Priority actions for elevating liver health in Canada: A call to action

Abstract

Chronic liver disease (CLD) has become a silent epidemic in our country and has resulted in significant physical, psychosocial, and financial burden. Although other international liver associations have published frameworks for the principal actions required to improve liver health across health systems, Canada does not have a strategy to address the growing concerns of CLD. Thus, a multidisciplinary group of care providers involved in CLD management in Canada gathered to review the current burden of disease, gaps in management, and key opportunities for improving the identification and management of people at risk of developing progressive CLD.

Key Points

• 1.Chronic liver disease affects one in four Canadians causing significant morbidity and mortality.
• 2.Although effective treatments for viral hepatitis (HBV and HCV) exist, obesity and alcohol have now emerged as a major cause of liver transplantation, hepatocellular carcinoma, hospital admissions, and costs.
• 3.Early identification of individuals at risk of liver disease can alter the trajectory of illness.
• 4.Health policies targeting upstream, midstream, and the downstream effects of liver health are urgently needed in Canada.

Introduction

Chronic liver disease (CLD) has become a silent epidemic with one in four Canadians affected and is a top 10 cause of death nationally (1,2). CLD often progresses to cirrhosis silently, from an asymptomatic compensated phase to a symptomatic decompensated phase in which median survival is 2 years without liver transplantation (LT) (3). This natural history, coupled with the stigmatization of CLD, results in significant but preventable physical, psychosocial, and financial burden (4). Recently, major international liver associations have published positions on the need for greater action related to CLD and hepatocellular carcinoma (HCC), proposing frameworks for the principal actions required to improve liver health across health systems (5,6). In Canada, there are national strategies to address diabetes, breast cancer, and other diagnoses of significance, but none to address the growing concerns of CLD. In early 2022, a multidisciplinary group of care providers involved in CLD management in Canada gathered to review the current burden of disease, gaps in management, and key opportunities for improving the identification and management of people at risk of developing progressive CLD. This report is a summary of that analysis.

How has the Burden of CLD Changed Over the Last Decade?

Chronic liver disease (CLD) refers to a spectrum of conditions from inflammation to fibrosis to cirrhosis. Common disease processes include metabolic disease (non-alcohol-associated fatty liver disease, NAFLD), alcohol-associated liver disease (ALD), viral hepatitis (hepatitis C virus [HCV] and hepatitis B virus [HBV]), and autoimmune liver disease. Cirrhosis typically progresses silently and irreversibly to decompensation resulting in serious medical complications (ie, ascites, variceal bleeding, hepatic encephalopathy, liver failure, and HCC). Decompensation is a watershed event associated with significant physical, psychosocial, and financial burden (4). At a population level, improvements to liver health realized by the availability of direct-acting antivirals (DAAs) to cure HCV along with vaccinations and antiviral treatment for HBV have been counteracted by the damaging effects of increased alcohol misuse (ALD) and the obesity epidemic (NAFLD), especially in underserved, rural/remote, and marginalized populations (5). Thus, similar to other countries, CLD burden in Canada has been increasing over the past decade (7).

General trends related to CLD

Recently, it has been found that up to 27% of CLD patients have fibrosis at diagnosis, paralleling the rising incidence of cirrhosis among Canadian adults and children over the last decade (7,8). Just as alarming, a recent study of Toronto-area hospitals shows internal medicine hospitalizations for CLD outranked other major cardio-pulmonary conditions in rates of mortality, admissions, and hospitalization costs (9). Furthermore, although the incidence of HCC in Canada is relatively low, it has been associated with the largest increase in mortality rate of all cancers. This is unfortunate as resectable HCC is associated with 70% survival at 5 years, whereas advanced HCC has a median survival of approximately 9 months (10). Various interventions and treatments exist to manage decompensated cirrhosis and HCC but some curative therapies (ie, LT, hepatic resection) are limited and rely on early detection (4,10).

Non-communicable CLD trends: NAFLD/ALD

The rates of obesity in Canadian children and adults continue to rise, which are among the highest globally, and as a consequence, NAFLD has become the most prevalent form of CLD in children and adults (11,12). In parallel, Canadian LT data in adults show a >12% increase in the proportion of LTs performed due to NASH and modelling forecasts a doubling of decompensated cirrhosis with an 80% increase in HCC incidence due to NASH by 2030 (12,13).

ALD prevalence is on the rise as well, as are rates of related cirrhosis deaths. In Canada, average alcohol consumption is higher than the global average (8.8 L versus 5.8 L per capita in 2019) and 19.1% of the population reports heavy drinking (14,15). According to a national multicenter registry, ALD-related LTs make up approximately 15% of LTs in Canada (13). ALD and NAFLD are expected to continue battling as the number one and two causes of LT in the future (16).

Communicable CLD trends: HBV/HCV

The overall prevalence of chronic HBV in Canada is low (<1%) and incidence declined by 10.9% from 2015 to 2019 (17). However, that decrease falls short of Canada’s commitment to the World Health Organization (WHO) target of a 30% reduction by 2020 (2,17). In Canada, those born outside Canada continue to have high rates of HBV (5%) and often progress to cirrhosis as they are unaware of their infection (40%) which results in disproportionately high rates of HBV-related hospitalizations (18). In addition, current HBV treatment rates suggest Canada would not achieve WHO elimination until 2051, which would be followed by decades of the devastating impacts of new, undiagnosed, and untreated infections (2,17).

Rates of HCV in Canada peaked in 2018 at 33.9 per 100,000, before decreasing by 10.2% in 2019, presumably owing to DAA treatment (17). Although this may seem like progress, testing, case-finding, and treatment have been on a sharp decline, especially in the context of the COVID-19 pandemic. Thus, rates are likely to be rising again as it is estimated that injection drug users, the homeless, and foreign-born populations account for almost 79% of HCV-positive cases in Canada with 44% of Canadians with HCV still remaining undiagnosed (19).

Unfortunately, a lack of large prospective databases and poor data collection/quality make it difficult to present a collective impact of CLD in Canada. However, the summaries above illustrate that Canadians continue to suffer from HBV/HCV-related CLD while increasing rates of NAFLD and ALD have created a “ticking timebomb” of CLD burden.

What are the Current Opportunities and Barriers to Supporting Liver Health in Canada?

The current approach to CLD health care focuses on the management of late-stage complications and requires high levels of specialty care with relatively little impact on outcomes and high costs to our health care system. The clearest way to prevent decompensated cirrhosis is to remove or suppress the cause of liver injury. Since CLD is largely silent in its progression, early detection by symptoms alone is difficult. However, the following major advances have uncovered an opportunity to improve liver health and are worth noting:

• (1)Technical advances in detection of fibrosis using non-invasive tests (NITs) such as serum biomarkers and elastography expand opportunities for early detection in regions, especially outside of major centres (20).
• (2)The high cure rates achieved by DAAs in HCV along with vaccination and effective therapies for HBV have decreased the rates of cirrhosis, decompensation, and cancer (6).
• (3)More effective surgical, locoregional, and pharmacological interventions offer cure and extended survival in HCC (6,10).

Early detection of fibrosis

Early detection of fibrosis offers opportunity for lifestyle intervention, treatment, and prevention of morbidity and mortality related to CLD. Although liver biopsy is the gold standard for fibrosis assessment, its cost, invasiveness, and susceptibility to sampling error preclude its common use. In many settings, elastography has been able to replace liver biopsy, however, its broad utility has been restricted due to limited access. Fortunately, various laboratory tests and scoring systems are available outside of specialty care that can effectively assess the risk of fibrosis for most forms of CLD (20). The importance of early detection of fibrosis across all CLD etiology cannot be overstated as it is a simple tool that can effectively triage a large patient pool to a manageable workload for downstream providers, thus ensuring the “sickest” are seen the most urgently.

Viral control

Globally, HBV vaccination has made the greatest contribution to declines in CLD mortality rates over the past 30 years (21). Birth dose vaccination in endemic regions has decreased the global prevalence of chronic HBV from 5% to 1% in children (21). In Canada, the absence of targeted screening and treatment at risk populations (ie, people who inject drugs, and those born outside Canada) as well as inconsistent birth dose vaccination programs perpetuate the public health threat of HBV and CLD (17). For HCV, the progress realized by DAA treatment and harm reduction efforts is threatened by the socioeconomic impacts of the COVID-19 pandemic and growing use of injection drugs, where new infections outpace cures. In addition, Canada lacks effective public health measures such as a national strategy and provincial consistency related to broader population-based screening such as age cohort (born 1945–1975) screening or screening in pregnancy for HCV (22).

Early intervention in HCC

Considering the advent of life-extending treatments for HCC and expanded eligibility for LT, routine surveillance by ultrasound with or without alpha-feto protein is recommended in patients with cirrhosis and high-risk non-cirrhotic HBV carriers as an evidence-based means of improving survival through early HCC detection (6,10). Unfortunately, HCC screening has been shown to be suboptimal in patients with cirrhosis likely due to a combination of patient, provider, and system issues (23,24). Thus, it is necessary for HCC secondary prevention programs to be established, recognized, and supported to help with guideline-based care across provinces. Currently, only Alberta has a defined ultrasound screening program for HCC and should be a model that is emulated across Canada.

Systemic hurdles

Beyond the opportunities and barriers discussed above, there are numerous other considerations for successful early case-finding efforts. Currently, CLD management requires fundamental changes at all levels of the health system (ie, patient, care team, organization, and environment) (Figure 1) (25). Ultimately, the current level of policy and attention for CLD is not proportionate to its complexity and poses a major threat to the health care system financially. Consistent across all major guidelines in the field is a call for a coordinated, national plan to address the myriad gaps in the system that perpetuate late diagnosis and high burden in CLD and late-stage complications like HCC and LT.

Figure 1:

Key barriers to effective chronic liver disease (CLD) management within a framework for health system change (25)

What can Governments and Policy Influencers do to Help Reduce the Impact of CLD?

Some of the greatest public health successes have been attributed to government-endorsed policy change (23). Policies have a strong influence on health care delivery, coordination of resource allocations, and health outcomes (23). Given the morbidity and mortality associated with CLD etiologies, intersecting comorbidities (eg, NAFLD and type 2 diabetes), and the breadth of challenges faced by all levels of health care to impact outcomes, we believe overcoming this silent epidemic requires public health policy change by federal and provincial governments. Health policies are wholly lacking for almost all aspects of CLD in Canada. We, therefore, advocate for an immediate, provincially, and nationally endorsed program to support case-finding among those at risk of CLD and liver-related complications (Figure 2). To assist with the prioritization of such policies and ensure the greatest impact according to Canadian needs, we recommend adapting the Organisation for Economic Co-operation and Development microsimulation model to reflect the Canadian health care system and burden of disease (5). Such research would show the relative effect of policies on economic and clinical outcomes and provide the economic rationale to support much-needed programs for liver health promotion.

Figure 2:

Strategies to reduce the burden and economic impact of CLD

CLD = Chronic liver disease; HBV = Hepatitis B virus; HCC = Hepatocellular carcinoma; HCV = Hepatitis C virus; NAFLD = Non-alcohol-associated fatty liver disease; PCP = Primary care provider; SDoH = Social determinants of health

What can Organizations and Care Teams do to Help Reduce the Impact of CLD?

By focusing on prevention and case-finding in typically asymptomatic patients, the management of CLD would increase in both specialty and primary care, thus collaborative partnerships would be necessary between all pillars of health care in Canada. Considering the barriers highlighted in Figure 1, it will be important to consider solutions that support simplified workflows and minimize added burden on already strained resources. Establishing support through alternative models of care and non-specialist providers, with the support of specialty triage protocols will be key to the efficient execution and successful interruption of CLD progression. Education related to CLD among primary care practitioners and fostering a deeper understanding of HCV, HBV, ALD, and NAFLD guidelines, including pediatrics, will require considerable focus. In the absence of pharmacological treatments for ALD and NAFLD, mental health and substance use support, lifestyle modifications, and education will be instrumental in preventing CLD progression and mortality.

Conclusion

Chronic liver disease and its complications impart tremendous patient and health system burdens that are largely preventable in Canada. In addition to crystallized efforts to eliminate viral hepatitis, prevention and early case-finding of patients at risk of ALD and NAFLD along with fibrosis detection offer opportunities to interrupt the disease process and extend survival. National policy and organizational support of care teams will be critical to the successful control of this silent epidemic in Canada.

Funding Statement

Funding: Medical writing support was provided by an independent contractor, Stevie Kenyon (Placencia Holdings Ltd.) and funded by Hoffmann-La Roche Canada Ltd.

Acknowledgements:

The authors gratefully acknowledge Hoffmann-La Roche Ltd. for hosting multidisciplinary meetings in support of the current manuscript. Participants included: Rishma Abdulhusein (Hoffmann-La Roche Ltd.), Karen Seto (Director of Research & Professional Partnerships; Canadian Liver Foundation), the authors, Sharlene Gill (MD; BC Cancer Agency), and Mark G Swain (MD, MSc, FRCPC, FAASLD, FCAHS; Cumming School of Medicine, University of Calgary). The authors also thank medical writer Stevie Kenyon for drafting and revising the manuscript according to their knowledge and insights.

Contributions:

Conceptualization, M Brahmania, MJ Biondi, S Joshi, E Lee, H-M Jung, M Kehar; Writing – Original Draft, M Brahmania, MJ Biondi, E Lee, H-M Jung, M Kehar; Writing – Review and Editing, M Brahmania, MJ Biondi, S Joshi, E Lee, H-M Jung, M Kehar; Supervision, M Brahmania, M Kehar.

Ethics Approval:

N/A

Informed Consent:

N/A

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

N/A

Funding:

Medical writing support was provided by an independent contractor, Stevie Kenyon (Placencia Holdings Ltd.) and funded by Hoffmann-La Roche Canada Ltd.

Disclosures:

M Brahmania has speaking, ad board, and/or research funding from Roche, Eisai, Merck, and AbbVie; MJ Biondi has received clinical consulting fees from Omega Specialty Nurses and McKesson Canada, as well as speaking, ad board, and/or research funding from Abbott, 
AbbVie, and Gilead; S Joshi has received speaking and advisory board consulting fees from Abbvie and Gilead; H-M Jung has received clinical consulting fees from Roche; M Kehar has received clinical consulting fees from Roche; E Lee has received speaking and advisory fees from AbbVie and Gilead.

Peer Review:

This manuscript has been peer reviewed.

Animal Studies:

N/A