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

Ilaria Serio, Lucia Napoli, Simona Leoni, Fabio Piscaglia


The advent of directly acting antivirals (DAA) has determined a showy change in the management of hepatitis C virus (HCV) infection, the most common cause of hepatocellular carcinoma (HCC) in many countries. It was demonstrated that the achievement of sustained virologic response (SVR) with interferon (IFN) reduces the incidence of HCC. Recently, published data in the literature suggested an increased risk of HCC after IFN free treatments. The mechanism evoked to explain this trend is the deregulation of antitumor response, following the sudden decrease of HCV viral load, due to immune subversion which could favour the progressive development of pre-existing neoplastic clones. The lack of randomised controlled trials (RCTs) with control groups of patients and the fact that majority of studies are limited by retrospective settings, recruitment bias and lack of clinical goals scheduled at the start of treatment make difficult an adequate analysis of data. Main evidence seems to confirm that DAA therapy has not a carcinogenic effect per se but can lead to the earlier manifestation of latent tumours still present but underestimated. At present patients with HCV infection should be encouraged initiating DAA therapy to prevent cirrhosis and HCC but intensive screening is necessary to exclude HCC before initiating DAA. Curing HCV infection does not eliminate the possibility of ongoing liver disease and HCC, as such an adequate monitoring should continue for an indefinite period after SVR.