Impact of peginterferon maintenance therapy on the risk of developing hepatocellular carcinoma in patients with chronic hepatitis C virus.

The incidence of hepatocellular carcinoma (HCC) is increasing worldwide. This is largely to do with the epidemic of chronic hepatitis C virus (HCV) in the USA and other developed countries and an increasing prevalence of cirrhosis. The current treatment for chronic HCV is peginterferon (Peg-IFN) and ribavirin. Unfortunately, response rates are limited especially in patients with cirrhosis. Several observations have led to the hypothesis that continuing Peg-IFN as maintenance therapy in patients with chronic HCV and cirrhosis could reduce the risk of developing complications including HCC. However, three large prospective controlled trials of maintenance therapy have now failed to demonstrate that Peg-IFN maintenance therapy reduces complications of cirrhosis, HCC and liver-related mortality. In the HALT-C trial, the only one of these three studies for which HCV RNA data is available during maintenance therapy, only a minimal reduction in serum HCV RNA level was observed during maintenance therapy. It therefore remains uncertain if profound and persistent virologic suppression to undetectable levels of HCV RNA impacts the risk of developing HCC in patients with chronic HCV and advanced fibrosis or cirrhosis. Based upon the available data, there appears to be no rationale for utilizing Peg-IFN maintenance therapy in patients with cirrhosis and this approach does not reduce the risk of HCC.