Persistence of HCV-induced epigenetic reprogramming drives liver cancer risk following viral cure

Chronic hepatitis C virus (HCV) infection is a major cause of hepatocellular carcinoma (HCC). Despite effective antiviral therapies, the risk to develop HCC is not eliminated following viral cure. Here, we show that chronic infection induces genome-wide changes in histone modifications and corresponding transcript/protein expression that persist following treatment-induced sustained virological response (SVR). Integrative pathway analyses of patient liver tissues combined with perturbation studies in a humanized mouse model demonstrate that the virus-induced epigenetic reprogramming drives hepatocarcinogenesis.