HEPATITIS-B-VIRUS-X ANTIGEN IN THE PATHOGENESIS OF CHRONIC INFECTIONSAND THE DEVELOPMENT OF HEPATOCELLULAR-CARCINOMA

Chronic infection with hepatitis B virus is associated with a high inc idence of liver diseases, including hepatocellular carcinoma. Hepatiti s-B-virus-encoded X antigen (HBxAg) stimulates virus gene expression a nd replication, which may be important for the establishment and maint enance of the chronic carrier state. Integration of viral DNA encoding HBxAg during chronic infection results in increased X antigen express ion. HBxAg overexpression may alter signal transduction pathways impor tant for the regulation of cell growth during hepatocellular regenerat ion. The finding that HBxAg binds to and inactivates negative growth-r egulatory molecules, such as the tumor suppressor p53, suggests additi onal ways that HBxAg may act in hepatocarcinogenesis. HBxAg may also s timulate the expression of positive growth regulators, such as insulin -lile growth factor II and the insulin-like growth factor I receptor T he finding that HBxAg may compromise DNA repair and that it may effect the normal turnover of growth-regulatory molecules in the proteasome may also contribute to its carcinogenic properties. Hence, HBxAg may c ontribute to the pathogenesis of chronic infection and development of hepatocellular carcinoma in a variety of ways.