De novo hepatitis B virus infection in hepatocellular carcinoma following eradication of hepatitis C virus by interferon therapy

Epidemiological studies have revealed that hepatocellular carcinoma (HCC) is still observed in hepatitis C virus (HCV)-positive patients with a sustained response to interferon (IFN) treatment, although a substantial decrease in the incidence of hepatocellular carcinoma (HCC) has been achieved in those patients. Why HCC develops in patients who have a complete clearance of HCV remains unclear. Here, we provided evidence of latent hepatitis B virus (HBV) infection in an initially HCV-positive chronic hepatitis patient who developed HCC after the complete eradication of HCV by IFN therapy. Although he was initially negative for anti-hepatitis B surface antigen (HBsAg) or circulating HBV DNA but positive for anti-hepatitis B core antigen (anti-HBc) in his sera, he developed HBsAg and HBV DNA during the course of the management of a series of cancers. HBV DNA was detectable in the liver tissues before HBV reactivation and the viral sequences derived from his anti-HBc-positive liver showed 100% homology to that from the serum after HBsAg appearance. These findings indicates that HCV-positive individuals who are positive for anti-HBc in the absence of HBsAg could have latent HBV infection in their liver tissues and intrahepatic HBV infection may play a pivotal role in the development of HCC after the IFN-mediated eradication of HCV.