Review: Hepatocellular Carcinoma and Hepatitis Virus

Integrated hepatitis B virus (HBV) DNA is present in many hepatocellular carcinomas (HCC), suggesting that HBV has a direct oncogenic effect through interaction with transformation-associated genes. Many genes involved in cell cycle regulation (cyclins, kinases, negative regulators, Wnt-beta-catenin) and the transcriptome profile are deregulated or altered in most HCC patients. The HBx protein, potentially oncogenic via multistep carcinogenesis, modifies apoptosis, inhibits nucleotide excision and repair of damaged cellular DNA, and modulates transcriptional activation of cellular growth regulating genes. Hepatocyte transformation may be indirectly influenced by HBV DNA integration, by the generation of mutagenic oxygen reactive species, or by acquisition of mutations in association with necroinflammatory disease. HBV replication, which may occur in HCC, affects the long-term survival of patients. Prevention of HBV infection is expected to decrease the incidence of endemic HCC. (received 24 April 2002, accepted 25 August 2002)