EXPRESSION OF HEPATITIS-C VIRUS IN HEPATOCELLULAR-CARCINOMA

Background. Epidemiologic studies have suggested a strong association between chronic hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC). To investigate the possible role of HCV in the pathobiology of HCC, the authors studied the expression of HCV in 10 cases of HCC with chronic HCV infection, Methods. The core, envelope, and nonstructural (NS) 3 and 5 proteins were localized in liver and tumor tissues by the immunoperoxidase technique using mouse monoclonal antibodies to recombinant proteins or synthetic peptide of HCV. In addition, the positive and negative strands of HCV RNA were detected in the tissues by strand-specific reverse transcription/double polymerase chain reaction using primers for the 5'-nontranslated region. Results. The HCV proteins were expressed in three of nine HCC specimens tested (the core protein in three HCC, the envelope, NS3 and NS5 proteins in one HCC) and in two of nine nontumorous liver specimens adjacent to the HCC (the core protein in two specimens, envelope, NS3 and NS5 proteins in one specimen). Positive-stranded HCV RNA was detected in all tumorous and nontumorous specimens except in one tumor. Negative-stranded HCV RNA was found in six of nine HCC tested and in all nontumorous livers. Conclusions. These findings suggest that HCV persists in hepatocytes during malignant transformation, although secondary infection of tumor cells by HCV cannot be excluded. Some HCC appear to support replication and expression of HCV,