Chronic hepatitis C and metabolic dysfunction-associated steatotic liver disease: converging pathobiology, hepatocarcinogenesis, and clinical implications in the post-SVR era

Abstract

Against the background of the growing global burden of obesity and metabolic disease, metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a leading cause of chronic liver disease worldwide. Simultaneously, many patients remain affected by chronic hepatitis C virus (HCV) infection or its long-term sequelae, reshaping the spectrum of liver disease in the direct-acting antiviral era. HCV may directly induce hepatic steatosis through genotype-specific mechanisms, whereas MASLD promotes steatosis through systemic metabolic dysregulation. Both pathways can independently cause liver injury, and their coexistence may accelerate fibrosis progression and increase the risk of hepatocellular carcinoma (HCC). Emerging evidence indicates that hepatic steatosis before and after sustained virologic response (SVR) is associated with suboptimal fibrosis regression and persistent HCC risk. These findings highlight the need for integrated clinical management incorporating metabolic optimisation and individualised surveillance. Patients with advanced fibrosis, persistent metabolic dysfunction, or residual steatosis remain at increased risk of HCC despite viral eradication and should not be uniformly classified as low risk. This review examines the biological and clinical intersections between chronic HCV infection and MASLD, focusing on fibrosis progression, hepatocarcinogenesis, and residual HCC risk after SVR. It also emphasises the importance of identifying and managing MASLD in patients with current or previous HCV infection to reduce long-term complications and improve clinical outcomes.

Keywords

Chronic hepatitis C / MASLD / sustained virologic response / hepatic steatosis / hepatocellular carcinoma

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