Beyond the Cure: Navigating Hepatocellular Risk and Surveillance after Hepatitis C Eradication in the Direct-acting Antiviral Era

Abstract

Direct-acting antivirals (DAAs) have dramatically changed the landscape of chronic hepatitis C virus (HCV) treatment and significantly reduced the risk of HCV-related hepatocellular carcinoma (HCC) after achieving sustained virologic response. However, the risk of HCC persists, particularly in patients with pre-treatment cirrhosis or fibrosis stage 3 (F3), even after DAA-induced viral eradication. While professional guidelines agree on the need for surveillance in cirrhotic patients, there is no consensus regarding surveillance for the pre-treatment F3 population following HCV eradication. The risk of HCC in the F3 population falls below the threshold for cost-effective surveillance. However, co-existing risk factors-such as diabetes, hepatic steatosis, alcohol use, advanced age, and elevated alpha-fetoprotein levels-may warrant reconsideration of HCC surveillance in this group. This underscores the need for an individualized, risk-based approach to HCC surveillance. This review provided a simplified algorithm to assist clinicians in managing patients with HCV after DAA-induced sustained virologic response.

Keywords: Cirrhosis; Direct-acting antivirals; Hepatic fibrosis; Hepatitis C virus; Hepatocellular carcinoma; Sustained virologic response.

Fig. 1. Pathogenesis of HCC development in HCV patients who achieve SVR by DAA.

DAA eradicates the HCV virus and the associated inflammatory process, halting further liver fibrosis progression or decompensation. However, the latent accumulation of genetic and epigenetic aberrations persists and eventually leads to HCC development, even after HCV eradication. HCC, hepatocellular carcinoma; SVR, sustained virologic response; DAA, direct-acting antiviral agent; HCV, hepatitis C virus.

Fig. 2. A simplified algorithm for HCC surveillance in HCV patients who have achieved SVR by DAA.

The algorithm provides recommendations for clinicians on HCC surveillance after HCV eradication. It is determined by the pre-treatment fibrosis stage, which is assessed by NITs (preferred) +/- liver biopsy. For F3 patients, clinicians need to apply individualized strategies and consider other associated risk factors for HCC. HCC, hepatocellular carcinoma; SVR, sustained virologic response; DAA, direct-acting antiviral agent; HCV: hepatitis C virus; F0-F4, fibrosis stages 0 to 4; DM, diabetes mellitus; US, ultrasound; AFP, alpha-fetoprotein.