Direct antiviral agents for HCV infection and hepatocellular carcinoma: facts and FADs

Hepatitis C virus (HCV) infection, affecting about 150,000,000 individuals, is the predominant cause of chronic hepatitis resulting in cirrhosis and hepatocellular carcinoma (HCC) (1). HCC is lethal cancer with overall 5-year survival of around 14%. HCC is considered the fifth most frequently diagnosed cancer and the second leading cause of cancer deaths among adult male (2). This high mortality is partly favoured by the co-existence of liver cirrhosis in most of the patients. Advent of direct antiviral agents (DAA) dramatically changed the therapy of hepatitis C (3) because of the high efficacy in all categories of HCV infected patients: sustained virological response (SVR), achieved in over 90% of treated patients whatever the stage of liver fibrosis, is associated with few side effects (4). In the past, therapeutic regimens based on interferon (IFN) resulted in a lower response rate (viral suppression in less than 50% of treated patients) with limited use by adverse effects and contraindications. The effects of IFN induced HCV clearance were three: decrease of cirrhosis-related complications, improvement in liver fibrosis and drop of overall mortality. In particular multiple studies have reported a decrement in “de novo HCC” among SVR patients compared to non-SVR ones (5-7). Antiviral and antiangiogenic properties of IFN seem to elide the pro-inflammatory and carcinogenic effects of HCV. Multiple studies have confirmed that the risk of HCC following an IFN induced SVR is around 1% (8) while the annual incidence of HCC in untreated HCV cirrhosis is 3–7% (9)