The 11th Canadian Symposium on Hepatitis C Virus: ‘Getting back on track towards hepatitis C elimination’

Abstract

Hepatitis C virus (HCV) affects approximately 204,000 Canadians. Safe and effective direct-acting antiviral therapies have contributed to decreased rates of chronic HCV infection and increased treatment uptake in Canada, but major challenges for HCV elimination remain. The 11th Canadian Symposium on Hepatitis C Virus took place in Ottawa, Ontario on May 13, 2022 as a hybrid conference themed ‘Getting back on track towards hepatitis C elimination.’ It brought together research scientists, clinicians, community health workers, patient advocates, community members, and public health officials to discuss priorities for HCV elimination in the wake of the COVID-19 pandemic, which had devastating effects on HCV care in Canada, particularly on priority populations. Plenary sessions showcased topical research from prominent international and national researchers, complemented by select abstract presentations. This event was hosted by the Canadian Network on Hepatitis C (CanHepC), with support from the Public Health Agency of Canada and the Canadian Institutes of Health Research and in partnership with the Canadian Liver Meeting. CanHepC has an established record in HCV research and in advocacy activities to address improved diagnosis and treatment, and immediate and long-term needs of those affected by HCV infection. The Symposium addressed the remaining challenges and barriers to HCV elimination in priority populations and principles for meaningful engagement of Indigenous communities and individuals with living and lived experience in HCV research. It emphasized the need for disaggregated data and simplified pathways for creating and monitoring interventions for equitably achieving elimination targets.

Introduction

Approximately 204,000 Canadians were living with hepatitis C virus (HCV) in 2019 (1). Reaching the World Health Organization (WHO) 2030 targets for HCV elimination will require a 90% reduction in new chronic infections and a 65% reduction in mortality compared to 2015 (2). Safe and effective direct-acting antiviral (DAA) therapies have greatly contributed to decreased rates of chronic HCV infection and increased treatment uptake in Canada (1). Yet, there remains major challenges for HCV elimination in Canada; a significant proportion of individuals are either undiagnosed or lost to care along the HCV cascade of care (1,3,4).

This commentary summarizes highlights from the 11th Canadian Symposium on Hepatitis C Virus (CSHCV), a hybrid conference which took place in Ottawa on May 13, 2022.

The Canadian Network on Hepatitis C (CanHepC)

CanHepC is a national collaborative HCV research and training network funded by the Canadian Institutes of Health Research (CIHR) and the Public Health Agency of Canada (PHAC). Currently, CanHepC links 62 researchers, 10 knowledge users, 22 trainees, as well as national and international partners and collaborators. The network was established in 2015 expanding the training mandate of its predecessor, the National CIHR Research Training Program in Hepatitis C (NCRTP-HepC), to become a transdisciplinary HCV research network (5). Since 2003, NCRTP-HepC and CanHepC have supported over 130 graduate and postdoctoral fellowships and 90 summer studentships. CanHepC's research program spans the following two specific areas of focus: (1) optimization of prevention and treatment programs to eliminate hepatitis C and (2) long-term consequences and health implications of hepatitis C infection, reinfection, and treatment. In addition to the training, education, and mentorship program, CanHepC includes three cross-cutting platforms (knowledge translation and exchange, Indigenous, and equity, diversity, and inclusion).

The 11th Canadian Symposium on Hepatitis C Virus

For the past 11 years, NCRTP-HepC/CanHepC have organized the CSHCV to facilitate interdisciplinary HCV research and knowledge translation (6–13). This 1-day Symposium—the fifth joint conference between CanHepC and the Canadian Liver Meeting (CLM)—was held under the theme of ‘Getting back on track towards hepatitis C elimination.’ The COVID-19 pandemic has had devastating effects on HCV care in Canada, with disproportionate impacts on priority populations (14,15). As a result, while pre-pandemic estimates indicated that Canada was on track to eliminate HCV by 2030 if 10,200 individuals living with chronic HCV were treated each year (16), it is now unclear whether elimination of HCV by 2030 is achievable in Canada.

The Symposium brought together research scientists, clinicians, nurses, community health workers, patient advocates, community members, and public health officials to discuss priorities for HCV elimination in the wake of the COVID-19 pandemic.

Biomedical Research: Beyond the Scar: Lasting Effects of HCV

The biomedical research session focused on the long-lasting effects of HCV following cure, including discussions on metabolic scars, extrahepatic manifestations, HCV life cycle, and cell death.

Dr Bertram Bengsch (University Medical Center Freiburg, Freiburg, Germany) presented work on T-cell exhaustion. A dysfunctional CD8+ T-cell response is associated with chronic HCV, and a proposed mechanism for this response is through T-cell exhaustion (17). Exhausted T cells functionally repress the ability of cells to respire and perform glycolysis, and are associated with profound alterations of the mitochondria, leading to decreased oxidative phosphorylation and increased reactive oxygen species (ROS) production (18). When comparing hepatitis B virus (HBV) and HCV-specific CD8+ T cells, HCV-specific CD8+ T cells show greater degrees of exhaustion, leading to more severe mitochondrial and glycolytic dysregulation (18). Finally, Dr Bengsch presented findings on the metabolic fitness of HCV-specific CD8+ T cells. Specifically, he demonstrated that metabolic activity, including mitochondrial function and glycolysis, increased after 2 weeks of DAA therapy. In addition, a heterogeneous subset of cells (PD-1+ CD127- phenotype) was unable to maintain metabolic improvements over time following DAA therapy, indicating that the majority of metabolic improvements after therapy were due to the homogenous phenotype (PD-1+ CD127+). Dr Bengsch concluded by reiterating that metabolic scars are an essential aspect of chronic HCV infection due to their relationships with T-cell exhaustion.

Dr Carla Coffin (University of Alberta, Edmonton, Canada) provided an overview of the extrahepatic manifestations of HCV and the related controversies and uncertainties. Two thirds of patients with chronic HCV present with one or more extrahepatic manifestations (19). Extrahepatic manifestations have a significant burden on morbidity and mortality related to chronic HCV infection as well as the health care system (20). Dr Coffin focused on the two main systemic extrahepatic conditions: mixed cryoglobulinemic vasculitis and B-cell lymphoma. Chronic HCV can result in a ‘hit and run’ effect resulting in a chain reaction that precedes the extrahepatic manifestation. For example, in mixed cryoglobulinemic vasculitis, chronic HCV induces B-cell hyperactivation and/or proliferation, leading to the formation of autoantibodies. These autoantibodies then bind to other antibodies, forming immune complexes, which can precipitate out of blood vessels (21). This, in turn, results in mixed cryoglobulinemia, which is most often associated with constitutional and non-specific symptoms. In the case of non-Hodgkin’s lymphoma, Dr Coffin noted this malignancy is 35 times more prevalent among people with chronic HCV (21). Interestingly, patients tend to present younger, and infection is more common among women than men. While they respond to DAAs, it is typically partial, and these patients can face recurring lymphoma (22). Dr Coffin also noted that among individuals with chronic HCV and non-Hodgkin's lymphoma, death occurs much earlier compared to the general population. Dr Coffin encouraged increased research and collaboration in this area, as well as the creation of sensitive and standardized assays in detecting low levels of the HCV genome, allowing further investigation of HCV proliferation outside of the liver.

Studying the HCV life cycle is also an important step in understanding the lasting effects of HCV infection. Marylin Rheault (Dr S Sagan Lab, McGill University, Montreal, Canada) presented work on miR-122, a liver-specific microRNA that binds to two sites in the 5' terminus of the HCV genome (site 1 and site 2) (10), leading to viral RNA accumulation and translation, instead of the downregulation (23). The three main roles of miR-122 in the HCV life cycle are: (1) riboswitch leading to the formation of an internal ribosomal entry site (IRES) (24), (2) stabilization of viral RNA and prevention of decay (25), and (3) translation of proteins through the interactions between the Argonaute:miR-122 complex and the HCV IRES (26). Rheault's data indicate that the stabilization and translation roles are equally dominant in the early stage (2–8 hours) of the HCV life cycle, while translation plays a much more dominant role in the maintenance stage (24–72 hours). These findings provide insights into the HCV cell culture system and possible outcomes, such as acute versus chronic infection.

Cell death can also be a lasting side effect of HCV infection, even after the virus has been cleared. Hannah Wallace (Dr R Russell lab, Memorial University, St. John's, Canada) discussed bystander pyroptosis, an inflammatory form of cell death by which the cell lyses and cytokines are released (27). Previous research indicated that HCV-infected cells undergo pyroptosis over time, and interestingly, uninfected cells in the same culture also undergo pyroptosis (bystander pyroptosis) (28). Wallace's data show that the inflammasome can trigger pyroptosis, which is dependent on viral replication, and immune cells are also targeted for pyroptosis. This research, coupled with future studies, can help further our understanding of inflammation, liver pathology, and immune dysfunction associated with chronic HCV infection.

Understanding the many long-lasting effects of HCV, even after cure, offers crucial insights into long-term consequences of HCV following treatment. In understanding these, we can potentially find ways to prevent and cure conditions for which patients remain at risk after sustained virologic response (SVR), thus reducing HCV-related morbidity and mortality.

Population Health Research: Overcoming Remaining Challenges and Barriers To HCV Elimination in Priority Populations

The population health research session focused on summarizing the groups who are disproportionately impacted by HCV, outlining remaining challenges and barriers to HCV elimination, and reviewing specific strategies to address HCV in priority populations.

Dr Margaret Hellard (Burnet Institute, Melbourne, Australia) provided key insights from ongoing HCV elimination efforts in Australia. Australia is one of the few countries on track for elimination due to a multifaceted approach in which community partnerships play a vital role from the onset (29–31). While numerous challenges remain in the way of achieving HCV elimination (32), important inroads have been made in reducing HCV incidence and increasing treatment uptake. Approximately 40% of the approximately 183,000 Australians who were living with hepatitis C in 2016 have been treated (32). This progress is reflected in declining incidence rates among high-risk populations (34,35). While this milestone is significant, it falls short of the 2022 target (65%) stipulated in Australia’s National Hepatitis C Strategy (33). In addition, modelling studies show that current testing levels in Australia are insufficient to achieve HCV elimination (36). Furthermore, declining treatment rates suggest that previous strategies to engage priority groups in care may not be as effective for those remaining untreated, since those who remain untreated may be hesitant, doubtful, and in need of social encouragement (32). In this context, Dr Hellard discussed new approaches and key initiatives to support HCV elimination in Australia. The Eliminate hepatitis C Australia Partnership (EC Australia) was formed in 2018 to bring together researchers, implementation scientists, government, health services, and community organizations to work toward elimination, an innovative partnership in its use of a health-system-strengthening approach (37). In July 2021, the Australian Government awarded funding for the development of a national hepatitis C point-of-care testing program, with the goal of establishing 65 to 80 point-of-care testing sites nationally and screening 50,000–60,000 people over two years. Importantly, these sites will be established within a wide range of organizations, including drug treatment clinics, needle and syringe exchange programs, community health centres, correctional settings, and peer and hepatitis organizations. Finally, Dr Hellard highlighted that gaps in linkage to care persist in key populations, including the Aboriginal and Torres Strait Islanders, and in people living in rural and remote areas of Australia.

Ensuring equity in the response to HCV elimination is a global concern. Dr Jordan Feld (Toronto General Hospital Research Institute, Toronto, Canada) discussed key considerations for an equitable approach to HCV elimination in Canada to ensure that none of the priority populations be left behind. Dr Feld first emphasized the importance of considering intersectionality, syndemics, language, and culture to ensure appropriate responses, as reflected in the Blueprint to Inform Hepatitis C Elimination Efforts in Canada (3). Dr Feld emphasized that the World Health Organization goals for HCV elimination (2) must be met in each subpopulation and as a whole. Key principles discussed to ensure equity in HCV elimination include the development of regional elimination roadmaps, broad consultations with priority populations and subpopulations, development of strategies with/by priority populations, and constant reflection for the possible revision of the priority populations. Ensuring equity also requires data for all; disaggregating data to understand how well elimination efforts are progressing in each priority population and subpopulation will be critical. Disaggregated data should be used in the context of a process to support reducing systemic racism and oppression. An example of a structuring effort is British Columbia's framework for disaggregated data collection, which ultimately aims to make societal systemic inequalities visible while simultaneously highlighting the need for a respectful relationship around data governance and community ownership (38).

Dr Andrew Mendlowitz (Toronto Centre for Liver Disease, Toronto, Canada) illustrated such an approach to data disaggregation in a study aiming to map the cascade of care and identify gaps in engagement and service delivery for First Nations individuals in Ontario. In partnership with the Ontario First Nations HIV/AIDS Education Circle (OFNHAEC), a retrospective cohort study was conducted to link individuals with registered First Nations status to Public Health Ontario Laboratory HCV records from 1999 to 2018, and health administrative data held at ICES. Through this study, Dr Mendlowitz demonstrated that substantial gaps in HCV care persist before treatment initiation among First Nations populations in Ontario.

A wide range of strategies must be considered to improve the acceptability, safety, and uptake of HCV testing in correctional settings, as introduced by Dr Sofia Bartlett (BC Centre for Disease Control, Vancouver, Canada) in the final presentation of the session. Dr Bartlett's work focused on optimizing implementation of routine HCV/sexually-transmitted and bloodborne infection (STBBI) testing, linkage to care, and treatment in correctional settings in British Columbia, and incorporated preferences of key stakeholders into the development of HCV/STBBI policies and guidelines. Results of stakeholder engagement workshops and surveys suggested multiple strategies to support the implementation of HCV testing in correctional settings, including offering multiple testing options and time points, ensuring there is privacy and confidentiality, and streamlining testing workflow to ensure linkage to testing, care, and treatment.

This session discussed the challenges and barriers to HCV elimination that still exist among priority populations, with a focus on gaps in linkage to care and strategies to ensure equity in HCV elimination. It also highlighted the importance of disaggregated data to monitor and evaluate ongoing elimination efforts in each group.

Panel Discussion: Approaching Research in a Good Way, from Principle to Practice, Unpacking the Meaningful Engagement of Indigenous Communities and Individuals with Lived Experience in Hepatitis C Research

This panel discussion explored the importance of meaningful engagement with Indigenous Peoples with lived and living experience of HCV in the context of research with Indigenous communities. The panel was a collaboration between CAAN Communities, Alliances and Networks (CAAN), World Indigenous Peoples' Conference on Viral Hepatitis, Pewaseskwan (the Indigenous Wellness Research Group), CATIE: Canada's Source for HIV and Hepatitis C Information, and CanHepC. Moderated by Renée Masching, (Six Nations of the Grand River First Nation), Director of Research, CAAN, organized by Carrielynn Lund (Métis), DRUM & SASH Coordinator, CAAN and Melisa Dickie, Director, Hepatitis C Knowledge Exchange, CATIE, panellists included Indigenous leadership: Carrielynn Lund, Gayle Pruden (Anishinaabe), Knowledge Holder and Two-Spirit Dancer, Alexandra King (Nipissing First Nation), Cameco Chair of Indigenous Health and Wellness (University of Saskatchewan), and non-Indigenous collaborators Catherine Worthington (Director/Professor, School of Public Health and Social Policy, University of Victoria) and Janet Jull (Faculty of Health Sciences, Queens University). This panel explored the following themes: ethical research engagement with Indigenous communities, reconciliatory and decolonizing research approaches, and the role of institutional leadership in championing ethical research engagement.

Panellists discussed ethical and respectful research engagement with Indigenous communities in practice. This included exploring facilitators to engage people with lived experience in research and how to create space in research for meaningful engagement. Promising practices included operationalizing shared decision-making, demonstrating how Indigenous Peoples are meaningfully engaged at each stage of the research process (including shaping the research questions and direction), recognizing and integrating the knowledge, expertise, and wisdom of people with lived and living experience in the context of research, and approaching the relationship between researcher and non-researcher with humility, reciprocity, and generosity (gifting each other with knowledge). The session also highlighted the importance of not making assumptions about experience or knowledge. In this context, panellists discussed the importance of reciprocal learning and the balance of power between researchers and community, the intersectional and dual roles of community members who are also researchers, as well as between non-Indigenous and Indigenous collaborators. Ensuring a common vision or destination is key to establishing trust, as is ensuring that community voices have the power to stop or change course at any stage of the research process. Additionally, engaging community leadership, for example, including Chiefs and Councils or delegated authority as appropriate, was discussed as necessary.

The session underscored the importance of approaching research in a reconciliatory and decolonizing way. This includes recognizing the unjust history of research on Indigenous communities and the importance of non-Indigenous-led research initiatives intentionally approaching a process relationally where relationships are reciprocal, starting from a place of humility and recognizing the need to build (and not assume) trust. The session underscored how reconciliatory research can be a healing and learning process for those directly involved, with the potential to be a deeply transformative journey more broadly, addressing health inequities. Reconciliatory and decolonizing approaches to research include approaching collaborations with the community as a lifelong process, where non-Indigenous collaborators are willing to listen and adapt their approach, and ultimately moving from a place of guilt and defensiveness to a sense of responsibility and a need for action.

The session emphasized practical approaches for researchers, comprising being open to bringing one's whole self to a process, not just the professional self—including emotions, personal stories, relationships, and spirituality. Indigenous Community Research Partnerships (ICRP), a Queen's University online open education training resource, was presented by Janet Jull, as a tool designed to assist researchers who are new to research in partnerships with Inuit, Métis, and First Nations communities or who are researchers in training or on lifelong learning journeys. This tool assists researchers in operationalizing regulatory policy requirements and research directives, offers support in assessing how to ensure equitable inclusion of Indigenous- and mainstream (Western)-oriented knowledge in research systems, and in the context of Indigenous-specific enquiry, how to privilege Indigenous ways of knowing, being, and doing.

It was also highlighted that institutional leadership in championing ethical research engagement with Indigenous Peoples is essential. Research institutions are responsible for creating an ecosystem within which good research can be nurtured. As research ethics is an evolving field, so must institutions evolve to both meet and even drive community-centred and community-driven research. The session also recognized that most research institutions have made calls for truth and reconciliation, and individual researchers who champion dialogue within their institutions for approaching research in a good way are ultimately supporting their institutions to meet their existing commitments.

Clinical Research: Treatment Simplification: Art or Science?

The clinical research session focused on treatment strategies in specific population groups, such as people with comorbidities and psychiatric patients. The optimization of HCV care in the modern DAA era was also discussed as well as the importance of finding patients who are lost to follow-up.

Dr Alexander Thompson (St Vincent's Hospital, Melbourne, Australia) discussed barriers to HCV treatment simplification in the modern DAA era with a description of the 6 Cs: cirrhosis, complicated drug-drug interactions (DDIs), co-infection with HIV/HBV, complex populations, comorbid liver disease, and HCV resistance. Dr Thompson outlined two key considerations for pre-treatment cirrhosis assessment: screening for cirrhosis and its complications. Non-invasive screening for cirrhosis should occur preferentially pre-treatment, as accurate assessment of fibrosis levels can be difficult during treatment due to viral suppression and rapid reduction in liver inflammation resulting in lower fibrosis biomarker scores (39). Although SVR has been associated with a significant decrease in the risk of hepatocellular carcinoma (HCC) and improved overall survival (40,41), patients with cirrhosis should be engaged in specialty care to monitor for cirrhosis complications including portal hypertension and HCC post-SVR (42). Dr Thompson underlined that while screening for cirrhosis and related complications is important, DAA treatment should not be delayed in a population with a high risk of loss to follow-up, as treatment can reduce the risk of HCC and other HCV-related disease sequelae. For complicated DDIs, although rare, some medications may require more considerations when combined with DAA therapy, such as antiretrovirals, anticonvulsants, and antibiotics. Checking for DDIs can be facilitated by an online tool developed by University of Liverpool (https://www.hep-druginteractions.org/checker). For patients with HIV or HBV co-infection, it is recommended that patients are managed by clinicians with experience in treating co-infected patients. DDIs should be considered when managing patients with HIV-HCV co-infection, whereas the risk of HBV reactivation should be considered among those who are HIV-HBV co-infected (43). For complex populations such as patients with decompensated liver disease, those with a history of liver or other organ transplants, and people with significant comorbidities (e.g., renal failure, HCC, etc), specialist involvement is beneficial to provide optimal care. For the majority of HCV patients, simplified monitoring is suitable and recommended. However, some patients may still require more intensive monitoring, including those with risk factors or a history of non-adherence, HBV co-infection, advanced liver disease or complex comorbidities. Patients with persistently abnormal liver function tests post-SVR need to be screened for concurrent liver diseases such as metabolic-associated fatty liver disease (MAFLD) or non-alcoholic fatty liver disease (NAFLD). Lastly, for HCV resistance, in patients who do not respond to first-line treatment, salvage therapy with sofosbuvir-velpatasvir-voxilaprevir (SOF/VEL/VOX) is considered first line (44). Dr Thompson highlighted that while some specific medical considerations remain for HCV treatment, the true challenge is engaging patients in care. Practical approaches to improving the cascade of care for those who are difficult to reach are essential.

Dr Alexander Wong (University of Saskatchewan, Saskatoon, Canada) also highlighted that in the modern DAA era, while medical considerations for HCV treatment have become simpler, the holistic management of the patient requires other considerations. People living with chronic HCV infection face multiple concurrent challenges such as substance use, overdose, poverty, unstable housing, and stigma. Dr Wong stressed the importance of integrating addiction medicine and harm reduction strategies in HCV care, as concurrent addiction management and harm reduction can reduce the risk of overdose, prevent reinfections, and improve adherence to HCV therapy. Harm reduction focuses on lessening the detrimental health consequences of substance use by delivering care to people where they are and giving people choices to increase autonomy, support informed decision-making, and focus on improving public health (45). People who use drugs experience many system-level (e.g., lack of adequate treatment settings for people who use drugs) and individual-level (e.g., perceived stigmatization and mistrust of the health system) barriers to accessing care. Integrating HCV care within harm reduction programs can help reach people who use drugs and who would benefit from HCV treatment (46,47). Dr Wong also highlighted the increasing rates of incident STBBIs), including syphilis, chlamydia, and gonorrhea in Canada (48,49), and that HCV care engagement can be an opportune time for STBBI screening and treatment.

People with mental health disorders are overrepresented among those living with HCV and experience significant barriers to obtaining care (50,51). While hospitalists in mental health facilities can effectively manage HCV as non-specialists (50), there is a lack of awareness and training for HCV care in these settings. The potential for HCV screening and treatment in mental health facilities was presented by Erin Mandel (University Health Network, Toronto, Canada). Data on HCV screening and treatment among psychiatry inpatients at the Centre for Addiction and Mental Health (CAMH) in Toronto from January 2017 to May 2021 was presented. Their findings showed that psychiatry inpatients may benefit from regular HCV screening and treatment onsite. In addition, increasing awareness and education in HCV management in mental health facilities may help improve HCV services for this population.

Understanding the factors associated with people being lost to follow-up is crucial to improving HCV services, retaining patients in care, and reaching HCV elimination goals. Dr Alnoor Ramji (University of British Columbia, Vancouver, Canada) shared data from the BC-HCV Network and discussed the potential for predicting loss to follow-up. From 2012 to 2021, over one-quarter of patients were lost to follow-up pre-treatment, and another 15% were lost to follow-up post-treatment. These were more likely to be male, younger, have an underlying psychiatric diagnosis, report active or recent injection drug and heavy alcohol use, but were less likely to be cirrhotic compared to those who completed treatment. Patients who were lost to follow-up post-treatment were similar to those who were lost to follow-up pre-treatment; however, they were less likely to have concurrent medical comorbidities than those who completed treatment. Both presentations from Ms Mandel and Dr Ramji emphasized the need to address the barriers to HCV-care engagement to minimize losses to follow-up.

This session highlighted the aspects beyond the clinical considerations of HCV treatment. With the advent of highly effective DAA therapy, HCV treatment has become simple for the majority of patients. However, moving beyond HCV treatment takes efforts. Engaging and maintaining patients in care and treating the whole patient with an overall holistic approach is crucial to improving health outcomes, preventing reinfections, and achieving HCV elimination.

Health Services Research: Embracing the Digital Transformation of HCV Care

The health services research session started with a presentation on digitizing HCV care by Dr John Dillon (University of Dundee, Dundee, Scotland), where he discussed the simplification of HCV care pathways as a strategy to reach the WHO 2030 HCV elimination goals. Dr Dillon presented data on clinical trials conducted in Tayside (East of Scotland), based on simplified, novel community HCV care pathways with ‘yes’ or ‘no’ steps for diagnosis and treatment. The testing step of digitized HCV care involves decentralized dried blood spot (DBS) testing to overcome venipuncture (52). Treatment directly follows diagnosis and includes a simple ‘yes’ or ‘no’ checklist to a series of questions that allow for tailored regimens to be prescribed. In a cluster-randomized trial where community pharmacies were trained to offer DBS testing and a pharmacist supervised DAA administration, users of opioid substitution therapy in the pharmacist-led care group were approximately two times more likely to initiate treatment and achieve SVR when compared to the conventional care group (53). This study showed that a simplified HCV pathway succeeded in increasing treatment uptake and SVR rates (53). This strategy has been validated in smaller pharmacies (54,55) and in injecting equipment provision sites (56) and has proven to be reproducible in large-scale and different settings (57). Tayside, Scotland is a success story of HCV elimination using digitized HCV care with 90% cured, thus meeting WHO elimination targets.

Dr Kate Dunn (Alberta Health Services, Alberta, Canada) followed with a presentation on ECHO+: innovation and relationality towards improving engagement for hepatitis C care with Indigenous communities (58). The ECHO program started in 2015 in Alberta to develop capacity to treat HCV safely and effectively. In 2019, it was expanded to ECHO+ to improve access to care in Indigenous communities. Dr Dunn described how the COVID-19 pandemic shifted the program to being one that is a fully digitized, with education materials co-created with the Elders to ensure cultural competency. The main barriers in Indigenous communities continue to be lack of access to laboratory services and awareness. Barriers to HCV care are almost universally described among Indigenous communities, with long distances required for testing. Lack of awareness includes a lack of knowledge of the role of the liver and the availability of interferon-free DAA therapy. As a result of ECHO+, the number of communities actively engaged with the program increased eightfold. Levels of engagement varied from adopting the ECHO+ model for HCV care, to attending virtual lessons, or receiving newsletters, with all communities having ECHO+ as a reference for HCV care when needed. Dr Dunn attributed the success of Indigenous engagement to relationality and the framework model developed by her team (58). It includes the 5R framework as a foundational hub (59–61), provides an ethical space of engagement, and adopts a Two-Eyed Seeing perspective (62,63). This allows for balancing funder-required work streams with a community-based participatory framework in approaches that pair HCV care from Western written evidence with community-directed priorities, oral knowledge, and Indigenous perspectives of wellness (58).

This was followed by a presentation by a postdoctoral fellow, Dr Aysegul Erman (Toronto General Hospital Research Institute, Toronto, Ontario, Canada). Dr Erman discussed the results of a population-based study in Ontario evaluating HCV care cascade engagement from 1999 to 2018. While there were substantial improvements in treatment initiation and SVR in the post-DAA era, there were many outstanding care gaps. Adjusted cause-specific hazard models identified history of substance use and social marginalization as factors associated with lower rates of engagement in HCV care.

Dr Farinaz Forouzannia (University of Waterloo, Waterloo, Ontario, Canada) presented a model-based analysis on the impact of new DAA therapy on the prevalence and undiagnosed proportion of chronic HCV infection in Ontario. Dr Farinaz showed data suggesting that one third of those living with HCV in Ontario in 2018 remain undiagnosed and concluded that the prevalence of chronic HCV and the proportion undiagnosed declined for all birth cohorts since the introduction of DAAs in 2015.

This session highlighted the digital transformation of HCV care and how linkage to care and treatment uptake can be improved with interventions using simple technology and simplified pathways. Improvements during the DAA era in Ontario were also discussed, and taken together, these data can guide decisions on current and future HCV screening, linkage, and treatment interventions to overcome gaps to achieve HCV elimination in Canada.

Outcomes of the 11th CSHCV

The 11th Canadian Symposium on Hepatitis C Virus highlighted recent work aimed at understanding the lasting effects of HCV, simplification of HCV treatment, digitization of HCV care, the meaningful engagement of Indigenous communities and individuals with lived and living experience in hepatitis C research, and strategies to overcome remaining challenges and barriers to HCV elimination in priority populations. The Symposium emphasized the need for disaggregated data and simplified pathways for creating and monitoring interventions for equitably achieving elimination targets.

Funding Statement

CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR; NHC-142832), and the Public Health Agency of Canada (PHAC). In addition, CanHepC has received funding for the training program from AbbVie, Gilead, and Merck. The 11th Canadian Symposium on Hepatitis C Virus was supported by CIHR (PCS-168232). Additional funding was provided by AbbVie, Gilead, Merck, Lupin, Intercept, Roche, Alexion, Alnylam, Altimmune, Astellas, Bristol-Myers Squibb, Eisai, Novartis, Specialty R Pharmacy, through the Canadian Liver Meeting and by the Réseau Sida and The Ottawa Hospital. The views expressed in this publication are those of the authors and do not reflect the position of the CIHR, PHAC, or other sources of funding. N Kronfli is supported by a career award from the Fonds de Recherche Québec—Santé (FRQ-S; Junior 1). G Fontaine is supported by a Banting Postdoctoral Fellowship (#202010BPF-453986-255367) from the Canadian Institutes of Health Research (CIHR), a Postdoctoral Fellowship Supplement from the University of Ottawa, and a Postdoctoral Fellowship from the CanHepC. D Jeong is supported by Doctoral Research Award (#201910DF1-435705-64343) from the CIHR and Doctoral Fellowship from CanHepC.

Acknowledgements:

CanHepC Investigators: Mohamed Abdel Hakeem (Emory Univeristy), Michel Alary (Centre de recherche du CHU de Québec), Fernando Alverez (CHU Sainte-Justine), Sofia Bartlett (University of British Columbia), Marc Bilodeau (Université de Montréal), Mia Biondi (Western University), Zahid Butt (University of Waterloo), Julie Bruneau (Principal Investigator, Université de Montréal), Carla Coffin (University of Calgary), Che Colpitts (Queen’s University), Brian Conway (Vancouver Infectious Diseases Centre), Curtis Cooper (University of Ottawa), Joseph Cox (McGill University), Angela Crawley (The Ottawa Hospital Research Institute), Jordan Feld (Principal Investigator, University Health Network), Jennifer Flemming (Queen’s University), Jeremy Grimshaw (Principal Investigator, University of Ottawa), Jason Grebely (UNSW Australia), Christina Greenway (McGill University), Michael Houghton (University of Alberta), Anita Howe (Centre For Excellence in HIV/AIDS), Naveed Zafar Janjua (Principal Investigator, University of British Columbia), Didier Jutras-Aswad (Université de

Montréal), Alexandra King (Principal Investigator, University of Saskatchewan), Marina Klein (McGill University), Mel Krajden (University of British Columbia), Nadine Kronfli (McGill University), Jeff Kwong (University of Toronto), Alain Lamarre (INRS-Institut Armand-Frappier), Sarah Larney (Université de Montréal), Samuel Lee (University of Calgary), Seung-Hwan Lee (University of Ottawa), Liang-Tzung Lin (Taipei Medical University), Simon Ling (University of Toronto), Sonya MacParland

(University of Toronto), Gisela Macphail (University of Calgary), Valérie Martel-Laferrière (Centre de Recherche du CHUM), Andrew Mason (University of Alberta), Ian McGilvray (University of Toronto), Thomas Michalak (Memorial University), Gerry Mugford (Memorial University), Mario Ostrowski (University of Toronto), Trushar Patel (University of Lethbridge), John Pezacki (University of Ottawa), Justin Presseau (University of Ottawa), Alnoor Ramji (University of British Columbia), Christopher

Richardson (Dalhousie University), Eve Roberts (University of Toronto), Rod Russell (Memorial University), Selena Sagan (McGill University), Beate Sander (University of Toronto), Giada Sebastiani (McGill University), Naglaa Shoukry (Nominated Principal Investigator, Université de Montréal), Daniel Smyth (Dalhousie University), Hugo Soudeyns (Université de Montréal), Rosie Thein (University of Toronto), Lorne Tyrrell (University of Alberta), Marie-Louise Vachon (Université Laval), Daniel Werb (University of Toronto), Joyce Wilson (University of Saskatchewan), Wendy Wobeser (Queen's University), Alexander Wong (University of Saskatchewan), William Wong (University of Toronto).

CanHepC Knowledge Users: Jason Altenberg (South Riverdale Community Health Centre), Anis Aslam (University of British Columbia), Melisa Dickie (Principal Knowledge User, CATIE), Lesley Gallagher (Canadian Association of Hepatology Nurses), Janet Hatcher Roberts (University of Ottawa), Carrielynn Lund (CAAN Communities, Alliances & Networks), Daryl Luster (BC HepC Network), Renée Masching (CAAN Communities, Alliances & Networks), Laurence Mersilian (Centre Associatif Polyvalent d'Aide Hépatite C), Jennifer Nebesky (Canadian Liver Foundation).

CanHepC Trainees 2021–2022: Marylin Rheault (McGill University), Simmone D’souza (University of Calgary), Ana Maria Passos-Castilho (McGill University), Charlotte Lanièce Delaunay (McGill University), Ching-Hsuan Liu (Dalhousie University), Dahn Jeong (University of British Columbia), Gayatri Marathe (McGill University), Gillian Kolla (University of Victoria), Guillaume Fontaine (University of Ottawa), Hannah Louise Wallace (Memorial University), Jawaira Atif (University of Toronto), Jean Damascene Makuza 11 (University of British Columbia), Jiafeng Li (University of Ottawa), Manolya Sag (McGill University), Michael Palmer (University of Saskatchewan), Mohamed Abdelnabi (Université de Montréal), Mohamed Shengir (McGill University), Sabrina Mazouz (Université de Montréal), Samaa Gobran (Université de Montréal), Sameh Mortazhejri (University of Ottawa), Sasha Tejna Persaud Udhesister (Université de Montréal), Yasmin Saeed (University of Toronto), Zoë Greenwald (University of Toronto).

Contributions:

Writing – Original Draft, AM Passos-Castilho, STP Udhesister, G Fontaine, D Jeong, M Dickie, C Lund; Writing – Review & Editing, AM Passos-Castilho, N Kronfli; Supervision, N Kronfli.

Ethics Approval:

N/A

Informed Consent:

N/A

Registry and the Registration No. of the Study/Trial:

N/A

Funding:

CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR; NHC-142832), and the Public Health Agency of Canada (PHAC). In addition, CanHepC has received funding for the training program from AbbVie, Gilead, and Merck. The 11th Canadian Symposium on Hepatitis C Virus was supported by CIHR (PCS-168232). Additional funding was provided by AbbVie, Gilead, Merck, Lupin, Intercept, Roche, Alexion, Alnylam, Altimmune, Astellas, Bristol-Myers Squibb, Eisai, Novartis, Specialty R Pharmacy, through the Canadian Liver Meeting and by the Réseau Sida and The Ottawa Hospital. The views expressed in this publication are those of the authors and do not reflect the position of the CIHR, PHAC, or other sources of funding. N Kronfli is supported by a career award from the Fonds de Recherche Québec—Santé (FRQ-S; Junior 1). G Fontaine is supported by a Banting Postdoctoral Fellowship (#202010BPF-453986-255367) from the Canadian Institutes of Health Research (CIHR), a Postdoctoral Fellowship Supplement from the University of Ottawa, and a Postdoctoral Fellowship from the CanHepC. D Jeong is supported by Doctoral Research Award (#201910DF1-435705-64343) from the CIHR and Doctoral Fellowship from CanHepC.

Disclosures:

N Kronfli reports research funding from Gilead Sciences, advisory fees from Gilead Sciences, ViiV Healthcare, Merck and AbbVie, and speaker fees from Gilead Sciences, AbbVie and Merck, all outside of the submitted work. The other authors have nothing to disclose.

Peer Review:

This manuscript has been peer reviewed.

Animal Studies:

N/A