Changing Etiology of Cirrhosis and Other Chronic Liver Diseases: Implications for Hepatocellular Carcinoma Surveillance in Non-Cirrhotic Patients
Author(s)
LIU MING, MSc1, Wai-kit Ming, MPH, PhD, MD1, Xue Xue, BSc2.
1Department of Infectious Diseases and Public Health, JCC of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong, Hong Kong, 2School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong.
1Department of Infectious Diseases and Public Health, JCC of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong, Hong Kong, 2School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong.
OBJECTIVES: Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol use are the fastest-growing causes of cirrhosis and other chronic liver diseases (CLD), challenging hepatocellular carcinoma (HCC) surveillance. Many HCC cases occur in non-cirrhotic patients, yet a consensus on surveillance for this group is lacking. This study evaluates the evolving etiology of CLD and the cost-effectiveness of HCC surveillance in non-cirrhotic patients.
METHODS: We analyzed data from the Global Burden of Disease Study 2021 to assess CLD-related disability-adjusted life years (DALYs) and annual transition rates to liver cancer from 1990 to 2021, with projections to 2040 using a Bayesian age-period-cohort model. Trends in age-standardized DALY rates (ASDR) were evaluated using estimated annual percentage change (EAPC). The cost-effectiveness of HCC surveillance in non-cirrhotic patients was assessed across 195 countries under reference, better, and worse scenarios, compared with surveillance guidelines from four regional and 30 national recommendations.
RESULTS: Globally, ASDR declined (EAPC: -1.07% [95% CI: -1.37% to -1.16%]) across all etiologies except MASLD, which remained stable but is projected to account for 81.53% of CLD prevalence by 2040. While hepatitis B and C remained the leading causes of CLD DALYs, the burden from alcohol use and MASLD increased across sexes and socio-demographic index (SDI) regions. Despite ASDR declines, total DALYs increased by 27.93% due to population growth and aging. The transition from CLD to liver cancer also increased, particularly higher in East Asia Pacific, South Asia, and high-SDI regions. Under the reference scenario, HCC surveillance was cost-effective in 26.15% of countries for hepatitis B and 2.56% for hepatitis C, but not for MASLD, with thresholds for initiating surveillance varying significantly by country.
CONCLUSIONS: The rising burden of MASLD and alcohol-related CLD underscores the need for tailored public health strategies. HCC surveillance in non-cirrhotic patients may not be broadly cost-effective, necessitating updated guidelines and validated risk stratification tools.
METHODS: We analyzed data from the Global Burden of Disease Study 2021 to assess CLD-related disability-adjusted life years (DALYs) and annual transition rates to liver cancer from 1990 to 2021, with projections to 2040 using a Bayesian age-period-cohort model. Trends in age-standardized DALY rates (ASDR) were evaluated using estimated annual percentage change (EAPC). The cost-effectiveness of HCC surveillance in non-cirrhotic patients was assessed across 195 countries under reference, better, and worse scenarios, compared with surveillance guidelines from four regional and 30 national recommendations.
RESULTS: Globally, ASDR declined (EAPC: -1.07% [95% CI: -1.37% to -1.16%]) across all etiologies except MASLD, which remained stable but is projected to account for 81.53% of CLD prevalence by 2040. While hepatitis B and C remained the leading causes of CLD DALYs, the burden from alcohol use and MASLD increased across sexes and socio-demographic index (SDI) regions. Despite ASDR declines, total DALYs increased by 27.93% due to population growth and aging. The transition from CLD to liver cancer also increased, particularly higher in East Asia Pacific, South Asia, and high-SDI regions. Under the reference scenario, HCC surveillance was cost-effective in 26.15% of countries for hepatitis B and 2.56% for hepatitis C, but not for MASLD, with thresholds for initiating surveillance varying significantly by country.
CONCLUSIONS: The rising burden of MASLD and alcohol-related CLD underscores the need for tailored public health strategies. HCC surveillance in non-cirrhotic patients may not be broadly cost-effective, necessitating updated guidelines and validated risk stratification tools.
Conference/Value in Health Info
2025-09, ISPOR Real-World Evidence Summit 2025, Tokyo, Japan
Value in Health Regional, Volume 49S (September 2025)
Code
RWD312
Topic Subcategory
Reproducibility & Replicability
Disease
SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity)