Hepatitis B virus-related hepatocarcinogenesis: molecular oncogenic potential of clear or occult infections

Chronic viral infection is the most important oncogenetic factor, and hepatitis B virus (HBV) plays an important role in the development of hepatocellular carcinoma (HCC). HBV-related carcinogenesis is a multi-step process, encompassing the combination of different, not mutually exclusive effects such as the induction of chronic liver inflammation and regeneration, its integration into the hepatocyte genome and the transactivating and transforming activity of several viral proteins (HBx and truncated Pre-S2/S) that may stimulate cellular oncogenes or suppress growth-regulating genes. Data related to the influence of different hepatitis B virus genotypes and the emergence of selective variants as biomarkers of HCC development still remain controversial. At last, recent studies on occult HBV infection, as defined by serologically undetectable hepatitis B surface antigen (HBsAg-), despite the presence of circulating HBV DNA, suggest that the occult viral strains, maintaining the transcriptional activity and the pro-oncogenetic assets of the clear HBV infection (HBsAg+), may harbour a potential risk for liver cancer development.