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Background: An increased incidence of C-to-T1653 transversion (T1653) in the enhancer II region of the core promoter of hepatitis B virus has been reported in Japanese and Chinese patients with hepatocellular carcinoma infected with genotypes B or C of the virus, but little information is available in patients infected with other genotypes., Aim: To document the prevalence of T1653 in Black Africans with hepatocellular carcinoma, in whom genotype A is the dominant genotype and subgenotype A1 the dominant subgenotype, and to correlate its presence with other core promoter mutations previously described in association with T1653., Methods: The presence of the mutations was determined in 84 patients with hepatitis B virus-induced hepatocellular carcinoma and 50 matched asymptomatic carriers of the virus by extracting viral DNA from serum, amplification by polymerase chain reaction assay, and nucleotide sequencing., Results: T1653 was not found significantly more often in the cancer patients with genotype A and subgenotype A1 than in the controls. An association was found not only between T1653 and T1762, A1764 and dual T1762/A1764 in the patients with hepatocellular carcinoma, but also in the asymptomatic carriers., Conclusion: T1653 mutation of hepatitis B virus does not occur more often in Black African patients with hepatocellular carcinoma with genotype A and subgenotype A1 than in asymptomatic carriers of the virus. No correlation specific to hepatocellular carcinoma was found between T1653 and other core promoter mutations in these patients. The presence of the T1653 mutation did not influence the e antigen status of the patients.

The purpose of this study was to identify mutations in the basic core promoter and enhancer II region of the hepatitis B virus (HBV) that might cause the HBV e antigen (HBeAg)-negative phenotype and contribute to hepatocarcinogenesis in black African carriers of the virus. The basic core promoter/enhancer II overlaps with the X gene. HBV DNA from serum of 47 asymptomatic carriers 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 completely 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 amino acid divergences were higher in the basic core promoter of hepatocellular 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 presence of 1762(T) 1764(A) and HBeAg negativity, although these mutations suppressed HBeAg titers in HBeAg-positive patients. Suppression of HBeAg expression as well as alteration of the amino acid sequence of the X protein may play a role in hepatocarcinogenesis.