Precision Strategy for Hepatocellular Carcinoma Surveillance after Hepatitis C Cure: Debates across Guidelines

Abstract

Hepatitis C virus (HCV) clearance markedly reduces the risk of hepatocellular carcinoma (HCC); however, HCC continues to develop in a subset of patients, particularly in those with advanced fibrosis or cirrhosis. Leading hepatology societies, including Asian Pacific Association for the Study of the Liver, European Association for the Study of the Liver, American Association for the Study of Liver Diseases, Korean Association for the Study of the Liver, Taiwan Association for the Study of the Liver, and Japan Society of Hepatology, have issued divergent guidelines for HCC surveillance after sustained virologic response, which reflects variations in regional patient populations, healthcare infrastructure, and policy priorities. While traditional risk stratification primarily centers on histological staging of fibrosis, an array of additional host-related factors, including age, sex, alcohol use, metabolic comorbidities, and genetic and epigenetic profiles, further influence individual HCC risks. Recently developed predictive models aim to improve risk discrimination and inform tailored surveillance intervals. Concurrently, health economic analyses support the continuation of surveillance in high-risk populations. Nonetheless, the optimal surveillance frequency and criteria for patient selection remain matters of ongoing debates. This review synthesizes current controversies across international guidelines, presents an evaluation of the supporting evidence for varied surveillance strategies, highlights emerging tools for individualized risk assessment, and discusses cost-effectiveness considerations to inform personalized, evidence-based HCC surveillance in the post-HCV cure landscape.