Hepatitis B virus and hepatocellular carcinoma

Hepatitis B virus (HBV) has been implicated as a causative factor for the development of hepatocellular carcinoma (HCC). However, no oncogenes have been identified within the HBV genome and furthermore, the virus is frequently fragmented after it integrates into the hepatocyte genome. Therefore it has been difficult to understand how HBV brings about genetic damage to result in HCC. Recent data from our laboratory show that despite fragmentation, the HBx gene is consistently retained in a functional form and therefore suggest that this gene is important to HCC development. In 4 out of 6 HCC cell lines studied, the DR2 integration sequence was destroyed during integration and points to a possible preferred target integration site. The growing importance of HBx in HCC development is supported by data from other laboratories showing that transgenic mice carrying the HBx gene alone frequently develop HCC. This review discusses the role of HBV and other factors involved in liver carcinogenesis.