High prevalence of 1762(T) 1764(A) mutations in the basic core promoter ofhepatitis B virus isolated from black Africans with hepatocellular carcinoma compared with asymptomatic carriers

The purpose of this study was to identify mutations in the basic core promo ter and enhancer II region of the hepatitis B virus (HBV) that might cause the HBV e antigen (HBeAg)-negative phenotype and contribute to hepatocarcin ogenesis in black African carriers of the virus. The basic core promoter/en hancer II overlaps with the X gene. HBV DNA from serum of 47 asymptomatic c arriers and 50 patients with hepatocellular carcinoma and from 28 tumor and 10 nontumor liver tissues was amplified and sequenced directly. That part of the enhancer II region not overlapping the basic core promoter was compl etely conserved in all samples. Missense mutations at nucleotides 1809 and 1812 in the basic core promoter were found in 80% of all sequences and may represent wild-type sequence in Southern African isolates. Nucleotide and a mino acid divergences were higher in the basic core promoter of hepatocellu lar carcinoma patients when compared with asymptomatic carriers (P <.0001). This applied particularly to the paired 1762 adenine to thymine (1762(T)) and 1764 guanine to adenine (1764(A)) missense mutations, the prevalence of which was 66% in patients with hepatocellular carcinoma compared with 11% in asymptomatic carriers (P <.0001), There was no association between the p resence of 1762(T) 1764(A) and HBeAg negativity, although these mutations s uppressed HBeAg titers in HBeAg-positive patients. Suppression of HBeAg exp ression as well as alteration of the amino acid sequence of the X protein m ay play a role in hepatocarcinogenesis.