Hepatitis B virus infection and hepatocellular carcinoma: Molecular genetics and clinical perspectives

Chronic hepatitis B progresses across a spectrum of asymtomatic carriers, a ctive hepatitis, and liver cirrhosis. With more advanced disease stage, the risk for developing hepatocellular carcinoma (HCC) becomes higher. Recent studies suggest that this progressive risk may reflect an accumulation of m ultistage genetic mutations in the chromosomes of affected hepatocytes. Mut ations of the known candidate genes such as p53 and beta-catenin have been found. Recent genome-wide analysis of HCC chromosomes by comparative genomi c hybridization or loss of heterozygosity have identified more new loci imp licated in hepatocarcinogenesis. Persistent hepatitis B is essential for in ducing these mutations through immune-mediated injuries of the hepatocytes and the resulting hyperplasia. Prevention of hepatitis B by active immuniza tion effectively interrupts persistent viral infections in children and sub sequently reduces the risk of childhood HCC. Treatment for chronic hepatiti s B by interferon or antiviral analogues can control hepatitis B activity, but its effect on controlling HCC remains to be seen. Insights for the hepa tocarcinogenesis process should come from a multidisciplinary collaboration to explore important viral and host genes so that new approaches to diagno sis and treatment can be developed.