺ myeloid cells, CD4⁺ T cells and CD19⁺ B cells were isolated using fluorescence-activated cell sorting and co-cultured with IL-2 and IL-12 for 24 hours. CD8 T cells enriched using magnetic selection were used to determine minimal cytokine combinations predicted from co-culture experiments. CD8 T_AGR activation was by assessed by measuring the induction of IFN-γ and 4-1BB with flow cytometry.

Result(s): Consistent with previous data, the combination IL-2 and IL-12 was unable to induce CD8 T_AGR activation in isolated CD8 T cells. Co-culture with CD14⁺ myeloid cells, but not CD4⁺ T cells or CD19⁺ B cells, could induce CD8 T_AGR activation. In silico analyses (NicheNet) implicated IL-15 and IL-18 as potential factors responsible for T_AGR activation. Co-culture of isolated CXCR6⁺ CD8 T cells with IL-18 was able to substitute for CD14⁺ myeloid cells in CD8 T_AGR activation, but could not maintain CXCR6 and FasL expression. The culturing of enriched CD8 T cells with the combination IL-12, IL-15, and IL-18 maintained the CD8 T_AGR marker CXCR6 and enhanced the expression of other CD8 T_AGR markers (CD27, PD-1, 4-1BB, and IFN-γ).

Conclusion(s): The combination IL-12, IL-15, and IL-18 was sufficient for CD8 T_AGR induction in the absence of other liver immune cell populations. Understanding the mechanism of CD8 T_AGR-mediated liver damage opens opportunities to better manage liver diseases and harness them for immunotherapy.

References:

Nkongolo, S. et al. Longitudinal liver sampling in patients with chronic hepatitis B starting antiviral therapy reveals hepatotoxic CD8+ T cells. J Clin Invest 133 (2023). https://doi.org:10.1172/JCI158903

Dudek, M. et al. Auto-aggressive CXCR6(+) CD8 T cells cause liver immune pathology in NASH. Nature 592, 444-449 (2021). https://doi.org:10.1038/s41586-021-03233-8

Tsutsui, H. et al. IL-18 accounts for both TNF-alpha- and Fas ligand-mediated hepatotoxic pathways in endotoxin-induced liver injury in mice. J Immunol 159, 3961-3967 (1997).

Wang, J. et al. CD137-mediated pathogenesis from chronic hepatitis to hepatocellular carcinoma in hepatitis B virus-transgenic mice. J Immunol 185, 7654-7662 (2010). https://doi.org:10.4049/jimmunol.1000927

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):125–126.

CLM-P023 Elucidating the switch from translation to replication in the HCV life cycle

MM Sag ¹, C Camargo ¹, S Sagan ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: As a positive-sense RNA virus, the Hepatitis C virus (HCV) genome acts a template for both translation and replication. Translation occurs in the in the 5’ to 3’ direction, while viral replication occurs 3’ to 5’, and as such, these events are mutually exclusive on a single molecule of genomic positive-sense viral RNA. Thus, there must be a mechanism to “switch” off translation, clear the RNA of ribosomes, and to initiate viral RNA replication. HCV has been documented to recruit two argonaute (Ago)-microRNA-122 (miR-122) complexes to the 5’ terminus of its genome which results in: 1) an RNA chaperone-like switch in conformation (or riboswitch); 2) viral RNA stability; and 3) translational promotion. Subsequently, the Ago:miR-122 complexes recruit trinucleotide-repeat containing gene 6 (TNRC6), the RNA silencing effector protein. Recruitment of TNRC6 suppresses translation, allowing for replication organelle (RO) biogenesis, primarily mediated by the NS5A protein.

Purpose: We hypothesize that the processes to turn off translation and initiate RO biogenesis is mediated by phase separation of the 5’ and 3’ ends of the viral RNA respectively. Herein, we are exploring the roles of Ago:miR-122, TNRC6, and NS5A in its ability to phase separate viral RNA and in the switch from translation to replication and the RO biogenesis of the HCV life cycle.

Method: We are using a G28A-BoxB system to explore the switch from translation to replication and RO biogenesis in the HCV life cycle. We previously demonstrated that a viral mutant (G28A), can accumulate to low levels in miR-122 knockout (KO) cells. In the absence of miR-122, G28A is defective in the “switch” from translation to replication; however, due to its translational advantage, it can establish ROs, albeit inefficiently. In combination with a BoxB loop in lieu of SLI, we can tether λN fusion proteins to the 5’ terminus of the G28A-BoxB genome, to test if we can restore the “switch”. Moreover, to explore whether overexpression of NS5A can augment G28A-BoxB replication, we are using an NS3-5A cis-overexpression system.

Result(s): Our preliminary data suggests that the tethering of Ago2 to the G28A-BoxB RNA restores the “switch” from translation to replication. We are currently testing the effects of TNRC6B and NS5A, on the restoration of the “switch” in G28A-BoxB. Other host and viral phase separating proteins will also be tested. Using a NS3-5A cis-overexpression system we will also test whether overexpression of NS5A in cis improves the efficiency of G28A-BoxB RO biogenesis.

Conclusion(s): We have shown that tethering of Ago2 is sufficient to restore the switch form translation to replication and rescue G28A-BoxB RNA accumulation in the absence of miR-122. Future work will focus on exploring the roles of TNRC6 and NS5A in the switch and RO biogenesis. We anticipate that this will reveal the mechanism(s) behind the switch from translation to replication and RO biogenesis in the HCV life cycle.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):126–127.

CLM-P024 Targeting hepatitis b virus (HBV) by pretending to be hepatitis delta virus (HDV): investigating the interaction between HDV proteins and HBV RNA

JM Beghin ^1,², M Badmalia ^1,³, N Shapka ³, V Meier-Stephenson ^1,^2,³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Hepatitis Delta virus (HDV) is a defective RNA virus that requires the surface proteins of Hepatitis B virus (HBV) to complete its replication. ∼5% of HBV-infected individuals also harbour HDV, giving estimates of ∼12 million people worldwide. Clinically, HBV DNA levels appear lower in HBV-HDV co-infection compared to HBV mono-infection, suggesting a degree of viral competition. The HDV genome encodes two proteins, the small hepatitis D (SHD) antigen, and the large hepatitis D (LHD) antigen. Recently, it was discovered that these proteins can bind the HBV pre-genomic RNA (pgRNA) which is sufficient to lower HBV levels, independent of interferons. If we could better understand this interaction, we may be able to create a novel class of HBV drugs, by pretending to be HDV!

Purpose: To structurally characterize the interaction between the SHD/LHD and HBV's pgRNA that the model can be used for the development of novel HBV or HDV therapeutics.

Method: HDV proteins were recombinantly produced in an E. coli expression system induced using 0.1M isopropyl β-d-1-thiogalactopyranoside (IPTG). The protein was purified via affinity column chromatography and size exclusion chromatography using a glutathione-S-transferase (GST) tag. Mass spectrometry was used to confirm the presence of the correct protein. The pgRNA segment of interest was cross-referenced across 13,216 HBV reference sequences and the consensus sequence inserted in a pUC plasmid for in vitro transcription. Pull-down assays of HBV-infected cell lysates, RNA-extracted lysates and/or in vitro transcription were used to confirm the functionality of the protein. This will be followed by further biophysical workup, including binding studies (using gel shift assays and microscale thermophoresis) and structural studies (CryoEM).

Result(s): Recombinant HDV proteins have been produced and the protocol optimized for maximum production. Mass spectrometry confirms the presence of the full length of HDV protein. The consensus sequence of the HBV pgRNA segment of interest has been determined, cloned, and produced by IVT. Pull-down assays are currently underway to confirm functionality of the protein, soon to be followed by further binding and structural studies.

Conclusion(s): Understanding the interplay between HDV and HBV may provide insight into novel approaches to target HBV.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):127–128.

CLM-P025 Activation of interferon regulatory factor 1 by cyclosporine a contributes to its antiviral activity against hcv and other RNA viruses

U Sangwan ¹, C Colpitts ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: Cyclosporine A (CsA) and its analogs have demonstrated safety and efficacy in hepatitis C virus (HCV) clinical trials (phase I and II) [1]. Studies in cell culture and animal models have shown that CsA is antiviral against many other viruses, including flaviviruses, hepatitis B, hepatitis D, hepatitis E, and coronaviruses. All this evidence underscores the potential of CsA as a broad-spectrum antiviral. However, the mechanisms underlying its broad-spectrum antiviral activity are still unclear. We are using HCV as a model to understand the antiviral mechanisms of CsA. Previous literature from our lab and others has shown CsA restricts the replication of HCV and two coronaviruses (HCoV-229E and MERS-CoV) in a manner that is at least partially dependent on the transcription factor interferon regulatory factor 1 (IRF1) [2,3,4], suggesting a link between IRF1 and the antiviral activity of CsA. IRF1 provides innate immunity against pathogens, particularly RNA viruses, by regulating the basal expression of diverse antiviral effector genes that restrict the replication of HCV and other hepatotropic viruses such as dengue virus (DENV) [5].

Purpose: Determine how CsA modulates IRF1 activity to restrict HCV and other RNA viruses

Method: We are employing virological, molecular, and biochemical approaches in cell culture models to determine the antiviral mechanisms of CsA against HCV and DENV

Result(s): We show that CsA inhibits HCV JFH-1 and DENV-2 16681 replication in human hepatoma Huh7 cell lines. Genetic depletion of classical CsA target proteins, cyclophilin (Cyp) A and cyclophilin B, inhibited HCV replication, consistent with the known roles of these Cyps during HCV infection. In contrast, silencing CypA or CypB expression did not affect DENV replication. However, in both cases CsA induces the expression of IRF1 and IRF1-dependent antiviral genes, which we hypothesize contributes to restricting HCV and DENV replication. Interestingly, sub-cellular localization experiments using immunofluorescence showed that CsA induces nuclear translocation of IRF1 in Huh7 cells and A549 lung epithelial cells. We are currently seeking to understand how CsA modulates IRF1 nuclear translocation and whether it might involve peroxisome-associated antiviral signalling or Toll-like receptor 4, both of which have been linked to IRF1 activation

Conclusion(s): CsA, a clinically approved immunosuppressive drug that inhibits T cell proliferation, restricts the replication of HCV and other viruses in a manner dependent on IRF1. Understanding how CsA induces IRF1-dependent antiviral responses could aid in the design and synthesis of non-immunosuppressive CsA-like molecules for further development as broad-spectrum antiviral drugs.

References: 1. Gallay (2012)Immunol Res, 52(3), 200-210

2. Colpitts et al., (2020)eLife, 9

3. Sauerhering et al., (2020)Eur Respir J, 56(5)

4. Mamatis et al., (2023) Antiviral Res. 219:105730

5. Yamane et al., (2019)Nat Microbiol, 4(7), 1096-1104

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):128.

CLM-P026 G4Q-binding ligands: a starting point for potential cure therapies for chronic hepatitis B infections

J Skoreyko ¹, E Kasinyabo ², S Polege ¹, K Sviderskaia ¹, H Lee ^2,³, MD Badmalia ², V Meier-Stephenson ^1,^2,³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Hepatitis B virus (HBV) chronically infects ∼300 million people worldwide, increasing an individual's chance of developing cirrhosis and hepatocellular carcinoma¹. HBV's chronicity is partly due to a form of the genome known as the covalently closed circular DNA (cccDNA). Current therapeutics target processes downstream of cccDNA, but not the cccDNA itself, and therefore viral rebound will likely occur with the cessation of medication. The key to a potential cure therefore lies within the capacity to target and eliminate the virus's cccDNA. With the recent discovery of a highly conserved G-quadruplex (GQ) structure in the pre-core promoter (PCP) region of HBV, this provides a unique target in cccDNA against which small molecule therapeutics can be designed². It was also reported that when this GQ's structural integrity is compromised, the amount of viral core protein within the cell is reduced³. There are currenly several GQ-binding ligands that are well explored in cancer, and several of those have been shown to reduce viral activity in other family of viruses such as Zika virus⁴.

Purpose: To study the effects of two G4Q-binding ligands, TMPyP4 and Braco19, on HBV replication.

Method: An alamarBlue assay was performed to test the optimal drug concentration in the HepG2-NTCP cell model. Infection studies were performed using HepAD38-derived HBV. HBV's viral and cellular markers were analyzed by HBsAg ELISA/Western blot, HBcAg immunofluorescence, and qPCR.

Result(s): Infection was confirmed in the cell culture model and the effects of Braco19 and TMPyP4 on HBV replication were quantified. Off-target effects were quantified using a panel of housekeeping genes.

Conclusion(s): G4Q-binding ligands may act as a reasonable starting template for potential future HBV therapeutics.

References: 1. Global Hepatitis Report 2017. Geneva: World Health Organization; 2017

2 Meier-Stephenson, V et al, Viruses, 603, 2018.

3. Meier-Stephenson, V et al, Journal of Biological Chemistry, 296, 2021.

4. Majee, P et al, Molecular Therapy- Nucleic Acids, 691, 2021.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):129–130.

CLM-P027 Development of a community informed and PEER-led public health promotion campaign using graffiti street art to increase hepatitis C awareness in the downtown eastside of Vancouver, BC

S Bartlett ^1,², T Helten ³, J Hardy ³, K Shipman ⁴, N Canuel ⁵, D Schmitz ⁶

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Poverty and housing insecurity experienced in the Downtown Eastside (DTES) of Vancouver results in community members having limited access to news & health information. To combat this, DTES community members and graffiti artists began creating street art to share “public service announcements” (PSAs) with commentary on health or safety issues impacting the DTES. These PSAs are conveyed through graffiti art works created in public spaces such as walls and alleys around the DTES. Hepatitis C virus (HCV) continues to disproportionately affect the DTES, despite the availability of new curative treatments, as there is limited knowledge or understanding of these new treatments among community members.

Purpose: We sought to bridge the gap in awareness about new HCV treatments among people experiencing social and economic marginalisation in the DTES, by partnering with DTES graffiti street artists and community members to create public artworks featuring hepatitis C related health promotion messages.

Method: Staff and clients from Overdose Prevention Society (OPS) who have lived experience of HCV were invited to participate in an exploratory workshop facilitated by a public health researcher and two local graffiti artists from the DTES who have lived experience of HCV infection. Topics explored in the workshop were current and previous knowledge gaps and attitudes related to hepatitis C testing and treatment, perceptions of graffiti street art PSAs, perceptions of previous traditional hepatitis C awareness campaigns and messages, and experiences accessing care and treatment. Artistic concepts and public health messaging were collaboratively developed during the workshop based on participants input and preferences, then executed by the artists.

Result(s): Ten OPS staff and clients participated in co-designing the graffiti artwork. Most commonly identified knowledge gaps were not being aware of newer hepatitis C testing options or of extra hepatic manifestations of hepatitis C infection. Participants felt that graffiti street art was highly engaging and an effective way to reach DTES community members. Participants shared that health promotion campaigns with messages or methods of delivery that were unexpected or innovative were an effective way to open up conversations and get community members talking about the topic.

graphic file with name canlivj-7.1-abst_fig15.jpg — Image:

Conclusion(s): Collaborating with community members and artists who have lived experience of HCV infection resulted in an innovative and engaging public health promotion tool tailored to the DTES community. The artwork will now be displayed in clinics and community settings to start conversations about hepatitis C testing and treatment. Posters and postcards featuring the artwork were also created containing HCV information, and a short film capturing the process of creating the art work will be shared online and on social media channels. Graffiti street art may be an effective method of engaging the DTES community in public health messaging related to infectious diseases such as HCV.

Disclosure of Interest: S. Bartlett Grant / Research support from: Gilead Sciences Inc., AbbVie Corp., Consultant of: Gilead Sciences Inc., AbbVie Corp., Cepheid Canada, Speakers bureau of: Gilead Sciences Inc., AbbVie Corp., T. Helten: None Declared, J. Hardy: None Declared, K. Shipman: None Declared, N. Canuel: None Declared, D. Schmitz: None Declared

Can Liver J. 2024 Feb 26;7(1):130–131.

CLM-P028 Predicting 6-month drug poisoning (overdose) mortality among people living with HIV-HCV CO-infection

ML Bédard ^1,², EEM Moodie ¹, J Cox ^1,², C Cooper ^3,⁴, M Hull ⁵, V Martel-Laferrière ⁶, S Walmsley ^7,⁸, MB Klein ^1,², CC-IC Investigators ⁹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: Drug poisoning, or overdose, is an important public health crisis in Canada, particularly among people living with HIV-HCV co-infection. Direct-acting antivirals for HCV result in high cure rates, successfully reducing liver-related mortality and increasing life expectancy in this population. However, increased rates of drug poisoning deaths will negate these benefits. Investigating the risk factors and potential predictors for drug poisoning could help to reduce excess mortality. Since individuals who are co-infected are typically linked to care, this provides an opportunity for healthcare providers to intervene if predictive risk factors could be identified.

Purpose: The primary aim is to predict 6-month drug poisoning mortality among people living with HIV-HCV co-infection using socioeconomic, behavioural, and clinical factors. The secondary aim is to determine if a smaller subset of routinely available variables can adequately predict drug poisoning in a simpler model that could be deployed in clinical settings to flag at-risk patients.

Method: Data from the Canadian Co-Infection Cohort (CCC) will be used. The CCC has followed over 2,000 participants with HIV-HCV co-infection across Canada since 2003. Available covariates for the prediction model include age, sex, race, frequency of drug use, mental health, housing, incarceration, use of harm reduction services, HCV RNA, and HIV viral load. Generalized Estimating Equations regression models will be developed using Least Absolute Shrinkage and Selection Operator, using each available visit for eligible participants to account for within-person correlation of repeated measures. Sensitivity analyses will examine the impact of the COVID-19 pandemic and explore deaths with no recorded cause, which may represent additional drug poisoning deaths.

Result(s): Of 2132 participants ever enrolled, 1753 reported using injection drugs and 1699 reported using non-injecting drugs ever in their lifetime. Drug poisoning, recorded for 84 (17%) out of a total of 491 deaths, is now the most frequently reported cause of death in the cohort. Of the 84 drug poisoning deaths, 31 (37%) occurred since 2017. This event rate is high enough to ensure adequate power to perform accurate prediction. Over one third (32; 38%) of drug poisoning deaths occurred among women. The median age of those dying from drug poisoning was 48 years (IQR 40-52); 21 (25%) self-identified as Indigenous, and 22 (26%) were HCV RNA negative at time of death. Results of the prediction models will be presented at the time of the conference.

Conclusion(s): Understanding the predictors of short-term risk of drug poisoning is an important first step for developing a tool for use in clinical settings to predict and prevent untimely deaths due to drug poisoning. Ultimately, research findings may improve the care and health of people living with HIV-HCV co-infection throughout their lifespan and prevent excess mortality.

Disclosure of Interest: M. Bédard: None Declared, E. Moodie Grant / Research support from: EEMM is supported by a Tier 1 Canada Research Chair in Statistical Methods for Precision Medicine and acknowledges the support of a chercheur de mérite career award from the FRQ–Santé., J. Cox Grant / Research support from: ViiV Healthcare, Consultant of: JC has received remuneration for advisory work from Gilead Canada and ViiV Healthcare, C. Cooper Grant / Research support from: Gilead Sciences, AbbVie and ViiV Healthcare., Consultant of: CC reports advisor fees from Gilead Sciences, AbbVie and ViiV Healthcare., Speakers bureau of: CC reports speakers fee from Gilead Sciences, AbbVie and ViiV Healthcare., M. Hull Grant / Research support from: Gilead, Speakers bureau of: MH reports honoraria for speaking engagements or advisory boards from Gilead., V. Martel-Laferrière Grant / Research support from: Gilead Science and Merck. V.M.L. is supported by Clinical Research Scholars– Junior 1 from the Fonds de recherche du Québec-Santé., Consultant of: V.M.L reports consluting fees from Abbvie., S. Walmsley Grant / Research support from: ViiV, Gilead and Merck., Speakers bureau of: SLW has served on advisory board, and spoken at CME event for Merck, Gilead, Viiv., M. Klein Grant / Research support from: MBK reports grants for investigator-initiated studies from ViiV Healthcare, AbbVie, and Gilead. MBK is supported by a Tier I Canada Research Chair in Clinical and Epidemiologic Studies of Chronic Viral Infections in Vulnerable Populations., Consultant of: MBK reports consulting fees from ViiV Healthcare, Merck, AbbVie, and Gilead., C. C.-I. C. Investigators Grant / Research support from: The Canadian Coinfection Cohort is funded by the Réseau sida/maladies infectieuses du Fonds de Recherche du Québec—Santé; the Canadian Institutes of Health Research (CIHR; FDN-143270); and the CIHR Canadian HIV Trials Network (CTN222).

Can Liver J. 2024 Feb 26;7(1):131–132.

CLM-P029 HCV reinfection among people who use drugs (PWUD) treated for HCV infection: a long-term view

B Conway ^1,², S Beitari ¹, R Yung ¹, S Yi ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Developing comprehensive programs of care for populations such as PWUD is needed to eliminate HCV infection as a public health concern by 2030. A primary challenge associated with such initiatives is the need for effective strategies to mitigate the risk of reinfection after successful therapy. Meta-analyses suggest a reinfection rate of approximately 5 per 100 person-years (py), but some real-world cohorts report significantly higher rates. We hypothesize that maintaining continuous engagement in care post-successful therapy would significantly reduce reinfection rates and maximize the benefits of HCV therapy in this population.

Purpose: The purpose of this evaluation is to assess reinfection rates among populations of PWUD successfully treated for HCV infection and maintained in long-term follow-up within a multidisciplinary program of care, including targeted interventions to address opiate addiction.

Method: In our program, we provide HCV therapy to PWUD within the context of a comprehensive, multidisciplinary addressing all medical, social, psychologic, and addiction-related needs with antiviral medications administered daily, or weekly as most appropriate, to maximize adherence and achievement of cure. Subsequently, patients continue to be integrated in care, including opiate agonist therapy and safe supply. HCV RNA testing is repeated annually, or more frequently if clinically indicated. We conducted an evaluation of the last 308 successful courses of HCV therapy administered to PWUD in our center to determine the rate of HCV reinfection and its correlates.

Result(s): All participants completed treatment between 03/19-08/23. We observed median age 47 (22-83) years, 28.2% female, 19.3% identifying as indigenous, 53.9% unstably housed, and 92.2% continuing active drug use (mostly fentanyl) after successful HCV cure. Since 2019, we documented 8 cases of reinfection, resulting in a rate of 0.88 cases per 100 person-years. Of these 8 reinfected patients, 2 were female, 2 identified as indigenous, and all were experiencing unstable housing and ongoing drug use.

Conclusion(s): To our knowledge, this is the largest single center longitudinal evaluation of HCV reinfection rates among active PWUD in a cohort enriched for factors of instability (high rates of fentanyl use, unstable housing). We demonstrate that a comprehensive, multidisciplinary approach to HCV therapy with maintenance in follow up after cure is achieved is associated with rates of reinfection below 1/100 py. Implementation of programs such as ours will contribute significantly to the goal of eliminating HCV infection as a public health concern by 2030, and maintaining the personal and societal benefits of therapy, particularly in this vulnerable population.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):132–133.

CLM-P030 A comparison of sofosbuvir/velpatasvir (S/V) and glecaprevir/pibrentasvir (G/P) for the treatment of hcv infection among HCV-infected people who use drugs (PWUD)

B Conway ^1,², S Beitari ¹, R Yung ¹, S Yi ¹, S Sharma ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Providing therapy to HCV-infected PWUD in a comprehensive way will be critical to achieve HCV elimination by 2030. Two highly effective regimens are available for initial therapy: S/V given as one tablet daily for 12 weeks; G/P given as 3 tablets/day for 8 weeks. Data evaluating the factors determining a choice of one regimen over another (as well as their relative safety and efficacy) among PWUD requiring treatment is limited.

Purpose: The objective of this study is to compare the safety, efficacy, and treatment preferences between two HCV regimens: G/P and S/V, within the population of PWUD in inner city Vancouver.

Method: Patients were dentified through outreach events in single room occupancy dwellings. Viremic men and women were offered HCV treatment within a multidisciplinary program to address their medical, social, psychiatric, and addiction-related needs, with antiviral medications provided daily or weekly. Patients were given the choice between G/P and S/V unless there were medical contraindications. This analysis focuses on the last 120 sequential individuals who chose either S/V or G/P, correlating treatment choice with safety, efficacy, and other outcomes.

Result(s): Among the 240 subjects enrolled in G/P or S/V, the median age was 47 for the G/P cohort and 46 for the S/V group. On average, 37.5% were female, 24% identified as indigenous, 98.2% had a history of drug abuse, 93.5% used opiates/fentanyl, and 68% reported unstable housing. Baseline characteristics showed no significant differences between those receiving G/P and S/V, except for variations in drug use profiles. Overall, 117 and 119 patients completed therapy on G/P and S/V, respectively, while 2 patients withdrew from G/P, all due to taking <1 week of medications. Relapse rates were three and four participants for G/P and S/V, respectively. The mITT cure rate for G/P and S/V were 97%, and 2 drug overdose deaths occurred among those who initiated treatment, one on S/V and one on G/P.

Conclusion(s): To achieve the WHO goal of HCV elimination by 2030, a systematic approach to the diagnosis and treatment of infection in all target populations will be needed, including among PWUD. We have evaluated two highly effective regimens in a group of inner city PWUD enriched for fentanyl use and unstable housing. Among 240 subjects included in this analysis, baseline demographic and diseases characteristics were comparable, except for a slight excess of patients with more advanced fibrosis in the S/V group. With treatment administered within the context of a multidisciplinary program of care, we note that 236/240 (99%) completed the entire course of therapy, be it for 8 or 12 weeks. By mITT, 97% of participants were cured, with no difference between G/P and S/V. Only 2 drug-overdose deaths were observed. Our data support the offer of both G/P and S/V within the setting of a program such as ours for the treatment of HCV-infected PWUD, irrespective of the level of stability.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):133–134.

CLM-P031 HBV care cascade in Rwanda: a population based-study from 2016 to 2023

JD Makuza ^1,^2,³, D Jeong ^1,², S Phyumar ¹, RL Morrow ^1,², G Cua ^1,², HA Velásquez García ^1,², MP Nisingizwe ¹, J Serumondo ³, A Tuyishime ³, A Ramji ⁴, M Law ¹, NZ Janjua ^1,^2,⁵

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: The global burden of viral hepatitis B (HBV) is substantial, and monitoring progress across the care cascade is essential for effective elimination strategies. In Sub-Saharan Africa, data on the HBV care cascade are limited.

Purpose: We aimed to quantify the HBV care cascade in Rwanda among diagnosed with HBV infection individuals from 2016 to 2023.

Method: In this population-based retrospective cohort study, we used routinely collected data from the District Health Information System 2, which included 4.5 million people screened for HBV from January 2016 to June 2023. During this period, individuals were included if they were >2 years old. The HBV care cascade was analyzed across five stages: (1) lifetime prevalence, (2) diagnosis, (3) enrolled in care, (4) treatment initiation, and (5) treatment continuation. Infections were identified by having at least one reactive antigen or nucleic acid test, and lifetime prevalence was estimated as the sum of diagnosed and estimated undiagnosed cases. Multivariable logistic regression was used to identify progression-related factors through the different cascade stages.

Result(s): Among the 4,604,468 persons screened, 55,820 tested positive for HBsAg (HBV infection diagnosed). Of these individuals, 51,065 (91.5%) were HBV mono-infected, and 4,755 (8.5%) were HBV/HIV co-infected. Among all HBV-positive cases, 21,182 (38.0%) were enrolled in care, 5,966 (28.2%) were eligible for HBV treatment, 4,746 (79.6%) initiated treatment, and 4,621 (97.4%) continued treatment at 1-year post-initiation. Individuals enrolled at district hospitals were more likely to be engaged in care (adjusted odds ratio [aOR], 2.09; 95% CI, 1.93, 2.26), eligible for HBV treatment (aOR: 1.82; 95% CI, 1.61, 2.07), initiate HBV treatment (aOR: 2.41; 95% CI, 1.85, 3.14), and be retained in care (aOR: 5.85; 95% CI, 2.74, 12.49), compared to those followed up at health centers. Compared to those at ≤ 30-minute distance, those living at a distance of >1 hour to reach a facility were more likely to be engaged with care, eligible for HBV treatment, and initiate treatment, while they were less likely to be retained in care. Individuals living with HIV were more likely to be engaged in care and less likely to initiate HBV treatment.

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Conclusion(s): Overall, engagement with care was low. Individuals followed at district hospitals were more likely to be engaged in care, eligible and initiate the HBV treatment, and retained in care, highlighting the need for strengthening decentralization and integration of HBV services to lower-level health facilities by increasing well-trained healthcare providers, and needed infrastructure for prevention and treatment of HBV at health center level.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):134–135.

CLM-P032 In-person interactions impact on HCV, HIV, and Syphilis rates in at risk populations

P Ford ¹, H House ¹

What is your preferred presentation method?: Poster Only

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: During Covid-19 restrictions, OSN/SRx worked with two community partners to address Saskatchewan's at-risk population's growing HCV, HIV, and Syphilis rates. Since June 2022, we’ve partnered with six more community groups. Public Health did not resume STBBI testing and community support when restrictions were eased. Our teams closed this screening gap.

Purpose: To show the importance of In Person interactions to test and treat our At-Risk population. This is due to the stigma attached to these viruses and the sensitive nature attached to them. By meeting people where they are at we are able to test and treat more people.

Method: A nurse, two phlebotomists, a peer support worker, and a community outreach worker make up the OSN/SRx teams. Our teams visit our community partners weekly to test for HCV, HIV, and Syphilis and connect clients to additional care, treatment, and support. Needle exchange clinics, drop-in centers, and safe injection sites are included. Addictions and harm-reduction education are also available. Offering enhanced supports, is “bringing the care where the individuals are at”.

Result(s): In 2021; 105 HCV, 24 HIV, and 13 syphilis positives were found in 368 individuals tested, 19 of 60 HCV RNA positive patients underwent therapy. February 2022 Covid-19 Restrictions ended in Saskatchewan, however, most places kept them in place. In 2022; 274 HCV, 51 HIV, (8 new HIV) and 36 syphilis positives were found in 629 individuals tested, 44 of 80 HCV RNA positive patients underwent therapy. January to June 2023; 244 HCV, 64 HIV, (3 new HIV) and 41 syphilis positives were found in 697 individuals tested, 53 of 83 HCV RNA positive patients underwent therapy.

Conclusion(s): Due to government restrictions on venue capacity during the COVID-19 pandemic, many at-risk communities were unable to access services. HCV, HIV, and Syphilis infections increased in 2022. Anecdotally, the pandemic, lack of services, scarcity of clean needles, and increased isolation that fostered drug use contributed. We can now offer in-person testing and meet clients where they are without restrictions. By adding testing sites, we’ve tested and connected more people to care. We expect this knowledge to help conference attendees tackle rising HCV infection rates.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):135–136.

CLM-P033 The impact of new DAA therapy on the prevalence and undiagnosed proportion of chronic hepatitis C infection in Alberta: a model-based analysis

F Forouzannia ¹, N Eze ², F Clement ², WWL Wong ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: The landscape of treatment for patients with chronic hepatitis C (CHC) has changed rapidly. Patients with diagnosed CHC can now be treated effectively using interferon-free DAA combinations. However, many infected individuals have not yet been identified. In Alberta, data on CHC prevalence are very limited. It is important to understand the impact of wider access to effective treatments and improved awareness of the disease on CHC prevalence and the undiagnosed CHC proportion, which are key factors in planning national screening and treatment interventions, achieving (WHO) 2030 elimination targets.

Purpose: The goal of this research is to estimate the CHC prevalence and undiagnosed proportion in Alberta using a back-calculation modeling approach informed by provincial population-level health administrative data.

Method: In this study a two step approach was used;1) a population-based retrospective analysis of health administrative data for Alberta (2001-2018) was conducted to generate annual incidence of newly diagnosed CHC cases, decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and HCV-related treatment cases for three birth cohorts: individuals born before 1945, individuals born between 1945 and 1965 and individuals born after 1965, 2) We applied a back-calculation approach, using a validated natural history model and a Bayesian Markov chain Monte Carlo (MCMC) algorithm to obtain historical prevalence and incidence estimates by comparing the model-generated predictions of the annual incidence of the CHC-related health events against the observed incidence generated in step 1.

Result(s): In Alberta, CHC prevalence in 2018 was estimated to be 0.68% (95% CI: 0.52% - 1.1%) among individuals born before 1945, 2.82% (95% CI: 1.98% - 3.92%) among individuals born between 1945 and 1965, and 0.72% (95% CI: 0.57% - 0.98%) among individuals born after 1965. Overall, the mean prevalence estimates over all birth cohorts were assessed to be 1.15% (95% CI: 0.91%-1.4%), falling from 1.23% since the introduction of DAAs in 2015. On the other hand, in 2018, the undiagnosed CHC proportion was 45.5% (95% CI: 25.2% - 58.3%) among individuals born prior to 1945, 41.9% (95% CI: 20.2% - 58.1%) among individuals born between 1945 and 1965, and 34.1% (95% CI: 24.8% - 45.2%) among individuals born after 1965. Overall, the mean undiagnosed CHC proportion estimates for Alberta over all birth cohorts were assessed to be 36.4% (95% CI: 27.5%-45.3%), falling from 39.6% since the introduction of DAAs in 2015. (Figure 1).

graphic file with name canlivj-7.1-abst_fig17.jpg — Image:

Conclusion(s): This is the first study to estimate CHC prevalence and undiagnosed proportion in Alberta after the introduction of new DAA treatment using provincial health administrative data. The results can provide vital evidence to guide decisions about current and future HCV strategies and help achieve the WHO goal of eliminating hepatitis C in Canada by 2030.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):136–138.

CLM-P034 Testing patterns for hepatitis C virus in infants born between 2010-2019 in British Columbia

W Fu ¹, K Twohig ², S Bartlett ^1,², O Guttman ^1,³, D Goldfarb ^1,^4,⁵, L Sauvé ^1,⁴

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: The cascade of care for infants exposed to HCV perinatally is incompletely characterized in BC. Based on 42,000 live annual births, HCV prevalence rates of 0.5% in pregnant people in the province, vertical transmission rates of 5-11%, and chronic HCV developing in 80% of infected children, there could be anywhere between 8-18 new cases of vertical transmission each year. The BC Centre for Disease Control receives an average of 2 HCV case reports each year among pediatric patients that meet the HCV case definition. Published and unpublished studies across Canada have found that a high proportion of infants exposed to HCV perinatally are lost to care.

Purpose: The purpose of this study was to describe hepatitis C testing patterns in infants less than 3 years of age at time of testing as part of a larger effort to describe the cascade of care for infants exposed to HCV in pregnancy.

Method: This was a retrospective cohort study on HCV testing in BC for infants born between 2010-2019. Data were obtained from Sexually Transmitted and Blood-borne Infections Data Mart, a provincial laboratory testing database. HCV test episodes for infants less than 3 years of age at the time of testing were included. Initial follow-up was defined as at least one PCR or serology test. Complete positive diagnostic follow up was defined as two positive PCR results at least 1 month apart at any age or positive antibody at 18 months of age or older. Complete negative diagnostic follow up was defined as two negative PCR results at least 1 month apart at any age or negative antibody at any age. Linkage to care was defined as quantitative PCR monitoring.

Result(s): 3247 infants born from 2010 to 2019 were tested at least once for HCV with serology or PCR before the age of 3. Of these, 24 (0.7%) infants were confirmed positive and 2704 (83.3%) were confirmed negative. Of those that were confirmed positive, 22 (91.7%) were linked to care with at least one quantitative PCR. Of those that were confirmed negative, 2208 (68.0% of the cohort) had one serology test only. The remaining 519 infants (16.0%) had incomplete follow-up; 474 (91.3%) of these had a single testing episode, 432 (91.1%) of which were a single negative PCR test.

graphic file with name canlivj-7.1-abst_fig18.jpg — Image:

Conclusion(s): The large proportion of confirmed negative cases by a single serology test suggests that many infants may have been tested for routine medical purposes unrelated to perinatal exposure (eg. oncological diagnoses, transplant preparation, hepatitis workup). The data source from this study used infant laboratory data in isolation; as such, the full cascade of care cannot be commented on. However, of those with a positive diagnosis, most were linked to care, suggesting that once connected with the healthcare system, infants receive appropriate monitoring. The main limitation of this analysis is understanding the full cascade of care using a linked maternal-infant database to assess loss to care at the initial point of testing after known perinatal exposure.

Disclosure of Interest: W. Fu: None Declared, K. Twohig: None Declared, S. Bartlett Consultant of: Sofia Bartlett has received speakers’ honoraria, consulted for, and participated in medical advisory board programs with Gilead Sciences, AbbVie, and Cepheid (no personal payments accepted), as well as investigator-initiated, unrestricted funding from Gilead Sciences and AbbVie, via the Provincial Health Services Authority and BCCDC Foundation for Public Health., O. Guttman Consultant of: Orlee Guttman has consulted and participated in advisory board activities for Mirum Pharmaceuticals., D. Goldfarb Grant / Research support from: David Goldfarb has received investigator initiated research funding from bioMerieux Inc., L. Sauvé Grant / Research support from: Laura Sauvé has research funding from PHAC and CIHR.

Can Liver J. 2024 Feb 26;7(1):138–139.

CLM-P035 Hepatitis C treatment challenges for individuals incarcerated in Alberta provincial correctional facilities: can we do better?

K Goralczyk ¹, A Draude ², C Diribe ³, C Egan ⁴, MG Swain ⁵

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Treatment rates for HCV-infected individuals incarcerated in provincial correctional facilities remain low, including Alberta, attributed in part to short incarceration periods.

Purpose: Therefore, Alberta Correctional Health Services (CHS) leadership partnered with the Alberta Innovates funded LiveRx program to try to better understand this issue and to potentially develop new ways to link incarcerated HCV-infected people to treatment using community pharmacy-based treatment hubs. As a first step in this partnership, CHS and LiveRx co-funded an HCV Navigator embedded within CHS to do an exploratory case finding/outcome assessment for HCV infection status among individuals incarcerated within CHS in Calgary, Alberta.

Method: The CHS HCV Navigator searched historical and current medical records for individuals that had been incarcerated in three provincial correctional centres in Calgary, Alberta (Calgary Correctional Centre [CCC], Calgary Remand Centre [CRC], Calgary Young Offender Centre and Female Annex [CYOCAFA]) between April 15 - September 15, 2023. People who were HCV antibody positive and RNA positive/negative were identified and documented, and successful linkage to HCV treatment was assessed.

Result(s): We found a total of 267 individuals incarcerated during this time period who had previously been identified as being HCV antibody +ve. Of these, 112 individuals (41.9%) were HCV RNA positive indicating ongoing infection (HCV RNA +ve rates for each center; CRC 41% [n=69/167]; CCC 47% [n=11/23]; CYOCAFA 41% [n=32/77]). Remanded patients were often unable to complete HCV treatment referral processes due to short incarceration periods (average length of stay 14-16 days). Specifically, early discharge was the reason given for non-treatment in 39% of HCV RNA +ve cases in CRC (n= 27/69) and 43% of cases in CYOCAFA (n=14/32). However, even for individuals meeting incarceration period HCV treatment eligibility criteria (24 weeks), treatment initiation rates remained low (7.1%; n=8/112). In addition, no actively infected HCV individuals recommended for therapy on release were successfully linked to treatment (0%; n=0/22). Follow up interviews are ongoing with patients who return to corrections but did not complete community-based treatment arranged during prior incarcerations. Barriers and facilitators to acceptance of treatment will be explored in Fall of 2023 with a focus on increasing the HCV treatment rate, including linking released individuals to HCV treating community-based pharmacists who are routinely interacting with priority populations.

Conclusion(s): HCV treatment processes must be considered within the unique challenges and life experiences of individuals interacting with the criminal justice system, and new approaches need to be created and prioritized. Identifying how to engage these individuals through people- and community-centered frameworks is paramount to successfully treating HCV in this setting.

Disclosure of Interest: K. Goralczyk: None Declared, A. Draude: None Declared, C. Diribe: None Declared, C. Egan: None Declared, M. Swain Grant / Research support from: This work was supported by a research grant from Alberta Innovates in partnership with AbbVie and Gilead Sciences.

Can Liver J. 2024 Feb 26;7(1):139–140.

CLM-P036 Mixed-genotype HCV direct acting antiviral outcomes: a CANUHC analysis

H Imsirovic ^1,², G Macphail ³, B Conway ⁴, C Fraser ⁵, SM Borgia ^6,⁷, D Smyth ⁸, A Wong ⁹, M-L Vachon ¹⁰, D Webster ⁸, J Feld ¹¹, S Lee ³, C Cooper ^2,¹²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Chronic HCV infection can result in serious liver disease and remains an important focus of public health attention in Canada. The role of HCV mixed-genotype infection in viral persistence and treatment outcome is not well described.

Purpose: To describe the CANUHC mixed-genotype HCV patient population derived from 17 sites across Canada and determine the proportion of Direct Acting Antiviral (DAA)-treated patients achieving a sustained virologic response (SVR).

Method: The CANUHC prospective cohort consists of chronic HCV patients enrolled between 2015-2023. Their baseline characteristics were recorded upon enrollment and the SVR was assessed at follow-up.

Result(s): 26 HCV patients with a mixed genotype were enrolled into CANUHC. Patients came from British Columbia (11.5%), Alberta (15.4%), Ontario (53.8%) and Atlantic Canada (19.2%). The mean baseline age was 52.4 (12.5 SD), 53.8% were male, 46.2% white, 15.4% Indigenous, 26.9% Asian, 3.8% Black, and 3.8% other. 26.9% were immigrants. The combination of genotypes included: 1a+1b (n=9), 1 unable to subtype+6 (n=7), 1a+2 (n=3), 1a+3 (n=3), 1a+5 (n=1), 1 unable to subtype+2 (n=1), 1 unable to subtype+4 (n=1), 2+4 (n=1). 11.5% were diabetic and 3.8% were HIV seropositive. Key characteristics included: 53.8% with history of incarceration, 38.5% with current alcohol use, 26.9% with recreational drug use within the last 6 months, 30.8% with mental health conditions. 19.2% of the patients were cirrhotic at baseline.

Of these 26 CAHUNC patients, there is data on prescribed DAA regimens for 24 (92.3%). Frequently utilized DAA regimens included sofosbuvir / velpatasvir (n=15), sofosbuvir / ledipasvir (n=4), and glecaprevir / pibrentasvir (n=2). Of 24 CAHUNC mixed-genotype HCV patients starting DAA treatment, 15 (62.5%) had follow-up data available. All the patients with available post treatment data achieved a SVR.

Conclusion(s): This descriptive summary of CANUHC reports the baseline characteristics and DAA treatment outcomes of a diverse sample of Canadians living with mixed-genotype HCV. The proportion of patients achieving SVR is very high suggesting that mixed-genotype infected patients can be readily cured. CANUHC data will be updated and linked to registry data to enable assessment of long term, post SVR outcomes.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):140–141.

CLM-P037 A descriptive analysis of CanHepC participants and HCV direct acting antiviral outcomes

H Imsirovic ^1,², B Conway ³, G Macphail ⁴, D Smyth ⁵, D Webster ⁵, C Fraser ⁶, SM Borgia ^7,⁸, J Feld ⁹, C Cooper ^2,¹⁰

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Chronic HCV infection can result in serious liver disease and remains an important focus of public health attention in Canada.

Purpose: To describe the Canadian Network for Hepatitis C (CanHepC) HCV patient population derived from 17 sites across Canada and determine the proportion of Direct Acting Antiviral (DAA)-treated patients achieving a sustained virologic response (SVR).

Method: The CanHepC retrospective cohort consists of chronic HCV patients initially assessed in CanHepC clinics between 1998-2018. Their baseline characteristics were recorded upon enrollment and the SVR was assessed at follow-up.

Result(s): 7,710 HCV patients were enrolled into CanHepC, of these 3,606 (46.8%) were prescribed a DAA regimen. The 3,606 patients came from Ontario (37.6%), British Columbia (26.4%), Alberta (9.8%), Atlantic Provinces (9.7%), Quebec (8.7%), and Saskatchewan (7.7%). The mean baseline age was 52.2 (10.8 SD), and 65.0% were male. Common genotypes included: 1a (42.4%), 1b (14.6%), 1 unable to subtype (13.3%), 2 (6.8%), 3 (16.4%) and 4 (1.9%). 42.4% of the patients were cirrhotic and 7.6% were HIV seropositive at baseline. The distribution of fibrosis stage for this cohort was 23.6%, 8.8%, 12.8%, 42.4% for F0-F1, F2, F3, F4 respectively.

Of 3,606 CanHepC HCV patients treated with DAA, 3,287 (74.4%) patients were treatment naïve before the most recent DAA treatment, 24.9% were on a prior interferon-based regimen before the most recent DAA treatment, and 0.7% were on a prior DAA only regimen before their most recent DAA treatment. 2,236 (62.0%) CanHepC HCV patients starting DAA treatment had serial data available. 2,108 (94.3%) achieved an SVR. SVR proportions did not differ by prior treatment experience or between cirrhotic and non-cirrhotic patients. Females were more likely to achieve SVR than males (97% vs 94%, p<.0001).

Conclusion(s): This descriptive summary of the CanHepC cohort reports the baseline characteristics and DAA treatment outcomes of a large and diverse sample of Canadians living with HCV. The proportion of patients achieving SVR is very high. CanHepC data will be linked to registry data to enable assessment of long term post SVR outcomes.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):141–142.

CLM-P038 A descriptive analysis of canuhc participants and hepatitis C virus (HCV) direct acting antiviral outcomes

H Imsirovic ^1,², C Cooper ^2,³, SM Borgia ^4,⁵, D Webster ⁶, D Smyth ⁶, L Barrett ⁶, G Macphail ⁷, C Fraser ⁸, L Bulinckx ⁹, M-L Vachon ¹⁰, A Wong ¹¹, K Stewart ¹¹, B Conway ¹², A Ramji ¹³, A Hamour ¹³, H Liu ⁷, J Feld ¹⁴, S Lee ⁷

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Chronic HCV infection can result in serious liver disease and remains an important focus of public health attention in Canada.

Purpose: To describe the CANUHC HCV patient population derived from 17 sites across Canada and determine the proportion of Direct Acting Antiviral (DAA)-treated patients achieving a sustained virologic response (SVR).

Method: The CANUHC prospective cohort consists of chronic HCV patients enrolled between 2015 and 2023. Their baseline characteristics were recorded upon enrollment and the SVR was assessed at follow-up.

Result(s): 3,267 HCV patients were enrolled into CANUHC. Patients came from British Columbia (27.1%), Alberta (25.2%), Ontario (20.2%), the Atlantic Provinces (14.9%), Saskatchewan (9.7%), and Quebec (2.9%). The mean baseline age was 50.3 (13.1 SD), 64.4% were male, 66.1% white, 17.4% Indigenous, 6.2% Asian. 15.8% were immigrants. Common genotypes included: 1a (46.1%), 1b (7.4%), 1 unable to subtype (2.2%), 2 (8.4%), 3 (23.0%) and 4 (1.7%). 6.6% were diabetic and 5.7% were HIV seropositive. Key characteristics included: 11.2% with transfusion history prior to 1992, 40.0% with history of incarceration, 35.8% with current alcohol use, 49.1% with recreational drug use within the last 6 months, 28.8% with mental health conditions. 19.3% were cirrhotic at baseline.

Of 3,267 CAHUNC HCV patients, there is data on prescribed DAA regimens at baseline for 2,867 (87.8%) patients. The top three regimens utilized included sofosbuvir / velpatasvir (48.1%), glecaprevir / pibrentasvir (21.4%) and elbasvir / grazoprevir (13.2%). Of 2,867 CAHUNC HCV patients starting DAA treatment, 1,671 (58.3%) had follow-up data available of which 1,648 (98.6%) achieved an SVR. SVR proportions did not differ by DAA regimen.

Conclusion(s): This descriptive summary of CANUHC reports the baseline characteristics and DAA treatment outcomes of a large and diverse sample of Canadians living with HCV. The proportion of patients achieving SVR is very high. CANUHC data will be updated and linked to registry data to enable assessment of long term, post SVR outcomes.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):142–143.

CLM-P039 The impact of the COVID-19 pandemic and related measures on the delivery of HCV-related care and services and preferred solutions for improving access to care: a survey of health care providers in Canada

T Buller-Taylor ¹, M Binka ¹, G Cua ¹, D Jeong ¹, R Morrow ², S Bartlett ², NZ Janjua ^1,^2,³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: The COVID-19 pandemic and related control measures required changes to the delivery of hepatitis C (HCV)-related services by health care providers and facilities which led to delays in HCV testing, diagnosis, treatment, and follow-up care for people affected by HCV^1,2.

Purpose: We aimed to address gaps in knowledge on how the COVID-19 pandemic affected facilities and providers in the provision and reach of HCV-related medical and support services.

Method: From June 2022 to March 2023 we invited providers of HCV-related medical and/or support services to complete an online survey assessing the impact of the COVID-19 pandemic on their service provision. Providers were recruited through Canadian organizations that have a significant interest in HCV. Survey topics included: populations served; impacts on services, staffing, and supplies; service delivery methods; and preferred solutions for improving access to HCV-related care.

Result(s): Of the 49 respondents who completed the survey, many were nurse practitioners or registered nurses (49.0%); predominantly from British Columbia (75.5%); and have been providing HCV-related medical or support services for 1-3 years (26.5%) or 11+ years (30.6%). As a result of the COVID-19 pandemic or related measures, 77.1% of respondents reported: a worsening in delivery of services (63.6%); of losing at least one nurse; and decreases in HCV antibody testing (59.3%), RNA testing (63.0%), liver health assessments (63.0%), liver cancer screening (65.4%), and mental health support (64.3%). Cancelled laboratory operations were cited as a key barrier to HCV testing (63.4%) and treatment (61.5%), while pandemic control measures were noted less frequently as barriers to HCV testing, treatment, and support services (29.3%, 30.8%, and 37.2% respectively). Patient concerns about getting COVID-19 was seen as more of a barrier to HCV treatment, testing, and support services than was patient fear of being stigmatized (see Fig 1). Respondents reported an increased use of telemedicine for discussing test results (64.7%) and for providing refills for HCV-related prescriptions (58.8%) compared to the pre-pandemic period. The top solutions identified for better pandemic preparedness included testing at harm reduction operations (75.5%), and education for providers (69.7%) and the general public (69.4%).

graphic file with name canlivj-7.1-abst_fig19.jpg — Image:

Conclusion(s): The COVID-19 pandemic presented substantial challenges to the delivery of HCV-related care and services by health care providers. Adverse effects on service delivery were noted, with most survey respondents reporting a deterioration in the provision of HCV-related services. The reliance on telemedicine by providers during COVID-19 warrants consideration of initiatives to address digital exclusion to ensure broader accessibility to HCV care and treatment in the future. Strategies like implementing HCV testing at harm reduction sites and providing education for providers and the general public could improve overall care and help with reaching HCV elimination goals.

References:

1. Binka, M., Bartlett, Velásquez García H.A., et al. Impact of COVID-19-related public health measures on HCV testing in British Columbia, Canada: An interrupted time series analysis. Liver Int.41, 2849–2856 (2021).

2. Janjua, N., Wong, S., Jeong, D., et al. The impact of COVID-19 pandemic control measures on HCV treatment initiation in British Columbia, Canada. J. Hepatol.77, S209 (2022).

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):143–145.

CLM-P040 The impact of COVID-19 on access to HCV-related care and services, and preferred solutions: a survey of people disproportionately affected by incarceration, under-housing and/or substance use in Canada

T Buller-Taylor ¹, G Cua ¹, M Binka ¹, D Jeong ¹, J Bruneau ², B Sander ³, M Korchinski ⁴, P Young ⁵, K Connolly ⁶, M Thomas ⁷, B Ellis ⁷, M Coughlan ⁸, J Wong ⁹, P Adu ¹, A Erman ¹⁰, D Schmitz ¹¹, Z Greenwald ¹², M Tadrous ^13,¹⁴, H Velásquez García ¹, C Greenaway ¹⁵, V Tran ¹⁶, W Wong ¹⁷, S Bartlett ⁹, J Kwong ¹², NZ Janjua ^1,^9,¹⁸

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: The COVID-19 pandemic and control measures disrupted access to hepatitis C (HCV)-related services leading to delays in HCV testing, diagnosis, treatment, and follow-up care. Historically marginalized communities are at greater risk of barriers to accessing care due to factors such as limited resources, transportation challenges and discrimination.

Purpose: To address knowledge gaps about pandemic-related barriers to accessing HCV-related medical and support services for historically marginalized communities and to identify preferences for improving access to HCV-related care and services.

Method: From September 2022 to June 2023, our partner community-based organizations and one clinic recruited and surveyed individuals who reported having received HCV-related medical care and/or HCV-related service appointments in the last three years. Organizations were based in British Columbia, Ontario, New Brunswick, and Newfoundland and Labrador and often serve individuals who have historically been marginalized. Participants were recruited through posters, e-mails to other organizations or people affected, and in-person invites to clients accessing their services. Surveys were conducted using web-and paper-based methods. Survey topics included background characteristics, type of HCV-related care accessed (medical or support services) during the pandemic, barriers to HCV-related care during the pandemic, pandemic-related impacts, list of preferred solutions to reduce barriers to HCV-related care, and an open-ended question to suggest solutions not listed.

Result(s): Most of the 243 respondents who completed the survey had been diagnosed with HCV (89%), were male (62%), white (51%), 35-54 years of age (57%), heterosexual (87%) and accessed services in BC (61%). Most had experienced drug use (95%), food insecurity (83%), a lack of housing (79%), and incarceration (63%). Respondents who accessed HCV-related (a) medical care only or medical and support services (n=141); or (b)or support services only or support and medical care (n=161; categories not mutually exclusive) indicated that because of the pandemic, access to HCV-related medical care and supports worsened (57% and 62%, respectively); and they had appointments cancelled or postponed (58% and 69%). Barriers to accessing HCV-related medical care or support services included: competing demands (39% and 54%, respectively), COVID-19 control measures (37% and 41%), fear of stigma (36% and 33%), and concern about getting COVID-19 (28% and 40%). Solutions for improving access to HCV-related care included same day HCV testing and diagnosis (64%), and testing at harm reduction sites (64%). There were some significant differences by background characteristics (e.g., Fig 1).

graphic file with name canlivj-7.1-abst_fig20.jpg — Image:

Conclusion(s): Findings suggest that individuals who have historically been marginalized faced multiple barriers to HCV medical and support services during the COVID-19 pandemic. Integrating HCV services with other health services can help improve access and mitigate barriers to HCV care.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):145–146.

CLM-P041 The perspectives of Canadian healthcare providers on hepatitis C care and services during the COVID-19 pandemic: a qualitative study

D Jeong ^1,², M Binka ^1,², G Cua ^1,², T Buller-Taylor ^1,², SR Bartlett ^1,², R Morrow ^1,², NZ Janjua ^1,^2,³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background:

The COVID-19 pandemic and subsequent responses led to disruptions and delays in healthcare provision, impacting services related to hepatitis C (HCV) prevention, testing, diagnosis, treatment, and post-treatment follow-up.^1,2 These interruptions could hinder Canada's progress towards achieving its HCV elimination goals. Gaining a deeper understanding of the experiences and lessons learned from the pandemic could better inform future service delivery and provision.

Purpose:

We aimed to understand the experiences of healthcare providers (HCPs) in Canada during the COVID-19 pandemic and assess the impact of the pandemic response on HCV-related care and treatment services.

Method:

Between June 2022 and March 2023, we invited HCPs from various professional and community groups involved in HCV-related medical and support services, research and advocacy. A total of 11 small group interviews involving 18 participants, in groups of 1 to 3, were conducted. Semi-structured interviews were facilitated online via Zoom. Interviews were transcribed, and analyzed in NVivo, using a codebook thematic analysis with an inductive approach.³

Result(s):

HCPs provided insights on three major discussion areas concerning HCV services and care during the pandemic: barriers to the provision of care, changes in practice made during the COVID-19 pandemic, and potential solutions to mitigate adverse effects of future pandemics or public health crises. Pandemic-related barriers were associated with prioritizing COVID-related needs over HCV care services, staffing shortages and burnout, as well as suspension of laboratory services and declines in referrals. Changes made to practice included increased use of telehealth, alleviation of HCV treatment eligibility criteria, and offering co-located screening, testing and treatment services. Support service providers highlighted unique changes such as providing transportation vouchers and bagged meals to clients. Potential solutions identified included streamlining the HCV treatment process, scaling up point-of-care testing, enabling self-referral and testing, expanding eligible prescribers of direct-acting antivirals, and integrating telehealth as an ongoing option.

Conclusion(s):

This study highlights the substantial impact of the COVID-19 pandemic on HCV-related care and services in Canada. Insights from healthcare providers emphasize the need for a comprehensive approach to HCV care and services, including streamlined treatment processes, expanded testing options, and increased opportunities for co-located services, to strengthen HCV care during future public health crises. With the increase of telehealth services, ensuring digital equity will be critical. As healthcare provision recovers from the lingering effects of the pandemic, applying these insights could contribute to sustaining progress towards Canada's HCV elimination goals amidst challenging circumstances.

References:

1. Binka, M. et al. Impact of COVID-19-related public health measures on HCV testing in British Columbia, Canada: An interrupted time series analysis. Liver Int.41, 2849–2856 (2021).

2. Janjua, N. et al. The impact of COVID-19 pandemic control measures on HCV treatment initiation in British Columbia, Canada. J. Hepatol.77, S209 (2022).

3. Braun, V. & Clarke, V. Using thematic analysis in psychology. Qual. Res. Psychol.3, 77–101 (2006).

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):146–147.

CLM-P042 Understanding perceptions of hepatitis C and its management among people with experience of incarceration in Quebec, Canada: a qualitative study guided by the common-sense self regulation model

A Mambro ¹, S Mortazhejri ^2,³, G Fontaine ^2,^4,^5,⁶, A Patey ^2,^3,⁷, D Ortiz-Paredes ¹, JM Grimshaw ^2,^3,⁸, J Cox ^1,^9,¹⁰, C Dussault ¹, J Presseau ^2,^3,¹¹, N Kronfli ^1,^9,¹⁰

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: To reach the World Health Organization 2030 hepatitis C virus (HCV) elimination goals, countries must focus their efforts on people with experience of incarceration (PWEI). However, there is a paucity of data regarding the beliefs and emotions of PWEI towards HCV and its management.

Purpose: To explore the beliefs and emotions of PWEI towards HCV and its management.

Method: We conducted a qualitative descriptive study using semi-structured interviews and guided by the Common Sense-Self Regulation Model (CS-SRM). Individuals living with chronic HCV incarcerated in the previous year were recruited from two harm reduction community sites in Montreal, Quebec. Directed content analysis was used to identify cognitive representations (i.e., perceptions of HCV encompassing six dimensions: cause, coherence, consequences, identity, perceived control, timeline), emotional representations (i.e., reflections on personal emotional responses to HCV), and coping strategies. Sampling continued until thematic saturation was achieved.

Result(s): Between July 2022 and January 2023, 19 PWEI were interviewed, including 11 who self-identified as men, five as women, and three as transgender women. Median age was 48 years. While the level of understanding and awareness of HCV varied among PWEI, there was a common goal of wanting to understand how to prevent HCV acquisition and transmission (coherence). Participants identified the prison environment as having a significant impact on individual health and access to healthcare services and expressed experiencing stigma and isolation due to HCV; few sought social support (coping strategy). This impacted their acceptance of HCV treatment. While most participants were diagnosed with HCV outside of prison (63%), they perceived the management of their HCV infection was influenced by gaps in continuity of care from HCV diagnosis to treatment initiation, as well as access to sources of information (perceived control). Emotions experienced by PWEI evolved across the care cascade, with shock at diagnosis, relief following successful cure, and anxiety around reinfection (emotional representations).

Conclusion(s): The CS-SRM was useful in identifying cognitive and emotional representations of PWEI towards HCV and its management. Notably, ongoing stigma and variable levels of HCV awareness, in combination with a lack of continuity in care, may affect PWEIs’ engagement in HCV-related care in prison and beyond. Future efforts to address stigma and awareness through education may improve engagement in HCV care among PWEI.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):147–148.

CLM-P043 Impact of COVID-19 pandemic on treatment for hepatitis B in British Columbia, Canada: An interrupted time series analysis

RL Morrow ^1,², SR Bartlett ^1,², M Irvine ^1,³, J Makuza ^1,², D Jeong ^1,², J Wong ^1,², A Yu ¹, J Li ¹, S Wong ¹, MJ Alvarez ¹, M Krajden ^1,⁴, A Ramji ⁵, HH Ko ⁵, NZ Janjua ^1,⁶

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Previous research suggests the COVID-19 pandemic was associated with a reduction in treatment for hepatitis B (HBV) early in the pandemic.¹ However, impacts of the pandemic on HBV treatment are not well understood, including impacts over a longer period and by sex, age and injection drug use (IDU) status.

Purpose: To investigate the impact of the COVID-19 pandemic and related policies on initiation of HBV treatment in British Columbia (BC) from 2020 to 2022 among the full population and by sex, age, and IDU status.

Method: Using nearly population-wide data from the BC COVID-19 Cohort, we conducted interrupted time series analyses to investigate the impact of the pandemic on the monthly number of individuals initiating HBV treatment in BC. We assessed HBV treatment initiation from BC PharmaNet dispensation data and IDU status with a previously validated algorithm. The study included a pre–pandemic policy period (January 2017 to Feb 2020), a transition period (March to May 2020), and three pandemic policy periods (June to December 2020, January to December 2021, and January to December 2022). We calculated absolute and percentage differences in monthly treatment initiation during each follow-up period by comparing estimates based on pre–pandemic policy and pandemic policy data with counterfactual estimates (expected treatment initiation) based on pre–pandemic policy data only. To conduct stratified analyses, a separate model was used for each specific population analyzed.

Result(s): During June to December 2020, 58 (95% CI: 46 to 70) fewer individuals initiated treatment each month relative to expectation, representing a decrease of 55.5%. Similarly, treatment initiation levels were 50.5% and 57.3% lower than expected in 2021 and 2022, respectively. (See Figure.) During June to December 2020, the number of individuals initiating treatment decreased by 16 (95% CI: 11 to 22) for females and 33 (95% CI: 25 to 40) for males; 46 (95% CI: 34 to 57) for individuals under 65 years and 3 (95% CI: 0 to 5) for those 65 years or older; and 7 (95% CI: 5 to 9) for people who inject drugs (PWID) and 42 (95% CI: 31 to 53) for people who do not inject drugs (non-PWID). Percentage decreases in treatment initiation relative to expectation during June to December 2020 were greater for males than females (-57.5% vs –42.3%), individuals under 65 years compared to those 65 years or older (-56.7% vs -18.0%), and PWID compared to non-PWID (-89.3% vs -47.9%). Discrepancies by sex in the relative impact of the pandemic on HBV treatment initiation were attenuated after 2020, but discrepancies by age and IDU status persisted.

graphic file with name canlivj-7.1-abst_fig21.jpg — Image:

Conclusion(s): After the introduction of COVID-19 pandemic–related policies, HBV treatment initiation decreased and remained lower than expected from 2020 to 2022 in BC. The relative impact of the pandemic and related policies on HBV treatment initiation was greater for males, individuals under 65 years, and PWID.

References: 1. Kondili LA, Buti M, Riveiro-Barciela M, Maticic M, Negro F, Berg T, et al. Impact of the COVID-19 pandemic on hepatitis B and C elimination: An EASL survey. JHEP reports: innovation in hepatology. 2022;4(9):100531.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):148–149.

CLM-P044 Understanding the factors that impact access to screening and treatment for hepatitis C among immigrants – an implementation science-informed qualitative study

S Mortazhejri ^1,², C Cooper ^1,³, C Greenaway ^4,⁵, S Pakhale ^1,^2,³, A Patey ^1,^2,⁶, J Presseau ^1,^2,⁷, G Fontaine ^1,^5,^8,⁹, J Grimshaw ^1,^2,³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: Yes

Background: Canada is committed to the elimination of Hepatitis C Virus (HCV) by 2030. Immigrants from countries with high rates of HCV infection make up 35% of all cases in Canada. Despite the availability of effective treatment options, uptake of screening and treatment remains suboptimal. There is an average 10-year delay in diagnosis, resulting in poor health outcomes and high healthcare system costs. To address this gap, we need to understand the factors that impact access to HCV screening and treatment among immigrants.

Purpose: Egypt has one of the highest rates of HCV infection worldwide and the city of Ottawa has a large Egyptian community. Our project therefore aimed to use an implementation science-based approach to identity barriers and enablers to HCV screening and treatment among immigrants to Canada from Egypt.

Method: We established a Community Advisory Group (CAG) to provide advice and recommendations on all stages of the research study, ensuring that the project reflects the perspectives of the community members, and respects their values and beliefs. Using a qualitative descriptive design, adult immigrants from Egypt (with or without HCV) in Ottawa were recruited with help from the CAG. Participants were interviewed using semi-structured interviews based on the Theoretical Domains Framework (TDF) in English or Arabic. The interviews were translated, transcribed verbatim and double-coded according to TDF domains. Sampling continued until thematic saturation was achieved.

Result(s): We interviewed 13 individuals (eight males and five females). Participants were between 19 and 78 years old (Median: 44) and four participants had a history of HCV who were treated in Canada. Most without a history of HCV mentioned that they would not visit their doctors for testing if they did not have serious symptoms (Memory and decision making). This was in part because they believed doctors would not take them seriously (Social influences), and in part due to their beliefs that one should tolerate the minor symptoms and resolve them by themselves (Social, professional role and identity). Most mentioned difficulty in accessing family doctors (either finding one or booking an appointment) and long wait times for referrals as factors discouraging them to seek care (Environmental context and resources, Reinforcement). Some discussed the differences between the Canadian and Egyptian healthcare systems and how here they could only discuss one thing per visit and needed to prioritize their health issues (Social, professional role and identity, Environmental context and resources).

Conclusion(s): There is an urgent need to improve access to care for immigrants from endemic countries to eradicate HCV in Canada. Taking a systematic, implementation science informed approach to understanding lived experiences and views across immigrants to Canada will help to shape interventions tailored to best support them.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):149–150.

CLM-P045 Joining forces to advocate for the right to provide easy access to community-based screening in Québec

M Pruvost ¹, T Delbano ¹, L Mersilian ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: In Canada, an estimated 44% people living with HCV are not aware of their status. In 2016, Canada signed on to the World Health Organization's (WHO) Global Hepatitis Strategy aiming to achieve hepatitis elimination by 2030. Considering that public health is a shared responsibility between provincial and federal governments, access to HCV screening is uneven.

Purpose: In Québec, HCV testing is an act reserved to doctors and nurses, even if community-based screening has been proven to be efficient and safe in multiple contexts. This creates barriers that limit the diversification of HCV screening options, including point-of-care services that can be accessed by a greater range of individuals, especially those who are more isolated or face barriers when accessing services in more traditional healthcare settings.

Method: To reach the WHO's targets, increased outreach is necessary. Access to STBBI screening in Québec, including HCV, was inadequate before the COVID-19 pandemic; now it is even lower. As the WHO's strategy calls for decentralization and simplification of service delivery, community organizations have requested that the Québec government grant them the right to offer HCV antibody quick tests.

The communities most at-risk of contracting HCV in Canada are people who inject and use drugs, immigrants and newcomers from countries where HCV is endemic, Indigenous people, people with experience in the prison system, gay, bisexual, and other men who have sex with men, and people born between 1945-1975. A coalition of 31 community organizations who work with these communities has developed a detailed evidence-based document to request the right for community workers to offer HCV rapid tests.

Based on the coalition's understanding of these key populations’ realities, and the barriers they face within the healthcare system (delays, understaffed teams, stigmatisation and discrimination), the coalition argues that being able to offer point-of-care HCV rapid testing would greatly increase access to treatment and the proportion of people living with HCV who know their status.

Result(s): Organizations already have a strong trust-based relationship with their participants. They also have experience providing linkage to care and support to people with a hepatitis C diagnosis, and have developed connections with healthcare professionals experienced in HCV treatment and in understanding the stigmatization faced by key populations. The document has been shared with key Québec government representatives, and organizations are awaiting a response with the ultimate goal of getting Québec on the track toward HCV elimination by 2030.

Conclusion(s): Québec is still facing major barriers to the implementation of a more diverse offer of services. A shift in Québec's policy landscape, starting with broadening who can offer HCV testing, would help strengthen the place of community organizations as valuable partners in the HCV elimination process, and facilitate access to screening for thousands of people.

References: https://www.canada.ca/en/public-health/services/publications/diseases-conditions/hepatitis-c-screening-testing-health-professionals.html

Canadian Society for International Health (CSIH). “Le Canada Prend Position Contre l’Hépatite Virale.” Www.newswire.ca, 16 June 2016, www.newswire.ca/fr/news-releases/le-canada-prend-position-contre-lhepatite-virale-583291441.html. Accessed 12 Apr. 2023.

The Canadian Network on Hepatitis C Blueprint Writing Committee and Working Groups. Blueprint to inform hepatitis C elimination efforts in Canada. Montreal, QC: Available at: canhepc.ca/sites/default/ files/media/documents/blueprint_hcv_2019_05.pdf

https://www.capahc.com/plaidoyer/

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):151.

CLM-P046 Epidemiology, treatment pattern, and survival in Canadian patients with chronic hepatitis B-related hepatocellular carcinoma

Y Sachar ¹, C Coffin ², A-A Shaheen ², A Ramji ³, S Rahman ⁴, J Talia ⁵, DKH Wong ⁵, S Fung ⁵, C Cooper ⁶, M Ma ⁷, R Bailey ⁸, G Minuk ⁹, A Wong ¹⁰, KE Doucette ⁸, M Elkhashab ⁵, M Brahmania ¹¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second-most frequent cause of malignancy-associated death. Chronic hepatitis B (CHB) infection is the leading cause of developing HCC. We aimed to describe and evaluate the outcomes of CHB-HCC patients in Canada, addressing a paucity of such data in large North American patient populations.

Purpose: To observe the existing trends in patient diagnosis of Hepatocellular Carcinoma amongst mono-infected CHB patients, and appreciate outcomes from a long-term follow-up perspective

Method: Data was collected from January 1, 2012, to December 31, 2022, from a cross-sectional cohort of subjects mono-infected with CHB and HCC (per AASLD guidance) from the Canadian HBV Network - a national consortium involving 10 Canadian provinces and 19 academic and community hospitals. Descriptive analysis and Chi-square modeling were used to develop statistical outcomes for the comparison of cohorts. Statistical analyses were done in R (version 4.1.1).

Result(s): Of the 6711 CHB patients who met inclusion criteria, 232 (3.5%) developed HCC. The median age for the HCC cohort was 65 years (IQR 57-73) with a population of 80% male and 71% Southeast Asian (SEA) patients. The HCC cohort had a median HBV DNA of log 3.67 IU (IQR1.86-5.62), and 16% of HCC patients had a positive HbeAg status (vs 47% in the CHB group, p<0.0001). Relative to the CHB cohort, the CHB-HCC cohort had a higher proportion of male (80% vs 55%; p<0001) and SEA patients (71% vs 55%; p<0001). A greater number of HCC patients were born in an endemic region (63% vs 40%; p<0001). 92% of HCC patients had advanced liver disease (minimum Fibrosis Stage 3 or known diagnosis of cirrhosis). A greater proportion of HCC patients underwent antiviral treatment with Tenofovir (50.9% vs 19.7%; p<0.0001), Lamivudine (19.8% vs 12.2%; p=0.0012), and Entecavir (23.3% vs 5.8%, p<0.0001). HCC patients were followed for a median of 15 months (IQR 2-69) before diagnosis and a median of 41 months (IQR 19-87) post-diagnosis. 53% of patients were diagnosed with HCC as part of surveillance protocols. The median lesion number was 1(IQR 1-1), with a median lesion size of 2.5 cm (IQR 1.7-4.0). HCC diagnoses skewed towards early-stage BCLC 0-A disease (81%). There was an overall 84% survival rate post-HCC diagnosis during follow-up. Overall, 38% of patients received ablation, 16% received TACE, 25% underwent resection, 17% underwent a liver transplant, 8% required systemic therapy, and 6% received palliative therapy. Patient treatment was compared to recommendations per BCLC with an 82% treatment concordance.

Conclusion(s): In this large multi-ethnic cohort of patients with CHB-HCC, the majority of patients were detected with early-stage HCC and received treatment with curative intent, resulting in excellent survival rates, likely driven by surveillance practices in tertiary centers.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):152–153.

CLM-P047 Preliminary insights on the interplay between oat, chronic pain, and pain dimensions among people who inject drugs in Montreal, Canada

STP Udhesister ^1,², S Hoj ¹, N Minoyan ^1,³, D Jutras-Aswad ^1,⁴, G Pagé ^1,⁵, V Valérie Martel-Laferrière ^1,⁶, S Larney ^1,², J Bruneau ^1,²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: Up to 50% of people who inject drugs (PWID) live with chronic pain (intermittent or continuous pain lasting >3 months) ^1,2. Opioid agonist therapy (OAT), commonly prescribed for opioid dependence, may contribute to the currently limited management options for chronic pain in this population ^3,4. However, little is known about how OAT exposure is related to chronic pain, and to chronic pain management, intensity, and interference, referred to as chronic pain dimensions.

Purpose: (i) examine the association between being on OAT and chronic pain among PWID; (ii) compare chronic pain dimensions among PWID reporting chronic pain, according to whether or not they are currently on OAT.

Method: A cross-sectional investigation was conducted among participants of the HEPCO cohort, a cohort study involving three-monthly interviews with active PWID in Montreal (first visit data, 02.2017-03.2020). The Brief Pain Inventory was administered to characterize chronic pain dimensions. We conducted univariable and multivariable regression analyses to examine the association between current OAT and chronic pain, adjusting for past-month substance use and sociodemographic factors. Among participants reporting chronic pain, we conducted descriptive analyses comparing pain dimensions according to OAT current exposure, with chi-square and unpaired t-tests for continuous (scale: 0-10) and categorical (yes/no) indicators, respectively.

Result(s): Data from 541 participants were included (mean age= 45.0 years, 84% male), 250 participants (46%) reported chronic pain, and 222 (41%) were on OAT. In the multivariable logistic regression model, male gender (OR=1.9, 95% CI:1.2-3.3), heroin use (OR= 5.2, 95% CI:3.1-8.8), and alcohol use (OR=1.7, 95% CI:1.3-2.8) were associated with OAT, and chronic pain (OR=1.29, 95% CI:0.9-2.1) was not significant. Among participants reporting chronic pain, a greater proportion of the OAT group reported using pain medication at a higher frequency than prescribed (24.5% vs 10.1%, p=0.04) and for another reason, e.g., opioid use disorder (32.1% vs 1.69%, p<0.01), compared to the non-OAT group. There was no significant difference in use of alcohol, cannabis, or illegal substances to manage pain between participants on and not on OAT (36.2% vs 26.7%, p=0.31), nor in average pain intensity (5.7 vs 5.8, t=0.8, p=0.41, respectively). Pain interference was similar between participants on and not on OAT.

Conclusion(s): Consistent with previous results, a high proportion of PWID in this sample reported chronic pain. Although OAT exposure was not associated with chronic pain and average pain intensity and interference did not differ based on OAT exposure, there were significant differences in the use of pain medication. This suggests that participants on OAT may be more likely to experience inadequate management of pain and other concerns and self-medicate to cope. There is a need to further explore factors related to pain management in relation to OAT, to help improve pain management among PWID.

References: [1] M. C. Bicket et al., “Factors associated with chronic pain and non-medical opioid use among people who inject drugs,” Addictive Behaviors, vol. 102, p. 106172, Mar. 2020, [2] J. L. Kaboré et al., “Prevalence, Characteristics, and Management of Chronic Noncancer Pain Among People Who Use Drugs: A Cross-Sectional Study,” Pain Med, vol. 21, no. 11, pp. 3205–3214, 2020, [3] J. Bruneau et al., “Management of opioid use disorders: A national clinical practice guideline,” CMAJ, vol. 190, no. 9, pp. E247–E257, Mar. 2018, [4] J. W. Busse et al., “Guideline for opioid therapy and chronic noncancer pain,” CMAJ, vol. 189, no. 18, pp. E659–E666, May 2017.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):153–154.

CLM-P048 The impact of first-wave COVID-19 restrictions on HCV testing trends among the birth cohort in Alberta

L Thompson ^1,², SS Plitt ^3,⁴, R Zhuo ^5,⁶, CL Charlton ^1,^2,^5,^7,⁸

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: The birth cohort (those born between 1945-1975) is outlined as a priority population for HCV elimination efforts in Canada. Prior to COVID-19, Alberta was on track to meet HCV elimination targets by 2029. However, it is unclear how the COVID-19 pandemic has impacted HCV elimination efforts in Alberta, particularly among the birth cohort.

Purpose: We aimed to investigate HCV testing trends among the birth cohort before, during, and after the implementation of first-wave COVID-19 restrictions in Alberta.

Method: HCV antibody and RNA testing data was extracted from the provincial public health laboratory from January 1, 2019-December 31, 2022 and stratified by individuals born between January 1, 1945-December 31, 1975. HCV antibody and RNA testing trends were evaluated for the birth cohort across the following outcomes: (1) number ordered, (2) number positive, and (3) percent positivity. Analyses were further stratified by individuals without a history of antibody positivity (IWHAB) and individuals with a history of antibody positivity (IHAB). Mann-Kendall and Cochran-Armitage tests were used to evaluate changes in HCV testing levels across the study period. An interrupted time-series analysis was used to identify population-standardized average monthly testing rates before (January 2019-March 2020), during (April 2020), and after (May 2020-December 2022) first-wave COVID-19 restriction implementation.

Result(s): Overall, trends in HCV antibody testing significantly changed over the study period for IWHAB in the birth cohort (ordered: p=0.032; positive: p<0.001; and percent positivity: p<0.001), as did RNA testing among IHAB (ordered: p<0.001; positive: p<0.001; and percent positivity: p<0.001). Among the birth cohort, monthly HCV antibody testing rates across IWHAB were slightly decreasing in the pre-restriction period (-6.53 antibody tests ordered per 100,000, p=0.011) and dropped significantly with the introduction of first-wave COVID-19 restrictions (-64.3 antibody tests ordered per 100,000, p=0.031). Similarly, monthly HCV RNA testing rates among IHAB were decreasing in the pre-restriction period (-0.34 RNA tests ordered per 100,000, p=0.023), and further decreased during first-wave restrictions, though not significant (-2.03 RNA tests ordered per 100,000, p=0.257). By the end of 2022, monthly HCV antibody testing levels among IWHAB were rebounding back to pre-restriction levels (+8.86 antibody tests ordered per 100,000, p=0.004), while HCV RNA testing levels among IHAB continued to decrease (-0.16 RNA tests ordered per 100,000, p=0.002).

Conclusion(s): The emergence of first-wave COVID-19 restrictions significantly impacted HCV testing across the birth cohort in Alberta. If testing rates are to return to pre-restriction levels and elimination goals are to be met, more work is needed to engage the birth cohort in HCV testing. As antibody testing rates are slowly starting to rebound, reengaging those with a history of HCV into viral load monitoring and treatment should be prioritized.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):154–156.

CLM-P049 Progress towards HCV elimination among people living with HIV-hepatitis C virus (HCV) co-infection

MZ El Sheikh ^1,², J Young ^1,², D Panagiotoglou ¹, C Cooper ^3,⁴, J Cox ^1,², J Gill ⁵, M Hull ^6,⁷, V Martel-Laferrière ⁸, N Pick ^7,^9,¹⁰, S Walmsley ^11,¹², MB Klein ^1,², CCC Study Investigators ²

What is your preferred presentation method?: Poster Only

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: The World Health Organization (WHO) elimination targets require that 80% of those diagnosed with Hepatitis C virus (HCV) infection are treated by 2030. In late 2013, direct-acting antivirals (DAAs) for HCV were approved in Canada. Initially treatment was restricted to those with advanced fibrosis because of cost. Restrictions have been removed gradually across provinces and by 2018 they had been lifted in all provinces, making DAAs universally accessible, in theory.

Purpose: We assessed progress towards HCV elimination in the DAA era (2014-2022) within the Canadian Co-infection Cohort (CCC).

Method: The CCC is a multi-site open prospective cohort of people living with HIV-HCV co-infection. Participants are recruited from clinic sites across Canada and cohort visits are scheduled biannually. We calculated annual cure rates (defined as sustained virologic response, SVR, among those HCV RNA positive with visits in a given year, per 100 person-years) overall, by province and by key population: gay bisexual and other men who have sex with men (gbMSM), people who inject drugs (PWID), and Indigenous peoples.

Result(s): Among the 952 participants eligible for DAAs, 22% (n=208) were gbMSM, 29% (n=278) women, 43% (n=406) PWID, 27% (n=255) Indigenous, 32% (n=300) in Quebec (QC), 27% (n=261) in British Columbia (BC), 25% (n=236) in Ontario (ON) and 14% (n=134) in Saskatchewan (SK). Overall, 3% (n=26) achieved late spontaneous clearance (more than one year after infection) and 72% (n=684) initiated treatment of whom 91% (n=623) achieved SVR for an overall clearance rate of 68% (n=649); 10% (n=95) died. Of those who remained viremic (n=303), 46% (n=138) were lost to follow-up, 31% (n=95) died, 19% (n = 58) were untreated at their last cohort visit and 4% (n=12) withdrew from the cohort. The percentage of participants who were HCV RNA negative by the end of follow-up was highest among gbMSM (77%) followed by women (71%) and was lower among active PWID (66%), heterosexual men (65%) and Indigenous peoples (64%). Annual cure rates increased from 2014 to 2019 then dropped appreciably during COVID overall and in key populations (Figure 1). Before 2019, gbMSM had higher cure rates than the cohort overall and other key populations, but by 2019 rates among PWID and Indigenous peoples had caught up. The percentage of participants who were HCV RNA negative by the end of follow-up was highest in BC (75%) and QC (73%) and lowest in ON (64%) and SK (59%). Annual cure rates dropped in all provinces after 2019 except in BC where rates dropped after 2020 (Figure 1).

graphic file with name canlivj-7.1-abst_fig22.jpg — Image:

Conclusion(s): Making DAAs universally accessible in Canada was an important step towards HCV elimination among all key populations living with HIV and HCV, but alone was not sufficient. Disengagement from care, exacerbated by the COVID pandemic, suggests WHO targets may not be achieved by 2030. Mortality was also unacceptably high. Efforts are needed to re-engage those who remain to be cured and reduce mortality in people living with HIV-HCV co-infection.

References: 1) Stanaway JD, Flaxman AD, Naghavi M, Fitzmaurice C, Vos T, Abubakar I, et al. The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013. The Lancet. 2016 Sep;388(10049):1081–8

2) Klein MB, Saeed S, Yang H, Cohen J, Conway B, Cooper C, et al. Cohort Profile: The Canadian HIV-Hepatitis C Co-infection Cohort Study. International Journal of Epidemiology. 2010 Oct 1;39(5):1162–9

3) Canadian Co-infection Cohort. Canadian Co-infection Cohort. [cited 2022 Feb 11]. About the Cohort – Cocostudy. Available from: http://cocostudy.ca/the-study/about-the-cohort/

Disclosure of Interest: M. El Sheikh: None Declared, J. Young: None Declared, D. Panagiotoglou: None Declared, C. Cooper Grant / Research support from: program support from Gilead Sciences, AbbVie and ViiV Healthcare., Consultant of: advisor fees from Gilead Sciences, AbbVie and ViiV Healthcare., Speakers bureau of: speakers fees from Gilead Sciences, AbbVie and ViiV Healthcare., J. Cox Grant / Research support from: received funding for investigator-initiated research from ViiV Healthcare, Consultant of: received remuneration for advisory work from Gilead Canada and ViiV Healthcare, J. Gill Consultant of: consulting fees from serving as ad hoc member of National advisory boards to Merck Gilead and ViiV Healthcare., M. Hull Grant / Research support from: received research funding from Gilead, Consultant of: received honoraria for being on advisory boards for Gilead, Speakers bureau of: received honoraria for speaking engagements from Gilead, V. Martel-Laferrière Grant / Research support from: grants from Gilead Science and Merck, Consultant of: consulting fees from Abbvie, N. Pick: None Declared, S. Walmsley Grant / Research support from: received research funds from ViiV, Gilead and Merck, Consultant of: served on advisory board, Speakers bureau of: spoken at CME event for Merck, Gilead, Viiv, M. Klein Grant / Research support from: grants for investigator-initiated studies from ViiV Healthcare, AbbVie, and Gilead, Consultant of: consulting fees from ViiV Healthcare, Merck, AbbVie, and Gilead, C. C. C. Study Investigators: None Declared

Can Liver J. 2024 Feb 26;7(1):156–157.

CLM-P050 Estimating hepatitis D virus prevalence among Canadian immigrants

J Zhao ¹, W Wong ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Hepatitis D continues to pose a detrimental health concern globally. Hepatitis D virus (HDV) is a derivative viral infection from a well-known virus, hepatitis B virus (HBV). HDV only occurs in people who are also infected with HBV. HDV can be infected either simultaneously with HBV, where patients are diagnosed with HBV and HDV at the same time, known as acute coinfection, or infected chronically, meaning patients diagnosed with chronic hepatitis B (CHB) first and then infected with HDV after, known as superinfection. Acute coinfection can resolve itself over time. However, superinfection can lead to rapid progression of an already present HBV infection, resulting in liver cirrhosis and failure. Currently, there are no vaccines, but a potential new treatment is available for HDV. Being such a new virus, the prevalence of HDV is still largely unknown in a Canadian setting.

Purpose: The objective of this study is to estimate the prevalence of HDV among immigrants in Canada.

Method: To estimate the prevalence of HDV among immigrants in Canada, we first estimated number of immigrants for HBV residing in Canada in 2021. This number was estimated by multiplying the number of people who immigrated to Canada from each country of origin by the prevalence of HBV in that country. The number of immigrants from each country of origin was determined using data from the 2021 Statistics Canada census. The HBV prevalence in various countries was obtained from review of the literature. The prevalence of HDV from each country of origin was obtained from another literature review, in which the prevalence of HDV was reported as HBV prevalence percentage. Finally, to estimate the prevalence of HDV among immigrants in Canada, we multiply the estimated number of immigrants with HBV with the prevalence percentage of HDV from each country of origin.

Result(s): The overall prevalence of HBV among all immigrants in Canada is 3.1% (2.8% - 3.5%), which is equivalent to around 259,394 immigrants who are estimated to be affected by HBV in 2021. Among immigrants infected with HBV, we estimated that 7.8% (5.7% – 9.7%) were also infected with HDV. Thus, HDV had an overall prevalence of 0.24% (0.15%-0.33%), which is equivalent to around 20,094 immigrants in Canada. The top 5 countries with the highest HDV infections are the Philippines 0.59% (0.39% – 0.85%), China 0.45% (0.30% – 0.61%), India 0.22% (0.15% – 0.31%), Vietnam 1.02% (0.72% – 1.33%) and Congo 3.46% (2.76% – 4.21%) (Table 1).

graphic file with name canlivj-7.1-abst_fig23.jpg — Image:

Conclusion(s): Our study gives the most fundamental prevalence information for decision-makers to assess policy related to hepatitis D. HDV has a reasonable burden among immigrants living in Canada. Government and Health systems need to develop policies that promote early recognition of HDV and raise public awareness regarding HDV to extend the lives of infected immigrants.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):157–158.

CLM-P051 Serum fibrosis and steatosis biomarkers for the prediction of mortality in liver transplant recipients

A Alhinai ¹, TF Tadjo ¹, M Deschenes ¹, P Wong ¹, T Chen ¹, F Lamonde ¹, A Ramanakumar ¹, N Saberi ¹, J Barkun ¹, G Sebastiani ¹

What is your preferred presentation method?: Poster Only

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: After liver transplantation (LT), recipients often develop graft steatosis, fibrosis, and graft loss, frequently leading to patient mortality. This is mainly because the metabolic risk factors for nonalcoholic fatty liver disease (NAFLD) and associated fibrosis persist and potentially worsen in the post-transplant setting. Liver biopsy is the gold standard to diagnose NAFLD and liver fibrosis, however it is invasive and less than ideal for serial monitoring.

Purpose: We aimed to investigate the association of serum steatosis and fibrosis biomarkers with mortality and graft loss in LT recipients.

Method: We included consecutive adults who received a liver transplant at the McGill university Health Centre (MUHC) between 2014-202. Patients were followed up annually. The outcomes measured were death and graft loss, graft loss being defined as graft failure leading to death or re-transplantation. We assessed the prognostic value of the biomarkers ALT, AST, GGT, AST-to-Platelet Ratio Index (APRI), fibrosis-4 index (FIB-4), and hepatic steatosis index (HSI). Hepatic fibrosis was characterized as FIB-4 > 3.64 or APRI > 1 and hepatic steatosis was defined as HSI >36. Survival analysis and Generalized Estimating Equation (GEE) models were used to assess the association between the biomarkers and the outcomes.

Result(s): 219 patients were followed for an average of 30 months. Graft loss and mortality occurred in 12 patients (9%) and 38 (29.5%) with an incidence rate of 29.5 (95% CI 20.9-40.6) and 9.6 (95% CI 5-16.8) per 100 person-years, respectively. Patients who died during the follow-up were older, had an older donor, and had a history of diabetes. On multivariable analysis using the GEE model (see Table), higher ALT and higher AST were associated with mortality after adjustment for sex, BMI, age, albumin, and platelets. In the time-to-event analysis, the Kaplan Meier curves showed that APRI >1 could be a potential predictor of mortality (P=0.0729 see Figure). Neither FIB-4 (log-rank, p = 0.199) nor HSI (log-rank, p = 0.919) were associated with mortality. None of the biomarkers or liver transaminases were associated with graft loss.

graphic file with name canlivj-7.1-abst_fig24.jpg — Image:

Conclusion(s): Liver transaminases and the serum fibrosis biomarker APRI are associated with mortality in LT recipients. The hepatic steatosis biomarker HSI does not seem to be valuable in predicting outcomes in this population. None among liver transaminases, steatosis or fibrosis biomarkers predicted graft loss.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):158–160.

CLM-P052 Validation of FIB-4 for the diagnosis of liver cirrhosis in metabolic dysfunction-associated steatotic liver disease

C Bera ¹, HM Kosick ¹, N Hamdan ¹, M Shengir ², O Adeyi ³, G Sebastiani ⁴, K Patel ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and advanced fibrosis (F3–4) are at risk of liver disease progression and adverse clinical outcomes. Non-invasive methods are used to detect advanced fibrosis (F3-4) and cirrhosis (F4) in patients with NAFLD. These include simple serum-based tests such as the FIB-4 score. The recent AASLD guidance suggests use of ‘rule-in’ and ‘rule-out’ cut-offs, FIB-4 ≥ 3.48 and < 1.67, respectively, to detect F4. The ’rule-in’ cut-off for detecting cirrhosis was determined by a recent meta-analysis on individual patients data, with sensitivity of 38% and specificity of 90% and with 19% needing liver biopsy. There have not been studies validating the FIB-4 cut-offs in this population against liver biopsy.

Purpose: Our aim was to validate and assess performance of FIB-4 cut-offs for cirrhosis in our cohort of patients with biopsy-proven NAFLD from two Canadian tertiary care centres.

Method: Adult patients with biopsy-proven MASLD seen between 2010 – 2021 at two tertiary care centres (University Health Network, Toronto, ON; McGill University Health Centre, Montreal, QC), were included. FIB-4 scores were available within ± 6 months of biopsy. Alternate causes of liver disease were excluded based on clinical review, laboratory parameters and histopathology. Diagnostic test performance for FIB-4 < 1.67 and ≥ 3.48 to predict F4 was assessed using area under the receiver operating characteristic (AUROC).

Result(s): 390 patients were included with mean age 48.7 ± 12.9 years, 54.6% were male, and 30.8% had diabetes. Prevalence of F4 was 22% (n = 87), with 21% (n = 83) F3, and 56.4% (n = 220) F0-2. Overall, mean FIB-4 score was 1.81 ± 1.75 for F0-4, and 3.24 ± 2.16 for F4. FIB-4 had AUROC 0.76 at “rule out” cut off <1.67 with specificity of 75.6%. FIB-4 had AUROC of 0.68 at “rule in” cut off ≥ 3.48 with a specificity 94.4%. At this proposed threshold, 32% were classified as indeterminate (FIB-4 ≥ 1.67 and < 3.48) (Table 1). Among patients with F4, 57.8% (n=50) had a FIB-4 score <3.48, and 23.0% (n = 20) had a FIB-4 score <1.67.

graphic file with name canlivj-7.1-abst_fig25.jpg — Image:

Conclusion(s): In our cohort of biopsy-proven MASLD patients, FIB-4 with cut-offs ≥ 3.48 and < 1.67 to ‘rule in’ and ‘rule out’ F4, respectively, performed with high specificity but limited sensitivity. However, using an upper FIB-4 cut-off of 3.48 would have missed almost 60% of cirrhosis patients. As such, the proposed FIB-4 thresholds for F4 have limited practicality for use in tertiary center cohorts.

References: 1. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D, Kleiner DE, Loomba R. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023 May 1;77(5):1797-1835.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):160–161.

CLM-P053 Discrete choice experiments to elicit the preferences of people living with diabetes for health screening: a scoping review

F Cinque ^1,², DA Dinh ³, G Gore ⁴, M Swain ⁵, A Ramji ⁶, K Patel ⁷, M Betel ⁸, C Long ^1,², S Saeed ⁹, G Sebastiani ^1,²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: International guidelines recommend screening for metabolic dysfunction-associated steatotic liver disease (MASLD) in people living with type 2 diabetes (T2DM). However, this has not been adopted in real practice. Integrating preferences of patients and physicians in healthcare decision-making may optimize screening strategie. Discrete choice experiments (DCE) are commonly used to quantify stakeholder preferences in healthcare, but it is unknown if this systematic methodology has been used for T2DM to inform screening programs.

Purpose: To summarize the evidence on the use of DCE for screening programs for people with T2DM.

Method: We conducted a scoping review about: a) evidence on DCE use to elicit preferences in screening programs for T2DM, liver disease and T2DM complications b) which attributes of screening were included and most preferred. With the assistance of a librarian, five databases (PubMed, PubMed Central, EMBASE (Ovid), Google Scholar, Europe PMC preprints) were searched, and deduplicated records were then screened by two independent reviewers. Inclusion criteria: (i) using DCE or conjoint analysis (ii) eliciting stakeholders (patients/healthcare providers) preferences towards a screening program for T2DM, liver disease or T2DM complications (iii) published in English after January 1990. The DCE/conjoint analysis attributes were divided into three dimensions: “structure” referring to the objective organizational parameters of the screening, “process” referring to all the activities occurring during screening, and “outcome” referring to the effects of the screening.

Result(s): The search strategy resulted in 2282 findings. Nine studies (7 from high and 2 from low-income countries) in people with T2DM that elicited preferences for screening programs for liver disease (n=1), hepatitis C (n=1), hepatitis B (n=1), hepatocellular carcinoma (n=2), noncommunicable diseases (n=2), diabetic retinopathy (n=1) and cardiovascular diseases (n=1) met the predetermined inclusion criteria. No studies specifically addressed MASLD screening in T2DM. Seven studies (77%) used DCE, while 2 (23%) conjoint analysis. The target population was patients (n=3), healthcare providers (n=1), patients plus healthcare providers (n=2) and the general population (n=3). The attributes were identified by published literature (n=7), expert discussions (n=8) and focus groups (n=2). Altogether, the studies used 16 structure attributes, 7 process attributes and 4 outcome attributes (Table 1). Screening cost was the most applied attribute. Structure attributes were ranked the highest importance, with accuracy being deemed the most important attribute.

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Conclusion(s): There is significant heterogeneity in stakeholders’ preferences for screening programs among people with T2DM. No studies were focused on screening for MASLD. Our scoping review highlights the need to develop a DCE to elicit the preferences of people with T2DM and their physicians for MASLD screening to provide a patient-centered continuum of care.

Disclosure of Interest: F. Cinque: None Declared, D. Dinh: None Declared, G. Gore: None Declared, M. Swain: None Declared, A. Ramji: None Declared, K. Patel: None Declared, M. Betel: None Declared, C. Long: None Declared, S. Saeed Grant / Research support from: Served as an advisory board member for Novo Nordisk, G. Sebastiani Grant / Research support from: GS has acted as speaker for Merck, Gilead, Abbvie, Novo Nordisk, Pfizer, served as an advisory board member for Pfizer, Merck, Novo Nordisk, Gilead and Intercept

Can Liver J. 2024 Feb 26;7(1):161–163.

CLM-P054 Validation of AGILE 3+ for MASLD advanced fibrosis in a Canadian cohort

N Hamdan-Perez ¹, C Bera ¹, HM Kosick ¹, K Patel ¹

What is your preferred presentation method?: Poster Only

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Agile 3+ is a novel non-invasive test (NIT) that has been proposed to identify patients with advanced fibrosis or cirrhosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), it includes serum and imaging parameters of age, AST/ALT, PLT, gender, presence of diabetes and liver stiffness measurement (LSM by VCTE). There are few external validation studies for this NIT.

Purpose: Our aim was to assess the diagnostic performance of Agile 3+ in comparison with other simple serum markers scores, and LSM by VCTE for the identification of MASLD advanced fibrosis (≥F3).

Method: This is a retrospective single-center cohort study that included adult patients with biopsy-proven MASLD between 2010 – 2021. Alternate causes of liver disease were excluded based on clinical review, available laboratory parameters, VCTE, and histopathology. Diagnostic test performance was assessed using validated thresholds for NIT and Agile 3+ <0.451 and >0.679 to rule-out and rule-in ≥F3 using the area under the receiver operating characteristic (AUROC).

Result(s): Our cohort included 76 patients, with mean age was 48 ± 13 years, mostly male (56%), diabetes mellitus in 35%, and F3-4 prevalence 60%Using validated thresholds, the proportion of patients with indeterminate scores were Agile+3 (0.451-0.679) 10.3%, LSM (8-12 kPa) 26%, FIB-4 (1.3-2.67) 32%, NFS (-1.455-0.676) 33%, APRI (0.5-1.5) 42%. For our overall cohort, all NITs had high specificity for F3-4, with AUROC > 0.90 for Agile 3+ and VCTE.

graphic file with name canlivj-7.1-abst_fig27.jpg — Image:

Conclusion(s): In our tertiary center cohort Agile3+ had a good diagnostic performance for advanced fibrosis, with relatively lower proportion of patients classified in the indeterminate zone at specified thresholds. Further validation of Agile 3+ in lower prevalence cohorts is required.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):163–164.

CLM-P055 Prevalence of metabolic associated steatotic liver disease (MAFLD) by transient elastography in patients with cardiovascular and chronic kidney disease: a cross-sectional study

VH Chen ¹, SX Jiang ², K Wang ¹, F Ghobani ³, S Gill ⁴, P Darras ⁴, M Farah ⁵, C Taylor ⁶, K Ramanathan ⁶, A Ramji ², HH Ko ²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Metabolic associated steatotic liver disease (MAFLD) has an estimated 25% prevalence globally, with higher prevalence associated with cardiovascular disease (CVD) and chronic kidney disease (CKD). While liver biopsy remains the gold standard, transient elastography (TE) is a validated method of assessing both degree of fibrosis and steatosis, providing a non-invasive assessment tool. No guideline currently exists on screening in CVD and CKD populations on the basis of metabolic disease alone.

Purpose: To determine the prevalence of MAFLD, liver fibrosis and metabolic comorbidities in CVD and CKD patients.

Method: Patients from Cardiology or Nephrology Clinic with established CVD and CKD were invited to complete lab work and TE to assess for MAFLD. Patients were excluded if alcohol use exceeded 14 units per week or have prior known liver disease. Data was recorded for clinicodemographic, comorbidities (including diabetes (DM), uncontrolled dyslipidemia (DLD), and obesity), laboratory, physical, and TE variables. MAFLD was defined as controlled attenuation parameter (CAP) ≥288 dB. Fibrosis-4 (FIB-4), AST-to-Platelet ratio (APRI), NAFLD fibrosis scores (NFS) were calculated.

Result(s): Of 17 patients enrolled, 13 completed lab work and TE. Mean age was 62.4 years (SD 15.8), 9 (69%) were male, 8 (62%) had CVD and 5 (38%) had CKD. Comorbid conditions included 7 (54%) pre-DM/DM, 9 (69%) obesity and 8 (62%) dyslipidemia (DLD).

5 (38%) patients had MAFLD, comprised of 4 (80%) CVD patients and 1 (20%) CKD patient. MAFLD patients had a higher rate of pre-DM/DM (4, 80% vs. 3, 38% in non-MAFLD), higher rate of obesity defined by waist circumference/sex (4, 80% vs 3, 38% in non-MAFLD), similar rate of obesity defined by BMI (3, 60% vs. 4, 50% in non-MAFLD), and lower rate of DLD (1, 20% vs. 7, 88%).

Median CAP was 331 dB in MAFLD patients, compared to 209 dB in nonMAFLD patients. Stage 0-I, II, III, and IV fibrosis was found in 3 (%), 0 (0%), 2 (40%), and 0 (0%) of those with MAFLD. 2 (40%) patients with MAFLD had elevated AST or ALT, although neither had advanced fibrosis by TE. The 2 patients with stage III fibrosis had normal ALT and AST. 1 (12.5%) patient without MAFLD had stage III fibrosis. The rate of advanced fibrosis in MAFLD patients by FIB-4, APRI, and NFS was 0%, 0%, and 20%. Advanced fibrosis in MAFLD was concordant with TE in 2 (40%) patients by FIB-4, 1 (20%) by APRI, and 2 (40%) by NFS, excluding grey-zone scores seen in 2 (40%), 3 (60%) and 2 (40%) MAFLD patients in FIB-4, APRI and NFS respectively.

Conclusion(s): In this cohort of CVD and CKD patients, MAFLD prevalence was elevated at 38% and associated with other metabolic diseases. The majority of MAFLD patients did not have elevated AST or ALT, including those with MAFLD and significant fibrosis. Importantly, 40% of MAFLD patients had significant fibrosis and ongoing study is underway. Given the higher rate of MAFLD and significant fibrosis in CVD and CKD patients, further research can inform the role of screening high risk patients.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):164–166.

CLM-P056 Assessing the utilization and perspectives of weight loss medications in pediatric gastroenterology and hepatology when managing metabolic dysfunction-associated steatotic liver disease: current practices, barriers, and future implications

M Kehar ¹, SH Ibrahim ², C Ramirez ³, T Diamond ⁴, S Mohammad ⁵

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: There are no data on utilization, practices, or barriers for the utilization of weight loss medications to achieve metabolic benefits within the field of pediatric gastroenterology and hepatology when managing metabolic dysfunction-associated steatotic liver disease (MASLD).

Purpose: The survey aimed to elucidate current practices, and perspectives related to utilizing weight loss medications in pediatric gastroenterology and hepatology to attain metabolic benefits in the context of MASLD.

Method: This cross-sectional survey was conducted among pediatric gastroenterologists and hepatologists using the PedsGI international Listserv.

Result(s): A total of 164 responses were collected, the majority from the United States (73.78%). 72% of respondents identified as full-time academic practitioners. A significant portion engaged in both pediatric gastroenterology and hepatology practices (72, 44%), while 19 (12%) practiced pediatric hepatology with a focus on MASLD. Currently, 63 respondents (38%) utilize these medications, with 28 (44%) self-prescribing. The majority of respondents indicated considering these medications when associated with Diabetes (49%), depending on BMI (37%), failure of lifestyle management after 12 months (21%) or 6 months (18%), or associated dyslipidemia (24%). The most frequently considered medications were Semaglutide (N=47) and Liraglutide (N=34). The majority (75%) referred these children to an endocrinologist to prescribe these medications. Most respondents (82%) were familiar with the metabolic benefits of GLP-1RAs. and (66%) were knowledgeable about their safety and efficacy profiles. The primary challenge by the majority (86%) of respondents was obtaining insurance coverage for GLP-1RAs. The majority (68%) believed that prescribing these medications falls within the scope of pediatric gastroenterology/hepatology practice. Additionally, 75% of respondents foresaw the significant future impact of GLP-1RAs in pediatric MASLD management. In the future, 118 respondents foresee the role of pediatric hepatologists in managing MASLD through these medication prescriptions. Concurrently, 99 respondents highlighted the vital role of pediatric gastroenterologists in the same context. Respondents identified significant challenges (Figure 1) and showed strong interest in educational resources: 76.22% were interested in webinars and workshops, 65.24% in educational sessions with experts, 75.61% in easy access to online resources like articles and guidelines, and 43.29% in real-life scenario sharing.

graphic file with name canlivj-7.1-abst_fig28.jpg — Image:

Conclusion(s): This survey highlights the strong interest in utilizing weight loss meds for metabolic benefits in pediatric MASLD. Challenges stress the need for enhanced knowledge, emphasizing vital educational initiatives in this evolving pediatric gastroenterology and hepatology field. A clear call for prioritized training and education to enhance care for these young patients.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):166.

CLM-P057 Breaking boundaries: unraveling metabolic dysfunction-associated steatotic liver disease in children of India and Canada

V Sood ¹, BB Lal ¹, A Deshmukh ¹, R Khanna ¹, CJ Rivera ², S Alam ¹, M Kehar ²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of chronic liver disease in children. Its prevalence is rising globally, yet it's uncertain if its onset and severity vary between countries

Purpose: This study aims to fill this knowledge gap by examining and comparing the fundamental characteristics of pediatric MASLD/NAFLD patients in two tertiary care centers in Canada and India.

Method: This study was conducted as a retrospective cohort study and patient related details were retrieved from the electronic records and reviewed.

Result(s): The study analyzed a total of 184 children with NAFLD/MASLD (94 from the Indian site and 89 from the Canadian site) with concordance between NAFLD and MASLD definitions. The Indian children had a higher proportion of symptomatic presentations and family history of metabolic disorders (p = 0.0001) while the Canadian children had higher median weight, BMI, blood pressure, and waist circumference (p < 0.05). Indian children had higher hepatic transaminases and low density lipoprotein levels, while the Canadian site had higher serum insulin, blood glucose, homeostasis model assessment of insulin resistance, high density lipoprotein cholesterol levels, liver stiffness and controlled attenuation parameter values (p < 0.05). Majority (78%) of the Canadian children who underwent liver biopsy had significant fibrosis (> stage 2). In the overall cohort, waist circumference could be identified as an independent risk factor, irrespective of country of origin, predicting hepatic fibrosis.

Conclusion(s): The study found significant differences between cohorts. Canadian children showed higher obesity grades and greater hepatic steatosis & fibrosis severity. To comprehend the underlying causes, future studies are imperative.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):166–167.

CLM-P058 Fecal micrornas as predictors of persistent non-alcoholic steatohepatitis in patients with obesity who underwent bariatric surgery

P Massara ¹, KJ Schwenger ², A Taibi ¹, Y Ghorbani ², SE Fischer ^3,⁴, TD Jackson ^5,⁶, A Okrainec ^5,⁶, JP Allard ², EM Comelli ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Morbid obesity (MO-body mass index (BMI) ≥ 40 kg/m2) is associated with non-alcoholic fatty liver disease (NAFLD) and with non-alcoholic steatohepatitis (NASH). Although Roux-en-Y Gastric Bypass (RYGB) is a gold standard treatment, there is variability in the response magnitude, and some patients have persistent NAFLD (perNAFLD), making clinical decisions difficult. Epigenetic factors may be involved. MicroRNAs (miRNA) expression is altered in NAFLD, and serum miRNA may predict weight loss after surgery. Fecal miRNAs, which are non-invasive and measurable in a reproducible manner, have been proposed as biomarkers of colorectal and pancreatic cancers but have not been investigated in this context.

Purpose: To predict SS/NASH and perNAFLD in patients who underwent RYGB using fecal miRNA.

Method: Liver biopsies, stool samples, blood metabolites, and clinical variables were collected from 61 patients with MO before (baseline) and 12 months post-RYGB and from 14 healthy liver donors as we previously described^1,2. MO patients were either diagnosed as having normal liver (NL), simple steatosis (SS) or NASH. PerNAFLD was defined as continuing to have either SS or NASH 12 months after surgery. The expression of 799 fecal miRNA was assessed via NanoString Technology, and their differential expression was determined using generalized linear models of the negative binomial family. Ensemble machine learning (EML) classifiers were used to predict NAFLD/perNAFLD using miRNAs, metabolites and clinical variables.

Result(s): 64 miRNAs were differentially expressed between patients with MO and healthy. At baseline, 7 participants with MO had NL, 30 had SS and 24 had NASH. Seven miRNAs were differentially expressed when patients with NL were compared to those with SS or NASH and 1 miRNA in patients with perNAFLD (q<5%). EML model accuracy was 82% and 76%, respectively. The most important predictors were MIR1276, MIR1297, MIR26b5p, MIR1423p and BMI for NAFLD categories and HbA1c, BMI, age, sex and MIR596 for perNAFLD.

Conclusion(s): Fecal miRNAs are differentially expressed between MO patients and healthy controls. Both NAFLD and perNAFLD are associated with specific miRNAs expression. Moreover, miRNAs were among the most important predictors of both outcomes, which indicates that they may be utilized as biomarkers in clinical settings. Because fecal miRNAs are largely derived from intestinal cells, they may also be considered treatment targets in patients with NAFLD.

References: 1. Schwenger, K.J. et al. In nonalcoholic fatty liver disease, Roux-en-Y gastric bypass improves liver histology while persistent disease is associated with lower improvements in waist circumference and glycemic control. Surgery for Obesity and Related Diseases, 2018. 14(9): p. 1233-1239.

2. Schwenger, K.J. et al. Non-alcoholic fatty liver disease in morbidly obese individuals undergoing bariatric surgery: prevalence and effect of the pre-bariatric very low calorie diet. Obesity surgery, 2018. 28(4): p. 1109-1116.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):167–168.

CLM-P059 Non-invasive biomarkers predicting the progression of MASLD to advanced fibrosis: a prospective cohort study based in southwestern Ontario

YN Song ¹, R Mortuza ¹, JP Arab ¹, MQ Khan ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects around 30% of the global population and is one of the most prevalent non-communicable diseases. Due to its high prevalence, it is becoming the most common cause of liver-related mortality in all populations worldwide. Current standards of care for the treatment of MASLD encompass mostly lifestyle measures that are nonspecific and difficult for clinicians to ensure compliance. Although not all patients with MASLD progress to more advanced disease, the high prevalence of MASLD in the general population means the absolute number of “at risk” individuals are substantial and places a significant burden on the healthcare system. As a result, MASLD is currently viewed as a heterogeneous disease with varying rates of disease progression.

Purpose: We aim to elucidate the predictors of disease progression in MASLD to develop and guide interventions while the disease is reversible.

Method: Prospective chart review on patients seen in MASLD clinic at LHSC on CERNER from Sept. 2021 – Apr. 30, 2023. A REDCap database was constructed pertaining to (a) basic patient information (b) basic medical history (c) patient lifestyle habits (d) InBody bioimpedance analysis, if available (f) laboratory data; (g) elastography, including liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). Collected data were exported into a spreadsheet to allow for analysis. IBM SPSS was used to analyze descriptive statistics and regression analyses.

Result(s): A total of 116 encounters were reviewed, including both enrolment and follow-ups. HbA1c percent is positively correlated with LSM (r=0.28, p<0.05). The longer that the patient has been diagnosed with NAFLD (current age minus age of initial diagnosis), the more likely the patient has higher LSM scores (r= 0.23, p<0.05). Platelet levels are negatively correlated with LSM (r=-0.28, p<0.05). In patients who are currently drinking alcohol (<15 drinks/week for men and <10 for women), there is no difference between the amount of alcohol drank and the degree of CAP or LSM. There is no difference between cannabis users and non-users in the degree of CAP or LSM. Only n=15 InBody bioimpedance analyses were included, preliminary results showed Trunk Reactance at 250 kHz is correlated with LSM with (r=0.593 p<0.05).

Conclusion(s): Patients with higher HbA1c, lower platelets and longer duration of disease are at higher risk for developing advanced fibrosis. This can allow the development of a better predictive model to find F2-F3 patients without using FibroScan or a liver biopsy, which is helpful in the primary care setting, given the prevalence of MASLD. InBody bioimpedance studies are a useful tool to predict LSM, although more data is needed to ensure the correlation is sufficiently powered. Phenotyping patients would lead to more accurate prognostication, facilitate better monitoring to prevent decompensation and allow for the development of precision-based, personalized management plans.

References: Alexander, M., Loomis, A. K., Fairburn-Beech, J., van der Lei, J., Duarte-Salles, T., Prieto-Alhambra, D., Ansell, D., Pasqua, A., Lapi, F., Rijnbeek, P., Mosseveld, M., Avillach, P., Egger, P., Kendrick, S., Paik, J. M., Golabi, P., Younossi, Y., Mishra, A., & Younossi, Z. M. (2020). Changes in the Global Burden of Chronic Liver Diseases From 2012 to 2017: The Growing Impact of NAFLD. Hepatology (Baltimore, Md.), 72(5), 1605–1616. https://doi.org/10.1002/HEP.31173

Younossi, Z. M., Golabi, P., de Avila, L., Paik, J. M., Srishord, M., Fukui, N., Qiu, Y., Burns, L., Afendy, A., & Nader, F. (2019). The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis. Journal of Hepatology, 71(4), 793–801. https://doi.org/10.1016/J.JHEP.2019.06.021

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):168–170.

CLM-P060 Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with impaired health-related quality of life in people with HIV

M Nudo ¹, F Cinque ¹, A Lupu ¹, JP Gazetas ¹, LR Ballestreros ¹, W Elgretli ², C Price ³, K Monteith ⁴, C Cooper ⁵, N Kronfli ¹, J Cox ¹, C Costiniuk ¹, A De Pokomandy ⁶, J-P Routy ¹, MB Klein ¹, B Lebouche ⁶, S Saeed ⁷, G Sebastiani ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) often experience a range of mental, health and social problems, resulting in impaired health-related quality of life (HRQoL). However, little is known about the association of MASLD with the HRQoL in people with HIV (PWH).

Purpose: To explore the association of MASLD with the various domains of HRQoL using the Short Form-36 (SF-36) and Chronic Liver Disease Questionnaire (CLDQ) in PWH.

Method: This was an ad interim analysis of the first consecutive 100 participants enrolled in the LIVEr disease in HIV (LIVEHIV) Cohort, a multicenter prospective cohort enrolling PWH without viral hepatitis coinfection, significant alcohol intake, or advanced chronic liver disease (liver stiffness measurement ≥10 kPa by Fibroscan). Participants are followed annually for four years by clinical evaluation, HRQoL questionnaires, laboratory testing and Fibroscan with controlled attenuation parameter (CAP). The main exposure was MASLD, defined as presence of hepatic steatosis (CAP ≥248 dB/m), and any of the following: overweight (body mass index >25 Kg/m²), type 2 diabetes, hypertension, dyslipidemia, or hypertriglyceridemia. Liver fibrosis was defined as liver stiffness ≥7.1 kPa. The outcome was HRQoL, measured by: (i) SF-36, consisting of 36 items divided into 8 domains, scored from 0 to 100, with higher scores indicating a better HRQoL; (ii) CLDQ specifically developed for people with liver diseases, consisting of 29 items divided into 6 domains, scored from 1 to 7, with higher scores indicating better HRQoL. Multivariable linear regression analysis was employed, controlled for other explanatory confactors associated with HRQoL.

Result(s): From the cohort of the 100 participants (mean age 44 years, 81% male, 100% on antiretroviral therapy, 86% with suppressed viral load, 4% with liver fibrosis), the prevalence of MASLD was 46%. PWH with MASLD were significantly older (48 vs 37 years, p=0.006) and had higher liver stiffness (5.1 vs 4.4 kPa, p=0.01) compared to PWH without MASLD. The table depicts the mean (standard deviation) of SF-36 domain scores and mean CLDQ domains scores. The most impaired domain was fatigue by both SF-36 and CLDQ questionnaires. When comparing PWH with and without MASLD, the activity domain of the CLDQ was significantly more impaired in PWH with MASLD compared to those without (mean 6.4±0.8 vs. 5.8±1.6, p=0.02). No differences were found between the two groups in other domains of the SF-36 or CLDQ. After adjusting for age, gender and undetectable viral load, MASLD was significantly and negatively associated with CLDQ activity domain (correlation coefficient -0.54, 95% CI -1.1 − -0.1).

graphic file with name canlivj-7.1-abst_fig29.jpg — Image:

Conclusion(s): In this analysis of the LIVEHIV cohort, fatigue is the most impaired HRQoL domain in PWH. Interestingly, MASLD appears to worsen HRQoL in PWH, as it is independently associated with impairment of the activity domain. Further longitudinal studies will be necessary to confirm these results.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):170–171.

CLM-P061 Liver fibrosis is associated with cardiovascular disease burden amongst patients with non-alcoholic steatohepatitis: the uncover-nash longitudinal cohort study

MQ Khan ¹, KE Corey ², A Mehta ³, KK Mangla ⁴, AS Chandramouli ⁵, AS Patel ⁴, S Varma ⁴, E Bugianesi ⁶

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Cardiovascular (CV) disease (CVD) burden in patients with non-alcoholic steatohepatitis (NASH) is incompletely understood.

Purpose: The unCoVer-NASH longitudinal cohort study assessed baseline CVD burden and subsequent CV events in patients with NASH stratified by Fibrosis-4 Index (FIB-4) using real-world de-identified US healthcare data from a federated network (TriNetX).

Method: Patients were identified using the International Classification of Diseases code (ICD-10-CM) for NASH from October 2015–June 2022 and required ≥ 1 FIB-4 measurement(s) calculated from data obtained 180 days prior to, or 30 days after diagnosis (index date) in addition to ≥ 12 months of data prior to index date (baseline period). FIB-4 score categories were low (< 1.3), intermediate (1.30–2.67) and high (≥ 2.67). Exclusion criteria included baseline evidence of cirrhosis, viral hepatitis, human immunodeficiency virus, liver-related complications and alcohol use disorder. Data analysed were baseline characteristics, CVD prevalence and risk of CV events(s) in follow-up (index date to end of enrolment, death or study end) amongst patients with no history of respective CV event(s) during baseline. For CV risk, cumulative incidence was plotted, incidence rate (IR) was presented per 100 person-years (PY) and hazard ratios (HR) were calculated using Cox proportional hazard models (crude and adjusted for CV risk factors [age, sex, type 2 diabetes (T2D), chronic kidney disease, obesity, hyperlipidemia, hypertension]).

Result(s): Of 717 patients included, those with high FIB-4 (N = 102) vs intermediate (N = 201) and low (N = 414) were older (60 vs 57 and 44 years), less likely to have obesity (38% vs 45% and 54%), more likely to have T2D (50% vs 45% and 36%) and be female (71% vs 54% and 57%). The most prevalent CVD phenotypes in all FIB-4 groups (high, intermediate and low FIB-4, respectively) were ischaemic heart disease (18%, 17%, 11%), cerebrovascular disease (16%, 7%, 8%) and heart failure (10%, 9%, 6%). Cumulative incidence of any CV event increased with FIB-4 score (Figure). IRs for any CV event was 24.6, 17.2 and 10.4 per 100 PY for high, intermediate and low FIB-4, respectively. HRs (95% confidence interval) for high and intermediate vs low FIB-4 were 3.43 (2.21, 5.31); p < 0.0001 and 1.53 (1.02, 2.29); p = 0.04 and remained significant for high vs low FIB-4 after adjustment for CV risk factors, similar to results for individual CV events.

graphic file with name canlivj-7.1-abst_fig30.jpg — Image:

Conclusion(s): CVD prevalence and incidence in patients with NASH was associated with baseline FIB-4 score, indicating higher CV burden as fibrosis worsens. CV risk with high vs low FIB-4 was significantly higher even after adjusting for CV risk factors. Patients with intermediate FIB-4 had an increased incidence of CV event(s) relative to those with low FIB-4 and should be monitored and managed; further research around CV risk in this group is needed.

Disclosure of Interest: M. Q. Khan Consultant of: Speaker Honoraria, Ontario Association of Gastroenterology Abbvie Corp., K. Corey Grant / Research support from: Bristol-Meyers Squibb and Novartis, Consultant of: Theratechnologies and Novo Nordisk, A. Mehta: None Declared, K. Mangla Shareholder of: may have employee shares/stocks, Employee of: Novo Nordisk A/S, A. Chandramouli Employee of: Novo Nordisk A/S, A. Patel Employee of: Novo Nordisk A/S, S. Varma Employee of: Novo Nordisk A/S, E. Bugianesi Consultant of: AstraZeneca, Boehringer Ingelheim, Bristol-Meyers Squibb, Gilead Sciences, Intercept, Inventiva, Merck Sharp & Dome, Novo Nordisk, and Pfizer

Can Liver J. 2024 Feb 26;7(1):172–173.

CLM-P062 Autoantibodies in non-alcoholic fatty liver disease: implications for early intervention

M Ragheb ^1,², MGV Iderstine ³, G Minuk ⁴, N Faisal ⁴

What is your preferred presentation method?: Poster Only

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH) represents escalating public health challenges worldwide. Early identification of predictive markers for advanced liver disease in NAFLD patients is of paramount importance to facilitate timely interventions.

Purpose: The study aimed to investigate the potential association between the presence of autoantibodies and the risk of developing severe fibrosis or cirrhosis in various subgroups of NAFLD patients.

Method: We conducted a retrospective study of 2,749 adult patients diagnosed with NAFLD between 1994 and 2019. Autoantibody status (anti-nuclear antibodies and anti-smooth muscle antibodies) was assessed alongside clinical and laboratory data. Logistic regression analyses were employed to evaluate the strength of the association between autoantibody positivity and the development of severe fibrosis or cirrhosis. We conducted separate assessments for NAFLD patients with co-morbid viral and alcohol-related liver diseases.

Result(s): Among 2,749 NAFLD patients, 1425 (51.8%) were males and 1324 (48.2%) were females with a mean age of 58.6 years. A total of 541 (20%) patients tested positive for autoantibodies. Autoantibody positivity was significantly associated with an increased risk of developing severe fibrosis or cirrhosis in the NAFLD only cohort (adjusted odds ratio 1.28, 95% CI [1.0-1.6]). This association remained consistent across various subgroups, even when accounting for concurrent diagnoses of hepatitis B virus and hepatitis C virus (Table 1). Notably, in patients with alcohol liver disease, those who tested positive for autoantibodies exhibited a lower risk of progressing to severe fibrosis or cirrhosis.

graphic file with name canlivj-7.1-abst_fig31.jpg — Image:

Conclusion(s): The presence of autoantibodies emerges as a potential predictive marker for advanced liver disease in NAFLD patients, offering valuable insight for risk stratification and tailored interventions. This study highlights the clinical relevance of autoantibodies in NAFLD and underscores the urgent need for prospective validation and mechanistic investigations to refine risk assessment and management strategies.

References: 1. Sebastiani, G., Patel, K., Ratziu, V., Feld, J., Neuschwander-Tetri, B., Pinzani, M. et, al. Current considerations for clinical management and care of non-alcoholic fatty liver disease: Insights from the 1^st international workshop of the Canadians NASH network. Can Liver J. 2022;5(1):61-90.

2. Peng, C., Stewart, A., Woodman, O., Ritchie, R., and Qin, C. Non-Alcoholic Steatohepatitis: A Review of Its Mechanism, Models and Medical Treatments. Front Pharmacol. 2020;11:603926.

3. Tesfay, M., Goldkamp, W., and Neuschwander-Tetri, B. NASH: The Emerging Most Common Form of Chronic Liver Disease. Mo Med. 2018;115(3):225-229.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):173–175.

CLM-P063 Probe to capsule distance measured during point of care liver assessment

C Schneider ¹, A Ramji ², EM Yoshida ², R Loomba ³, E Pang ⁴, T Hassanein ⁵, M Curry ⁶, N Afdhal ⁷

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Metabolic dysfunction associated liver disease (MASLD) is a growing problem in Canada and the world. Measurements of liver elasticity and attenuation have been shown to be correlated with liver fibrosis and steatosis. These two measurements are possible through non-invasive means, using ultrasound (Velacur™ or FibroScan®) /or MRI based methods. To ensure accurate quantification and severity of the disease, the measurements must be taken within the liver parenchyma, 1 cm beneath the liver capsule.

Velacur incorporates a real-time ultrasound (US) image to determine the location for measurement and real time guidance to help the user interpret the B-Mode ultrasound image.

Purpose: The aim of this analysis was to compare the measurement depths of Velacur and FibroScan in comparison to the liver capsule, in a cohort of patients with well characterized MASLD.

Method: The study included patients with well-characterized MASLD, scanned as part of a clinical study sponsored by Sonic Incytes. Patients ranging in age between 19 and 75 were scanned with both Velacur and FibroScan at five sites in Canada and the US. The probe to capsule distance (PCD) is measured in the ultrasound images captured during the Velacur scan and compared to the fixed depth of FibroScan measurements.

For FibroScan, the measurement depth was determined by the probe used. For the M probe, the depth is from 25 to 65 mm and the XL probe measures from 35 to 75 mm.

Result(s): 100 patients were included in this analysis. Overall 64 patients were scanned with the M probe and 36 were scanned with the XL probe. The average BMI was 30.3 kg/m² and ranged from 22.4 to 41.6 kg/m².

The average PCD for all patients was 29.3 mm. For patients scanned with the M probe the PCD was 27.5 mm and 32.5 mm for patients scanned with the XL probe.

In patients measured with the M probe, 38/64 (59%) had an average PCD larger than 25 mm, the starting depth measured with the M probe. In patients measured with the XL probe, 11/36 (30%) had an average PCD larger than 35 mm, the starting depth measured with the XL probe.

The figure below shows a scatter plot of patient BMI and Probe to Capsule Distance. The red dots represent patients measured with the FibroScan M probe, and the blue those measured with the XL probe. The horizontal lines represent the starting measurement depth of the two probes. Those patients marked with an ‘O’ symbol represent those measurements where the region of interest may include unwanted liver capsule and tissue outside the liver.

graphic file with name canlivj-7.1-abst_fig32.jpg — Image:

Conclusion(s): This analysis shows that there may be an underestimation of the optimal measurement depth in many patients being scanned with FibroScan. This could lead to inaccuracies in liver stiffness measurements and overestimation of liver attenuation. Velacur, with its B-Mode imaging guidance, ensures measurements are taken within the liver parenchyma, potentially providing more accurate results.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):175.

CLM-P064 Age-dependent differences in FIB-4 predictions of fibrosis in patients with nafld referred from primary care

S Sung ¹, T Davyduke ², M Al-Karaghouli ¹, M Ma ¹, JG Abraldes ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Non-alcoholic fatty liver disease (NAFLD) incidence is rising in Canada. Fibrosis 4 (Fib-4) index is a simple, laboratory-marker based non-invasive test (NIT) used to predict the presence of advanced fibrosis in NAFLD patients. Given that age is a component of the Fib-4 index calculation, higher scores may be expected in elderly population. This led to the proposal of using a higher threshold of Fib-4 index to rule out advanced fibrosis in older patients.

Purpose: Our main objective is to evaluate how advanced age modifies the association between Fib-4 index and fibrosis.

Method: In this cross-sectional study we prospectively analyzed collected data from a primary care referral pathway. Adult participants with NAFLD, without alternative liver diagnoses or significant alcohol use were included. We used different thresholds of vibration controlled transient elastography (VCTE) to classify the patients according to the severity of fibrosis, and studied the impact of age, diabetes and BMI with logistic and ordinal regression.

Result(s): 985 participants with NAFLD were used for the modeling. Participants older than 65 had a larger proportion of high Fib-4 values than those less than 65 (85.9% vs 20.2% for a threshold of 1.3, and 46.5% vs 6.5% for a threshold of 2.0). In participants with age ≥ 65, the negative predictive value (NPV) for VCTE ≥10 kPa for Fib-4 index <1.3 was 100%, while the NPV for Fib-4 index <2.0 was 83%. Age significantly modified Fib-4 index's prediction of fibrosis. However, this effect was mediated by a different distribution of risk factors related to age, since it was no longer significant when diabetes and body mass index (BMI) were added in addition to Fib-4 index. We provide a model to calculate exceeding probabilities of any given VCTE value for its use in a triage office to select patients for elastography.

Conclusion(s): The previously reported difference in performance of Fib-4 index at older ages is likely related to different distribution of risk factors for fibrosis. Diabetes and BMI markedly modify Fib-4 index's prediction of fibrosis. Rather than using age specific Fib-4 index thresholds, an interpretation of Fib-4 index in the context of the presence of diabetes and BMI would enhance its predictions.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):175–177.

CLM-P065 Efficacy of GLP-1 receptor agonists and SGLT-2 inhibitors for the treatment of diabetes mellitus in liver transplant recipients

K Zheng ¹, A Azhie ², X You ³, M Naghibzadeh ², E Tan ^2,^4,⁵, S Naimimohasses ², V Sridhar ², S Gupta ¹, S Chen ², S Dash ², E Jaeckel ², M Woo ¹, S Singh ⁶, D Cherney ⁶, M Bhat ²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background:

Liver transplant (LT) recipients with diabetes mellitus (DM) are at increased risk of cardiovascular events and progressive chronic kidney disease. GLP-1 receptor agonists (GLP-1RA) and SGLT-2 inhibitors (SGLT2i) have known cardio-renal benefits in DM, but their safety and benefits in LT recipients are unknown.

Purpose: We aimed to investigate their efficacy and safety in LT recipients with diabetes.

Method: A single-center, retrospective analysis of prospectively collected data from a LT recipient database was conducted (1990 – 2023). We included adults with Type 2 or post-transplant DM following LT taking GLP-1RA and/or SGLT2i for at least 3 months. Metabolic and biochemical parameters and outcomes were collected up to 24 months after starting medications and compared to the dipeptidyl peptidase 4 inhibitor (DPP4i) group and general DM population. Statistical analysis included descriptive, paired two-sample t-tests and linear mixed models.

Result(s): We included participants on GLP-1RA (n=47), SGLT2i (n=91), and combination therapy (n=13). At months, HbA1c improved in the GLP-1RA and combination groups (-1·4%, p=0·03 and -2·3%, p<0·01). At 12 months, AST and ALT improved in the combination group (-26·3, p=0·04 and -48·3, p=0·01), and SGLT-2i, GLP-1RA, and combination groups had decreased weight (-2·7, -5·3, and -11 kg, all p<0·01)There were no consistent changes in eGFR. Significant improvements in HbA1c and weight were not seen in the DPP4i comparator group.

graphic file with name canlivj-7.1-abst_fig33.jpg — Image:

Conclusion(s): GLP-1RA and SGLT2i use results in significant weight loss in LT recipients with DM while maintaining renal function. Further studies are required to evaluate the long-term safety and efficacy in this population.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):177–178.

CLM-P066 Loss of hepatic BRCA1 protects against fatty liver and tumourigenesis

M Ghebreselassie ^1,², YJ Park ², D Nakib ^2,³, P Patel ^2,⁴, R Hakem ^4,⁵, S MacParland ^2,³, M Woo ^1,^2,^3,^6,⁷

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is the leading cause of chronic liver disease globally and is projected to continue rising. MAFLD encompasses a spectrum of liver disorders beginning with intrahepatic fat accumulation, also called fatty liver, which can progress to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis and ultimately hepatocellular carcinoma (HCC). However, the pathophysiology of MAFLD and particularly its progression to HCC remains unclear. While breast cancer susceptibility gene 1 (BRCA1) is a well-known and ubiquitously expressed tumour suppressor, emerging evidence suggests its role in metabolism, such as adipogenesis and lipid synthesis. Yet, the role of BRCA1 in the liver remains unclear.

Purpose: The objective of this project is to investigate the role of BRCA1 in MAFLD progression to HCC.

Method: To investigate the role of hepatic BRCA1 in vivo, we generated Brca1-deficient mice using the Cre-loxP system, driven by the albumin promoter (L-Brca1-knockout (KO)). To induce fatty liver, 6-week-old mice were placed on 60% high fat diet (HFD) for 16 weeks. To induce liver tumour formation, diethylnitrosamine (DEN) was administered to 14-day-old mice and sacrificed at 10-12 months of age. To investigate liver tumour development in the context of fatty liver, mice were administered DEN and placed on HFD simultaneously.

Result(s): L-Brca1-KO mice were protected against hepatic steatosis and glucose intolerance compared to wildtype (WT) littermate controls. L-Brca1-KO mice were also protected against liver tumour formation compared to WT controls in both DEN-only and DEN/HFD cohorts, exhibiting lower tumor incidence, fewer tumour numbers and smaller maximum tumour size. To investigate the molecular mechanisms underpinning Brca1-deficiency mediated protection against liver tumour formation in an unbiased manner, single nuclear RNA sequencing of non-tumour liver tissue from DEN-only L-Brca1-KO and WT control mice was performed. Gene set enrichment analysis (GSEA) on hepatocyte clusters, investigating for carcinogenesis-specific differences, revealed a downregulated ”Liver Adenoma“ signature with the most downregulated gene being betaine-homocysteine S-methyltransferase (Bhmt), a liver-specific enzyme in one-carbon metabolism, specifically in the methionine and choline synthetic pathway. Bhmt suppression was confirmed by RT-qPCR in L-Brca1-KO mice liver tissue and HepG2 and Huh7 hepatoma cell lines after BRCA1 siRNA knockdown.

Conclusion(s): Our findings uncovered a novel role of hepatic Brca1 in MAFLD-associated HCC. Given that methionine and choline are implicated in hepatic inflammation, further work is required to understand mechanisms behind the regulation of BRCA1 in the regulation of these critical metabolites in hepatic tumourigenesis.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):178.

CLM-P067 IRP1 deficiency triggers metabolic reprograming, increases insulin sensitivity and protects mice against liver steatosis

W Gu ¹, K Pantopoulos ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Iron regulatory protein 1 (IRP1) is a post-transcriptional regulator of cellular iron metabolism. While IRP1 operates as cytosolic aconitase in iron-replete cells, iron deficiency promotes its conversion to an RNA-binding protein that controls expression of mRNAs containing “iron responsive elements” (IREs). Irp1^-/- mice develop polycythemia due to unrestricted translation of HIF2α mRNA, an IRP1 target, which in turn stimulates erythropoiesis via transcriptional induction of erythropoietin (1).

Purpose: Aberrant HIF2α regulation has been linked with metabolic reprogramming. Thus, we investigated whether IRP1 ablation affects metabolism.

Method: We assessed metabolic features in Irp1^-/- mice and control wild type littermates, as well as in primary hepatocytes and myocytes from these animals.

Result(s): Irp1^-/- mice exhibit fasting hypoglycemia. Moreover, the male animals are protected against hyperglycemia that develops in wild type littermates in response to a high fat diet. This is due to insulin-mediated decreased gluconeogenesis in the liver and increased glucose uptake in skeletal muscles. Mechanistically, decreased gluconeogenesis is caused by induction of insulin receptor substrate 2 (IRS2), a HIF2α target in the liver, which increases insulin sensitivity. Nevertheless, without insulin stimulation, expression of gluconeogenic G6pc mRNA was induced in Irp1^-/- mice. Furthermore, expression of Srebp1 mRNAs, which encodes a gene involved in de novo lipogenesis, was suppressed. Proteomics analysis revealed mitochondrial dysfunction and metabolic reprogramming in the liver and skeletal muscles of Irp1^-/- mice. Seahorse assays using primary hepatocytes and differentiated myotubes validated the impaired respiratory capacity and switch to glycolytic metabolism.

Conclusion(s): Our data suggest that mitochondrial dysfunction decreases energy production in skeletal muscles, which triggers increased insulin sensitivity and glucose uptake. However, the energy yield is low, and starvation signals stimulate expression of gluconeogenic genes and suppress lipogenesis in the liver overriding high insulin sensitivity, in a futile attempt to meet energetic needs. Thus, IRP1 emerges as an important metabolic regulator.

References:

Wilkinson N, Pantopoulos K. IRP1 regulates erythropoiesis and systemic iron homeostasis by controlling HIF2alpha mRNA translation. Blood 2013;122:1658-1668.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):178–179.

CLM-P068 Evaluating the liver immune environment in a preclinical model of pathobiont accelerated metabolic dysfunction associated steatotic liver disease

EP Munhoz ¹, HH Nguyen ²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) encompasses a range of liver pathology including simple fat accumulation in the liver (steatosis) to progressive liver inflammation and scarring (MASH). Treatment options for MASLD are currently very limited. Understanding the drivers that promote the progression of liver injury will be important for the diagnosis and treatment of MASLD. Others have implicated the host microbiota as a contributor to disease progression. We have consistently observed that a particular gut pathobiont can accelerate histological liver steatosis in a high-fat diet (HFD) animal model of MASLD.

Purpose: We aim to evaluate the impact of this pathobiont on local immune responses within the liver in the setting of accelerated steatosis.

Method: 6-week-old C57BL/6 mice were gavaged with the pathobiont and fed a high-fat diet (HFD) for a total of 8 weeks, an early time point that does not typically lead to MASLD development in our SPF mice not colonized with this pathobiont. The livers were subsequently collected and analyzed for immune cell profiling using flow cytometry and histology.

Result(s): Mice colonized with the pathobiont had a significantly higher degree of liver steatosis noted on H&E histology and blinded quantification of steatosis with Oil Red staining. Immune cells within the liver of pathobiont colonized mice fed HFD showed decreased frequencies of Treg cells (1.50% vs 2.47%), CD8+ T cells (10.94% vs 14.96%), B cells (32.13% vs 36.61%) and NK cells (9.79% vs 13.97%) and increased frequencies of Mo/MF cells (7.63% vs 5.19%) vs SPF mice without the pathobiont. Although segmented filamentous bacteria (SFB) has been implicated in metabolic disease, we did not find any differences in SFB levels in stool of both groups, using quantitative PCR.

Conclusion(s): An altered pathobiont associated liver immune environment may drive progression of liver injury in the setting of MASLD. Additional investigation is underway to better elucidate the contributions of these immune cells to MASLD progression.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):179–180.

CLM-P069 The protective mechanism of the A165T variant of MTARC1 on the development of metabolic dysfunction-associated steatotic liver disease (MASLD)

A Kapilan ¹, A Dufour ¹, P Colarusso ¹

What is your preferred presentation method?: Poster Only

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is a liver disease characterized by increased levels of fat in the liver. The current treatments for MASLD include lifestyle modification as well as pharmacological treatments, such as insulin sensitizers, lipid lowering agents, & antioxidant agents ⁴. However, these treatments only postpone further complications. Currently, it is challenging to discover a treatment due to the complexity of creating an adequate disease model, and a lack of understanding of targets that can prevent this disease

Purpose: A mutation in the enzyme Mitochondrial Amidoxime Reducing Component 1 (MTARC1), which is a molybdenum containing metabolic enzyme, was found to be protective against the progression of MASLD ¹. Despite the pivotal discovery of the link between the MTARC1 mutation and the protection against MASLD development, the mechanism of action remains elusive. We hypothesize that MTARC1 plays a role in lipid metabolism and the MTARC1 A165T mutation is a loss of function mutation, which alters the metabolism of cells into a catabolic state, thus driving the breakdown of lipids and protecting against NAFLD pathogenesis.

Method: We must first aim to understand MTARC1's physiological relevance within cells. Proteomic, and metabolomic experiments have been conducted by comparing WT and MTARC1 knockout cells (MTARC1-/-) using a cell biology approach to understand MTARC1's physiological relevance

Result(s): Metabolomic Results detected a significant increase in 7 metabolites (ATP,UTP,GTP,CTP, Fructose-1,-6-Bisphospate, Thymine and Gluthionine) in MTARC1-/- cells. Proteomic results concluded that in the absence of MTARC1 there is a decrease in the citric acid cycle and cellular respiration, but an increase in glycolysis and gluconeogenesis. The metabolomic and proteomic data were combined in a joint pathway enrichment analysis, where the significant gene hits from proteomics as well as the significant metabolite hits from metabolomics were combined to see which pathways were substantially elevated. From the joint analysis we could see an increase in the glycolysis and gluconeogenesis pathway.

Conclusion(s): MTARC1 may play a role in regulating the TCA cycle. An increased citric acid flux can cause increase production of ROS, which in results causes the progression of liver steatosis to liver steatohepatitis ². In contrast, increased gluconeogenesis can lead to alleviation from ROS due to the drive towards gluconeogenesis ². Thus, in the absence of this protein there is alleviation from ROS, and protection against the progression of liver steatosis. Further research needs to be conducted about the mutation's function and role in the protection of this disease.

References: 1. Klein, J. M., Busch, J. D., Potting, C., Baker, M. J., Langer, T., & Schwarz, G. (2012). The mitochondrial amidoxime-reducing component (mARC1) is a novel signal-anchored protein of the outer mitochondrial membrane. The Journal of biological chemistry, 287(51), 42795–42803. https://doi.org/10.1074/jbc.M112.419424.

2. Lu, Q., Tian, X., Wu, H., Huang, J., Li, M., Mei, Z., Zhou, L., Xie, H., & Zheng, S.(2021). Metabolic Changes of Hepatocytes in NAFLD. Frontiers in physiology, 12, 710420. https://doi.org/10.3389/fphys.2021.710420

3. Luukkonen, P. K., Sakuma, I., Gaspar, R. C., Mooring, M., Nasiri, A., Kahn, M.,Zhang, X. M., Zhang, D., Sammalkorpi, H., Penttilä, A. K., Orho-Melander, M., Arola, J., Juuti, A., Zhang, X., Yimlamai, D., Yki-Järvinen, H., Petersen, K. F., & Shulman, G. I. (2023). Inhibition of HSD17B13 protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitis. Proceedings of the National Academy of Sciences of the United States of America, 120(4), e2217543120. https://doi.org/10.1073/pnas.2217543120

4. Pais, R., Barritt, A. S., 4th, Calmus, Y., Scatton, O., Runge, T., Lebray, P., Poynard, T.,Ratziu, V., & Conti, F. (2016). NAFLD and liver transplantation: Current burden and expected challenges. Journal of hepatology, 65(6), 1245–1257. https://doi.org/10.1016/j.jhep.2016.07.033

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):180–181.

CLM-P070 Hedgehog signalling and metabolic responses drive CD8 T cell hyperfunction in advanced liver diseases

J Li ^1,^2,³, K Jorritsma ^1,^2,³, A Vranjkovic ², KR Levesque ^1,², J Madani ^1,², D Read ^1,², WL Stanford ^3,^4,^5,⁶, AC Cheung ^3,⁷, CL Cooper ^3,^8,^9,¹⁰, M Ardolino ^1,^3,¹¹, AM Crawley ^1,^2,^3,¹²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: Prolonged liver insult in metabolic dysfunction-associated liver disease (MASLD) and chronic HCV infection (cHCV) results in progressive liver damage and increased risk for hepatocellular carcinoma. CD8 T cell function is altered in infectious and non-infectious liver diseases regardless of antigen-specificity. We previously reported long-lasting bulk CD8 T cell hyperfunction in cHCV associating with fibrosis severity, yet specific underlying mechanisms remain elusive.

Purpose: To investigate mechanisms of generalized CD8 T cell dysfunction in advanced liver disease.

Method: We isolated blood CD8 T cells from MASLD or cHCV patients with varying degrees of liver damage. Gene Set Enrichment and Gene Ontology analyses of RNA-seq data were performed on stimulated cells from cHCV, which lead to flow cytometry probing of Hedgehog (Hh) signalling using pathway inhibitors, and cell death assessment. We established mouse models of T cell hyperfunction in liver disease by exposure to hepatotoxin carbon tetrachloride (CCl₄), or high-fat, methionine-choline deficient diet (HFMCDD), the latter mirroring human MASLD pathophysiology. T cell function and metabolic activity in these models were assessed by flow cytometry and Seahorse XF Mito Stress test.

Result(s): RNA-seq identified 362 differential genes in CD8 T cells from cHCV patients with cirrhosis vs minimal fibrosis, highlighting genes associated with T cell metabolism and function, including Hh signalling, apoptosis, glycolysis, oxidative phosphorylation, cytoskeletal regulation, inflammatory processes, and cell cycle regulation. RT-qPCR confirmed increased Hh pathway gene expression (PTCH1, GLI1) in cHCV patients with cirrhosis. Hh signalling inhibition in hyperfunctional CD8 T cells from cHCV patients with cirrhosis restored T cell function to healthy control levels, while functional cells also express higher cell death markers. Hyperfunction was also observed in HCV⁻ MASLD patients with biopsy-proven advanced fibrosis/cirrhosis. In CCl₄-treated mice, CD8 T cell hyperfunction was coupled to impaired responses to ectopic tumour growth and immunotherapy. In HFMCDD-treated mice, cells also exhibited hyperfunction, coupled with increased glycolytic activity and mitochondrial respiration. HFMCDD-treated mice also exhibited increased metabolic activity in CD4 T cells and elevated inflammatory profiles in systemic and hepatic macrophages (see abstracts: N. Campeau, D. Lawton).

Conclusion(s): In advanced liver disease, CD8 T cell hyperfunction appears driven by an overall disruption in inflammatory and metabolic processes upon activation, which may involve dysfunctional Hh signalling and a greater propensity for apoptosis. In mice, CD8 T cell hyperfunction is coupled to host and cellular metabolic disruptions, which may contribute to impaired anti-tumour and immunotherapy responses. Understanding mechanisms of chronic immune dysfunction may translate to therapeutic strategies to improve clinical outcomes for individuals living with advanced liver diseases.

References: (1) Vranjkovic, A., F. Deonarine, S. Kaka, J. B. Angel, C. L. Cooper, and A. M. Crawley. 2019. Direct-Acting Antiviral Treatment of HCV Infection Does Not Resolve the Dysfunction of Circulating CD8+ T-Cells in Advanced Liver Disease. Front Immunol 10:1926. (2) Li, J., A. Vranjkovic, D. Read, S. P. Delaney, W. L. Stanford, C. L. Cooper, and A. M. Crawley. 2023. Differential and lasting gene expression changes in circulating CD8 T cells in chronic HCV infection with cirrhosis and related insights on the role of Hedgehog signaling. BioRxiv (Pre-print) BIORXIV/2023/557725. (3) Madani, J., J. Li, A. Vranjkovic, K. Jorritsma, M. S. Hasim, M. Daneshmand, A. C. Cheung, A. M. E. Ching, J. E. Bruin, M. Ardolino, and A. M. Crawley. 2023. CD8 T cell hyperfunction and reduced tumour control in models of advanced liver fibrosis. BioRxiv (Pre-print) BIORXIV/2023/557752.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):181–183.

CLM-P071 Severe metabolic dysfunction-associated steatotic liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota in people with HIV

LR Ballestreros ¹, B Lebouche ², J-P Routy ¹, MB Klein ¹, J Szabo ², J Cox ¹, J Falutz ¹, L-P Haraoui ³, C Costiniuk ¹, A De Pokomandy ², F Cinque ¹, T Pembroke ⁴, M Constante ⁵, M Santos ⁶, G Sebastiani ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) to its severe forms, including metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis, is influenced by a combination of lifestyle and genetic factors. Recently, several studies have emphasized gut microbial dysbiosis as a key driver in this process. However, the role of gut dysbiosis in people with HIV (PWH), a population with a complex MASLD pathogenesis and at risk for severe liver disease, is not known.

Purpose: To evaluate the association between gut dysbiosis and severe MASLD, that is, MASH and liver fibrosis, in a well-characterized population of PWH.

Method: Consecutive PWH from a prospective Cohort in Montreal, Canada (LIVEr disease in HIV, LIVEHIV), underwent liver stiffness measurement (LSM) with controlled attenuation parameter (CAP) by Fibroscan and the measurement of serum cytokeratin-18, a biomarker of hepatocyte apoptosis used to diagnose MASH. We included patients with a diagnosis of MASLD, defined as CAP ≥238 dB/m without viral hepatitis coinfection or alcohol abuse. Severe MASLD was defined as presence of MASH (cytokeratin-18 ≥130.5 U/L) and/or significant liver fibrosis (LSM ≥7.1 kPa). Taxonomic composition of gut microbiota was determined using 16S ribosomal RNA gene sequencing of stool samples. PICRUSt-based functional prediction was employed. Bacterial and functional differences were assessed using a generalized linear model, with adjustment for age and sex as confounding factors, using a negative binomial distribution.

Result(s): 34 patients with MASLD were enrolled (mean age 52 years, 15% females, mean LSM 6.7 kPa, mean cytokeratin-18 184 U/L). Among them, 32% had severe MASLD. After adjusting for age and sex, liver health status (severe MASLD yes vs. no) explained seven percentage of the overall variation (r2 = 0.07, p = 0.09) in bacterial composition. Several genera were found to be significantly different between PWH with severe MASLD. Notably, participants with severe MASLD had increases of genera Eubacterium, Bacteroides, Roseburia, Ruminococcus, Slackia, Holdemanella, Bilophila and decreases of Alloprevotella, Paraprevotella, Prevotella, Olsenella, Oribacterium, Romboutsia, Desulfovibrio, Dialister (See Figure). In severe MASLD, functional analysis revealed increases in fatty acid degradation and flavonoid biosynthesis, and decreases in pyrimidine metabolism, steroid biosynthesis, folate biosynthesis, and alanine, aspartate, glutamate metabolism.

graphic file with name canlivj-7.1-abst_fig34.jpg — Image:

Conclusion(s): In PWH, MASLD severity is associated with gut dysbiosis and a shift in metabolic function of the gut microbiota. Some of these taxa are similar to those associated with MASLD in populations without HIV. Thus, gut microbiota analysis adds information to classical predictors of MASLD severity and suggests novel metabolic targets for pre-/probiotics therapies. Larger, longitudinal studies are needed to define the role of the gut microbiota in the pathogenesis of liver disease in this high risk population.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):183–185.

CLM-P072 The rise of metabolic dysfunction-associated steatotic liver disease (MASLD) among adults in Canada between 2012 and 2018

J Burnside ¹, F Cinque ², G Sebastiani ³, S Saeed ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a highly prevalent yet largely underappreciated liver condition, absent from public health agendas. A recent study suggested substantial improvements in epidemiological assessments would be necessary to improve national preparedness. Based on the lack of routine ultrasounds and the paucity of transient elastography across Canada, serum biomarkers are the only option to identify steatosis at a population scale. To address this need for routine surveillance, the NAFLD Ridge Score (NRS) was developed using a machine-learning approach and validated against proton magnetic resonance spectroscopy with a sensitivity of 92% and specificity of 90%.

Purpose: To estimate the prevalence of MASLD using a pan-Canadian cohort between 2012-2018.

Method: We used data from the comprehensive cohort of the Canadian Longitudinal Study on Aging (CLSA), which prospectively follows community-dwelling adults (45 and 85 years old) from 11 sites (7 provinces) across Canada. The CLSA collects sociodemographic, lifestyle, and clinical data every three years. We estimated the annual prevalence of MASLD using the new definition (steatosis + one cardiometabolic risk factor) as well as MetALD (140-350 g alcohol/week (F) and 210-420 g alcohol/week (M)). Steatosis was identified by an NRS >0.44, which utilizes seven components: serum ALT, high-density lipoprotein cholesterol, triglycerides, hemoglobin A1c, leukocyte count, and the presence of hypertension. We compared the prevalence of MASLD using the NRS score to a non-specific measure of liver damage, ALT (> 40U/L).

Result(s): 30 079 CLSA participants were included in the analysis. At baseline, 51% were female (F), with a median age of 62 years (IQR: 54-71 years), median ALT was 21 U/L (IQR: 16-27 U/L). 83% met at least one of five MASLD cardiometabolic criteria, the most common being 70% BMI > 25 kg/m²; 41.5% having high triglycerides ≥ 1.70 mmol/L; 33% HbA1c ≥ 5.7%; 30% with hypertension; and 25% having high HDL ≤ 1.0 mmol/L (Males) or ≤ 1.3 mmol/L (F). There was a significant rise in MASLD prevalence from 32.3% (95%CI 32.2, 32.5%) in 2012 to 39.1% (95%CI: 39.0-39.3%) in 2018. MetALD prevalence varied over time, ranging from 2.2% (95%CI: 2.2-2.2%) in 2016 to 3.5% (95%CI: 3.4-3.5%) in 2012. Males had an average 1.9 times higher prevalence of MASLD and 2.6 times higher prevalence of MetALD compared to females. Only 7.6% (95%CI: 7.5-7.6%) of the cohort had elevated ALT (> 40U/L) and at least one of the cardiometabolic factors.

graphic file with name canlivj-7.1-abst_fig35.jpg — Image:

Conclusion(s): This is the first Canadian study to estimate MASLD and MetALD prevalence which exceeds previous modelling estimations. Prevalence was significantly greater among men, and this was consistent between 2012-2018. ALT alone, routinely used in clinical practice as a first-line indicator of liver damage, vastly underestimated the prevalence of MASLD. Further studies are underway to elicit phenotypes at the greatest risk of MASLD and the bidirectional relationship between liver and metabolic diseases.

Disclosure of Interest: J. Burnside: None Declared, F. Cinque: None Declared, G. Sebastiani Grant / Research support from: Unrestricted research funding from Theratecnologies Inc., Consultant of: Served as an advisory board member for Merck, Gilead, Pfizer, Novo Nordisk, Intercept., Speakers bureau of: For Pfizer, Merck, Novo Nordisk, Gilead, and AbbVie, S. Saeed Consultant of: Served as an advisory board member for Novo Nordisk

Can Liver J. 2024 Feb 26;7(1):185–186.

CLM-P073 Material deprivation is associated with liver stiffness measurement and liver-related events in people with HIV

C Long ^1,², F Cinque ^1,², D Kablawi ^1,², DH Kim ^1,², TF Tadjo ^1,², W Elgretli ³, LR Ballesteros ^1,², A Lupu ^1,², M Nudo ^1,², B Lebouché ¹, N Kronfli ¹, J Cox ^1,⁴, C Costiniuk ¹, A De Pokomandy ¹, J-P Routy ¹, M Klein ^1,⁴, F Lamonde ⁵, R Agnihotram ⁵, S Saeed ⁶, G Sebastiani ^1,^2,³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Socioeconomic status drives health disparities and may lead to poorer control of chronic diseases and increased mortality. People with HIV (PWH) are at high risk for chronic liver diseases. The association between material deprivation and hepatic outcomes in PWH has not been evaluated.

Purpose: To evaluate the association between material deprivation and liver fibrosis, metabolic dysfunction-associated steatotic liver disease (MASLD) and clinical outcomes in a cohort of PWH.

Method: We used data from the LIVEr disease in HIV (LIVEHIV) cohort, a prospective cohort of PWH undergoing routine screening for liver disease with Fibroscan. MASLD was defined as the presence of hepatic steatosis, diagnosed as controlled attenuation parameter (CAP) ≥248 dB/m, plus any of the following: overweight (BMI>25 Kg/m²), type 2 diabetes, hypertension, or dyslipidemia. Significant liver fibrosis was defined as liver stiffness measurement (LSM) ≥8 kPa. Socioeconomic status was assessed using the Pamplon Material Deprivation Index (MDI), which is calculated by linking patient postal code to the 2016 Canadian census data in order to classify our population into quintiles of material deprivation, from most privileged (quintile 1) to most deprived (quintile 5). We further dichotomized MDI as “deprived” by collapsing quintiles 4 and 5 together, and “privileged” by combining quintiles 1 and 2. Multivariable linear regression analysis was used to investigate associations of MDI with LSM and CAP. The Kaplan Meier method was used to assess the incidence of liver outcomes (ascites, variceal bleeding, hepatic encephalopathy, hepatocellular carcinoma, liver transplantation), extrahepatic outcomes (cancer, cardiovascular disease) and overall mortality.

Result(s): Among the 768 PWH included, the median age was 54 years, 76% were males, 25% and 10% had HCV and HBV coinfection, respectively, 23% had significant liver fibrosis and 33% had MASLD. Overall, 305 (40%) lived in materially privileged dissemination areas while 359 (47%) were materially deprived. At baseline, materially deprived PWH were more frequently female, of Black ethnicity and had a higher prevalence of metabolic comorbidities. After adjustments, material deprivation was associated with a significant increase in fibrosis at baseline (LSM β=1.9, 95%CI 0.5-3.2; p=0.006) but not with steatosis (CAP β=6.5, 95%CI -5.6-18.5). During a median follow-up period of 3.8 years, incidence rates of liver-related events, extrahepatic events and mortality were 14.6 (95%CI 10.3–20.7), 25.5 (19.6–33.1) and 7.6 (95%CI 7.6–12.4) per 1000 person-years, respectively. Incidence of liver-related events was higher among materially deprived PWH than privileged (see Figure), while there was no difference in extrahepatic events or overall mortality.

graphic file with name canlivj-7.1-abst_fig36.jpg — Image:

Conclusion(s): Material deprivation, reflecting socioeconomic status, is associated with liver fibrosis and liver-related events in PWH. Future strategies should assess whether improved material security may result in improved liver outcomes.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):186–187.

CLM-P074 Projected healthcare system cost burden of metabolic dysfunction-associated steatotic liver disease in Canada

A Memedovich ¹, AA Shaheen ², MG Swain ², F Clement ^1,³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously Non-Alcoholic Fatty Liver-Disease (NAFLD), is the most common cause of chronic liver disease in the western world, affecting about 25% of the adult Canadian population. Alarmingly, with growing rates of obesity and diabetes, the prevalence of MASLD and associated complications has been projected to significantly increase in near future; however, the healthcare costs associated with MASLD and MASLD-related complications remains poorly defined.

Purpose: Our objective was to calculate the liver-related and total healthcare costs for people living with MASLD and predict the increase from 2020 to 2050.

Method: The healthcare utilization of patients diagnosed with MASLD within the Calgary NAFLD clinical care pathway (CNCCP) in Calgary, Alberta between March 2018 and June 2022 was retrieved. We analyzed the clinical, radiological and administrative data associated with each individual's unique healthcare identifier number. Within the CNCCP, shear wave elastography scores were used to define liver fibrosis stages (F0 to F4) based on published cut-offs. ICD9/ICD10 codes were used to classify patient visits to liver and non-liver related contacts. Both liver-related and total average cost per year per patient were calculated. Projected costs were calculated by multiplying the average cost per patient within each fibrosis stage by the projected Canadian prevalence of each fibrosis stage. These projected estimates came from previously published work. To understand the common reasons MASLD patients might be seeing physicians, a frequency of the most common billing codes for physician visits was calculated.

Result(s): There were 6,358 MASLD patients in the cohort identified within the CNCCP. The annual average liver-related cost per patient was $7.02 for F0/F1, $35.30 for F2, $60.46 for F3, $72.55 for F4, $933.26 for patients with decompensated cirrhosis, and $10,074.23 for patients with hepatocellular carcinoma (HCC). The estimated Canada-wide liver-specific burden was $289.5 million in 2020 and is expected to increase by $143 million by 2050. The average annual total healthcare cost per patient was much higher at $397.90 for F0/F1, $781.53 for F2, $2,881.84 for F3, $1,598.82 for F4, $933.26 for patients with decompensated cirrhosis, and $10,074.23 for patients with HCC. The estimated Canada-wide total healthcare cost associated with MASLD patients was $4.20 billion in 2020 and is expected to increase by almost $2 billion by 2050. The most common reasons for seeing physicians within our cohort were diabetes, hypertension, and mental illness.

Conclusion(s): These estimates underscore expected rapid growth of the cost of MASLD to the healthcare system. There is a need for a MASLD framework that focuses on both prevention and care models. Further, most of the healthcare costs for people with MASLD were due to non-liver chronic conditions highlighting the need to focus on collaborative care approach to address common comorbidities.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):187–188.

CLM-P075 Nutritional management is an urgent need in patients on the waiting list for liver transplantation!

I Ruiz ^1,², M Tremblay ¹, M Bouhraoua ¹, C Hogue ¹, A Trigui ¹, G Huard ², C Vincent ², CF Rose ¹, C Bémeur ^1,³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Metabolic dysfunction–associated liver disease (MASLD) is a major cause of cirrhosis and the leading indication for liver transplantation (LT). With the ongoing obesity epidemic, the problem will only increase, making nutritional management a cornerstone. The period between listing and LT is a missed opportunity to improve preoperative patient management.

Purpose: The objective of this study was to evaluate the weigth status of patients on the waiting list for liver transplantation.

Method: This is a retrospective study including all consecutive patients who underwent LT at the Centre hospitalier de l’Université de Montréal (CHUM) between 2019 and 2021. Only patients with biologically, clinically, pathologically and/or radiologically confirmed cirrhosis were included. Weigth status was classified by body mass index (BMI) as: obese, equal to or greater than 30.0; overweight, between 25.0 and 29.9; normal, between 18.0 and 25.0; or underweight, less than 18. Delta BMI was calculated between weight at listing and LT. BMI results were corrected for the presence of ascites.

Result(s): During the study period, 181 patients were transplanted of which 155 with cirrhosis were included. 104/155 (67.1%) were men, median age was 52 years (18-69). Median BMI was 24.7 (13.8 - 41.0). Underweight was present in 11/155 (7.1%), overweight in 37/155 (23.9%), and obesity in 38/155 (24.5%).

Concerning the delta BMI, 12.2% (19/155) gained at least one BMI point, 23.9% (37/155) had no change, and 63.9% (99/155) lost at least one BMI point.

According to the main etiology (Figure 1), the prevalence (%) of underweight/overweight/obesity and the delta BMI in patients with:

- MASH was 5/24/45; 76.2% (32/42) lost at least one BMI point.

- Hepatitis B was 0/50/0; 50.0% (4/8) lost at least one BMI point.

- Primary biliary cholangitis was 0/23/31; 76.9% (10/13) lost at least one BMI point.

- Hepatitis C was 0/50/38; 50.0% (4/8) gained at least one BMI point.

graphic file with name canlivj-7.1-abst_fig37.jpg — Image:

Conclusion(s): At the time of listing for LT, 55.5% had a suboptimal weigth status. This study highlights the suboptimal weigth status of patients with cirrhosis as well as etiologic differences. These results urge the implementation of nutritional interventions before LT, while emphasizing awareness of weight stigma.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):189–190.

CLM-P076 “YOUR LIVER, YOUR HEALTH”: an innovative approach to improve public health awareness of metabolic dysfunction-associated steatotic liver disease (MASLD)

S Saeed ¹, F Cinque ², G Sebastiani ³, M Betel ⁴, OBOTCNN Fatty Liver Alliance ^4,⁵

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Metabolic dysfunction-associated Steatotic Liver Disease (MASLD) affects 1 in 3 Canadians, yet public awareness remains limited. Empowering communities with the knowledge about its prevalence, prevention and screening is foundational to fostering a healthier and more informed society. In collaboration with the Canadian NASH Network and the Fatty Liver Alliance, we secured funding from the Canadian Institutes of Health Research (CIHR) to organize a ”Café Scientifique“ to facilitate knowledge exchange between the scientific community and the general public.

Purpose: To improve the public's awareness and understanding of the relationship between liver disease, diabetes and metabolic health. Secondarily, assess the effectiveness and acceptability of the Café Scientifique model for knowledge dissemination targeting the public.

Method: The public was invited to attend a two-hour Café Scientifique entitled ”Your Liver, Your Health“ on September 19, 2023, at the Westmount Public Library in Montreal, Quebec. The event was advertised through social media, the library's newletter and press releases. A panel of two researchers, one knowledge user, and one person with lived experience presented current research on MASLD epidemiology, clinical care pathways and prevention strategies. Subsequently, the panellist engaged in an open forum discussion with the attendees. A certified technician offered complimentary transient elastography with controlled attenuation parameter (Fibroscan®) assessment and a physician interpreted the results. Attendees completed an anonymous post-event survey using a five-point Likert scale (unsatisfied to very satisfied) and open-ended questions.

Result(s): Seventy people registered, and 45 attended the event. The majority of participants were English-speaking females over the age of 65. The open forum discussion extended for over an hour, revolving around key themes: (1) clinical risk factors, (2) specific dietary and lifestyle inquiries, (3) accessibility to screening and diagnosis and (4) individual and societal costs associated with screening. Notably, 29 participants expressed interest in undergoing a Fibroscan assessment; due to time constraints, 13 attendees were randomly selected. Of the 39 participants who completed the survey, 92% reported being ’very satisfied’ with the event, 97% were interested in attending future Cafés, and 95% would recommend it to family and/or friends. Twenty-one attendees wrote comments including: “This event exceeded all expectations” “Excellent presentations, excellent speakers, lots of great information” “Excellent presenters who spoke simply without overwhelm of science” ...“Knowledge is power for consumers”.

Conclusion(s): Increasing public health awareness is crucial in improving health outcomes through advocacy and informed healthcare decision-making. Based on the overwhelming demand, engaging discussion and positive feedback, our Café Scientifique was shown to be an effective upstream model to promote awareness for MASLD.

Disclosure of Interest: S. Saeed Grant / Research support from: Served as an advisory board member for Novo Nordisk, F. Cinque: None Declared, G. Sebastiani Grant / Research support from: GS has acted as speaker for Merck, Gilead, Abbvie, Novo Nordisk, Pfizer, served as an advisory board member for Pfizer, Merck, Novo Nordisk, Gilead and Intercept and has received unrestricted research funding from Theratec., M. Betel: None Declared, O. B. O. T. C. N. N. Fatty Liver Alliance: None Declared

Can Liver J. 2024 Feb 26;7(1):190–191.

CLM-P077 Low skeletal muscle index is a predictor of liver-related events and mortality in patients with cirrhosis independently of portal hypertension

I Abow-Mohamed ¹, B Alabdulkarim ¹, X Zhao ¹, D Kablawi ¹, E Desgagne-Martineau ², M Deschenes ¹, P Wong ¹, T Chen ¹, G Sebastiani ¹, B Rehany ², M Abu-Nada ², D Valenti ², A Bessissow ², A Benmassaoud ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Sarcopenia is prevalent in cirrhosis and is linked with mortality. However, its role in relation to portal hypertension is unclear.

Purpose: This study investigated the impact of muscle mass and portal hypertension on major liver events and mortality.

Method: This retrospective cohort study included adult patients with cirrhosis and available Hepatic Venous Pressure Gradient (HVPG) from 2012 to 2022. Total skeletal and psoas muscle indices (SMI, PMI) and subcutaneous adipose tissue index (SATI) at the 3^rd lumbar vertebrae were measured at the time of HVPG using computed tomography images and CoreSlicer, a body composition analysis software. Sarcopenia was defined as SMI < 39cm²/m² in females and < 50cm²/m² in males and its predictors were assessed by logistic regression. Predictors of (i) new hepatic decompensation (ascites, hepatic encephalopathy, variceal bleeding), (ii) liver-related event (decompensation, hepatocellular carcinoma, liver transplantation, death), and (iii) mortality were assessed by Cox regression analysis.

Result(s): Overall, 121 patients were included (46% with sarcopenia, 38% males, mean age 58.3 years, 34% with non-alcoholic fatty liver disease, median HVPG 10mmHg, median Model for end-stage liver disease (MELD) 13, 55% with prior decompensation). Sarcopenia was more likely in those with a prior decompensation (70% vs 43%, p<0.003), lower ALT (21 vs 40, p<0.001), lower PMI (4.1cm²/m² vs 5.9cm²/m², p<0.001), lower SATI (37.4cm²/m² vs 76.4cm²/m², p<0.001). After adjusting for age, prior decompensation, and ALT, SATI was the only independent predictor of sarcopenia (aOR 0.98, 95%CI 0.97-0.99). Over a median follow-up of 14.5 months, 32% of patients had a decompensation, 59% had a liver-related event, and 29% died. For new decompensation, after adjusting for HVPG and MELD, SMI (aHR 0.97, 95%CI 0.94-1.00) and sarcopenia (aHR 1.83, 95% CI 0.95-3.54) tended towards being independent predictors. For liver-related events, after adjusting for HVPG and MELD, SMI was an independent predictor (aHR 0.97, 95%CI 0.95-0.99), but not sarcopenia. For mortality, after adjusting for HVPG and MELD, SMI was significant predictor (aHR 0.96, 95% CI 0.92-0.99) while sarcopenia tended towards significance (aHR 1.95, 95%CI 0.98-3.89).

graphic file with name canlivj-7.1-abst_fig38.jpg — Image:

Conclusion(s): Our study demonstrates that low SMI is an important predictor of significant liver-related events and mortality, independently of portal hypertension in patients with cirrhosis.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):191–192.

CLM-P078 Low subcutaneous adipose tissue index is a predictor of mortality in female patients with cirrhosis, independently of portal hypertension

I Abow-Mohamed ¹, B Alabdulkarim ¹, X Zhao ¹, D Kablawi ¹, E Desgagne-Martineau ¹, M Deschenes ¹, P Wong ¹, T Chen ¹, G Sebastiani ¹, B Rehany ², M Abu-Nada ², D Valenti ², A Bessissow ², A Benmassaoud ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Sarcopenia is an established predictor of worse outcomes in patients with cirrhosis. The clinical significance of low adipose tissue mass in this population is not well defined.

Purpose: This study investigated the impact of adipose tissue mass on mortality in patients with cirrhosis.

Method: This retrospective cohort study included adult patients with cirrhosis and available Hepatic Venous Pressure Gradient (HVPG) from 2012 to 2022. Subcutaneous, visceral, and total adipose tissue indices (SATI, VATI, TATI) and total skeletal and psoas muscle indices (SMI, PMI) at the 3^rd lumbar vertebrae were measured at the time of HVPG using computed tomography images and CoreSlicer, a body composition analysis software. Sarcopenia was defined as SMI < 39cm²/m² in females and < 50cm²/m² in males. Youden's Index (YI) cut-off was determined using the area under the receiver operating characteristics (AUROC) curves for SATI, VATI, TATI and mortality. Predictors of adipopenia and mortality were assessed by logistic and Cox regression analyses, respectively.

Result(s): Overall, 121 patients were included (38% males, mean age 58.3years, 34% with non-alcoholic fatty liver disease, median HVPG 10mmHg, median Model End-Stage Liver Disease (MELD) 13, 55% with prior decompensation). Over a median follow-up of 14.5months, 35 (29%) patients died. SATI had highest AUROC (0.64, 95%CI 0.53-0.74) to predict death compared to VATI (ROC=0.57) and TATI (ROC=0.61). Based on YI, adipopenia^SATI was ≤ 91.98cm²/m² (sensitivity 94%, specificity 35%). Adipopenia^SATI was present in 89 (74%) patients. Predictors of adipopenia^SATI included male sex (OR 0.43, 95%CI 0.19-0.97), prior decompensation (OR 2.70, 95%CI 1.17-6.21), low SMI (OR 0.93, 95%CI 0.89-0.97), and sarcopenia^SMI (OR 2.86, 95%CI 1.19-6.87). After adjustment, male sex (aOR0.43, 95%CI 0.18-0.99) and sarcopenia^SMI (aOR 2.85, 95%CI 1.17-6.94) were independent predictors of adipopenia^SATI. For mortality, HVPG (aHR 1.06, 95%CI 1.01-1.11), MELD (aHR 1.07, 95%CI 1.01-1.14), and Adipopenia^SATI (aHR 5.46, 95%CI 1.30-22.85) remained independent predictors. When stratified by sex, Adipopenia^SATI was an independent predictor of mortality only in females (aHR 5.91, 95%CI 1.09-31.97).

graphic file with name canlivj-7.1-abst_fig39.jpg — Image:

Conclusion(s): Our study reveals a significant association between low subcutaneous adipose tissue and mortality in female patients independently of portal hypertension. We propose a cut-off to identify adipopenia to allow risk stratification in female patients.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):192–193.

CLM-P079 Serial MELD and prognosis in alcohol-associated hepatitis: opportunities for trial design

M Al-Karaghouli ¹, M Ventura-Cots ^2,³, YJ Wong ¹, R Bataller ^4,⁵, JG Abraldes ¹, OBOI Consortium ⁶

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Alcoholic-associated hepatitis (AAH) is associated with significant mortality. MELD score is used to predict short-term mortality and aid in treatment decisions. MELD value is frequently updated in day-to-day practice. However, the value of serial MELD measurements for predicting short-term mortality up to 90 days has not been assessed.

Purpose: We aimed at investigating the predictive value of serial MELD scores in patients with AAH and to estimate whether MELD updates accurately reflect the contemporaneous mortality risk.

Method: Data were collected prospectively by the InTeam international consortium. 307 patients (with a total of 857 MELD values within 60 days of admission) fulfilled the inclusion criteria for the present study. The main endpoint was time to death or transplant up to 90 days. We used a joint model approach to assess the predictive value of updated MELDs.

Result(s): Serial MELD measurement had a strong prognostic value for death/transplant (HR 1.20, 95% CI 1.14-1.27) (P<0.0001). Previous MELD values did not add predictive value to the most current MELD. We also showed that MELD-28 had a significant predictive value for subsequent mortality/transplant in a landmark analysis (HR 1.18, 95% CI 1.12-1.23), suggesting that it could be used as part of a surrogate outcome for randomized trials. We show that the use of such an ordinal scale could reduce by ∼60% the sample size to demonstrate benefit.

Conclusion(s): We showed that updated MELDs during the trajectory of AAH strongly predict subsequent mortality or need for transplant. MELD inclusion in an ordinal outcome (together with death or transplant) could markedly increase the efficiency of RCTs.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):193–194.

CLM-P080 The neutrophil-lymphocyte ratio improves prediction of liver-transplant-free survival beyond risk factors in existing prognostic scores for patients with PBC: a machine learning study

K Bashiri ¹, B Aziz ², H Syed ², S Roberts ³, LJ Worobetz ⁴, J Hercun ⁵, E Lytvyak ², C Vincent ⁵, J Flemming ⁶, K Qumosani ⁷, MG Swain ⁸, D Grbic ⁹, HH Ko ¹⁰, K Peltekian ¹¹, N Selzner ¹², A Gulamhusein ¹², HL Janssen ¹³, A Montano-Loza ², BE Hansen ^12,¹⁴, M Cameron ¹², T Chen ¹⁵, A Cheung ¹⁶, G Hirschfield ¹², AL Mason ²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Prognostic models using combinations of alkaline phosphatase (ALP), bilirubin, albumin, platelets, ALT/AST and age are employed for predicting outcomes of patients with PBC. Using the CaNAL registry of 2,239 PBC patients, we found the neutrophil-to-lymphocyte ratio (NLR) to be an independent risk factor for predicting liver transplantation or liver-related death (AASLD 2021).

Purpose: We aimed to assess the utility of NLR as a predictive factor and evaluate whether NLR can contribute to a competitive predictive model.

Method: Machine learning algorithms were employed to rank predictive features in combination with Inverse Probability of Censoring Weighting (IPCW) to alleviate bias resulting from censoring time to liver transplantation or liver-related death. The selection process was performed using weighted voting and aggregated normalized scores to identify five key CaNAL features using multiple methods, including Linear Regression, Random Forest Regressor, and Gradient Boosting Classifier and Regressor. The performance of the top-ranked CaNAL features was then compared to the GLOBE score, and UK-PBC features using random forest, gradient boosting, and extreme gradient boosting for the ability to predict liver transplantation or liver-related death.

Result(s): The top five CaNAL features were ranked as bilirubin, platelets, and INR after 1 year of UDCA, combined with NLR and age at diagnosis. The Random Forest algorithms provided the best discrimination (c-index) and lowest mean squared error (MSE) versus the other 2 machine learning algorithms using the CaNAL, Globe score and UK PBC features (Figure). The CaNAL features provided superior c-index vs. GLOBE score and UK-PBC features for predicting liver transplantation or liver-related death (0.804 vs. 0.730 vs. 0.779) and the lowest mean squared error (34.4 vs. 35.2 vs. 36.1).

graphic file with name canlivj-7.1-abst_fig40.jpg — Image:

Conclusion(s): Incorporation of NLR with age at diagnosis, as well as bilirubin, platelets and INR into a prognostic score, improved our current predictive capability for PBC patient outcomes in the CaNAL database. The machine learning analyses have validated the prognostic importance of NLR and underline the importance of investigating NLR as a surrogate of lymphopenia in the pathogenesis of PBC.

References: Aziz, B., Roberts, S. B., Lytvyak, E., Montano-Loza, A. J., Hansen, B. E., & Mason, A. L. (2020, November). ELEVATED NEUTROPHIL/LYMPHOCYTE RATIO (NLR) ONE-YEAR POST-DIAGNOSIS IS ASSOCIATED WITH DECREASED LIVER TRANSPLANT-FREE AND OVERALL SURVIVAL IN PBC. In The Liver Meeting Digital Experience™. AASLD.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):195.

CLM-P081 A dedicated automatic recall hepatocellular cancer surveillance program improves retention rates: a population based cohort study

M Brahmania ¹, S Congly ¹, K Burak ¹, Y Sachar ², B Lethebe ³, JH Szostakiwskyj ³, D Lautner ⁴, A Medellin ⁴, D Bhayana ⁴, J Wong ⁴, M Sadler ¹, M Borman ¹, A Aspinall ¹, C Coffin ¹, M Swain ¹, A-A Shaheen ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Hepatocellular carcinoma (HCC) surveillance programs are affected by adherence, which may be due to patient, clinician and system barriers. The impact of a dedicated automatic recall HCC surveillance program on retention rates in patients eligible for screening is unknown.

Purpose: We aimed to describe and evaluate the largest HCC surveillance program in the Canadian public health care system.

Method: Data was collected from January 1, 2013 to December 31, 2022 from a retrospective cohort of subjects enrolled in a semi-annually surveillance program as per AASLD HCC guidance. The program is a publicly funded automated recall system servicing eligible patients in the Calgary Health Zone (∼1.6 million), Canada. Patients were excluded if there was incomplete data or did not meet indications for screening. Multivariable logistic regression was used to identify predictors of non-retention to surveillance. All statistical analyses were done in R (version 4.1.1).

Result(s): A total of 7,432 patients were included in the study. The median was age 55.5 years (IQR: 45.5-63.8), 60% were male, 46% of Asian descent, and 53% with HBV infection as the reason for HCC surveillance, while 46% had cirrhosis (36% alcohol). Median follow-up was 4.9 years (IQR: 1.5-7.2). Overall, 54% of patients were retained in the surveillance program, while 21% left for potential medical reasons at some point of time in the study (7% death; 62.3% with a high risk (>1cm) or an inconclusive lesion identified or did not scan well), and 25% were not retained. Median time in the program for those not retained was 0.78 (IQR: 0.0-2.0) years (vs 6.4 years retained; IQR: 5.0-8.3; p=<0.001). Subjects not retained (vs retained) were more commonly male (61% vs 58%; p=<0.001), Caucasian (42% Caucasian vs 38% Asian vs 12% African; p=0.001), and had either HBV (46%) or HCV (22%) as their primary diagnosis for screening (vs 17% alcohol; 5% autoimmune; 7% NASH; p=0.001). In multivariable logistic regression analysis, older age at enrollment (OR=0.99; CI=0.98-0.99), Asian descent (OR=0.64; CI=0.54-0.76) and having a non-HCV etiology (Alcohol OR=0.75; CI: 0.58-0.98; HBV: OR=0.54; CI=0.38-0.69; NASH: OR=0.55, CI=0.42-0.74) were factors associated with enhanced retention in the screening program.

Conclusion(s): A dedicated automated recall HCC surveillance program has a high retention rate in a large multi-ethnic cohort of patients. Significant factors associated with with non-retention included a diagnosis of HCV and younger age, highlighting potential populations to target for intervention.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):195–196.

CLM-P082 A mixed methods process evaluation of a consultative, collaborative outpatient palliative care clinic for patients with end-stage liver disease

A Bruni ¹, L Cohen ¹, G Warmels ¹, S Isenberg ², A Wills ²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: End-stage liver disease (ESLD) is a life-limiting illness with high symptom burden and mortality. Palliative care (PC) aims to improve quality of life for patients with life-limiting diseases. Research demonstrates limited access to PC for patients with ESLD. Further research is required to determine the optimal model for provision of early outpatient PC to patients with ESLD.

Purpose: To perform a process evaluation of the novel outpatient PC clinic for patients with ESLD in Ottawa. Using a process evaluation framework, we aimed to: 1. Develop a logic model of the clinic. 2. Leverage chart reviews and qualitative interviews to assess five process evaluation domains.

Method: Clinic success is determined by achievement of logic model outcomes, and performance in five process evaluation domains: fidelity, patient experience, reach, recruitment, and context. Evaluation entails a chart review and qualitative interviews. The chart review includes referral numbers, patient demographics, care processes, and outcomes. The qualitative interviews explore healthcare provider (HCP), patient, and caregiver perspectives related to the clinic. Analysis entails descriptive statistics, thematic qualitative analysis, and mixed methods triangulation.

Result(s): 90 referrals were received by the ESLD PC clinic from 2020 to 2023. 54 patients were seen in consultation, 29 of whom received further follow-up. The ongoing chart review has revealed changes in patterns of care accompanying the transition from a part-time consultative model to a full-time, shared-care model in 2023. For instance, the transition coincided with number of patients who died prior to scheduled consult decreasing from 31.3% to 0.1%.

Qualitative data collection is ongoing. Preliminary data shows positive perception of the clinic by HCPs, patients, and caregivers.

Two patients and five caregivers were interviewed. Participants described a positive change in their perceptions of PC upon consultation. No barriers to consultation or follow-up were described. Patients reported improved quality of life, alignment of care with their goals, and preparation for disease progression and death. When comparing the periods before and after PC consult, participants observed no difference in use of acute care resources. Caregivers agreed that their needs were met by the PC clinic, including clarity of available care and reassurance regarding future planning.

Five HCPs were interviewed. HCPs noted that the PC team was able to address needs, such as transitions of care, that were previously unmet by the hepatology team alone. HCPs described positive reciprocal collaboration, communication, and education from the PC team. Participants agreed that patients’ access to PC should continue, while recognizing logistical barriers that clinic expansion may pose.

Conclusion(s): The results of this study will inform ongoing delivery of early outpatient PC for patients with ESLD and guide future development of PC clinics for other subtypes of organ failure.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):196–198.

CLM-P083 Harnessing the synergy of add-on FXR and PPAR agonism in patients with primary biliary cholangitis: the Toronto centre for liver disease experience of ‘Triple’ therapy

GG Cancado ¹, B Chen ¹, M Cameron ¹, I Houri ¹, KK Leung ¹, AF Gulamhusein ¹, B Hansen ¹, GM Hirschfield ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Treatment goals in primary biliary cholangitis (PBC) are increasingly aspirational aiming for normal serum liver tests. Currently add-on therapy to Ursodeoxycholic acid (UDCA) is with the approved FXR agonist Obeticholic acid (OCA), alongside off-label use of fibric acid derivatives (PPARs), pending future approval of licensed PPAR agents. Such therapies have mechanistic synergy hence ‘triple’ therapy has been described.

Purpose: Report our off-label experience of synergistic FXR-PPAR-UDCA combination therapy in PBC.

Method: Chart review of patients with PBC (as per EPIC coding) seen between July 2022 and July 2023 was performed.

Result(s): 470 PBC patients were seen of which 71% were treated with UDCA only, 7% UDCA + OCA, 11.3% UDCA + fibrates and 10.6% UDCA + OCA + fibrates. Among 50 patients on triple therapy [86% female, median age at diagnosis 43.5 (14.6) years, median age at triple therapy 53.6 years (13.0), 96% AMA positive, 36% cirrhotic], 82% had OCA as the first add-on therapy. Most patients (92%) received bezafibrate, while 8% had fenofibrate. Median follow up time was 17.6 months; at last follow up, 54.2% were on OCA 10 mg daily, and 70.8% bezafibrate 400 mg daily. Available biochemical data on 48 patients with triple therapy demonstrated mean ALP reductions after 6 months of 31.1% (95%CI 25.4-37.0%) and 37.8% (95%CI 31.6-44.0%) at last follow up; 43.2% of the patients had a normal serum ALP at 6 months, while 23% had normal ALP, AST, ALT, and bilirubin. Patients with cirrhosis demonstrated similar efficacy: 25.2% (95%CI 17.6-32.8%) ALP reduction at 6 months; 31.2% (95%CI 20.6-42.0%) at last follow up; 41.2% ALP normalization rate at 6 months. The odds ratio of achieving ALP normalization was not statistically different between OCA-fibrate and fibrate-OCA sequences at 6 months. Out of 34 patients with self-reported pruritus before triple therapy, 64.7% reported improvement, 11.8% worsened and 23.5% had no change in itching intensity. Creatinine did not change significantly over time (p=0.18). On multivariable analysis, higher levels of ALP before triple therapy were associated with lower odds for ALP normalization at 6 months (OR = 0.98; 95%CI 0.96-0.99; p=0.02), while older age at diagnosis (OR = 1.34; 95%CI 1.15-1.74; p<0.01) and reduced interval between PBC diagnosis and triple therapy (OR = 0.98; 95%CI 0.95-0.99, p=0.03) positively impacted ALP normalization.

graphic file with name canlivj-7.1-abst_fig41.jpg — Image:

Conclusion(s): We report a large real-world off-label experience of synergistic FXR-PPAR-UDCA triple therapy for patients with PBC. We demonstrate clinically meaningful improvement in ALP values with ALP normalization in 43.2% of patients.

Disclosure of Interest: G. Cancado: None Declared, B. Chen: None Declared, M. Cameron: None Declared, I. Houri: None Declared, K. Leung: None Declared, A. Gulamhusein Consultant of: Intercept and CymaBay, Speakers bureau of: Intercept, B. Hansen Consultant of: Albireo, Calliditas Therapeutics, CymaBay, Intercept, Mirum, HighTide, Ipsen, Pliant, G. Hirschfield Consultant of: GlaxoSmithKline, Intercept Pharma, Ipsen, CymaBay, Escient, Gilead, Mirum, and Pliant., Speakers bureau of: GlaxoSmithKline, Intercept Pharma, and Ipsen

Can Liver J. 2024 Feb 26;7(1):198–199.

CLM-P084 Evaluation of APOBEC3 expression in patients with inflammatory bowel disease: a similar pattern between Crohn's disease and primary biliary cholangitis

AJ Castillo-Gurdian ¹, K Bashiri ¹, N Perkins ¹, N Sun ¹, H Syed ¹, D Waly ¹, S Islam ¹, O Oyegbami ¹, E Wine ¹, K Madsen ¹, T Perry ¹, AL Mason ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Apolipoprotein B mRNA Editing Catalytic Polypeptide-like (APOBEC) proteins are a family of cytidine deaminases that are important in innate immunity. The APOBEC3 (A3) family of 7 proteins are responsible for viral restriction against both RNA and DNA viruses by mutagenizing the viral genome during replication. Other studies have observed increased A3 expression in patients with Hepatitis B and C infection (Vartanian et al., PLoS Pathog, 2010). We have been working on the hypothesis that autoimmune liver diseases may be triggered by viral infection and observed increased levels of APOBEC3 expression in whole blood of patients with primary sclerosing cholangitis and primary biliary cholangitis (PBC). However, we lack data on the APOBEC viral restriction factors in patients with inflammatory bowel disease.

Purpose: To evaluate APOBEC3 mRNA expression in patients with Ulcerative Colitis (UC), and Crohn's Disease (CD) using healthy and non-alcoholic fatty liver disease (NAFLD) subjects as controls and patients with PBC as a comparison group.

Method: We extracted total RNA from 138 whole blood samples: CD n = 29, UC n = 26, PBC n = 26, NAFLD n = 26 and Healthy n = 31. We then converted to cDNA and processed duplicate samples by qPCR using primers complementary to A3A, A3B, A3C, A3D, A3F, A3G and A3H. For analysis, we used the relative quantification method to calculate our fold change values using our healthy controls as a normalizer. A Mann-Whitney t-test was used to calculate significance between groups.

Result(s): CD patients demonstrated increased expression of A3A, A3B, A3C, A3F, A3G, and A3H mRNA (p < 0.05) compared to healthy and NAFLD control subjects, whereas UC patients showed an increased expression of A3B, A3C, and A3D (p < 0.01) (Fig. 1). Notably, the APOBEC reactivity in CD patients shared a similar expression profile to patients with PBC with elevations of A3C, A3F, A3G, and A3H mRNA (Fig. 1).

graphic file with name canlivj-7.1-abst_fig42.jpg — Image:

Conclusion(s): PBC, UC, and CD patients were observed to have alterations of A3 expression in whole blood which suggests a role for APOBEC transcriptional activity in disease pathogenesis. Interestingly, PBC and CD were found to have similar A3 expression profiles, as well as a shared genetic predisposition reported by others (Huang et al., medRxiv, 2023). Because PBC, UC, and CD are pro-inflammatory diseases, A3 expression may also be triggered due to interferon signalling. Therefore, mechanistic investigations are required to further study the role of A3 activity in propagating an antiviral innate immune response in these diseases as well as study any potential viral association between PBC and CD.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):199–201.

CLM-P085 Patient, caregiver and provider perspectives on the transition from pediatric to adult care in liver diesase: reducing the trauma of transition and transfer of care

AC Cheung ^1,^2,³, C Okwor ⁴, A Chow ⁵, T Sue ⁶, J Huynh ⁶, C Jimenez ⁷

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Transition care is a complex process that occurs before age 18 and prepares patients to progress from pediatric to adult healthcare. Successful transition ensures that patients can confidently navigate their medical needs by establishing the psychosocial, educational and support framework required for competent and ultimately independent self-management.

Purpose: The study goals were to: 1) Understand the current landscape of transition care across Canada and 2) Understand the barriers and facilitators to transition care in liver disease from patient and caregiver perspectives.

Method: An online survey was distributed to pediatric & adult liver providers across Canada. Patients & families who were involved in liver care at the Children's Hospital of Eastern Ontario (CHEO), and the liver unit at The Ottawa Hospital, the Centre for Liver of Eastern Ontario (CLEO), were invited to participate in online interviews. Thematic analysis was performed to identify barriers and facilitators to transition care.

Result(s): A total of 98 surveys were sent to providers across Canada. The response rate was 49% (n=47, 13/27 [48%] pediatric providers, 35/86 [41%] adult providers). Key results showed that 31% & 27% of pediatric & adult providers respectively had a standardized introduction to the adult program. Only 8% of pediatric & adult providers noted the transition program offered adult facility tours or patients & caregiver support groups. Formal transition programs were noted to be offered by 38% pediatric providers & 27% adult providers. At least 50% of pediatric and adult providers felt there was inadequate training/knowledge in adolescent medicine/congenital disease.

A total of 37 individuals were interviewed and included (patients, n=18; caregivers, n=19) (Figure 1). Many patients had multiple comorbidities & underwent transition through other programs/cities. The majority of patients & caregivers (70%) were worried about transition/transfer. The majority (92%) felt a joint clinic with the pediatric & adult provider was critical. Many (62%) felt peer support would be useful. Patients & caregivers also wanted basic information, such as a hospital orientation, understanding the rationale/frequency of tests/appointments, review of disease/tests and treatments.

Patients & caregivers described the transfer as ”traumatic“, ”cold“, and ”abrupt“. Key themes were 1) Transparent transfer of responsibility from pediatric to adult provider, 2) Fear of quality of care decline, 3) Transition as a process for the patient & family, 4) Transition as structured, but personalized, 5) The need for trust & rapport with their new provider.

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Conclusion(s): The lack of formalized transition care causes significant patient and caregiver anxiety and fear, compromising the journey of both adolescents/young adults and their families into adult care. Importantly, many factors can be mitigated by concrete, low-cost solutions which have the potential to be implemented widely to improve quality of care.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):201–202.

CLM-P086 Prediction of survival benefit of living donor liver transplant versus deceased donor liver transplant for waitlisted patients with decompensated liver disease using deep learning

J Chon ¹, A Gangadhar ^2,³, Y Sun ^2,³, C McIntosh ^2,⁴, M Bhat ^1,³

What is your preferred presentation method?: Poster Only

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Liver transplantation (LT) is the gold standard treatment for end-stage liver failure.1 Living donor liver transplant (LDLT) remains an underutilized method to greatly extend the donor pool in North America and Europe. 1,2 There has been conflicting and limited retrospective evidence directly comparing LDLT to DDLT (Deceased Donor Liver Transplant) survival outcomes 3–7 Hence, there are currently no clinical prediction tools to delineate how many years of life a patient may gain from a LDLT vs a DDLT.

Purpose: To design a machine learning tool that predicts the survival benefit (years of life gained) of LDLT compared to a DDLT for an individual patient.

Method: This is a retrospective study which examined the clinical data from the Scientific Registry of Transplant Recipients in the U.S., comprising approximately 145,000 patients from 2002 - 2023. We included 13 variables in the analysis; Age, Gender, Race, Blood group, BMI, Height, Weight, Primary pay, Life support, Functional status, Diagnosis, MELD and Time on waitlist. Survival analysis was performed using DeepHit, Random Forrest Survival (RSF), and Cox proportional Hazards (CPH) for LDLT and DDLT respectively.

Result(s): The DeepHit Algorithm outperformed RSF and CPH models for both LDLT and DDLT, with a C-index of 0.85 ± 0.04 versus RSF and CPH models with a C-index of 0.72 ± 0.09, and 0.67 ± 0.09 respectively. Further analysis comparing survival benefit for individual patients with a certain set of clinical characteristics is currently in progress, along with the personalized list of predictors of outcome.

graphic file with name canlivj-7.1-abst_fig44.jpg — Image:

Conclusion(s): The DeepHit survival prediction ML tool outperforms RSF and CPH models. Herein, we report the first utilization of ML to predict and compare survival (number of years of life gained) between LDLT and DDLT.

References:

1. Ivanics T, Wallace D, Claasen MPAW, et al. Low utilization of adult-to-adult LDLT in Western countries despite excellent outcomes: International multicenter analysis of the US, the UK, and Canada. J Hepatol. 2022;77(6):1607-1618. doi:10.1016/j.jhep.2022.07.035

2. Müller PC, Kabacam G, Vibert E, Germani G, Petrowsky H. Current status of liver transplantation in Europe. International Journal of Surgery. 2020;82:22-29. doi:10.1016/J.IJSU.2020.05.062

3. Maluf DG, Stravitz RT, Cotterell AH, et al. Adult living donor versus deceased donor liver transplantation: A 6-year single center experience. American Journal of Transplantation. 2005;5(1):149-156. doi:10.1111/j.1600-6143.2004.00654.x

4. Pomposelli JJ, Verbesey J, Simpson MA, et al. Improved survival after live donor adult liver transplantation (LDALT) using right lobe grafts: program experience and lessons learned. Am J Transplant. 2006;6(3):589-598. doi:10.1111/J.1600-6143.2005.01220.X

5. Olthoff KM, Merion RM, Ghobrial RM, et al. Outcomes of 385 Adult-to-Adult Living Donor Liver Transplant Recipients: A Report From the A2ALL Consortium. Ann Surg. 2005;242(3):314. doi:10.1097/01.SLA.0000179646.37145.EF

6. Olthoff KM, Smith AR, Abecassis M, et al. Defining Long-term Outcomes with Living Donor Liver Transplantation in North America. Ann Surg. 2015;262(3):465. doi:10.1097/SLA.0000000000001383

7. Hoehn RS, Wilson GC, Wima K, et al. Comparing living donor and deceased donor liver transplantation: A matched national analysis from 2007 to 2012. Liver Transplantation. 2014;20(11):1347-1355. doi:10.1002/LT.23956

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):203.

CLM-P087 Evaluation the 6 month abstinence rule prior to liver transplant: a clinical practice guideline

JC Dionne ^1,², S Oczkowski ¹, S Abbey ³, J Chandler ⁴, V Gruben ⁴, M-C Fortin ⁵, V Marquez ⁶, T Christou ⁷, S Gilmour ⁸, S Carbert ⁸, M Swintson ⁹, F Dharsee ¹⁰, C Gillrie ¹⁰, C Parsons ¹¹, P Chaudhury ¹², N Selzner ³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Until recently, patients in Canada, with alcohol associated liver disease (ALD) had to be abstinent from alcohol use for 6-months prior to assessment for liver transplantation (LT). This rule has been called into question from evidence, ethical and legal lenses.

Purpose: The purpose of this clinical practice guideline (CPG) is to guide the assessment and management of ALD and LT.

Method: A committee including medical and surgical experts in liver transplant, addiction, ethics, law, methodology and patient partners developed a CPG according to GRADE Methodology. The steering committee generated and answered questions in the population, interventions, comparison and outcome format. Five conditional recommendations (very low certainty of evidence) and 2 best practice statements for patients undergoing LT were made.

Result(s): Our recommendations included: 1)To not use the six-month rule as a sole criterion for liver transplant in ALD 2)The definition of relapse should distinguish between: 1. non harmful relapse (e.g. occasional drinking or slip), 2. harmful drinking (e.g. physical, psychosocial implications, binge drinking/escalation drinking) and 3. relapse monitored by biochemical markers when available. 3) During liver transplant workup, assessment of risk factor associated with post-transplant relapse (presence of uncontrolled psychiatric disease, history of smoking and multiple failed attempts of alcohol treatment) and protective factors (social support and employment) should be part of the holistic multidisciplinary assessment to allow for early intervention to mitigate risk factors. 4)The use of validated screening scoring systems and biomarkers for screening post-transplant relapse. 5)Integrated multidisciplinary teams with psychiatrists and addiction services to prevent relapse pre and post-transplant. Our best practice statements included: 1)Listed and transplanted ALD patients should be intermittently screened for relapse pre and post-transplantation. 2) We suggest a holistic assessment for patients being evaluated for liver transplant, that not only take into account risk factors or other screening modalities, but a multi prong, multidisciplinary approach

Conclusion(s): This CPG provides evidenced based recommendations for listing and transplanting patients with ALD and represents a pradigm shift in practice.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):203–206.

CLM-P088 Dynameld: a nonlinear, dynamic model of end-stage liver disease for accurate and fair risk assessment

M Cooper ^1,², X Gao ³, Y Wang ⁴, X Zhao ², A Azhie ⁵, M Naghibzadeh ², S Holdsworth ⁶, J Gross ², M Brudno ^1,², E Jaeckel ², G Hirschfield ², R Krishnan ^1,⁷, M Bhat ^2,^8,⁹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: The current MELDNa-based prioritization system results in disadvantage to specific patient subgroups, including women and those with primary biliary cholangitis [1,2].

Purpose: We present DynaMELD, a deep learning-based model that leverages additional patient covariates, including the rates-of-change of time-varying laboratory covariates, to obtain superior relative risk identification to the MELD-Na, and reduce sex-based disparities in prioritization.

Method: DynaMELD was trained on data from 15,373 waitlisted patients in the Scientific Registry of Transplant Recipients listed between 2016 and 2018 (inclusive). Each patient record contained 15 features collected at time of listing, 7 features collected at each check-in prior to transplant, and time of event/censorship. We compare the performance of our DynaMELD model, a neural network trained on the aforementioned 22 features, against benchmarks of the MELD [3], MELD-Na [4], MELD 3.0 [5].

Result(s): On a held-out test set of patients, DynaMELD obtained a significantly 90-day higher concordance index than the benchmark models (DynaMELD: 0.834, MELD: 0.796, MELDNa: 0.791, MELD 3.0: 0.797, p < 0.001). DynaMELD also obtains a significantly higher ”pooled group concordance index,“ a variant of concordance that measures equity in survival predictions with respect to a certain sub-population, for female patients (DynaMELD: 0.840, MELD: 0.793, MELDNa: 0.789, MELD 3.0: 0.813, p < 0.001), and for patients listed with primary biliary cholangitis (DynaMELD: 0.907, MELD: 0.805, MELDNa: 0.799, MELD 3.0: 0.818, p < 0.001).

Furthermore, in a 5-year simulation (2016-2021) over 19,070 patients using the LivSim simulator, allocating livers according to the DynaMELD risk score resulted in 192 fewer instances of pre-transplant mortality than the MELD-Na (a 1% reduction). Additionally, whereas the MELD-Na yielded a 0.9% higher rate of pre-transplant mortality in women, DynaMELD admitted only a 0.4% higher rate of pre-transplant mortality in women in simulation; 96 fewer women died under the DynaMELD policy.

graphic file with name canlivj-7.1-abst_fig45.jpg — Image:

Conclusion(s): Our results suggest that leveraging nonlinear risk models on longitudinal data, and incorporating additional patient covariates (including rates of change), provide superior estimates of relative mortality risk to the MELD-Na, the existing clinical standard of care. We find that these models may better serve disadvantaged subpopulations of patients, such as women. We propose that such work has the potential to improve and render more equitable the allocation of deceased donor livers.

References: [1] Locke, Jayme E., Brittany A. Shelton, Kim M. Olthoff, Elizabeth A. Pomfret, Kimberly A. Forde, Deirdre Sawinski, Meagan Gray, and Nancy L. Ascher. ”Quantifying sex-based disparities in liver allocation.“ JAMA surgery 155, no. 7 (2020): e201129-e201129.

[2] Singal, Ashwani K., Robert J. Wong, Rajiv Jalan, Sumeet Asrani, and Yong-Fang Kuo. ”Primary biliary cholangitis has the highest waitlist mortality in patients with cirrhosis and acute on chronic liver failure awaiting liver transplant.“ Clinical Transplantation 35, no. 12 (2021): e14479.

[3] Kamath, Patrick S., Russell H. Wiesner, Michael Malinchoc, Walter Kremers, Terry M. Therneau, Catherine L. Kosberg, Gennaro D’Amico, Rolland E. Dickson, and Ray W. Kim. ”A model to predict survival in patients with end–stage liver disease.“ Hepatology 33, no. 2 (2001): 464-470.

[4] Kim, W. Ray, Scott W. Biggins, Walter K. Kremers, Russell H. Wiesner, Patrick S. Kamath, Joanne T. Benson, Erick Edwards, and Terry M. Therneau. ”Hyponatremia and mortality among patients on the liver-transplant waiting list.“ New England Journal of Medicine 359, no. 10 (2008): 1018-1026.

[5] Kim, W. Ray, Ajitha Mannalithara, Julie K. Heimbach, Patrick S. Kamath, Sumeet K. Asrani, Scott W. Biggins, Nicholas L. Wood, Sommer E. Gentry, and Allison J. Kwong. ”MELD 3.0: the model for end-stage liver disease updated for the modern era." Gastroenterology 161, no. 6 (2021): 1887-1895.

Disclosure of Interest: M. Cooper: None Declared, X. Gao: None Declared, Y. Wang: None Declared, X. Zhao: None Declared, A. Azhie: None Declared, M. Naghibzadeh: None Declared, S. Holdsworth: None Declared, J. Gross: None Declared, M. Brudno: None Declared, E. Jaeckel: None Declared, G. Hirschfield: None Declared, R. Krishnan Grant / Research support from: Iterative Scopes: Advisory Committee or Review Panel, M. Bhat Grant / Research support from: CareDx: Grant/Research Support; Lallemand: Grant/ Research Support; Oncoustics: Grant/Research Support; Natera: Grant/Research Support; Novo Nordisk: Grant/Research Support; Paladin: Grant/Research Support; Ipsen: Grant/Research Support, Speakers bureau of: Lupin: Speaking and Teaching; Novartis: Speaking and Teaching

Can Liver J. 2024 Feb 26;7(1):206–207.

CLM-P089 OPAL: online prehabilitation for patients awaiting liver transplantation - a multicenter randomized controlled trial to reduce physical frailty and improve health outcomes

C Cruz ¹, M McNeely ², N Selzner ³, A Benmassaoud ⁴, P Wong ⁴, JP Arab ⁵, MQ Khan ⁵, M Brahmania ⁶, V Marquez ⁷, C Rose ⁸, C Bemeur ⁹, C Prado ¹⁰, P Tandon ¹, OBOATR OPAL investigators ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Liver transplantation (LT) remains the only curative option for many individuals with cirrhosis. LT candidates have high rates of frailty that impact clinical outcomes both pre- and post-transplantation. Given the unpredictable wait time for LT, multidimensional prehabilitation programs have gained attention to combat frailty prior to surgery. A large-scale, multicentre trial is needed to provide the evidence needed so that prehabilitation can become part of routine healthcare for patients on the LT wait list.

Purpose: Study recruitment has started and this early abstract is to raise awareness of the trial across Canada. As compared to usual care, the main aim of the trial is to determine the impact of a 12-week digital platform supported prehabilitation program in people with cirrhosis awaiting LT on physical function as assessed by the sit-to-stand test.

Method: Setting: This multi-centre randomized controlled trial will be completed across five major LT programs in Canada. Participants: LT candidates with cirrhosis who are pre-frail or frail on the liver frailty index (LFI). Randomization: Random allocation to either the intervention arm (prehabilitation: n=∼118) or the control arm (usual care: n=∼59) in a 2:1 ratio. Intervention: Access to a digital platform with a 12 week nutrition, exercise, and behavioural program, with dietary and exercise assessments and access to online exercise group classes. Control: Nutrition, exercise, and behavioural handouts. Outcomes: Primary: Physical function via sit-to-stand test (time to do 5 sit-to-stands). Secondary: Frailty via the LFI and 6 minute walk test, Hepatic Encephalopathy, Quality of life, Behavioural outcomes, Sarcopenia, Clinical and Post-transplant outcomes, Economic evaluation, Malnutrition, and Acceptability. Data Collection: Quantitative data will be collected at baseline, end of trial at week 12 and every 12 weeks after the trial completion (up to 6 months). A subset of patients who receive a LT will also have data collected ∼6-12 weeks post transplant. Qualitative data on participant experiences with the OPAL program will be collected from interviews at the end of study. Data Analysis: Descriptive statistics will be conducted for all quantitative variables adhering to the intention-to-treat principle. Primary and secondary outcomes will be analyzed by linear models with random effects, adjusted for baseline score as a covariate. Qualitative data will be analyzed inductively with a theoretical thematic approach.

Result(s): Recruitment began at the Edmonton site in July 2023. To date, 17 participants have been randomized. Ethics applications for other sites are underway.

Conclusion(s): This study is unique given its size, its multicenter nature, and use of a digital platform for program delivery. With a range of secondary outcomes our hope is that it will help increase knowledge in the area of prehabilitation in LT and improve patient care for future transplant candidates.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):207–208.

CLM-P090 Fosfomycin-induced liver injury: a case report and literature review

K Faragalla ¹, D Cohen-Lyons ², N Parvinnejad ², HL Wang ³, J Lu ^2,⁴

What is your preferred presentation method?: Poster Only

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Fosfomycin is an antibiotic often used to treat urinary tract infections (UTIs) with only rare and often transient hepatotoxicity.

Purpose: We present a case of fosfomycin-induced liver injury and describe the histopathologic findings on biopsy.

Method: We compare and contrast findings in our case to other case reports of DILI needing a liver biopsy.

Result(s): A 64 year-old female patient with no prior liver disease or risk factors was started on fosfomycin as prophylaxis for recurrent UTIs. Within a week of her first dose she presented with fatigue, jaundice, and mixed liver enzyme elevation. Clinical workup for acute liver injury was unremarkable, and biopsy showed panacinar and portal necroinflammation with predominantly lymphocytic infiltrate and cholestasis. This was thought to be likely related to fosfomycin exposure. While liver enzymes trended down with bilirubin initially remained elevated. However, within three months the patient achieved clinical and biochemical recovery. Only two other reports of fosfomycin-induced liver injury requiring biopsy were found. Both developed acute cholestatic hepatitis within days of exposure, and subsequent biopsy similarly showed lymphocytic necroinflammation. Though one patient initially developed acute liver failure, both recovered within few months.

Conclusion(s): These cases suggest a likely idiosyncratic or immune-mediated liver toxicity of fosfomycin which is typically self-limited with rapid recovery.

References: 1. Patel SS, Balfour JA, Bryson HM. Fosfomycin tromethamine. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy as a single-dose oral treatment for acute uncomplicated lower urinary tract infections. Drugs. 1997;53:637-56.

2. Ferreira R, Torres J, Raposo J, Ferreira M, Mendes S, Agostinho C, et al. Acute hepatitis induced by fosfomycin: A case report and review of the literature. GE Port J Gastroenterol. 2012;19:263-6.

3. Matsumori A, Yoneda S, Kobayashi Y, Takeda K, Andoh M, Yamane Y, et al. [A case of acute severe hepatitis induced by fosfomycin] Japanese. Nihon Shokakibyo Gakkai Zasshi. 2005;102:1207-11.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):208–209.

CLM-P091 The new paradigm in HCV treatment in Alberta provincial corrections – review of the first year

K Newcombe ¹, GLP Macphail ^1,², N Gale ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Prior to Sept 2022, very few people incarcerated in Alberta provincial facilities were able to access HCV treatment, despite this group being disproportionately affected and deemed a priority population for HCV elimination. Only those with advanced liver disease and whose sentence was ≥24 weeks were able to start treatment. Others were occasionally referred for assessment while incarcerated, but asked to connect with providers post-release, which rarely happened. The fibrosis criteria were removed one year ago, but the length of sentence requirement was not changed. An exception was people with non-insured health benefits (NIHB) coverage, who could be offered treatment regardless of their length of incarceration.

Purpose: Purpose: Assess the impact of this change in policy on linkage to care through the CUPS Liver Clinic in Calgary, treatment initiation, and sustained virologic response. Examine the relative treatment initiation and completion rates by treatment funder and thereby indirectly assess whether current length of stay criteria should be reassessed.

Method: Method: For many years, the CUPS Liver Clinic has been providing HCV consultations and treatment for the Calgary Correctional Centre (CCC), Calgary Remand Centre (CRC), Calgary Young Offender Centre and Female Annex (CYOCAFA). Since COVID-19, these have largely become virtual or electronic consults, eliminating the transportation barrier. The Corrections nurses are the primary contacts for the patient, but the CUPS Liver Clinic nurse, clinical pharmacist and/or peer often contact people via telephone, especially to make post-release follow-up plans.

Result(s): Results: In the past year, 10 individuals from CCC, 5 from CRC and 2 from CYOCAFA have been treated while incarcerated. Of the 17 individuals accessing HCV treatment, 75% had NIHB coverage, compared to the corrections average of approximately 35%. Twelve treated individuals achieved a sustained virologic response (SVR12). Four are not yet at that time point and 1 has been released and has not yet had the SVR12 bloodwork.

A further 10 people from CCC, 1 from CYOCAFA, and one from CRC were connected with the Liver Clinic for follow-up post-release. Of these, only 1 individual has started treatment and achieved SVR12. Two connected but did not follow through and 7 never connected. None of these individuals had NIHB coverage.

This is only a small percentage of those known to have HCV within the corrections setting.

Conclusion(s): The new paradigm for HCV treatment is a significant improvement over the previous criteria restricted treatment based on fibrosis. However, there is a considerable difference in linkage to treatment between those with with length of stay restrictions and those without. The high success rate for those treated underscores the feasibility of treatment while in Corrections and suggests that the current criteria could be expanded further for this priority population.

Disclosure of Interest: K. Newcombe: None Declared, G. Macphail Grant / Research support from: CanHepC Network, TD Bank, Coverdale, Gilead, AbbVie, Consultant of: Gilead, AbbVie, Paid Instructor of: University of Calgary, INHSU, Speakers bureau of: AbbVie, Gilead, N. Gale: None Declared

Can Liver J. 2024 Feb 26;7(1):209–210.

CLM-P092 Impact of an interdisciplinary alcohol-associated liver disease clinic on alcohol use disorder treatment and patient engagement

A Goytan ¹, E Knight ^2,³, C Taylor ⁴, J Sareen ³, E Renner ⁵, N Brainch ³, N Faisal ⁵

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Treating alcohol-related liver disease (ALD) hinges on addressing alcohol use disorder (AUD), yet access to appropriate treatment remains limited. Current data indicates that less than 5% of ALD patients receive treatment for AUD.

Purpose: This retrospective cohort study explores the influence of an interdisciplinary ALD clinic on AUD treatment initiation and patient engagement among individuals with ALD.

Method: The study encompasses patients who attended the interdisciplinary ALD clinic at Health Sciences Centre, Winnipeg, from March 2022 to July 2023. The clinic's multidisciplinary team consisted of a hepatologist, addiction medicine specialist, and a case manager. Enrolled participants included those with alcohol-associated cirrhosis or acute alcoholic hepatitis willing to engage in AUD treatment. Treatment plans were tailored during interdisciplinary discussions, considering patient preferences and needs. Baseline demographic, medical, liver disease, psychosocial metrics, and AUD treatment data were systematically collected. The study also documented AUD treatment discussions, initiation, alcohol cessation, and subsequent follow-up.

Result(s): Over the study period, a total of 43 patients were evaluated in the interdisciplinary ALD clinic. Of the participants, 53% were male with the median age of 52 years (33-65) and 30% were rural residents. Approximately two-third had cirrhosis (60% were in a decompensated cirrhosis) and 30% had alcoholic hepatitis. A significant majority (70%) had severe AUD. Of these 80% chose to initiate AUD treatment (Figure 1). Among them 72% were prescribed pharmacotherapy for relapse prevention, and 28% were referred for cognitive behavioral therapy and mindfulness (CBTm). Additionally, 18% received prescriptions to address co-occurring psychiatric disorders, 20% were referred to local peer support groups, and 10% were facilitated to residential treatment facilities. By the end of the study, 25 patients remained actively engaged in the clinic (3 died, 8 were discharged, 2 were transferred to a transplant clinic, and 5 were lost to follow-up).

graphic file with name canlivj-7.1-abst_fig46.jpg — Image:

Conclusion(s): This study highlights the positive impact of implementing an interdisciplinary ALD clinic on the initiation of AUD treatment and patient engagement in ALD individuals. These findings underscore the crucial role of such clinics in addressing the complex needs of ALD patients and enhancing their overall care outcomes.

AUD: alcohol use disorder, ALD: alcohol associated liver disease, CBTm: cognitive behavioural therapy with mindfulness.

References: Degenhardt L, Charlson F, Ferrari A, Santomauro D, Erskine H, Mantilla-Herrara A, et al. The global burden of disease attributable to alcohol and drug use in 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Psychiatry. 2018;5(12):987-1012.

Grant BF, Goldstein RB, Saha TD, Chou SP, Jung J, Zhang H, et al. Epidemiology of DSM-5 Alcohol Use Disorder: Results From the National Epidemiologic Survey on Alcohol and Related Conditions III. JAMA Psychiatry. 2015;72(8):757-66.

Vannier AGL, Shay JES, Fomin V, Patel SJ, Schaefer E, Goodman RP, et al. Incidence and Progression of Alcohol-Associated Liver Disease After Medical Therapy for Alcohol Use Disorder. JAMA Network Open. 2022;5(5):e2213014-e.

Osna NA DT, Kharbanda KK. Alcoholic liver disease: Pathogenesis and current management. Alcohol Research: Current Reviews. 2017;38(2):7-21. Alcoholic liver disease: Pathogenesis and current management. Alcohol Research: Current Reviews. 2017;38:7-21.

Mellinger JL. Epidemiology of Alcohol Use and Alcoholic Liver Disease. Clinical Liver Disease. 2019;13(5):136-9.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):210–211.

CLM-P093 Impact of maralixibat on cholestatic pruritus in young adults aged 16 years and older with alagille syndrome

G Hirschfield ¹, DB Mogul ², M Baek ², P Vig ², B Kamath ³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Data in ALGS has primarily focused on pediatric patients, however adults with ALGS who survive with their native liver may require treatment for cholestasis and pruritus.

Purpose: We report on the efficacy and safety of MRX, an IBAT inhibitor, in young adults aged ≥16 years with ALGS transitioning to adult care.

Method: Participants received ≥1 dose of MRX ≥16 years of age within the MRX ALGS clinical development program. Pruritus [ItchRO(Obs)] and serum bile acids (sBA) were assessed at Baseline, before and after 16 years, and at study end.

Result(s): 14 individuals were included; 11 began treatment at <16 years of age and 3 patients began MRX ≥16 years. Baseline mean (SE) pruritus score was 2.5 (0.21), and significantly decreased to 0.8 (delta = -1.7; p = 0.002); pruritus response was durable with no significant change before and after age 16 years (delta = -0.2; p = 0.2), or to end of therapy (delta = 0.2; p = 3) in individuals that started MRX <16 years old. Baseline mean sBA was 130 μmol/L, significantly decreased to 52 μmol/L (delta = -79; p = 0.03) prior to 16 years; no significant change before and after age 16 years (delta = -7; p = 0.3), or to end of therapy (delta = 3; p = 0.4) was observed. Three individuals that started MRX ≥16 years had improvements in pruritus from Baseline (delta = -2.8, -0.6, and -1.0). One patient had a large decrease in sBA (delta = -112 μmol/L) and two had small increases in sBA (delta = 8 and 11 μmol/L). MRX was generally well tolerated with the same safety profile previously reported.

Conclusion(s): MRX was effective, durable, and well tolerated in ALGS patients ≥16 years, providing critical data for patients who transition to adulthood while on therapy.

Disclosure of Interest: G. Hirschfield: None Declared, D. Mogul Shareholder of: Mirum Pharmaceuticals, Employee of: Mirum Pharmaceuticals, M. Baek Shareholder of: Mirum Pharmaceuticals, Employee of: Mirum Pharmaceuticals, P. Vig Shareholder of: Mirum Pharmaceuticals, Employee of: Mirum Pharmaceuticals, B. Kamath Grant / Research support from: Mirum Pharmaceuticals, Albireo, Consultant of: Mirum Pharmaceuticals, Albireo, Audentes

Can Liver J. 2024 Feb 26;7(1):211–212.

CLM-P094 The impact of scalable mind-body internet and mobile-based interventions on depression and anxiety in adults living with chronic physical conditions: a systematic review and meta-analysis of randomized controlled trials

E Johnson ¹, SC Corrick ¹, S Isley ¹, B Vandermeer ¹, N Dolgoy ¹, J Bates ¹, E Godfrey ², C Soltys ¹, C Muir ¹, S Vohra ¹, P Tandon ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Depression and anxiety are common in people living with chronic physical conditions, including gastrointestinal and liver conditions. These symptoms are associated with increased morbidity and reduced quality of life. Mind-body wellness techniques are gaining evidence as practical strategies to reduce these symptoms and improve quality of life across a range of chronic physical conditions. Internet and mobile platforms allow for delivery of the interventions in the convenience of a patient's home and across geographical boundaries and have become increasingly popular since the COVID-19 pandemic. To update our current understanding, the aim of this systematic review and meta-analysis was to examine the effectiveness of mind-body internet and mobile interventions (IMIs) including yoga, Tai-chi, breathwork, and CBT delivered with limited or no personnel support on symptoms of anxiety and depression relative to control conditions.

Purpose: To examine the effectiveness of scalable mind-body internet and mobile-based interventions (IMIs) on depression and anxiety symptoms in adults living with chronic physical conditions.

Method: MEDLINE, PsycINFO, SCOPUS, EMBASE, CINAHL, and CENTRAL were searched for randomized controlled trials published from database inception to March 2023. Mind-body IMIs included cognitive behavioral therapy, breathwork, meditation, mindfulness, yoga or Tai-chi. To focus on interventions that had a greater potential for scale, the intervention delivery needed to be online with no or limited ongoing facilitation by study personnel. The primary outcome was the mean change scores for anxiety and depression (Hedges’ g). In subgroup analyses, random-effects models were used to calculate pooled effect size estimates based on personnel support level, intervention techniques, chronic physical condition, and survey type. Meta-regression was conducted on age and intervention length.

Result(s): Fifty-six studies met inclusion criteria (sample size 7691, mean age of participants 43 years (range 18 - 86 years), 58% female): 34% (n=19) neurological conditions, 12% (n=7) cardiovascular conditions, 11% cancer (n=6), and 43% other chronic physical conditions (n=24), including digestive disease. Mind-body IMI's demonstrated pooled reductions in depression (SMD = -0.33 [-0.40, -0.26], p<0.001) and anxiety (SMD = -0.26 [-0.36, -0.17], p<0.001) without significant differences identified by age or intervention length. Heterogeneity was moderate across most meta-analyses.

Conclusion(s): Scalable mind-body IMIs hold promise as interventions for managing anxiety and depression symptoms in adults with chronic physical conditions without differences seen with age, intervention length or type of chronic physical condition. While modest, the effect sizes are comparable to those seen with pharmacological therapy. The field would benefit from detailed reporting of participant demographics including those related to technological proficiency, as well as further evaluation of non-CBT interventions.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):212–213.

CLM-P095 Evaluation of a nurse-led paracentesis model for patients with decompensated liver disease in ambulatory care: a retrospective review

M Mcdonald ¹, C Fang ¹, C Yim ¹, P Hubley ¹, I Cherepaha-Kantorovich ¹, S Chamaya ¹, C Song ¹, E Lee ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Ascites is a common symptom of decompensated liver disease, managed by large volume paracentesis (LVP) when low-sodium diets and diuretics are ineffective. Typically LVPs are performed by a physician (MD) or a nurse practitioner (NP), and treatment delays can occur due to limited personnel and competing clinical responsibilities. An ambulatory liver clinic located in a quaternary care hospital in Toronto, Canada, opened a procedure room staffed by a trained registered nurse (RN) to perform LVPs for the purposes of accommodating increasing numbers of patients requiring LVPs to reduce Emergency Room (ER) and General Internal Medicine (GIM) admissions for ascites management.

Purpose: This study evaluates the safety of this RN-led paracentesis model and examines the geographic range served by this hospital for ambulatory LVPs.

Method: A retrospective chart review (June 6, 2022 - Feb 28, 2023) was conducted on patients who underwent LVPs in this hospital's designated ambulatory settings (Medical Day Unit (MDU) and the liver clinic's procedure room). A frequency analysis of post-LVP complications subgrouped by the type of healthcare practitioner who performed the procedure (RN, NP, MD) was completed. Post-LVP complications were reviewed: skin infection, bowel perforation, abdominal wall abscess, hematoma/hemorrhage, arterial injury, and catheter fragment left in the abdominal wall/cavity. Spontaneous bacterial peritonitis was not considered a post-LVP complication. Other data collected for this study included: disease etiology, procedure location, proceduralist's designation, post-LVP related hospital admissions, and the patient's residential postal code.

Result(s): 124 unique patients underwent LVPs in the designated ambulatory settings. A total of 580 LVPs were performed. 55.2% (n=320) were performed in the liver clinic's procedure room, and 44.8% (n=260) were performed in MDU. Disease etiologies included: alcohol associated liver disease (40.3%), nonalcoholic fatty liver disease (22.6%), viral hepatitis infection (13.7%), autoimmune liver disease (5.6%), and other etiologies (17.7%). Out of the 580 LVPs, 55.5% (n=322) were performed by an RN, 33.6% (n=195) were performed by an MD; and 10.9% (n=63) were performed by an NP. There were no identified post-LVP complications, regardless of the proceduralist. 118 of the 124 patients live within the city of Toronto and the Greater Toronto Area (GTA), areas that are notably served by at least 15 academic and community hospitals. Of note, patients are currently travelling up to 360 km (224mi) to undergo LVPs due to limited local access to care.

Conclusion(s): This RN-led paracentesis model demonstrated an equivalent level of safety to their NP and MD counterparts. This data could lead to the adoption of similar models of care in centers that deliver ambulatory care for patients with decompensated liver disease as a strategy for readmission avoidance and timely access to local care

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):213–214.

CLM-P096 The rate and risk factors for postoperative mortality in patients with cirrhosis undergoing surgery: a longitudinal cohort study

E Medawar ¹, J Philteos ¹, D Semenova ¹, A Cheung ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Patients with cirrhosis are at increased risk of perioperative complications and surgical morbidity and mortality.

Purpose: This study aimed to determine the rate of post-operative mortality at 30 days, 90 days and 1 year and its risk factors in a consecutive cohort of patients with cirrhosis undergoing surgery.

Method: We conducted a longitudinal single-center retrospective cohort study. Through an administrative database, we identified all consecutive patients with cirrhosis who have undergone a surgery at The Ottawa Hospital between January 2002 and December 2021. We included patients 18 years or older with any etiology of cirrhosis who underwent surgery and excluded endoscopies and procedures. Patient files were reviewed for demographic data, surgical factors and pre-operative laboratory values. The primary outcome was 30-day mortality. We also aimed to determine the demographic, surgical and laboratory risk factors affecting 30-day mortality. Continuous and categorical variables were compared using the student t test, Pearson chi-squared test or Mann-Whitney test. We conducted univariate and multivariate logistic regressions to determine risk factors affecting post-operative mortality.

Result(s): 614 patients with cirrhosis underwent surgery at our centre during the study period (mean age 63.2 years, 42.4% female, median time from cirrhosis diagnosis to surgery 559 days (1.53 years), median MELD 9.4, mean MELD 11.4, mean AST 67.0 U/L, mean bilirubin 32.6 μmol/L, mean platelet count 175.0 × 10⁹/mcL, mean albumin 30.9 g/L, mean creatinine 99.9 μmol/L, mean INR 1.4). 65.8% of surgeries were elective, 54.7% were done under general anesthesia, 52.9% of patients were ASA 3 and 31.4% were ASA 4. The 30-day, 90-day and 1-year mortalities were respectively 3.3% (20/614), 3.4% (21/614) and 3.9% (24/614). All 20 patients with 30-day mortality were male (100.0% vs 57.6%, p<0.001) (surgeries: 3 craniotomies, 6 orthopedic, 6 abdominal, 2 vascular, 2 tracheostomies, 1 organ retrieval). Compared to patients who were alive at 30 days post-operatively, risk factors for 30-day mortality included the MELD score (mean 15.9 vs 12.3, OR 1.1 (1.0-1.2), p=0.018), general anesthesia (80.0% vs 54.0%, OR 5.3 (1.2-23.4), p=0.018), urgent surgery (25.0% vs 6.9%, OR 24.5 (4.6-130.4), p<0.001) and emergent surgery (65% vs 25%, OR 17.3 (3.9-77.6), p<0.001). In our logistic regression models, the age, time from diagnosis of cirrhosis until surgery, surgical wound classification (degree of contamination), and individual laboratory values (excluding the MELD score) were not significantly associated with 30-day mortality.

Conclusion(s): In this cohort study, consecutive patients with cirrhosis undergoing surgery had relatively favorable MELD scores and laboratory markers of disease. The 30-day postoperative mortality was relatively low, at 3.3%, and the major risk factors for mortality were male sex, higher ASA class, higher operative stress score, urgent or emergent surgery, general anesthesia, and higher MELD scores.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):214–215.

CLM-P097 Hepatosplenic T-cell lymphoma diagnosed on liver explant in a patient with ulcerative colitis

A Pedicelli ¹, Z Al-Naamani ²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive non-Hodgkin lymphoma, representing only 1.4% of all peripheral T-cell lymphomas diagnosed annually^1-2. HSTCL primarily affects younger patients with a significant male predominance¹. Presenting features usually include constitutional symptoms and more than 20% of patients will have a history of an immunocompromised state, including solid organ transplant recipients and patients with inflammatory bowel disease (IBD) treated with thiopurine monotherapy or in combination with a tumor necrosis factor alpha (TNF-α) inhibitor^1-2. Despite treatment with chemotherapy and/or stem cell transplantation, HSTCL remains highly deadly, with a median overall survival less than 1 year³.

Purpose: Here we present, to the best of our knowledge, the first ever case of hepatosplenic T-cell lymphoma diagnosed on an explanted liver after transplantation for cryptogenic cirrhosis in an immunocomprised patient with ulcerative colitis.

Method: Clinical case report presented based on information gathered from the electronic medical record.

Result(s): A 44-year-old man was referred to our centre for consideration of orthotopic liver transplantation (OLTx) for cryptogenic cirrhosis. The patient's past medical history was significant for ulcerative colitis which was previously treated with azathioprine. His pre-transplant workup was negative for alcoholic and non-alcoholic steatohepatitis/cirrhosis, viral hepatitis, auto-immune hepatitis, Wilson's disease, hemochromatosis, and alpha-1-antitrypsin deficiency. Transjugular liver biopsies revealed septal fibrosis without definite cirrhosis and foci of sinusoidal dilatation of unclear etiology. Given ongoing synthetic dysfunction, the patient underwent OLTx. Subsequent pathologic evaluation of the explanted native liver revealed marked diffuse intrasinusoidal infiltration by medium atypical T-cells with immunophenotypic features consistent with hepatosplenic T-cell lymphoma as well as periductal onion skin fibrosis suggesting an element of primary sclerosing cholangitis. Analysis of the bone marrow showed extensive infiltration by atypical T-cells, consistent with the aforementioned lymphoma. The patient was started on chemotherapy but unfortunately developed septic shock and acute respiratory distress syndrome, which resulted in his death.

Conclusion(s): The clinical report above represents, to the best of our knowledge, the first published case of hepatosplenic T-cell lymphoma diagnosed by pathologic evaluation of an explanted liver after orthotopic transplantation. This case reiterates the important relationship between inflammatory bowel disease, the use of thiopurine and anti-TNF-α medications, and this rare but deadly hematologic malignancy. Gastroenterologists and hepatologists alike should continue to pay special attention to the risks and benefits associated with IBD treatments, especially for young males, who are most at risk of developing this devastating lymphoma.

References: 1. Pro, B., Allen, P., & Behdad, A. (2020). Hepatosplenic T-cell lymphoma: A rare but challenging entity.Blood, 136(18), 2018–2026. https://doi.org/10.1182/blood.20190041182. Bojanini L, Jiang L, Tun AJ, et al. Outcomes of hepatosplenic T-cell lymphoma: The Mayo Clinic experience. Clinical Lymphoma Myeloma and Leukemia. 2021;21(2). doi:10.1016/j.clml.2020.09.013 3. Bron, D., De Leval, L., Michiels, S., & Wittnebel, S. (2021). Hepatosplenic T-cell lymphoma: Treatment challenges. Current Opinion in Oncology, 33(5), 406–411. https://doi.org/10.1097/cco.000000000000077

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):215.

CLM-P098 Phenotype and long-term outcome in recurrent pediatric acute liver failure secondary to NBAS, RINT1, LARS1, and SCYL1 mutations: a review and individual participant data analysis

O Steg Saban ¹, H Sutton ¹, B Sayed ^2,³, RH Bandsma ¹, VL Ng ^1,³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Recurrent acute liver failure (RALF) in children is defined as two or more episodes of acute liver failure with complete recovery in between. Several genetic mutations have been found to be associated with this condition, including NBAS, RINT1, LARS1, and SCYL1.

Purpose: We aimed to conduct a literature review to characterize the hepatic manifestations of the 4 mentioned mutations. A secondary goal was to compare liver disease progression and outcomes between them.

Method: To describe the prognosis and disease course of this rare condition we conducted a review using PubMed for English-language studies of RALF occurring in children with NBAS, RINT1, LARS1, or SCYL1 mutations.

Result(s): A total of 123 (61 males, 49.5%) patients were identified, with first presentation at a median age of 9 months (range 1 month-18 years) and preceded by fever in 99 (80%) children. Last episode was documented at a median of 3 years (range 1 month-21 years). The median period between episodes is 12 months (range 1-53 months). Patients had a median of 4 (range 1- 30) RALF/ severe hepatitis episodes with only 8 (6.5%) patients experiencing events after age 10 years. Commonest mutated genes identified were NBAS (79.7%, n=98) and SCYL1 (12.2%, n=15). Liver transplant was undertaken in 12 (9.8%) patients, including 9 (75%) performed during a RALF episode, with no recurrences reported post-transplant. The other patients were transplanted pre-emptively. Death was reported in 15 (12.2%) patients, 14 with their native liver. Ten of them died during an acute episode. RINT1 was associated with only 50% native liver survival, unlike the other mutations which had native liver survival rates of 79%, 89% and 92% for LARS1, NBAS, and SCYL1 respectively.

Conclusion(s): Most patients with RALF present in the first year of life and have a self-limiting course. Although RALF is rare, it should be considered in any patient with severe acute liver injury associated with fevers. Parents should be instructed to treat fever aggressively and seek medical advice. Genetic investigation should be obtained with whole exome sequencing, but a designated genetic panel is needed. Management is largely supportive ideally in an experienced LT center, as liver transplantation might be indicated in selected cases.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):216.

CLM-P099 Evaluation of a nutritional education guide developed for patients with cirrhosis: impact of hepatic encephalopathy

M Sophasath ^1,², M Tremblay ¹, C Hogue ¹, G Huard ³, CF Rose ^1,⁴, C Bémeur ^1,²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Liver disease affects 1 in 4 Canadians. One of the most common complications of chronic liver disease is malnutrition, which is associated with poor quality of life and prognosis. Nutritional education resources for this population are lacking.

Purpose: The general objective is to assess the impact of the evidence-based Nutrition in Cirrhosis Guide on patients living with cirrhosis. Specifically, the aim is to assess malnutrition risk, nutritional knowledge and quality of life as well as the impact of history of hepatic encephalopathy (HE) on nutritional knowledge over 6 months.

Method: An on-going randomized controlled study including 100 patients with cirrhosis divided in 2 groups: Guide+ (n=50) and Guide- (n=50). All patients are assessed for malnutrition risk (Liver Disease Undernutrition Screening Tool), knowledge (questionnaire based on the Guide) and quality of life (Chronic Liver Disease Questionnaire) at baseline, 3 and 6 months. History of HE is collected. The Guide+ group of patients are provided with the Guide for 6 months and Guide- patients are not.

Result(s): To date, 24 patients have completed the study: Guide+ (n=11) and Guide- (n=13). Characteristics of participants are comparable at baseline. The preliminary results show a significant improvement of nutritional knowledge for Guide+ patients (from 76.2% at baseline to 84.4% after 6 months, p=0.016). The Guide- patients’ knowledge remained unchanged throughout the study. In the Guide+ group, 2 patients had a history of HE which did not lead to improvement of nutritional knowledge (from 82.0% at baseline to 77.0% after 6 months), whereas in patients without history of HE, improvement was observed (74.7% at baseline to 86.0% after 6 months). In the Guide- group, 2 patients also had a history of HE, and an improvement of 4% in nutritional knowledge was observed, similar to the improvement in patients without history of HE, which was of 3.4% after 6 months. No significant changes were observed in quality of life and malnutrition risk.

Conclusion(s): There is a significant improvement of patients’ nutritional knowledge following 6 months of using the Guide. However, preliminary results suggest that a history of HE could possibly negatively impact their level of nutritional knowledge overtime. This denotes HE may play a role in learning new knowledge and patients with HE may require closer follow-up in regards to nutritional guidance.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):216–217.

CLM-P100 Children with aih receiving standard-of-care therapy demonstrate long-term excess weight gain and obesity: an under-recognized complication of pediatric AIH therapy

O Steg Saban ¹, SASS Fatima ¹, SM Vandriel ¹, C Bourdon ¹, A Mundh ¹, VL Ng ¹, SC Ling ¹, RH Bandsma ¹, BM Kamath ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: The management of autoimmune hepatitis (AIH) can be challenging, given the need for chronic therapy with potential side effects. Standard-of-care (SOC) treatment in children includes induction with Prednisone 1-2mg/kg daily, combined with Azathioprine(1). In patients responsive to SOC, the dose of Prednisone is gradually reduced over 6 months to 5-10 mg daily. There are limited data showing reduction in height in patients treated with high-dose prednisone(2), but no literature available about growth in SOC AIH treatment.

Purpose: We aimed to test the hypothesis that children with AIH on SOC treatment have altered growth trajectories.

Method: Children newly diagnosed with AIH 2000-2022 in a single tertiary center had weight and height measurements every 6 months for 2 years, then yearly for up to 5 years and Z-scores were calculated. Patients were excluded if not treated with SOC treatment or if <1 year of follow-up. Chi-squared test was applied to obesity prevalence. Wilcoxon signed-rank tests were used to compare Z-scores for weight, height, and BMI at baseline (before therapy) and 1 and 2 years (after therapy).

Result(s): 43 patients (65% females, median age at diagnosis 10.4 years, IQR 7.5-13.4) were included and followed for a median of 4 years (IQR 3-5). 91% of the patients had AIH type 1. The median Z-scores for baseline weight, height, and BMI were 0.3, 0.3, and 0.4, respectively. 1 year after treatment, Z-scores for weight (1.0, p<0.01) and BMI (1.4, p<0.01) increased substantially. 2 years after treatment, Z-scores for weight and BMI remained significantly elevated (p<0.01 and (p<0.01). The prevalence of obesity increased significantly between baseline and Year 1 (4.6% vs. 32.6%, p<0.01) and remained significant in Year 2 (35.1%, p<0.01). 10 patients (23.2%) had excessive weight gain (increase of ≥1.0 SD in BMI Z- score) after 1 year of treatment, and 8 patients (21.6%) had excessive weight gain after 2 years. No patients had new-onset short stature (height z- score≤-2), but 7 patients (16.2%) had new-onset growth delay (a decrease of ≥1.0 in height Z- score) during follow-up.

Conclusion(s): It is well-established that excessive steroid exposure is associated with weight gain. This study demonstrates that children with AIH receiving SOC treatment demonstrate long-term excess weight gain and obesity. These data indicate the need to re-evaluate treatment algorithms for pediatric AIH in terms of steroid dosing and potential non-steroid alternatives.

References: 1. Mack CL, Adams D, Assis DN, Kerkar N, Manns MP, Mayo MJ, Vierling JM, Alsawas M, Murad MH, Czaja AJ. Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases. Hepatology. 2020 Aug;72(2):671-722.

2. Cortez, Ana Paula Bidutte MSc^∗; de Morais, Mauro Batista MD, PhD^∗; Speridião, Patrícia da Graça Leite PhD^†; da Motta Mattar, Regina Helena Guedes MSc, MD^∗; Calanca, Flávia MD^‡; Neto, Ulysses Fagundes PhD, MD^∗. Food Intake, Growth and Body Composition of Children and Adolescents With Autoimmune Hepatitis. Journal of Clinical Gastroenterology 44(3):p 200-207, March 2010.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):217–218.

CLM-P101 Long-term prevalence of malnutrition, sarcopenia, and frailty after liver transplantation: impact of hepatic encephalopathy

A Trigui ^1,², M Tremblay ¹, C Hogue ¹, G Huard ³, C Rose ^1,⁴, C Bémeur ^1,²

What is your preferred presentation method?: Poster Only

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: The liver is the second most transplanted organ worldwide. Despite the high survival rate after liver transplant (LT), malnutrition, sarcopenia and frailty are still present in 47%, 80% and 59%, respectively, three months after surgery. These post-LT complications are associated with adverse clinical outcomes and decreased quality of life. However, long-term data assessing these outcomes after LT remains undocumented.

Purpose: The primary objective was to determine the prevalence of malnutrition, sarcopenia, and frailty at 1, 2 and 3 years after LT. The secondary objectives were to describe muscle function, quality of life and employment status in LT recipients and to compare patients with and without history of hepatic encephalopathy (HE).

Method: A cross-sectional observational study included 80 patients transplanted between 2019 and 2021 at the CHUM in Montreal, Canada. A single virtual meeting was performed with each patient during which nutritional risk (Canadian Nutrition Screening Tool), sarcopenia (SARC-F questionnaire), frailty (FRAIL questionnaire), muscle function (chair stand test), quality of life (SF-36) and employment status were assessed.

Result(s): 65 patients completed the study (63.1% male, mean age of 58.8 ± 10.1 years). We observed that 12.3% of patients were at risk of malnutrition, 20.0% were at risk of sarcopenia whereas 46.2% and 18.5% were prefrail and frail, respectively. The prevalence of the risk of malnutrition, sarcopenia, and frailty remained unchanged up until 3 years after LT. Muscle function was impaired after LT (15.8 ± 5.5s vs 12.6s in healthy people). Patients with a history of HE (HE+) were at higher risk of frailty (23.4% HE+ vs 5.6% HE-) and had a poorer muscle function after LT (16.7 ± 5.8s EH+ vs 13.9 ± 4.7s EH-). Regarding quality of life, the score of physical heath (61.3% ± 21.7) was slightly below normal and remained unchanged up until 3 years after LT. Unemployment was noted in 69.2% of patients of which 40.0% were in early retirement for a liver disease-related cause.

Conclusion(s): Up to 3 years after LT, patients are still at risk of malnutrition, sarcopenia, and frailty. Patients with a history of HE are at higher risk of frailty and have a poorer muscle function after LT. The results of this project may help identify appropriate interventions to reduce or prevent complications in the long-term post-LT.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):218–220.

CLM-P102 Real-world study of transient elastography with liver stiffness measurement and spleen stiffness measurement in a tertiary center

MV Edwards ¹, ACY Ma ¹, EMM Kelly ¹, N Gotlieb ¹, PY Tan ¹, M Moini ¹, F de Quadros Onofrio ¹, N Trudel ¹, J-A Lamoureux ¹, AC Cheung ^1,²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Clinically significant portal hypertension (CSPH) is defined as a hepatic venous pressure gradient (HVPG) ≥10 mmHg, which leads to varices and portends a high risk of decompensation.¹ Several non-invasive methods exist to predict CSPH, including liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE).¹ In a systematic review where LSM was compared with HVPG as the reference standard, area under the receiver operating curve (AUROC) for LSM was 0.67-0.91, sensitivity 52-97% and specificity 37-97% in predicting CSPH.² Spleen stiffness measurement (SSM) via VCTE has been endorsed by the Baveno group as a test that can be used in conjunction with LSM to predict CSPH.³ SSM has an AUROC of 0.53-0.97 with sensitivity 40-99% and specificity 34-97% in predicting CSPH.²

Purpose: To describe the real-world performance of LSM ± SSM in predicting CSPH.

Method: A retrospective chart review was done of adult patients at The Ottawa Hospital who underwent VCTE with LSM ± SSM (May to September 2023). Patients were advised to fast for ≥3 hours prior to VCTE. VCTE was performed by two experienced operators. Charts were reviewed for demographics, LSM, SSM, evidence of decompensation, endoscopy, imaging, and lab results. Patients were included if they had VCTE, imaging and esophagogastroduodenoscopy (EGD). Preliminary analysis was performed for positive predictive value (PPV) and/or negative predictive value (NPV) of LSM, SSM, and thrombocytopenia cut-offs. CSPH was defined as findings of portal hypertension on imaging, history and/or endoscopy.

Result(s): A total of 892 patients underwent VCTE during the study period. Preliminary data was collected on 223 patients, with 114 included (Table 1). All had LSM and 28 had SSM (including 25 with LSM >20kPa). The PPV in predicting any CSPH for LSM was 0.48, 0.52 and 0.55 with cut-offs of LSM >20 kPa, >25 kPa and >30 kPa, respectively. The PPV for predicting varices at endoscopy dropped to 0.24, 0.29, and 0.30 with cut-offs of LSM >20 kPa, >25 kPa and >30 kPa, respectively. The NPV for LSM <15 kPa for predicting varices at endoscopy was 0.69. The PPV for predicting any CSPH for SSM was 0.70, 0.68, and 0.60 with cut-offs of SSM >35 kPa, >40 kPa, and >45 kPa, respectively. The PPV for predicting varices at endoscopy was 0.42, 0.46, and 0.47 with cut-offs of SSM >35 kPa, >40 kPa and >45 kPa, respectively. Platelet count <150x10⁹/L had a PPV of 0.42 and platelet count >150x10⁹/L had a NPV of 0.83 with respect to varices at EGD. AUROC to predict varices was 0.49 for LSM and 0.68 for SSM.

graphic file with name canlivj-7.1-abst_fig47.jpg — Image:

Conclusion(s): In this retrospective study, SSM appears to better predict CSPH than LSM alone. Further analysis is required to determine if performance of SSM remains consistent across LSM values. Additionally, it is important to determine if the recent ANTICIPATE criteria may perform better in our population with a high prevalence of metabolic dysfunction-associated steatotic liver disease.⁴ Analysis is ongoing.

References: 1. Reiberger T. The value of liver and spleen stiffness for evaluation of portal hypertension in compensated cirrhosis. Hepatol Comm. 2022;6(5):950-64.

2. Lessard-Vuille E, Rodrigues SG, and Berzigotti A. Noninvasive detection of clinically significant portal hypertension in compensated advanced chronic liver disease. Clin Liver Dis. 2021;25:253-89.

3. de Franchis R, Bosch J, Garcia-Tsao G, et al. Baveno VII- Renewing consensus in portal hypertension. J Hepatol. 2022. 76(4):959-74.

4. Abraldes JG, Bureau C, Stefanescu H, et al. Hepatology. 2016;64(6):2173-84.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):220–221.

CLM-P103 The role of HBRV infection in CD and UC

D Waly ¹, C Allerd ¹, A Castillo-Gurdian ¹, O Oyegbami ¹, N Sun ¹, H Syed ¹, E Wine ¹, K Madsen ¹, T Perry ¹, W Wang ¹, A Mason ¹

What is your preferred presentation method?: Poster Only

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: We have been working on the hypothesis that inflammatory bowel disease (IBD) may be mediated, in part, by viral infection in genetically susceptible individuals. Using the SvEv IL10 -/- mouse model of colitis with mouse mammary tumor virus (MMTV) infection, we found that combination antiretroviral therapy resulted in reduced inflammation of the colon, lowered inflammatory cytokine production, reduced colonic MMTV levels, and diminished microbial dysbiosis. Notably, we found evidence of MMTV infection by demonstrating viral superantigen (SAg) activity. MMTV uses this SAg activity to replicate in proliferating lymphocytes activated by a SAg mechanism. Moreover, MMTV utilizes IL-10 production to tolerize the host to infection, and we hypothesize that the lack of IL-10 leads to colitis in the knockout model (Armstrong et al., Microbiome, 2023).

Purpose: To assess SAg activity in IBD patients (Ulcerative colitis (UC) and Crohn's disease (CD)). We investigated the skewing of specific T cell receptor variable beta region (TCR-Vβ) subsets as a surrogate indicator of SAg activity.

Method: Over 2500 peripheral blood samples were obtained from IBD patients through the IBD Plexus database. We evaluated TCR- Vβ skewing patterns in patient samples by establishing a range for normal TCR expression based on +/- 2 SD.

Result(s): Blood isolated from subjects with CD (n=1901), UC (n=913), and healthy controls (n=192) revealed evidence of SAg activity in patients with CD and UC but not in healthy controls. The distribution of TCR-Vβ in healthy controls showed a diverse polyclonal TCR-Vβ repertoire, whereas repertoires from IBD patients exhibited skewing, indicating the expansion and contraction of specific TCR-Vβ subsets. Approximately 60% of UC patients and 55% CD patients exhibited notable skewing, impacting 1 to 3 specific TCR-Vβ subsets in each sample, a phenomenon rarely observed in the healthy control group (Fig.1). Only 20% of healthy controls had skewed TCR-Vβ (p = <0.0001).

graphic file with name canlivj-7.1-abst_fig48.jpg — Image:

Conclusion(s): Distinct SAgs contribute to the selective skewing of particular TCR-Vβ subsets. Various Vβ subsets were found to be skewed in CD and UC patients, indicating the existence of multiple SAgs. Bacterial SAgs are linked to severe fulminating disease; thus, the observed results are unlikely to be caused by bacterial SAgs. Our preliminary findings demonstrated TCR-Vβ skewing in both UC and CD, suggesting a potential involvement of SAg activity in the onset of these conditions.

References: Armstrong, H., Rahbari, M., Park, H., Sharon, D., Thiesen, A., Hotte, N., ... & Mason, A. (2023). Mouse mammary tumor virus is implicated in severity of colitis and dysbiosis in the IL-10−/− mouse model of inflammatory bowel disease. Microbiome, 11(1), 39.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):221–222.

CLM-P104 Clinical impact of clinically significant portal hypertension among primary biliary cholangitis patients

YJ Wong ¹, R Kaviani ¹, D Shreekumar ², E Lytvyak ², A Montano Loza ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Primary biliary cholangitis (PBC) patients may harbour clinically significant portal hypertension (CSPH) in the absence of cirrhosis due to pre-sinusoidal component. Hepatic venous pressure gradient (HVPG) might underestimate CSPH in PBC patients, is invasive, and is not widely available for prognostication in PBC patients.

Purpose: In this study, we aimed to determine whether the radiological evidence of CSPH could predict index decompensation in PBC patients.

Method: PBC patients diagnosed between 1984 and 2023 at the University of Alberta with available radiological imaging were retrospectively reviewed. Patients with decompensating (defined as ascites, variceal bleeding and hepatic encephalopathy) events before and within 6 months of the diagnosis of CSPH were excluded. Primary predictor was CSPH, defined as the presence of splenomegaly or collaterals based on radiological imaging. The primary outcome was index liver decompensation. Cox regression was used to estimate the hazard ratio with adjustment to baseline cirrhosis, age, serum ALP and MELD score.

Result(s): A total of 80 PBC patients were included. Radiological features of CSPH were found in 30% [24/80] of PBC patients without prior decompensation. Patients with CSPH were more likely to be male (37.5% vs 8.9%, p=0.004), having cirrhosis at the diagnosis of PBC (34.8% vs 7.1%, p=0.004), higher MELD score (8.8 vs 6.6, p=0.012), higher bilirubin (21 vs 10 mmol/L, p=0.025) and lower albumin (39 vs 42 g/L, p=0.031). Over a median follow-up of 130 (IQR: 76-179) months, new decompensating events and death occurred in 26.3% [21/80] and 10% [8/80], respectively.

Radiological features of CSPH were associated with a higher risk of new decompensation after adjusting for baseline cirrhosis (HR: 9.3, 95%CI: 2.9-29.3, p<0.0001). Findings remained robust when sensitivity analysis was performed with various Cox-regression models (adjusting to age, ALP, and MELD score, baseline ALP), and after excluding patients who had undergone liver transplantation (p<0.0001 for all). CSPH appeared to be superior to LSM>25kPa and cirrhosis at diagnosis of PBC to predict first decompensation (AUROC: 0.85 vs. 0.64 vs 0.65). The median time of decompensation from the onset of CSPH was 19 (IQR: 8-47) months.

Conclusion(s): Splenomegaly and collaterals are non-invasive radiological features of CSPH which predict a higher risk of liver decompensation in PBC patients. The prognostic value of radiologically diagnosed CSPH should prompt physicians for closer monitoring for new decompensation and consideration of treatment intensification in PBC patients.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):222–223.

CLM-P105 Leveraging machine learning to improve the diagnostic accuracy of ultrasound screening for hepatocellular carcinoma

M Zeghal ¹, V Govardhanam ², J Pichovsky ³, S Prabhakar ³, C Roda ⁴, J Philteos ⁴, D Semenova ⁴, A Carrington ³, N James ⁵, W Shabana ^3,^6,⁷, R Thornhill ^3,^7,⁸, AC Cheung ^2,^6,⁹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Ultrasound screening is the only widely approved modality to screen for hepatocellular carcinoma (HCC) given its widespread availability, non-invasiveness, and cost-effectiveness. However, the five-year survival rate for HCC is only 32.7%, with ineffective screening posing as a significant factor in poor survival. In recent years, machine learning models utilizing artificial neural networks have demonstrated remarkable success with predictive tasks in the medical field, particularly with convolutional neural networks (CNNs) that dominate in the realm of medical image analysis.

Purpose: To train and test a machine learning algorithm using pre-trained CNNs to improve early detection of HCC through ultrasound screening.

Method: In this retrospective study, 1835 charts of patients with chronic liver disease were reviewed: 346 with histologically confirmed HCC and 1457 with ultrasounds without HCC. A diagnosis of HCC was confirmed pathologically on biopsy or surgical resection, and/or radiographically with a Liver Imaging Reporting and Data System (LI-RADS) score of five on CT and/or MRI. Patients with benign lesions were required to have at least two ultrasounds three years apart that confirmed benign characteristics. Cases were excluded if they had a prior history of treated HCC, post-transplant HCC, or HCC with Barcelona Clinic Liver Cancer (BCLC) Stage B and above. All ultrasound images were reviewed by experienced radiologists, and segmented as liver lesion (HCC versus benign) and surrounding liver.

Result(s): A total of 149 patients have been included to date, comprising 72 with benign lesions, 73 with HCC, and four with both benign and malignant lesions. 224 lesions have been segmented, consisting of 87 HCC and 137 benign lesions. Candidate networks are under development and evaluation for the classification of liver lesions. Imaging pre-processing was performed such that the liver region of interest (ROI) and the lesion ROI were standardized, with 2-channel greyscale images on two-separate channels. The algorithm was constructed using a per lesion analysis. Initial testing has achieved an area under the curve (AUC) of 73.3%, 95% CI [68.6, 77.0] with 2 repetitions of 10-fold cross validation.

Conclusion(s): Enhancing ultrasound screening for HCC is imperative for improving patient care. Analysis of remaining cases is ongoing. Future studies will be essential, including prospective evaluation and external validation.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):223–224.

CLM-P106 Clinical presentation of patients with autoimmune hepatitis stratified by immunoglobulin G levels

Y Zhao ¹, C Vincent ^1,², M Bilodeau ^1,², P Lapierre ¹, J Hercun ^1,²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Immunoglobulin G (IgG) levels are among the most commonly used biochemical markers in autoimmune hepatitis (AIH). However, the role of IgG in predicting outcomes in that setting remains unclear. While persistently elevated IgG levels are associated with incomplete response to therapy, they are not associated with long-term adverse outcomes.

Purpose: The objective of this study was to evaluate the initial clinical picture of AIH based on IgG levels and to assess its correlation with patient outcomes.

Method: Patients included in our institution AIH Biobank, with clinical follow-up for AIH at our institution with documented serum IgG levels at baseline were selected. Patient charts were reviewed for clinical and histological data, and separated into four groups: new-onset AIH with elevated IgG levels, new-onset AIH with normal IgG levels, chronic AIH with elevated IgG levels, and chronic AIH with normal IgG levels. New-onset AIH was defined as patients recruited at the time of diagnosis, whereas chronic AIH included patients on therapy for at least a year. Elevated IgG levels were defined as ≥ 13.0 g/L. Biochemical tests were correlated between groups and Kaplan Meier survival analysis was performed for a composite outcome of death, transplantation or hepatic decompensation (variceal bleed or new onset ascites).

Result(s): 118 patients were considered for analysis. Among new-onset patients, IgG levels were elevated in 14 and normal in 10 cases. In chronic patients, IgG levels were elevated in 31 and normal in 63 cases. At baseline visit, the proportion of patients with elevated ALT differed significantly between groups and was higher in new-onset AIH (79%, 80%, 30%, 30% in respectively new-onset high IgG, new onset normal IgG, chronic high IgG and chronic normal IgG, p=0.0003) as was the proportion of patients with elevated bilirubin (36%, 20%, 10%, 5% across the same groups, p=0.0092). However, this was not significantly different between both chronic AIH groups (p=0.4 and p=0.9 for ALT and bilirubin). In addition, the proportion of patients with advanced fibrosis and cirrhosis was similar amongst all groups (Advanced fibrosis: 57%, 50%, 67% and 60% p=0.8, Cirrhosis: 50%, 50%, 60% and 37.5% p=0.3). In the overall cohort, ALT levels did not correlate with IgG levels (Pearson r=0.21). During short-term follow-up in the chronic AIH cohort (median 24 months), 78% of patients with baseline high IgG remained with elevated IgG which led to significantly more treatment increase in this group (17 vs 3% in the normal IgG group, p=0.015). However, liver-related outcomes and deaths did not differ based on IgG levels (log-rank p=0.93).

Conclusion(s): In this prospectively followed AIH cohort, the severity of liver disease and stage of fibrosis did not differ in chronic AIH patients based on IgG levels. Furthermore, stratification by serum IgG levels did not allow to discriminate between clinically relevant outcomes.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):224–225.

CLM-P107 Reduced inflammatory potential of tumor associated macrophages promotes t cell tolerance and exhaustion in human hepatocellular carcinoma

J Atif ^1,², L Wood ¹, L Liu ¹, C Perciani ², XZ Ma ², J Manuel ², R-I Mahalingam ², M Claasen ², T Ivanics ², R Bucur ², N Rukavina ², T Andrews ³, A Ghanekar ^2,⁴, TJ Pugh ^5,^6,⁷, ID McGilvray ², GD Bader ^8,⁹, G Sapisochin ^2,⁴, S MacParland ^1,^2,¹⁰

What is your preferred presentation method?: Poster Only

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: While hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, it is the third most lethal, reflecting the inadequacy of its current treatments. Despite recent advances in immunotherapy, response rates in HCC are still relatively low. HCC commonly occurs on a background of chronic liver disease (CLD) due to hepatitis C virus (HCV) or hepatitis B virus infection, or alcohol use disorder.

Purpose: The sequential changes to the immune microenvironment in the liver from health to CLD to HCC tumors are not well characterized. Immunoregulatory tumor-associated macrophages (TAMs) are enriched in the tumor microenvironment (TME) and have been linked to T cell tolerance and dysfunction in an HCC setting and represent potential targets for the treatment of HCC.

Method: Using single-cell RNA and TCR sequencing, we generated a transcriptomic atlas of 237,983 cells from healthy human livers (n=13, 69,494 cells), chronic HCV infection (n=5, 48,765 cells), and treatment-naive HCC resection samples from the tumor core (n=12, 49,765 cells), the tumor-margin (n=12, 25,785 cells), and adjacent-normal livers (n=11, 27,008 cells) of varying etiologies. Intracellular cytokine staining andin vitro assays were employed to determine the functional state of primary tumor-associated macrophages (TAM). Flow cytometry was used to validate T cell and TAM phenotypes.

Result(s): All major non-parenchymal cell types display gradients of cell phenotypes spanning the healthy tissue to the tumor core, suggesting a sequential reprogramming of the cellular landscape with respect to the tumor. An enrichment of exhausted and clonally expanded CD8+ T cells (TOX, PDCD1), regulatory T cells (FOXP3) (Tregs), and immune-regulating macrophages (MRC1, TREM2, CD9) define the tumor-core relative to the healthy and the adjacent-normal liver. We note the presence of a TAM population in all patients, regardless of etiology. With increased proximity to the tumor, macrophages secrete less TNF-α following in vitro LPS and IFN-γ stimulation and interact with T cells through more immunoregulatory pathways. Furthermore, TAMs exhibit reduced expression of pro-inflammatory genes, such as those in the cGAS-STING pathway.

Conclusion(s): We present a geographically resolved single-cell transcriptional examination of the immune landscape in human HCC. Etiology-conserved pathways driving an immunoregulatory TAM phenotype are enriched in the TME and present opportunities for generating unified approaches to targeting all types of HCC.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):225–226.

CLM-P108 Intestinal retoxification of bile acids by the beta-glucuronidase enzymes from the mictobiota: a potential novel target for the treatment ofcholestatic autoimmune liver diseases

S Dzanouni ^1,², W Gagnon ^1,², J Trottier ¹, M Verreault ¹, MR Redinbo ³, M-C Vohl ^4,⁵, O Barbier ^1,²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: High bile acid (BA) levels exacerbate liver damages and inflammation in cholestatic auto-immune liver diseases. Glucuronidation, a phase II conjugation reaction, converts toxic BAs into nontoxic glucuronide derivatives (BA-G) and favors their elimination. The absence of BA-G in feces from most mammalian species, and the relative abundance in urine led to the general concept that glucuronidation serves as a rerouting mechanism for BA elimination through the renal route. However, our group recently made the exciting discovery that feces from intestinal germ-free mice were enriched in BA-G, suggesting the presence of deconjugating β-glucuronidases enzymes (GUS) in the intestinal microbiota.

Purpose: This study aimed at quantifying GUS activity toward BA-G, and investigating how this activity is altered by pharmaceutical and nutritional interventions.

Method: Enzymatic GUS assays were performed at 37°C for 30 min in the presence of 50μM BA-G and 5 mg of human or murine fecal proteins. BA formation was then resolved using LC-MS/MS. For enzymatic screening, 11 BA-G species were assayed with human (5♀: 5♂) or CD1-Elite mice feces (2♀:2♂). For inhibition assays, the enzymatic reaction was performed with a pool of human (5♂: 5♀) or murine (4♂:4♀) feces in the presence of 200μM amoxapine, a known GUS inhibitor. Finally, GUS assays were also performed using feces from human donors harvested before and after consumption of either 280g/day of raspberries (16♀:7♂) or 50g/day of freeze dried blueberry powder (13♀:11♂) for 8 weeks, and incubated with BA-G as described above.

Result(s): All tested BA-Gwere reactive with human and murine feces, with deconjugationpercentages ranging from 0.8±0.5%(mean±SEM)for HDCA-6G to 41.4±11.0% for CDCA-24G in women's feces. Compared to vehicle alone, the inhibition rate caused by amoxapine was higher with thepool of women's feces than in men's (68.3% for LCA-3G to LCA conversion and 49.6% for LCA-24G to LCAfor women vs 66.4% and 33% respectively for men). Similar experiments performed with the murine-specific acid, β-MCA-24G and pool of mice feces revealed sexual dimorphism with amoxapine being more efficient in female samples. Interestingly, in human volunteers, the consumption of blueberry extracts caused a significant (p<0.01) reduction of LCA-3G deconjugation, while the GCDCA-3G to GCDCA conversion remained unaffected after an 8-week raspberry-enriched diet.

Conclusion(s): These data showthatbacterial GUS enzymatic activity toward BA-G can be modulated by pharmacological and nutritionalinterventions, suggesting that its modulation could be targeted to ensure an optimal BA detoxification in cholestatic liver diseases.

References: - Keith D. Lindor, Christopher L. Bowlus, James Boyer, Cynthia Levy, Marlyn Mayo. Primary biliary cholangitis: 2021 practice guidance update from the American Association for the Study of Liver Diseases. Practice guidanceAASLD. 2021,

- Christopher L. Bowlus, Lionel Arrivé, Annika Bergquist, Mark Deneau, Lisa Forman, Sumera I. Ilyas et al. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Practice guidzanceAASLD. 2022,

- Gina M. Gallucci, Jocelyn Trottier, Christopher Hemme, David N. Assis, James L. Boyer, Olivier Barbier, Nisanne S. Ghonem. Adjunct Fenofibrate Up-regulates Bile Acid Glucuronidation and Improves Treatment Response For Patients With Cholestasis. Hepatology. communications. 2021;5 (12):2035-2051

- Martin Perreault, Andrzej Białek, Jocelyn Trottier, MélanieVerreault, Patrick Caron, Piotr Milkiewicz, Olivier Barbier. Role of Glucuronidation for Hepatic Detoxification and Urinary Elimination of Toxic Bile Acids during Biliary Obstruction. PLoS ONE. 2014; 8(11): e80994.

- Robin Durník, Lenka Šindlerová, Pavel Babica and Ondřej Jurček. Bile Acids Transporters of Enterohepatic Circulation for Targeted Drug Delivery. Molecules. 2022, 27(9), 296.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):226–227.

CLM-P109 HCV-specific CD4+ T-cells are targeted by HIV-1 infection and viral reservoir persistence

ST Gobran ^1,², J Dion ², J Bruneau ^2,³, P Ancuta ^1,², N Shoukry ^2,⁴

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: Hepatitis C virus (HCV) infection is a serious comorbidity in people living with human immunodeficiency virus (HIV) (PLWH) [1]. Antiretroviral therapy (ART) reduces HIV replication to undetectable levels but does not eliminate HIV reservoirs, which persist in long-lived memory CD4+ T-cells of various antigenic specificities [2]. HCV coinfection is associated with a larger HIV-DNA reservoir size in CD4+ T-cells than mono-infected subjects [3] suggesting that HCV-specific CD4 T-cells may be highly susceptible to HIV infection.

Purpose: Herein, we aimed to investigate whether HCV-specific CD4+ T-cells are permissive to HIV infection and whether they contribute to HIV reservoir persistence in ART-treated subjects.

Method: Memory CD4+ T-cells from chronic HCV patients and negative controls (n=20 per group) were infected with HIV_NL4.3BaL strain in vitro. HIV integration and replication were measured by real-time PCR and HIV-p24 flow cytometry/ELISA analysis, respectively. The CFSE-based T-cell proliferation assay was used to examine the phenotype and susceptibility of HCV-specific T-cells to HIV_NL4.3BaL infection in eight HCV resolvers and two HCV chronic subjects. S. aureus, C. albicans, CMV lysates, and Staphylococcal Enterotoxin B (SEB) were used as controls. HIV replication was measured by intracellular/soluble HIV-p24 expression. A monocyte-derived dendritic cell-based viral outgrowth assay (MDDC-based VOA) was used to detect the presence of replication-competent HIV reservoir in HCV-specific T-cells from HCV+/HIV+ subjects on ART.

Result(s): We observed that T-cells from chronic HCV-infected individuals compared to HCV-negative controls were more susceptible to HIV_NL4.3BaL infection in vitro, as demonstrated by intracellular (p=0.332), soluble HIV-p24 expression (p=0.0298), and integrated HIV-DNA levels (p=0.0559). Similar to C. albicans and S. aureus but not CMV and SEB, a fraction of HCV-specific T-cells highly supported productive HIV infection, as confirmed by intracellular/soluble HIV-p24 expression. Compared to the other antigen-specific cells, HCV-specific CD4+ T-cells expressed relatively high levels of CXCR6+ (a minor HIV co-receptor and a liver homing marker), which correlated positively with HIV replication in vitro (Spearman r=0.788, p=0.0466). The MDDC-based VOA demonstrated that HCV-specific T-cells harbor replication-competent HIV reservoirs. UMAP clustering algorithm combined with Leiden phenograph showed that HCV-specific T- cells distinguish from the other antigenic specificities by a predominant Th1 biased Tfh phenotype (CXCR3+/Tbet+/BCL6+).

Conclusion(s): Our results provide evidence that HCV-specific CD4+ T-cells are highly susceptible to HIV infection and may represent long-lived HIV reservoirs in ART-treated PLWH co-infected with HCV.

References: Gobran ST, et al. Front Immunol 12:726419 (2021)

Gantner P, et al. Nat Commun 11:4089 (2020)

López-Huertas MR, et al. Sci Rep 9:5606 (2019)

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):227–228.

CLM-P110 Protectin dx improves the response to obeticholic acid in liver cells

A-A Lavoie ^1,^2,³, M Verreault ^1,², J Trottier ^1,², R Maltais ¹, D Poirier ^1,⁴, A Marette ^2,^4,⁵, O Barbier ^1,^2,³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Primary biliary and sclerosing cholangitis (PBC and PSC) are rare and progressive autoimmune liver diseases, characterized by an accumulation of toxic bile acids (BA) in liver cells [1]. The reduction of these pro-inflammatory and pro-cirrhotic toxins is therefore an important pharmacological target for PBC and PSC treatments [1]. Currently, obeticholic acid (OCA), an inhibitor of BA synthesis, is one of the only two drugs approved for the treatment of these diseases [2,3]. Despite being efficient in normalizing liver enzymes, OCA is also associated with dose-related side effects that recently led Health Canada to publish novel contraindications for the treatment of decompensated PBC patients [4,5]. Hence, it is imperative to identify safer therapeutic alternatives.

Purpose: The present study investigates whether protectin DX (PDX), an omega-3 fatty acid derivative with hepatic anti-inflammatory properties, can improve the response to low Ocaliva dose in terms of bile acid reduction [6].

Method: Human hepatoma HepG2 cells were treated for 24 hours with vehicle (DMSO/ethanol; 0.01%/0.01% v/v), and 1μM OCA with or without PDX (5μM) and DHA (50μM) [positive control]. Transcriptomic (qRT-PCR), proteomic (Western blot), or metabolomic targeted (LC-MS/MS) approaches were employed to assess the effects of the various treatments.

Result(s): In the presence of PDX and DHA, liver cells exhibited a stronger response to 1μM OCA when compared to the drug alone. Indeed, OCA 1μM caused a 54.3% reduction of the CYP7A1 transcript levels, a gene coding for the rate-limiting enzyme in BA synthesis, while in the presence of PDX, the same amount led to stronger (p<0.05) reduction of this transcript to 64.7%. Interestingly, the combination of OCA and PDX (p<0.05) led to a stronger reduction of chenodeoxycholic acid (CDCA) secretion in cell media (figure 1). PDX also significantly enhanced the ability of OCA to increase the mRNA expression of BA export transporters such as OSTα and β, MRP2 and 3 (p<0.001).

graphic file with name canlivj-7.1-abst_fig49.jpg — Image:

Conclusion(s): These experiments demonstrate that, like DHA, protectin DX improves the ability of a low OCA dose to inhibit BA synthesis and export in HepG2 cells. Considering the crucial role of bile acids’ accumulation in the pathogenesis of cholestatic autoimmune liver diseases such as PBC and PSC, the use of PDX + low OCA dose combinations may provide a safer pharmacological option for these diseases. Further analyses are, however, required to validate this hypothesis.

References: (1) PMID: 31169523

(2) PMID: 36289726

(3) PMID: 12166927

(4) PMID: 31680292

(5) PMID: 29928160

(6) PMID: 34920958

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):228–229.

CLM-P111 Uric acid in chronic liver disease and its cognitive complications: lessons from a rat model

S L’ecuyer ^1,², M Steger ³, F Tamnanloo ^2,⁴, M Oliveira ², M Tremblay ², E Charbonney ^4,⁵, CF Rose ^2,⁴

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Episodic and reversible hepatic encephalopathy (HE) episodes are associated with an increase in ammonia circulation and affects around 40% of patients with chronic liver disease (CLD). However, increasing evidence suggests that cognitive impairments in CLD can be irreversible. This raises the question of the implication of other circulating mediators in CLD-associated cognitive impairment. Hyperuricemia, due to increased plasma levels of uric acid (UA), is known for its association with fructose and alcohol consumption. These factors are also considered to contribute to the onset of CLD. Additionally, uric acid contributes to neuroinflammation and brain oxidative stress leading to an increase in anxiety and memory impairments. This justifies focusing on uric acid as a potential mediator in cognitive impairments in CLD.

Purpose: This study investigates the impact of hyperuricemia on cognitive impairments in a rat model of chronic liver disease with HE.

Method: To induce CLD, we used the model of bile-duct ligation leading to liver fibrosis and hyperammonemia. For hyperuricemia, a diet containing 3% uric acid (HUAD) is administered compared to a regular diet (RD). Fifty-six male Sprague-Dawley rats are randomly assigned to 1 of 4 experimental groups: (1) SHAM+RD, (2) SHAM+HUAD, (3) BDL+RD et (4) BDL+HUAD. Behavioral assessment for anxiety-like behavior (Open-field and Elevated Plus-Maze) and memory (New-object recognition) is performed at day 14. At day 33, animals are sacrificed, and plasma UA and liver injury markers are measured. The liver is collected for histological analysis by H&E and Sirius Red staining. The frontal cortex, amygdala and hippocampus are isolated to measure apoptosis (caspase-8, 9 and 3) and neuronal cell loss (NeuN and SMI311).

Result(s): The administration of the HUAD diet leads to a significant increase in plasma UA levels in BDL animals but does not lead to a significant increase in liver injury evaluated by plasma liver injury markers and histology. For behavioral assessment, we detected an increase in anxiety-like behavior and an impairment of short-term memory for both SHAM+HUAD and BDL+HUAD animals. We also observed a long-term memory impairment for BDL+HUAD rats. For neuronal cell loss in the frontal cortex and hippocampus, we detected an increase of both apoptosis pathways (caspase-8, 9 and 3) and a decrease in neuronal markers (NeuN and SMI311) for both HUAD groups. In the amygdala, only the intrinsic pathway of apoptosis (caspase-9 and 3) is activated in BDL-HUAD rats. This activation is associated with a decrease in neuronal markers.

Conclusion(s): In a rat model of CLD, the administration of a high UA diet leads to the early-onset of anxiety-like behavior and memory impairments. The behavioral alterations are associated with increased apoptosis and neuronal cell loss in the frontal cortex, amygdala and hippocampus. These results suggest a potential role for UA in irreversible brain damage in the context of chronic liver disease.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):229–230.

CLM-P112 The association of body cell mass with bedside body composition tools and frailty in patients with liver cirrhosis

AT Limon-Miro ¹, K Sekulic ², S Isley ¹, CM Prado ³, P Tandon ¹

What is your preferred presentation method?: Poster Only

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Low muscle mass and impaired contractile function are prevalent prognostic conditions in patients with cirrhosis. Accurate body composition assessments are essential yet challenging in this population, as most techniques are affected by fluid overload (e.g. edema and ascites). The whole-body potassium counter (WBKC) is a reference technique available at only a few centers in the world. It measures total body potassium (TBK) and body cell mass (BCM) unbiased by fluid alterations.

Purpose: In patients with cirrhosis, to evaluate: (I) the association between BCM and frailty (II) the relation between BCM and innovative bedside body composition tools.

Method: Outpatient adults with confirmed cirrhosis were recruited. Participants were asked to fast (≥8 h) and to remove shoes and metal items. Anthropometric measurements (body weight, height, calf circumference (CC)), body mass index (BMI), BMI-adjusted CC, and bioelectrical impedance analysis phase angle were assessed. The Liver Frailty Index (LFI) was obtained inclusive of handgrip strength, sit-to-stand and balance testing. TBK was measured in a WBKC with BCM derived using the Cohn equation. Baseline characteristics were presented as proportions for categorical variables and mean (SD) for continuous variables. Unpaired t-test for differences between sex, pearson's correlation coefficient, and a stepwise multiple linear regression analyses were performed using the IBM SPSS software.

Result(s): Twenty participants (50% females) with cirrhosis (Child-Pugh A 50%, B 40%, C 10%) and a mean age of 57 years (95% CI, 51-62) were included. TBK and BCM were lower in females versus males with cirrhosis (2062±355 vs 3115±466 mmol and 19±3 vs 29±4 kg; p=0.00002), respectively. BCM was correlated with the LFI (r=-0.6, p=0.009) and CC (r=0.4, p=0.031). On regression modeling, LFI was predictive of BCM (p=0.002) while controlling for sex (p<0.001) and ethnicity(p=0.006).

Conclusion(s): These findings support the association between reduced body cell mass, frailty and CC in individuals with cirrhosis. Ongoing data collection will confirm and better understand the relationship between BCM, frailty, and demographic characteristics in this population.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):230–231.

CLM-P113 Establishing a viable in vitro platform to culture primary murine hepatic myeloid cells

M Sekhon ^1,², S Chung ^1,³, X-Z Ma ¹, J Manuel ¹, S MacParland ^1,^2,³

What is your preferred presentation method?: Poster Only

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Liver repair and regeneration is impaired when macrophage depletion models are implemented in liver injury and partial hepatectomy models ^1,2. As well, the liver retains a large pool of myeloid cells, which help promote immunotolerance by surveilling the liver sinusoid lumen and responding accordingly to retain homeostasis ³. Additionally, they are the most abundant immune cell population in the liver distributed across the organ, playing an essential role in eliciting immune responses ⁴. Due to myeloid cells being highly plastic, they have the potential to be used as a therapeutic agent to combat liver disorders by modulating their phenotype and function ⁵.

Purpose: However, a reliable in vitro platform for culturing primary hepatic myeloid cells must be first established to evaluate their identity after introducing interventions to reprogram their phenotype and function. The baseline effects of our in vitro platform must be examined to ensure that the primary hepatic myeloid cells are viable and the results of downstream analyzes are not impacted by the culturing conditions.

Method: To release viable primary hepatic cells, a 2-step collagenase mouse liver in situ perfusion and dissociation protocol was developed. The primary hepatic cells were isolated and purified to obtain F4/80 enriched hepatic myeloid cells. For our media, we supplemented it with macrophage colony stimulating factor (M-CSF), which has been used in macrophage media previously, but the minimal concentration to ensure viability has not been tested ^6-9. An annexin V red assay measured by the IncuCyte system was used to analyze early apoptosis of different M-CSF concentrations at different timepoints up to 8 days of culture. Phenotype and function were evaluated by surface staining and intracellularly staining after 6h LPS stimulation on days 0, 1, 3, 5 and 7 of cultured primary hepatic myeloid cells in different M-CSF concentrations.

Result(s): Based on the annexin V assay, the optimal range for greater survivability for cultured primary murine hepatic myeloid cells was 20 to 60 ng/mL (n = 3). Based on the flow cytometry data, by day 3, the minimal M-CSF concentration for viable primary murine hepatic myeloid cells was 20 ng/mL compared to M-CSF being absent (n=3). Also, the frequency of CD163+MHC-II+ decreased, while CD163-MHC-II- frequency increased, which may be a consequence of culturing duration instead of M-CSF presence. At all analyzed timepoints, TNF-α expression was stable after LPS stimulation.

Conclusion(s): Ultimately, establishing an in vitro platform to culture viable primary hepatic myeloid cells will provide a framework for reprogramming primary hepatic myeloid cells and aid in the path towards liver regeneration and repairment.

References:

1. Miura, A., Hosono, T. & Seki, T. Macrophage potentiates the recovery of liver zonation and metabolic function after acute liver injury. Sci. Rep.11, 9730 (2021).

2. Elchaninov, A. et al. MARCO+ Macrophage Dynamics in Regenerating Liver after 70% Liver Resection in Mice. Biomedicines9, (2021).

3. Kubes, P. & Jenne, C. Immune responses in the liver. Annu. Rev. Immunol.36, 247–277 (2018).

4. Guilliams, M. et al. Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches. Cell185, 379-396.e38 (2022).

5. Wen, Y., Lambrecht, J., Ju, C. & Tacke, F. Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities. Cell. Mol. Immunol.18, 45–56 (2021).

6. Aktories, P. et al. An improved organotypic cell culture system to study tissue-resident macrophages ex vivo. Cell Rep. Methods2, 100260 (2022).

7. Zhao, D. et al. ALK1 signaling is required for the homeostasis of Kupffer cells and prevention of bacterial infection. The Journal of Clinical Investigation (2022).

8. Bonnardel, J. et al. Stellate cells, hepatocytes, and endothelial cells imprint the kupffer cell identity on monocytes colonizing the liver macrophage niche. Immunity51, 638-654.e9 (2019).

9. Andreata, F. et al. Isolation of mouse Kupffer cells for phenotypic and functional studies. STAR Protocols2, 100831 (2021).

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):231–232.

CLM-P114 Diagnostic, prognostic, and therapeutic implications of glutamine metabolism reprogramming in hepatocellular carcinoma

V Tambay ^1,², V-A Raymond ², L Rousseau ³, S Turcotte ^3,⁴, M Bilodeau ^2,⁵

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality, given the lack of robust diagnostic biomarkers and curative therapies. Metabolic reprogramming, a hallmark of cancers, is a promising avenue to improve the clinical management of HCC.

Purpose: This study aimed to evaluate the clinical significance of alterations of glutamine synthetase (GS), kidney glutaminase (GLS1), and liver glutaminase (GLS2) in HCC. The importance of GLS1 for glutamine metabolism in HCC was also studied.

Method: GS, GLS1, GLS2, and albumin (ALB) mRNA (qPCR) and proteins (Western blot) were measured in HCC tumors (n=32), cirrhosis (CL, n=20), and normal livers (NL, n=20) from patients. Patient informed consent was obtained prior to surgery. Tumor gene expression was correlated with patient survival and tumor progression using The Cancer Genome Atlas (N=364). GLS1 was targeted using CB-839 in HCC cells (Huh7 and Hep3B): ammonia, glutamine/glutamate (LC/MS),³H-glutamine uptake, and cell viability (MTT) were measured.

Result(s): GS mRNA levels were found to be higher in HCC samples than CL and NL (p<0.05). GLS1 mRNA levels were also higher in HCC than NCL (p<0.05) but not CL. GLS2 mRNA levels were lower in HCC compared to CL and NL (both p<0.0001), similarly to ALB (both p<0.05), though ALB levels were also decreased in CL compared to NL (p<0.001). GS protein levels were higher in HCC than in CL and NL (both p<0.05), likewise GLS1 (both p<0.0001), whereas GLS2 protein levels were higher in CL and NL than HCC (both p<0.0001). Receiver operating characteristic (ROC) analyses between non-tumoral liver (CL and NL) and HCC samples were performed: for mRNA, GLS2 was the best classifier of tissue type (AUROC=0.947). Calculating the GS/(ALB∗GLS2) mRNA ratio improved ROC performance: AUROC=0.969 (95%CI=0.93-1.00, p<0.0001). For protein expression, GS (AUROC=0.926) and GLS2 (AUROC=0.925) had excellent classifying performances: calculating the (GS∗GLS1)/GLS2 protein ratio increased ROC performance (AUROC=0.986 (95%CI=0.96-1.00), p<0.0001). High GLS1 expression in tumors was associated with increased risk of mortality (p<0.05) and HCC progression (p<0.01). Patients having tumors with low GLS2 expression showed earlier death (p<0.01), more relapse (p<0.05), and faster tumor progression (p<0.01). Targeting GLS1 using CB-839 abrogated ammonia production in HCC cells (both p<0.05), which translated to increased glutamine/glutamate ratio (both p<0.05), suggesting decreased glutaminolysis. CB-839 decreased ³H-glutamine uptake (both p<0.01) and was cytotoxic on HCC cells in a dose-dependent manner (both p<0.01): at 10 μM, viability was decreased by 38.6% in Hep3B cells (p<0.001) and 32.5% in Huh7 cells (p<0.0001).

Conclusion(s): Glutamine metabolism reprogramming is a hallmark of HCC, characterized by increased GS expression and a specific switch in glutaminase expression from GLS2 to GLS1. Such alterations have important potential in the detection, prognostic evaluation, and therapeutic approach of HCC.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):232–233.

CLM-P115 Targeting glutamine consumption: insights on ASCT2 and SNAT2 as putative major glutamine transporters in hepatocellular carcinoma

V Tambay ^1,², V-A Raymond ², M Bilodeau ^2,³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Glutamine is a fundamental metabolite to liver metabolism and hepatocellular carcinoma (HCC) metabolic reprogramming. Targeting glutamine transport, including ASCT2 and SNAT2, could become an effective modality to harness the accelerated metabolism observed in HCC.

Purpose: We have previously shown major alterations in the expression of glutamine transporters, ASCT2 and SNAT2 being upregulated in HCC cells. This study aimed to evaluate the targeting of ASCT2 and SNAT2 on glutamine uptake and HCC cell survival.

Method: Expression and activity of ASCT2 and SNAT2 were targeted using siRNA in human HCC Hep3B and Huh7 cells. Gamma-p-nitroanilide (GPNA) was used to pharmacologically inhibit glutamine transport. mRNA was evaluated by qPCR, glutamine consumption by ³H-glutamine uptake assay, and cell survival by MTT assay.

Result(s): Pharmacological inhibition with GPNA [0.5 mM] decreased glutamine uptake by 34% in Huh7 and 46% in Hep3B cells (both p<0.05) but had no cytotoxic effect on HCC cells. ASCT2 siRNA successfully decreased mRNA by 85% in Hep3B and Huh7 cells (both p<0.001). Glutamine uptake was decreased by approximately 17% in both cell lines in glucose/glutamine-rich conditions (both p<0.05), which was potentiated by GPNA, with uptake decreased by 35% (both p<0.05). In glutamine-only conditions, glutamine uptake decreased by 35% (both p<0.05). SNAT2 siRNA decreased mRNA by 63% in Hep3B and Huh7 cells (both p<0.05). In Hep3B cells, SNAT2 molecular targeting decreased glutamine uptake by 34.6% in glutamine-depleted conditions, 30.8% with low glutamine, 13.7% with high glutamine, 30.2% in glucose/glutamine-rich conditions, and a mere 6.1% with GPNA inhibition. In Huh7 cells, inhibition of SNAT2 expression decreased glutamine uptake by 55.3% in glutamine-depleted conditions, 35.9% with low glutamine, 22.2% with high glutamine, and 2.9% with combined pharmacological inhibition with GPNA. For combined siRNA targeting of ASCT2 and SNAT2, efficacy on glutamine uptake was enhanced for all tested conditions in both HCC cell lines. For Hep3B, combined inhibition decreased glutamine uptake by 49.9% in glutamine-depleted conditions, 63.2% with low glutamine, 54.7% with high glutamine, 53.6% in glucose/glutamine-rich conditions, and 38.0% with combined GPNA treatment. In Huh7, glutamine uptake was decreased by 61.4% in glutamine-depleted conditions, 57.4% with low glutamine, 52.6% with high glutamine, 18.8% in glucose/glutamine-rich conditions, and 45.5% when combined with GPNA. Assessment of viability has shown that Hep3B and Huh7 cell survival is not negatively impacted by blocking ASCT2 or SNAT2 expression alone nor in combination.

Conclusion(s): In HCC cells, ASCT2 and SNAT2 are important transporters allowing the cellular uptake of glutamine. However, HCC cells develop mechanisms to escape possible cytotoxic effects of decreased glutamine uptake. Further studies need to address alternative transport and metabolic pathways to highlight the relative importance of glutamine uptake in HCC.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):233–235.

CLM-P116 Impact of the COVID-19 pandemic on temporal trends in alcohol-related and non-alcohol-related cirrhosis hospitalizations: a Canadian population-based study

LA Swain ¹, J Godley ^1,², J Abraldes ³, M Brahmania ⁴, AA Shaheen ^1,⁵

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Few studies have examined the impact of the COVID-19 pandemic on hospitalization rates for alcohol - (AC) and non-alcohol-related cirrhosis (NAC) separately in relation to age and sex.

Purpose: We aimed to examine sex and age stratified temporal changes in AC and NAC hospitalizations before the pandemic (2008-19) and during the pandemic (2020-21) in Alberta, Canada.

Method: We used validated international classification of diseases 10^th revision (ICD-10) administrative case definitions to select all adult (>20 years) AC and NAC hospitalizations from the Discharge Abstract Database (DAD) from April 2008 to March 2021. AC was defined as admissions coded with either the AC ICD-10 code alone, or both an alcohol use disorder (AUD) and decompensated cirrhosis-related condition code together. NAC was defined as admissions with a NAC ICD-10 code alone or decompensated cirrhosis-related condiition code, excluding all AUD-related codes. Age and sex standardized hospitalization rates/100,000 population were calculated using the 2016 Canada Census population estimates for Canada and Alberta. Temporal trends in yearly AC and NAC hospitalization rates were assessed using Joinpoint analysis and annual percent change (APC) stratified according to sex (male/female) and age groups (20-34, 35-49, 50-64, 65+ years).

Result(s): We identified 29,445 AC (66% male; median age 55 years) and 40,898 NAC hospitalizations (54% male; median age 64 years) during our study period. Annual AC sex-stratified hospitalizations rates (Fig. 1A) decreased for men from 2015-19 (APC -4%; 95% confidence interval [CI], -7 to -2), and plateaued during the pandemic (2019-21), whereas rates in women were not affected by the pandemic, remaining stable from 2010-21. Age-stratification (Fig. 1B) showed a significant decrease in AC hospitalization rates for the 50-64 age group from 2015-21 (APC -2%; CI, -7 to -0.5]) that was not altered by the pandemic. However, in the 20-34 age group, AC hospitalization rates increased during the pandemic (2019-21; APC 28%; CI, 12-42). AC hospitalization rates remained stable for the 35-49 and ≥65 age groups after 2010 and 2014 respectively, and were not affected by the pandemic. Sex-stratified NAC hospitalization rates (Fig. 1C) were not affected by the pandemic and remained stable in women from 2011-21 but increased in men from 2010-21 (APC 2%; CI 1-3). Age-stratification showed NAC hospitalization rates (Fig. 1D) were not impacted by the pandemic but increased in those ≥65 years from 2010-21 (APC 3%; CI, 1-4), and remained stable for all other age groups from 2011-21.

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Conclusion(s): AC hospitalization rates among younger patients and men increased during the pandemic. NAC hospitalization rates have steadily increased particularly in men and older patients with no impact of the pandemic on their trajectories.

Disclosure of Interest: L. Swain: None Declared, J. Godley: None Declared, J. Abraldes Grant / Research support from: received grants from Cook and Gilead (paid to the University of Alberta), Consultant of: received consulting fees from Boehringer Ingelheim, AstraZeneca, Inventiva and 89Bio, M. Brahmania: None Declared, A. A. Shaheen Grant / Research support from: participated in advisory boards and received research grants from Gilead and Intercept

Can Liver J. 2024 Feb 26;7(1):235–236.

CLM-P117 Developing and validating novel coding algorithms to improve case identification accuracy for alcohol- and non-alcohol-related cirrhosis in administrative databases

LA Swain ¹, J Godley ^1,², J Abraldes ³, M Brahmania ⁴, AA Shaheen ^1,⁵

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Alcohol- (AC) and non-alcohol-related cirrhosis (NAC) epidemiology studies are limited by the accuracy of available administrative case definitions.

Purpose: In this study, we examined and compared the performance of previously used and newly developed case definitions in identifying AC and NAC hospitalizations in Calgary, Canada.

Method: We randomly selected 700 hospitalizations from the Discharge Abstract Database using International Classification of Diseases 10^th revision (ICD-10) codes for AC, NAC, alcohol use disorder (AUD), and decompensated cirrhosis-related conditions (DC) from 2008-22. For AC case identification, we evaluated the standard approach using the AC code alone, as well as 2 novel AC case definitions that selected admissions with, (i) an AUD and DC code together, or (ii) using either the AC code alone, or both an AUD and DC code together. For NAC case identification, we evaluated the standard approach using a NAC code alone, and 2 novel case definitions that selected admissions with, (i) a NAC code alone, excluding AC, alcohol-related hepatitis (AH), and AUD codes (NAC1), or (ii) both a NAC and DC code together, excluding AC, AH, and AUD codes (NAC2). Using electronic medical record (EMR) review as the reference standard, we calculated case definition positive predictive value (PPV), sensitivity, and area under the receiver operating characteristic curve (AUROC). We used AUROC tests of equality to identify statistical differences between case definitions.

Result(s): Of the 700 hospitalizations, 671 had available EMRs (median age 60; 62% male), and 252 had AC, 195 NAC, 54 AH, and 263 AUD. Table 1 shows case definition accuracy estimates and ICD-10 codes used. The novel AC case definition selecting admissions with either the AC code alone or DC and AUD codes together had a PPV of 93% and was more sensitive (76% vs 44-63%) and accurate (AUROC 0.86 vs 0.71-0.81, p<0.001) than the other novel and standard AC case definitions. The novel NAC1 case definition had similar PPV (84% vs 84%) but better sensitivity (57% vs 52%) and AUROC (0.76 vs 0.74, p=0.006) compared to novel NAC2 case definition. The novel NAC1 case definition had better PPV (84% vs 79%) but similar sensitivity (57% vs 57%) and AUROC (0.76 vs 0.76, p=0.14) compared to the standard approach using a NAC code alone (not excluding AC/AH/AUD codes).

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Conclusion(s): Newly developed administrative case definitions show enhanced accuracy for identifying AC and NAC hospitalizations. Future studies evaluating our proposed algorithms in different databases are warranted.

Disclosure of Interest: L. Swain: None Declared, J. Godley: None Declared, J. Abraldes Grant / Research support from: received grants from Cook and Gilead (paid to the University of Alberta), Consultant of: received consulting fees from Boehringer Ingelheim, AstraZeneca, Inventiva and 89Bio, M. Brahmania: None Declared, A. A. Shaheen Grant / Research support from: participated in advisory boards and received research grants from Gilead and Intercept

Can Liver J. 2024 Feb 26;7(1):236–238.

CLM-P118 COVID pandemic impact on care delivery and quality of life among patients with primary biliary cholangitis: a large Canadian study

E Baguley ¹, M Knaub ², G Wright ³, J VanDyke ², MG Swain ¹, D McCaughey ², G Hirschfield ⁴, A-A Shaheen ¹

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: The pandemic-related restrictions impacted care delivery, particularly during the first year.

Purpose: We assess the impact of the pandemic on care delivery for patients with primary biliary cholangitis (PBC) and describe the quality of life they experienced during this time.

Method: The 29-item Patient Reported Outcomes Measurement Instrument Survey (PROMIS-29) and a PBC Care Delivery questionnaire were administered to patients with PBC (n=339), followed by two focus groups for patients (n=14) and stakeholders (n=3) between August 2021 and June 2022. The PROMIS-29 has seven health domains measured as T-Scores, including pain interference, depression, physical function, ability to participate in social roles/activities, fatigue, anxiety, and sleep disturbance, and a single pain intensity item. PROMIS-29 scores were compared between our PBC cohort and a general reference population from the 2000 General US Census. Additionally, we compared PROMIS-29 scores of our population based on experienced care delay (laboratory work and imaging) and appointment type (in person vs. virtual).

Result(s): Participants were primarily females (93.5%) and Caucasian (89.1%), with a median age of 62 yrs (IQR: 55-70). Median time from PBC diagnosis was 9 years (IQR: 4-18). During the pandemic, most participants (76.4%) had ≥ 50% of their hepatologist appointments virtually; however, post-pandemic only 22.4% preferred to continue with virtual appointments. Many participants (34.6%) experienced at least one delay in obtaining laboratory work, imaging, or medications. Participants scored significantly worse (p<0.001) in all PROMIS-29 domains compared to the general population. Participants who experienced delays in care had higher fatigue (p=0.001), anxiety (p=0.007), and sleep disturbance (p=0.006) scores, and more difficulty participating in social roles and activities (p=0.019), compared to individuals who had no care delays (Table 1). No significant differences were found between PROMIS-29 scores and appointment type (Table 1). Focus groups indicated both patients and stakeholders agreed on the importance of in-person appointments, while recognizing that virtual care may play a role in post-pandemic care.

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Conclusion(s): For post-pandemic care, the majority of PBC patients and providers preferred in-person appointments. PBC patients experienced poor quality of life during the pandemic compared to the general population, particularly those with delayed care.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):238.

CLM-P119 “The times have changed. HEP C treatment is readily available so why isn’t Hep C testing readily available” - Perceptions and experiences of people who inject drugs surrounding testing for Hepatitis C virus infection

C Balsom ¹, D Kelly ¹, S Bugden ¹, L Jackson ²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: In 2016, the World Health Organization called on all countries to invest in eliminating hepatitis and set a goal of eliminating viral hepatitis by 2030. Hepatits C Virus (HCV) is a blood borne virus; infection occurs through exposure to blood from an infected person, most commonly by sharing needles or other equipment used to prepare and inject drugs. Low testing rates and the asymptomatic nature of the acute infection mean that many people are diagnosed for the first time after presenting with late-stage disease. This is particularly problematic since there is a higher rate of complications and mortality when diagnosed late and people may unknowingly pass the infection to others while undiagnosed. People who inject drugs (PWID) make up the largest proportion of individuals with HCV infection in Canada but many are unaware of their infection. This qualitative study aimed to explore the experiences and perceptions of people who inject drugs surrounding testing for Hepatitis C Virus.

Purpose: This qualitative study aimed to explore the experiences and perceptions of people who inject drugs surrounding testing for Hepatitis C Virus to inform health policy and make a meaningful impact in increasing testing rates among this population.

Method: Between June and August 2022, eleven PWID were interviewed using semi-structured interviews. Data were transcribed verbatim and reflective thematic analysis was performed. There are multiple reasons why testing is not being done and feelings surrounding testing vary.

Result(s): Five key themes were produced: there are multiple reasons why testing is not being done, access to and relationship with primary care provider affects testing, testing can be emotionally uncomfortable for some but not for others, there is a need for increased awareness of treatment options, the importance of testing, and more testing options, and testing is important for one's own health and the impact on others.

Conclusion(s): This study demonstrated that the experience of PWID and their motivations for testing are complex and consideration is required when developing HCV screening initiatives in this population. To make progress towards HCV elimination efforts it will be important to combat stigma and make testing for HCV more user-focused. The results have potential to positively impact the development and successful roll-out of HCV screening programs that are attractive to this population and ultimately increase case-finding and access to treatment.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):239–240.

CLM-P120 HBV care cascade in Rwanda: the impact of integration and decentralization of HBV services on enhancing the HBV care continuum

JD Makuza ^1,^2,³, D Jeong ^1,², S Phyumar ¹, RL Morrow ^1,², G Cua ^1,², HA Velásquez García ^1,², MP Nisingizwe ¹, J Serumondo ³, A Tuyishime ³, A Ramji ⁴, M Law ¹, NZ Janjua ^1,^2,⁵

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: Rwanda adopted decentralization and integration of Hepatitis B Virus (HBV) services in July 2019 into existing health services. However, there is a lack of information regarding HBV care in Sub-Saharan Africa and how integration and decentralization impact it.

Purpose: We assessed the impact of decentralization and integration on HBV care services in Rwanda by comparing the HBV care cascade before and after their implementation.

Method: This retrospective cohort study used District Health Information System 2 data, covering 4.5 million individuals screened for HBV in Rwanda from January 2016 to June 2023. We included individuals aged >2 years and analyzed the HBV care cascade across five stages: lifetime prevalence, diagnosis, care engagement, treatment initiation, and treatment continuation. Infections were identified via reactive antigen or nucleic acid tests, and overall prevalence was estimated from diagnosed and estimated undiagnosed cases among the targeted 7 million individuals. We compared care cascade proportions before (January 2016 - June 2019) and after decentralization (July 2019 - June 2023), with most individuals receiving care at health centers. Stratified analyses and multivariable logistic regression were used to identify factors influencing progression through the cascade.

Result(s): Among the 4,604,468 persons included, 55,820 (21,641 before decentralization vs. 34,179 after) were diagnosed with HBV infections. Of those, 21,182 (38.0%) [5,034 (23.4%) vs. 16,137 (47.2%) before and after] were engaged in care, 5,966 (28.17%) [2,435 (40.9%) vs. 3,531 (21.9%) before and after] were eligible for HBV treatment, 4,746 (79.6%) [1,050 (80.1%) vs. 2,706 (79.2%) initiated treatment, and 4,621 (97.4%) [1,042 (89.6%) vs. 2,670 (95.8%) before and after] continued treatment at one-year post-initiation. The estimated number of cases was 186,423 individuals with HbsAg positive. Individuals screened post-decentralization were more likely to be engaged with care (adjusted odds ratio [aOR], 4.12; 95% CI, 3.93, 4.33), eligible for HBV treatment (aOR, 1.52; 95% CI, 1.36, 1.68), and initiate treatment (aOR, 4.49; 95% CI, 3.30, 6.10), compared to those screened pre-decentralization. However, they were less likely to be retained in HBV treatment (aOR, 0.18; 95% CI, 0.07, 0.46). Individuals screened pre-decentralization at provincial and referral hospitals showed higher engagement, eligibility, and treatment initiation than at health centers.

graphic file with name canlivj-7.1-abst_fig53.jpg — Image:

Conclusion(s): After decentralization, individuals screened for HBV showed better care engagement, including higher enrollment, treatment eligibility, and initiation. However, post-decentralization, care retention was lower. These findings highlight the significance of integrating HBV care into existing services and decentralization while highlighting the ongoing challenges of monitoring and retaining individuals in care post-treatment initiation.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):240–242.

CLM-P121 The impact of COVID-19-related public health measures on hepatocellular carcinoma screening in British Columbia, Canada: an interrupted time series study

JD Makuza ^1,², S Wong ², M Binka ², M Darvishian ³, D Jeong ^1,², RL Morrow ^1,², PA Adu ², G Cua ^1,², A Yu ², HA Velasquez García ^1,², M Alvarez ², S Bartlett ², E Yoshida ⁴, A Ramji ⁴, M Krajden ², NZ Janjua ^1,^2,⁵

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: Yes

Background: Incidence and mortality from Hepatocellular carcinoma (HCC) are increasing in Canada. Individuals with HCV diagnosed with cirrhosis should be screened twice yearly for HCC in Canada. Coronavirus disease 2019 (COVID-19) has disrupted many health services globally since early 2020, including HCC screening among eligible individuals.

Purpose: We assessed the impact of the COVID-19 pandemic on HCC screening using surveillance data from the BC-Hepatitis Testing cohort (BC-HTC).

Method: We performed a retrospective cohort study using BC-HTC data, including about 1.7 million individuals tested for HCV or HIV or reported as a case of HCV, HIV, or HBV from January 1990 to December 31, 2015. Our primary outcome was HCC screening among individuals with HCV diagnosed with cirrhosis according to Canadian guidelines. In the BC-HTC dataset, HCC screening was flagged by the HCC-related medical screening following the initial cirrhosis diagnosis with liver or abdomen ultrasound and CT scan if the ultrasound was unclear among individuals with HCV. We summarized the number of individuals screened each month between January 2018 and December 2020. We included interruption on March 2020 when the BC government implemented COVID-19 restriction measures. We conducted interrupted time–series (ITS) analysis using a segmented linear regression model to assess the impact of COVID-19 and included first-order auto-correlation terms to control for data correlation.

Result(s): Overall, 6546 HCC screenings were performed among 3429 individuals living with HCV and cirrhosis from January 2018 to December 31, 2020, and 1,476 (22.55%) during COVID-19 (March 2020 - December 2020). The average monthly number of individuals screened during the study period was 181. The number of individuals screened dropped to 138 in March 2020 and 54 in April 2020 (72% drop from April 2019), the lowest point during the pandemic, then recovered with 129 screening in May 2020. The ITS also showed an immediate decline in March 2020 and a sharp decline in April 2020, with some recovery afterward. The reduction was not demonstrated in individuals non-treated for HCV and those under 45 years of age.

graphic file with name canlivj-7.1-abst_fig54.jpg — Image:

Conclusion(s): There was a sharp decline in the number of individuals with HCV with cirrhosis screened for HCC immediately after implementing public health measures, with recovery later in 2020.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):242–243.

CLM-P122 The changing landscape of cirrhosis: impact on young adults and females

N Faisal ¹, LM Lix ², A Singer ³, R Walld ⁴, H Singh ¹, L Kosowan ³, E Renner ¹, A Mahar ⁵

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Cirrhosis exerts a substantial impact on both individual health and healthcare systems worldwide, contributing to over 2 million deaths annually, which accounts for approximately 4% of total global mortality (1-3).

Purpose: The evolving risk factors associated with cirrhosis highlight the ongoing significance of prevention and management in addressing this serious and potentially life-threatening condition. To facilitate the development of these strategies, we aimed to investigate the temporal trends of cirrhosis incidence in Manitoba, Canada, as well as assess changes in these estimates across different age groups and between males and females.

Method: Individual level administrative healthcare data from Manitoba was used to identify individuals with cirrhosis between 2010-2019 using a validation algorithm that required at least one hospitalization or physician claim for cirrhosis. The estimates of sensitivity and specificity of the algorithms when compared to a reference standard of validated primary care case definition was 68% and 97% respectively, using longitudinal data from 1998 to 2020. To establish incident cases, we used a five-year look back window. Annual incidence rates were estimated using a generalized linear model and generalized estimating equations with a negative binomial distribution adjusting for age and sex. Linear trends of incidence by calendar year, overall and by age and sex, were tested using linear regression models.

Result(s): Between 2010-2019, a total of 24,303 incident cases of cirrhosis were identified. Mean age at diagnosis was 50 years SD 15.8 and 51% were males. Age and sex adjusted incidence increased by 50% between 2010-2019 (264 vs 389/100,000). Incidence increased by 2-fold over the study period for aged 18-44 (144 vs 289/100,000) more among females than males (Figure 1). Cirrhosis incidence increased on average per year by 6% (95% confidence interval (CI) 5% to 7%, (p <.001), with the largest increase of 8% per year (95% CI 7% to 9%) p <0.0001 in those aged 18-44 years. The youngest age group (ages 18-44 years) also exhibited the highest rate of increase in the incidence of cirrhosis compared to other age groups (P <.001). The incidence of cirrhosis showed a greater annual increase in females, with a rate of 7% per year (95% CI 5% to 8%), compared to males, who had a rate of 5% per year (95% CI 4% to 6%) (p <0.0001). In addition, females demonstrated a significantly higher rate of change in cirrhosis incidence compared to males (p = 0.0025).

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Conclusion(s): The incidence of cirrhosis substantially increased, signaling an alarming shift in the disease burden towards younger individuals and females. Public health action is required to implement an effective multi-faceted approach encompassing prevention, early detection, provision of high-quality healthcare and public health initiatives to effectively tackle this escalating health burden.

References: 1. Lan Y, Wang H, Weng H, et al. The burden of liver cirrhosis and underlying etiologies: results from the Global Burden of Disease Study 2019. Hepatology Communications. 2023;7(2):e0026.

2. Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of liver diseases in the world. Journal of Hepatology. 2019;70(1):151-71.

3. Moon AM, Singal AG, Tapper EB. Contemporary Epidemiology of Chronic Liver Disease and Cirrhosis. Clin Gastroenterol Hepatol. 2020;18(12):2650-66.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):243–244.

CLM-P123 Predicting future decompensation in patients with cirrhosis: a machine learning approach to risk stratification at the first patient visit

M Grubert Van Iderstine ¹, B Griggs ¹, O Thorleifson ¹, GY Minuk ², N Faisal ²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Decompensation is a major turning point in the course of chronic liver disease. Determining which patients with cirrhosis will decompensate is challenging due to the complex non-linear relationships between lab values and patient outcomes. Machine learning classification algorithms can identify patterns in large datasets that reveal which patients are at heightened risk of decompensation in the future.

Purpose: We aimed to develop and validate machine learning (ML) models to predict hepatic decompensation in a timely and accurate manner at the first patient visit.

Method: This study used a retrospective province-wide cohort of 3483 adult patients with cirrhosis or its complications seen in hepatology clinics between 1987 and 2023. Patients were identified to have cirrhosis and classified as either compensated or decompensated based on diagnostic and prescribing codes. We identified eleven potential biochemical and demographic predictors that can be evaluated at the first clinic visit. Patients were randomly selected for model development (80%, n = 2786) and validation (20%, n = 697). Twelve ML classification models including Support Vector Machine, Random Forest, XGBoost and AdaBoost were trained and tuned to differentiate between compensated and decompensated patients. Predictor inclusion and model selection were conducted with 10-fold cross-validation. Model performance was evaluated using precision, recall and f1 scores.

Result(s): Of the 3483 patients with cirrhosis, 992 patients were eventually diagnosed with decompensation and 2491 patients remained compensated. The mean age was 51.8 years, 50.5% were male, and mean length of follow-up was 7.5 years. Prediction on the validation dataset indicated that the AdaBoost classifier performed best with a compensated precision rate of 0.893 and decompensated recall of 0.791. The compensated recall was 0.616, and f1 score was 0.729. The decompensated patient precision was 0.421, and f1 score was 0.55. Ten-fold cross validation accuracy was 71.6% (SD = 2.5%). The AUC-ROC for the binary decision was 0.76. The features of highest predictive value were found to be INR, platelets, sodium, creatinine, albumin and bilirubin.

Conclusion(s): The machine learning models developed using a province wide hepatology ambulatory database of cirrhosis patients can potentially define a high-risk group early in the course of disease. This, in turn, can lead to improved clinical outcomes and aid in treatment decision-making and prognostication. Additional external validation is needed to confirm the reliability and generalizability of these models.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):244–245.

CLM-P124 Evaluating the non-viral liver disease burden in people living with HIV and abnormal liver enzymes

D Katarey ¹, Y Tan ², A Mourad ², J Potts ¹, L Vickers ², A Beksinska ², H Sharp ², B Parnell ², Y Gilleece ², S Verma ²

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Liver disease in the absence of viral hepatitis co-infection is a growing problem in people living with HIV (PLWH). Likely contributors include alcohol excess, metabolic syndrome (MS), and hepatotoxic antiretrovirals (ARV), however prospective data defining the magnitude of this issue is lacking.

Purpose: We aimed to assess the prevalence of hepatic fibrosis and associated risk factors in HIV mono-infected individuals with abnormal liver tests.

Method: We recruited, from 2014-21, PLWH with persistently elevated serum alanine aminotransferase (ALT) levels for >6 months and negative hepatitis serology. Recruited individuals were prospectively assessed using transient elastography, AUDIT questionnaire, and screening for MS. Thresholds for clinically significant hepatic fibrosis (CSHF) and cirrhosis were >7.1kPa and >12.5kPa respectively, and hepatic steatosis (HS) by a controlled attenuation parameter (CAP) >237dB/m.

Result(s): Of 274 recruited individuals the median age was 52yrs (IQR 45-59), 93% men, median HIV duration 15yrs (IQR 10-20), and undetectable viral load in 96%. Overall, HS was seen in 169 (61.7%) and CSHF was seen in 54 (19.7%), of whom 19 (35.2%) had cirrhosis and 40 (74.1%) had HS. Alcohol, MS and ARV were implicated in 24 (44.4%), 31 (57.4%), and 15 (27.8%) of patients with CSHF, respectively. No risk factors were identified in 10 (18.5%) with CSHF. In those with CSHF (n=54) versus those without (n=220), no significant differences were seen in baseline demographic or metabolic co-factors, nor ARV use. On binary and multinomial logistic regression lower HDL cholesterol (HR 0.255, 95% CI 0.103-0.629, P=0.003) and diabetes (HR 2.558, 95% CI 1.175-5.571, P=0.018) were independent predictors of CSHF. Both FIB-4 and APRI performed poorly in identifying CSHF (AUROC 0.556 and 0.603 respectively; Figure 1).

graphic file with name canlivj-7.1-abst_fig56.jpg — Image:

Conclusion(s): In these PLWH and elevated ALT, ∼20% had CSHF and ∼60% had HS. Lower HDL and diabetes were independent predictor of CSHF. Hazardous drinking or MS were identified in most patients with CSHF, however no risk factors were identified in almost 20%. This raises the intriguing possibility that CSHF may be caused directly by the HIV infection.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):245–247.

CLM-P125 Access to systemic therapy in hepatocellular carcinoma in Canada is variable

H Nadeem ¹, D Ezeife ², M Brahmania ^1,³, KW Burak ^1,³, V Tam ², SE Congly ^1,³

What is your preferred presentation method?: Oral/Poster

Do you wish to apply for a travel grant?: Yes

Are you a CanHepC Trainee?: No

Background: Patients diagnosed with advanced hepatocellular carcinoma (HCC) have demonstrated improved quality of life and extended survival when treated with systemic chemotherapy. In Canada, the coverage and accessibility of licensed HCC medications are determined by individual provinces, guided by health technology assessment recommendations provided by the pan-Canadian Oncology Drug Review (p-CODR). Consequently, access to treatment for patients may vary depending on their province of residence.

Purpose: Given the documented disparity in drug coverage for chronic liver disease across Canada, our study aimed to identify potential disparities in access to systemic HCC treatment in different provinces.

Method: We conducted an extensive evaluation of government-funded formularies in all Canadian provinces and territories to assess the coverage criteria for approved first-line and second-line HCC treatments as of October 2023. Individual provincial cancer centres were contacted for clarification as required. Data collected included patient eligibility criteria, funding restrictions, and specific treatment indications.

Result(s): For first-line systemic therapy in HCC, universal coverage was observed for lenvatinib. Sorafenib was covered by most programs except Manitoba, Northwest Territories, and Nunavut, as well as the Non-Insured Health Benefits (NIHB) program. While the option to switch between sorafenib and lenvatinib was permitted in cases where patients experienced medication intolerance, such transitions were not sanctioned for disease progression. Almost all programs covered the combination therapy of atezolizumab + bevacizumab for HCC except Newfoundland and the Yukon. In the case of patients covered by the NWT/NIHB/Nunavut formulary, coverage was contingent upon their treatment location. None of the provinces and territories extended coverage for the combination of tremelimumab + durvalumab for first line HCC treatment.

In the context of second-line therapy, the Yukon emerged as the sole program not covering either regorafenib or cabozantinib. Across Canada, patients who have experienced disease progression while receiving atezolizumab + bevacizumab are considered ineligible for treatment coverage with regorafenib and cabozantinib. For systemic therapy, access was predominantly limited to patients with Child Pugh A liver disease and good functional status, requiring an Eastern Cooperative Oncology Group (ECOG) score between 0-1 for treatment. Notably, eight programs reported coverage of sorafenib for patients with ECOG scores up to 2, and only Ontario extended lenvatinib coverage to ECOG 2 patients. Indications for funded drugs aligned with national health technology recommendations.

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Conclusion(s): Overall, access to systemic HCC therapy across Canada exhibits substantial uniformity, with some provinces imposing more restrictive access criteria. Sustained advocacy efforts are necessary to enhance HCC care across the country.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):247.

CLM-P126 Validation of hepatorenal syndrome diagnostic code in hospitalized patients at the university health network

JM Yabut ^1,², A Imrit ³, M Ismail ³, SB Roberts ⁴, F Razak ^2,³, AA Verma ^3,⁵, GM Hirschfield ^1,², AT Ma ¹

What is your preferred presentation method?: Poster Only

Do you wish to apply for a travel grant?: No

Are you a CanHepC Trainee?: No

Background: Hepatorenal syndrome (HRS) is a specific type of acute kidney injury (AKI) that results in significant morbidity and mortality in patients with cirrhosis and ascites. The diagnostic criteria for HRS-AKI were revised in 2015 by the International Club of Ascites to improve early recognition and reduce time to treatment, removing barriers to life-saving interventions. Terlipressin, a vasopressin analogue used for the treatment of HRS, is already available in Europe, Asia and recently the U.S, and will be soon introduced in Canada. Thus, a better understanding of the burden of HRS-AKI is timely. Administrative data would likely provide the best assessment of the magnitude HRS-AKI in Canada, however, the accuracy of the ICD-10 diagnostic code for HRS has not yet been validated in Canada.

Purpose: Administrative data would likely provide the best assessment of the magnitude HRS-AKI in Canada, however, the accuracy of the ICD-10 diagnostic code for HRS has not yet been validated in Canada.

Method: Data from 09/2015 to 03/2021 were obtained from two hospitals at the University Health Network (Toronto, Canada) that are participating in the GEMINI collaborative. Patients with the international classification of diseases, 10^th Revision, enhanced Canadian version (ICD-10-CA) HRS diagnostic code (K76.7) on their discharge summary were included. Charts were manually reviewed for clinical and biochemical information related to the diagnostic criteria for HRS-AKI, including presence of cirrhosis and ascites, presence of AKI, absence of shock, absence of nephrotoxic drugs, absence of structural kidney injury signs, and absence of response to a 2-day albumin challenge.

Result(s): Of the 133 admissions with the HRS diagnostic code, 131 were included in the analysis since 2 datasets could not be extracted (corresponding to 126 individual patients, mean age 61 years, 62% male). HRS-AKI criteria were met in 91 admissions (69.5%). Of the 40 admissions that did not meet criteria, 11 did not have an AKI episode during admission (27.5%), 10 did not have cirrhosis or ascites or both (25%), 8 had AKI that resolved within 48 hours of plasma expansion (20%), 6 did not receive albumin at AKI diagnosis (15%), 3 presented at admission with shock (7.5%), 2 died before 48-hour creatinine could be retrieved (5%).

Conclusion(s): The positive predictive value of the HRS ICD-10 code is moderate, suggesting caution should be applied when analyzing large administrative datasets. Datasets extracted using diagnostic codes may still inform general trends that exist in this disease. Additional work is required including a cohort of patients without the HRS ICD-10 code to assess its sensitivity, specificity, and accuracy.

Disclosure of Interest: None Declared

Can Liver J. 2024 Feb 26;7(1):248.

CONTROL ID: 3991170 AI in hepatology: A comparative analysis of CHATGPT-4, BING, and BARD at answering clinical questions

S Anvari ¹, Y Lee ¹, D Jin ¹, S Malone ², M Collins ¹

Aims: To determine the ability of large language models (LLMs) to respond accurately to textbook questions in hepatology, as well as compare the accuracy and quality of responses provided by different LLMs.

Background: The role of artificial intelligence (AI) in hepatology is rapidly expanding. However, the ability of AI chat models such as ChatGPT to accurately answer clinical questions remains unclear. There is also a paucity of data directly comparing responses provided by various AI chatbots when answering clinical questions in hepatology.

Conclusions: LLMs demonstrate variable accuracy when answering clinical questions related to hepatology, though show comparable efficacy when presented with questions in an open-ended versus MCQ format. Further research is required to investigate the optimal use of LLMs in clinical and educational contexts.

Methods: Hepatology questions from the Digestive Diseases Self-Education Platform (DDSEP+ 2023) published by the American Gastroenterological Association were entered into three LLMs (OpenAI's ChatGPT-4, Microsoft's Bing, and Google's Bard) between September 7-13, 2023. Questions were posed twice: once with the inclusion of multiple-choice answers to choose from and once without. Generated responses were assessed based on overall accuracy and the number of correct answers. Statistical analysis was performed to determine the number of correct responses per LLM per category

Results: A total of 144 questions were used to query the AI models. When questions were posed alongside multiple choice answers, ChatGPT-4's accuracy was 62.5%, Bing's accuracy was 53.5%, and Bard's accuracy was 38.2% (p < 0.001). When questions were asked in an open-ended fashion, ChatGPT-4's accuracy was 44.4%, Bing's was 28.5%, and Bard's was 21.4% (p<0.001). ChatGPT-4 had the highest accuracy across all question categories (viral hepatitis, cirrhosis and liver transplant, and metabolic, hereditary, inflammatory and vascular diseases of the liver). ChatGPT-4 and Bing attempted to answer 100% of questions, whereas Bard was unable to answer 11.8% of questions posed to it. All three models provided a rationale in addition to an answer, as well as counseling where appropriate.

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TABLE: Accuracy of provided answers by AI chatbots

AI Model	Correct N(%)	Incorrect N(%)	Multiple answers given N(%)
Multiple Choice Questions
ChatGPT-4	90 (62.5)	54 (37.5)	0 (0)
Bard	55 (38.2)	89 (61.8)	0 (0)
Bing	77 (53.5)	67 (46.5)	0 (0)
P-value	<0.001	<0.001	-
Open Ended Questions
ChatGPT-4	64 (44.4)	59 (41.0)	21 (14.6)
Bard	31 (21.5)	104 (72.2)	9 (6.3)
Bing	41 (28.5)	76 (52.8)	27 (18.8)
P-value	<0.001	<0.001	0.006

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Can Liver J. 2024 Feb 26;7(1):248–249.

CONTROL ID: 3995455 Geographic and socioeconomic disparities in cirrhosis incidence and prevalence: A population-based study in Manitoba, Canada

MH Mikail ¹, A Mahar ², L Lix ¹, R Walld ¹, A Singer ¹, E Renner ¹, H Singh ¹, L Kosowan ¹, N Faisal ¹

Aims: This study aims to estimate and compare the incidence and prevalence of cirrhosis across distinct geographic health regions and income quintile within the province of Manitoba.

Background: Cirrhosis is a significant public health concern, ranking as the fifth leading cause of mortality in Canada. Its incidence and prevalence exhibit geographical and socioeconomic variations, necessitating a comprehensive understanding to facilitate effective healthcare planning and resource allocation.

Conclusions: This population-based study highlights substantial geographic and income-based disparities in cirrhosis incidence and prevalence estimates within Manitoba. The elevated risk in the Northern region underscores the need for targeted healthcare interventions and policy measures to reduce this disparity and improve the overall population's health.

Methods: A population-based study was conducted utilizing provincial administrative healthcare data spanning from January 2010 to December 2019. Individuals aged 18 years and older with cirrhosis were identified using a validated case definition which required at least one hospitalization diagnosis or one physician visit for cirrhosis related ICD-9-CM and ICD-10-CA codes. Generalized linear models with a negative binomial distribution were employed to estimate incidence and prevalence rates and incidence rate ratios (IRRs) adjusted for age and sex with 95% confidence intervals (CIs).

Results: The study included 29,943 cirrhosis patients, 51% were male and mean age of 54 years. Geographic disparities in cirrhosis incidence and prevalence estimates were observed based on the area of patient residence. Between 2010 and 2019, the provincial prevalence of cirrhosis was estimated at 3.6%. Notably, substantial regional differences were evident, with the Northern region exhibiting the highest prevalence estimates at 7%, while the South region reported the lowest prevalence at 2.9% (Figure 1[NF1]). Residents of Northern Manitoba had 78% higher risk of diagnosed cirrhosis (IRR = 1.78, 95% CI 1.62 to 1.95) than Winnipeg residents (p<0.0001). Cirrhosis prevalence estimates were significantly higher in the lowest income quintile compared to the highest income quintile (5.3% vs. [NF2] 3.73%, p<0.0001). [NF3] Furthermore, individuals from lower income quintiles exhibited 43% higher risk of diagnosed cirrhosis (IRR=1.48, 95% CI 1.38 – 1.48; p<0.0001) compared to those from higher income quintiles.

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Can Liver J. 2024 Feb 26;7(1):249–251.

CONTROL ID: 3999950 Immune checkpoint inhibitor liver-related adverse events: A case series

VV Nguyen ¹, E Lytvyak ¹, M Wells ¹, R Bhanji ¹, P Tandon ¹, C Moctezuma Velázquez ¹, A Montano Loza ¹

Aims: This case series reports seven patients who received ICI and developed liver-related adverse events.

Background: Immune-related adverse events (IRAE) are rising due to increasing use of immune checkpoint inhibitors (ICI) for cancer treatment. Liver-related adverse events occur in 5 to 10% of patients, with immune-mediated hepatitis (IMH) accounting for majority of cases. <3% result in severe hepatitis and <0.04% fulminant hepatitis. Severity is determined by the degree of LE (liver enzyme) elevation, which determines treatment. Most patients with mild to moderate hepatitis respond to discontinuation of ICI. In severe cases, immunosuppression is required with corticosteroids and/or a secondary immunomodulator. ICI-related biliary complications are less common and account for <3% of IRAE. Specifically, ICI-related sclerosing cholangitis (IRSC) is rare and accounts for <1% of cases. The pathogenesis of IRSC is not well understood and patients are typically refractory to corticosteroids.

Conclusions: Liver-related adverse events are becoming more common with widespread use of ICI. Patients should have baseline LE completed and frequent monitoring while on therapy. Prompt recognition of elevated LE is critical in the diagnosis of IMH. In moderate to severe cases, guidelines recommend holding ICI, monitoring LE closely, and initiating corticosteroids. IRSC is an uncommon liver related adverse event. Further prospective data is required to establish diagnostic criteria and treatment guidelines.

Methods: Electronic medical records were reviewed on 90 patients who received ICI therapy at a tertiary centre from January 2018 to October 2023. Data was reviewed to evaluate the development of IMH and IRSC, and severity was graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Results: Seven patients were identified to have IMH and/or IRSC during the study period. Patients received pembrolizumab (four), nivolumab (one), durvalumab (one), or atezolizumab (one). Five patients developed IMH requiring immunosuppression, one IRSC, and one IMH and IRSC. Five of six patients with IMH developed severe hepatitis and required corticosteroid therapy. Three of these patients required a secondary immunomodulator with mycophenolate mofetil or azathioprine. Five of six patients with IMH had normalization of LE. ICI therapy was only restarted in one patient. Two patients developed IRSC with cholestatic LE elevation and imaging suggesting sclerosing cholangitis. One patient was started on ursodeoxycholic acid, and the other patient had spontaneous normalization of their LE and radiographic improvement of biliary dilation. During a median follow-up of 13 months, one patient died due to progression of underlying malignancy. No patients died secondary to IMH and/or IRSC.

Can Liver J. 2024 Feb 26;7(1):251–252.

CONTROL ID: 4000412 Real-world performance of vibration-controlled transient elastography with liver stiffness measurement and spleen stiffness measurement in a tertiary center

M Edwards ¹, AC Ma ¹, EM Kelly ¹, PY Tan ¹, N Gotlieb ¹, M Moini ¹, F de Quadros Onofrio ¹, N Trudel ¹, J Lamoureux ¹, A Cheung ²

Aims: To describe the real-world performance of LSM ± SSM in predicting CSPH.

Background: Clinically significant portal hypertension (CSPH) is defined as hepatic venous pressure gradient (HVPG)

≥10 mmHg, which can lead to varices and decompensation. Several non-invasive methods exist to predict CSPH, including liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE). In a systematic review comparing LSM and HVPG, area under the receiver operating curve (AUROC) for LSM was 0.67-0.91, sensitivity 52-97% and specificity 37-97% in predicting CSPH. Spleen stiffness measurement (SSM) via VCTE has been endorsed by the Baveno group as a test that can be used with LSM to predict CSPH. SSM has an AUROC of 0.53-0.97 with sensitivity 40-99% and specificity 34-97% in predicting CSPH.

Conclusions: In this study, SSM appears to better predict CSPH than LSM alone. Further analysis is required to determine if performance of SSM is consistent across LSM values. It is also important to determine if the ANTICIPATE criteria may perform better in our population with a high prevalence of metabolic dysfunction-associated steatotic liver disease. Analysis is ongoing.

Methods: A retrospective chart review was done of adult patients at The Ottawa Hospital who underwent VCTE with LSM ± SSM (May to September 2023). VCTE was performed by two experienced operators. Charts were reviewed for demographics, LSM, SSM, endoscopy, imaging, and lab results. Patients were included if they had VCTE, imaging and esophagogastroduodenoscopy (EGD). Preliminary analysis was performed for positive predictive value (PPV) and/or negative predictive value (NPV) of LSM, SSM, and thrombocytopenia cut-offs. CSPH was defined as findings of portal hypertension on imaging, history, or endoscopy.

Results: 892 patients underwent VCTE during the study period. Data was collected on 223 patients, with 114 included (Table 1). All had LSM and 28 had SSM. The PPV for predicting CSPH for LSM was 0.48, 0.52 and 0.55 with cut-offs of LSM >20 kPa, >25 kPa and >30 kPa, respectively. The PPV for predicting varices at endoscopy dropped to 0.24, 0.29, and 0.30 with cut-offs of LSM >20 kPa, >25 kPa and >30 kPa, respectively. The NPV for LSM <15 kPa for predicting varices at endoscopy was 0.69. The PPV for predicting CSPH for SSM was 0.70, 0.68, and 0.60 with cut-offs of SSM

>35 kPa, >40 kPa, and >45 kPa, respectively. The PPV for predicting varices at endoscopy was 0.42, 0.46, and 0.47 with cut-offs of SSM >35 kPa, >40 kPa and >45 kPa, respectively. Platelets <150x109/L had a PPV of 0.42 and platelets

>150x109/L had a NPV of 0.83 with respect to varices at EGD. AUROC to predict varices was 0.49 for LSM and 0.68 for SSM.

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Can Liver J. 2024 Feb 26;7(1):252–253.

CONTROL ID: 4003416 Biliary atresia in pediatric patients with concurrent complete situs inversus and pathogenic variants in ciliary genes

I Birger ¹, N Samra Naser ², Y Mozer Glassberg ³, S Abozaied ⁴, A On ⁴, H Mandel ², R Arnon ⁵

Aims: Primary ciliary dyskinesia (PCD) is a genetic disorder defined by congenital ciliary structural or functional anomalies. Structural abnormalities of cilia were previously demonstrated in intrahepatic cholangiocytes of patients with both syndromic and non-syndromic BA.

Background: Biliary Atresia (BA) is a progressive obliterative cholangiopathy presenting in the newborn period, affecting both extrahepatic and intrahepatic bile ducts, leading to biliary cirrhosis. 10-15% of BA cases are associated with laterality malformations, collectively known as Biliary Atresia Splenic Malformation (BASM).

Conclusions: Previous studies suggested underlying genetic defects, mostly in ciliary genes, involved in the causation of BA. The patients herein described give support to potential contribution of ciliary dysfunction in the development of BA. We propose considering genetic screening in the evaluation of BA in infants presenting with or without laterality defects. Both DNAH11 and PIH1D2 might be added to the cholestatic liver disease gene panel.

Methods: We present two patients with BA and complete situs inversus, who presented with neonatal cholestasis, prompting further evaluation including genetic tests.

Results: The first patient was homozygous for a variant in DNAH11 gene, encoding the outer dynein arm, causing PCD in his kindred. In the second patient, Whole-Exome-Sequencing revealed a homozygous mutation in PIH1D2 gene, shown to-date only in zebrafish model to be associated with ciliopathy. Both patients underwent Kasai operation. The first patient, demonstrates efficient biliary drainage with clinical and biochemical improvement.

The 2nd patient died at age 11 months due to multiorgan failure while awaiting a liver transplantation.

PERMALINK

Annual Meeting of the Canadian Association for the Study of the Liver (CASL), the Canadian Network on Hepatitis C (CANHEPC) and the Canadian Association of Hepatology Nurses (CAHN) 2024 Abstracts

CLM-O01 Risk environments and binge drug injection in a cohort of people who inject drugs in Montreal

N Minoyan

S H⊘j

S Larney

D Jutras-Aswad

V Martel-Laferrière

M-P Sylvestre

J Bruneau

CLM-O02 Epidemiology of hepatitis C over 28 years of monitoring in nine provinces: Blood donors lend insight into the low-risk undiagnosed population

SF O’Brien

B Ehsani-Moghaddam

M Goldman

SJ Drews

CLM-O03 Impact of sex and type 2 diabetes mellitus on quality of life among non-alcoholic fatty liver disease patients: A large Canadian cohort study

E Baguley

M Knaub

W Schaufert

MG Swain

A-A Shaheen

CLM-O04 Estimating the prevalence and undiagnosed proportion of chronic hepatitis C infection among immigrants in Quebec using mathematical modelling and health administrative data

F Forouzannia

AM Passos-Castilho

N Janjua

B Sander

C Greenaway

WWL Wong

CLM-O05 Impact of the COVID-19 pandemic on hepatitis C virus (HCV) screening in provincial prisons in Quebec, Canada

N Kronfli

F Leone

C Dussault

M Maheu-Giroux

G Miliani

E Gallant

J Cox

CLM-O06 Comparative efficacy of fibrosis-4, liver stiffness measurement, and fibroscan-ast score to predict major liver-related outcomes in metabolic associated steatotic liver disease: An international multicenter study

YJ Wong

YH Chan

V Chen

CLM-O07 Steatotic liver disease in people living with hepatitis C virus following viral eradication with direct-acting antiviral therapy: a pilot study

M Shengir

W Elgretli

F Cinque

R Lombardi

A Cespiati

A Fracanzani

LE Ramos Ballesteros

M Deschenes

P Wong

T Chen

G Sebastiani

CLM-O08 Sofosbuvir/Velpatasvir (S/V) for the treatment of HCV infection among vulnerable inner-city residents

B Conway

S Beitari

R Yung

S Yi

CLM-O09 Prevalence of, and effect of semaglutide on, features of non-alcoholic steatohepatitis in patients with obesity with and without type 2 diabetes: analysis of data from two randomised placebo-controlled trials using somasignal tests

JP Arab

JM Schattenberg

H Gr⊘nbæk

I Kliers

S Ladelund

MT Long

SB Nygård

AJ Sanyal

M Davies

CLM-O10 Hedgehog signalling and metabolic responses drive CD8 T cell hyperfunction in advanced liver diseases

J Li

K Jorritsma

A Vranjkovic

KR Levesque

J Madani

D Read

WL Stanford

AC Cheung

CL Cooper

M Ardolino

AM Crawley

CLM-O11 Lack of protective immunity against hepatitis C virus reinfection post antiviral therapy