The influence of hepatitis B virus genotype and subgenotype on the natural history of chronic hepatitis B

Background  Chronic infection with hepatitis B virus (HBV) is associated with a high lifetime risk of developing hepatocellular carcinoma (HCC) and cirrhosis of the liver. Purpose  To review the studies published to date regarding the association of HBV genotypes and subgenotypes in the development of adverse sequelae from HBV. Methods  Review of the literature for articles describing studies of HBV genotype/subgenotypes and development of HCC, cirrhosis, and liver-related death. Results  Eight genotypes of HBV (A through H), which differ from each other in viral genome sequence by more than 8%, and multiple subgenotypes, which differ from each other by 4–8% have been identified. Recently, studies investigating the association between the risks of developing HCC and cirrhosis by specific HBV genotypes and subgenotypes have reported marked differences in outcome. Certain HBV genotypes and subgenotypes, including genotype C, B2-5, and F1, appear to be associated with a higher risk of developing HCC, and others, including genotypes B1, B6, and A2, appear to be associated with a lower risk of complications of HBV. Our understanding of the role of HBV genotypes and subgenotypes on the outcome of HBV infection is limited, as few population-based prospective studies have been performed and most studies compare only the outcome in areas where two genotypes predominate whereas others have not examined subgenotypes. Conclusions  Studies to date suggest that HBV genotypes/subgenotypes have important influences on the outcome of chronic HBV infection, but more population-based prospective studies examining multiple genotypes are needed.