Early molecular and genetic determinants of primary liver malignancy

Hepatitis B virus (HBV) infection is a major etiologic agent of hepatocellular carcinoma. The HBV encoded X antigen, HBxAg, contributes to hepatocarcinogenesis by upregulating the expression of genes promoting hepatocellular survival and growth. HBxAg also downregulates some genes that normally inhibit survival or growth. Integration of HBV DNA into host DNA, and the persistent generation of reactive oxygen intermediates resulting from cytotoxic immune responses against virus-infected cells, contribute to cellular gene mutations that contribute to early hepatocarcinogenesis. These may cause loss of tumor suppressor proteins that negatively regulate cell growth, and the activation of growth stimulatory pathways, such as those involving P-catenin. Other differentially expressed genes being revealed will provide a clearer picture of hepatocarcinogenesis on the molecular level and provide targets for meaningful intervention.