Pathogenesis of hepatocellular carcinoma: a review from the viewpoint of molecular analysis.

Chronic liver inflammation and hepatic regeneration by infection with hepatitis B (HBV) or C virus (HBC) seem to be important risk factors for hepatocellular carcinoma (HCC). Regarding the hepatocarcinogenesis of HBV DNA integration, it has been variously hypothesized that mechanisms such as the alteration of host chromosomal DNA and transcriptional trans-acting activity of the X gene are activated. On the other hand, integration of HCV virus into chromosomal DNA has not been reported. It is suggested that HCV could replicate more efficiently in noncancerous than in cancerous tissues. Therefore, it might affect some oncogenes or cause an inactivation of tumor suppressor genes in the early stage of HCC. Genetic alterations such as a point mutation and loss of heterozygosity are considered to be late events occurring after tumorigenesis. Regeneration of liver cells through chronic hepatitis increases the incidence of genetic alterations in hepatic cells and/or HCCs in both HBV- and HCV-infected patients.