Direct antiviral therapy for hepatitis C and hepatocellular carcinoma: facing the conundrum

Direct antiviral therapy has dramatically changed our possibility to eradicate hepatitis C virus (HCV) infection in all stages of chronic liver disease, with sustained virological response rates well above 90%. HCV eradication should lead to a better prognosis even after cirrhosis has established, including a reduced risk of developing hepatocellular carcinoma (HCC). Unfortunately, during the last two years different reports have raised the concern about a possible increased risk of developing HCC in cirrhotic patients treated with direct antivirals. In this review, we have evaluated the principal published data and have reached a few conclusions: (1) direct antiviral therapy does not seem to increase the cumulative annual rate of HCC de novo occurrence or recurrence; (2) direct antiviral therapy seems to accelerate the development of HCC, soon after the end of treatment, in those patients at higher risk of HCC occurrence or recurrence; and (3) preliminary reports seem to indicate that HCC developed after direct antiviral therapy has more aggressive features. These findings clearly indicate the need for aggressive and close monitoring of cirrhotic patients during and after antiviral treatment, to detect and treat HCC at their earliest occurrence.