Hepatocellular carcinoma after treatment of hepatitis C with direct-acting antivirals: a critical re-appraisal

Soon after introducing direct-acting antiviral agents (DAAs) for chronic hepatitis C treatment, there began a debate over the possibility of hepatocellular carcinoma (HCC) after viral clearance. Although several reports suggested that the question has been answered negatively, other reports suggested the opposite. The present review presents data in favor and against the null hypothesis and analyzes the scientific background of the possible participation of DAAs in HCC development. The reasons for the discrepancy among studies are presented. These include heterogeneity of patient selection, the nature of the studies, and the tumors themselves are responsible for varying results. Exogenous factors like alcohol consumption or metabolic syndrome confound these findings and suggest the need for statistical adjustments. The need for careful attention to the statistical details is exemplified, and the significant points of almost universal agreements are identified. The conclusion is that the definitive study is impossible for ethical and scientific reasons, and the physician should not ignore even simple personal observations and screening of all patients with extensive fibrosis in HCC, irrespective of sustained virologic response, until a robust, reliable prognostic model can be invented.