Influence of hepatitis B virus core promoter mutations on hepatocellular carcinoma among Japanese patients

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Viral differences in enhancer II/core promoter and precore regions between the subgenotypes and their association with hepatocellular carcinoma (HCC) were assessed in 3 independent studies; 1)a matched cross-sectional control study of 118 carriers with HBV/C1/Cs and 210 HBV/C2/Ce; 2) a control study among 8 IC and 8 HCC patients infected with HBV genotype C before and after seroconversion; 3)an age, sex, and HBeAg status matched cross-sectional control study between 80 Japanese patients infected with HBV/C2 with HCC and 80 without HCC. Our data indicate that T1653 and/or V1753 mutations in addition to T1762/A1764 are strongly associated with HCC in context of HBeAg status among HBV/C-carriers. HBV/C subgenotypes have specific mutation patterns, which is probably responsible for increased carcinogenesis of HBV/C2/Ce.HBV of various genotypes may induce liver disease of distinct severity, but the underlying virological differences are not well defined. Huh7 cells were transfected with plasmids carrying 1.24-fold the HBV genome of different genotypes/subgenotypes (2 strains each for Aa/A1, Ae/A2, Ba/B2 and D; 3 each for Bj/B1 and C). uPA/SCID mice with human hepatocytes were inoculated with mouse passages of virions recovered from culture supernatants. Serum levels of HBV DNA in these mice were higher for C than Ae by 2 logs during 4-7 weeks post-inoculation. In conclusion, virological differences among HBV genotypes were demonstrated both in tissue culture and chimeric mice. These differences may influence HBV infections with distinct genotypes in clinical and epidemiological settings.