Hepatocellular Carcinoma After HCV Eradication with Direct-Acting Antivirals: A Reappraisal Based on New Parameters to Assess the Persistence of Risk

Approximately 95% of patients with chronic hepatitis C achieve viral eradication through direct-acting antiviral (DAA) treatment. Ensuing clinical benefits include halting liver fibrosis, thereby reducing the need for liver transplantation, and decreasing both liver-related and overall mortality. It is well established that, although ameliorated, the risk of developing hepatocellular carcinoma (HCC) persists, particularly among patients with pre-treatment advanced fibrosis/cirrhosis. Current guidelines recommend indefinite HCC surveillance in these patients. However, a recent Markov model evaluation shows that HCC surveillance is cost-effective only for patients with cirrhosis but not so for those with F3 fibrosis, a finding which points out the need to better define the risk of HCC in hepatitis C patients after cure and further characterize pre- and post-treatment factors that might affect the incidence of HCC in this setting. We reviewed the literature analyzing this aspect. Here we summarize the main findings: male gender and older age are independent predictors of increased risk of post-cure HCC development. Moreover, non-invasive tests for hepatic fibrosis, namely FIB4, APRI, and liver stiffness, measured before and after treatment and their post-therapy change, contribute to better stratifying the risk of HCC occurrence. Furthermore, low serum albumin, as well as an AFP above 7 ng/mL prior to and after DAA therapy, also constitute independent predictors of HCC development. Considering these findings, we propose to classify patients with HCV viral eradication and advanced fibrosis/cirrhosis into groups of low, medium, or high risk of HCC and to adopt adequate surveillance strategies for each group, including protocols for abbreviated magnetic resonance imaging (MRI) for those at the highest risk.