Hepatitis B virus (HBV) genotypes/subgenotypes in China: Mutations in core promoter and precore/core and their clinical implications

Background: The association of hepatitis B virus (HBV) genotypes with clinical course of infection is increasingly recognized. Objectives: In order to investigate the genetic diversity of HBV and its clinical implications, 241 HBV-infected patients including 34 with hepatocellular carcinoma (HCC) were enrolled in this study. Methods: HBV genotyping was performed with an ELISA assay. HBV subgenotypes were determined by PCR-RFLP. HBV core promoter/precore/core mutations were analyzed by direct sequencing. Results: The overall prevalence of HBV/B and C was 65% and 33%, respectively. Among HBV/C, 42% were Cs/C1 and 58% were Ce/C2. The HBV/C1 was only found in the patients originating from Southern China (p = 0.0001). Among HCC patients, HBV/C2 was only found in the elder age group (>= 51 years; p < 0.05) and HBV/Ba was associated with young HCC patients (<35 years). Mutations associated with HCC were V1753 and T1762/A1764 (p < 0.01). The prevalence of the V1753 was higher in HBV/C1 strains (p < 0.04), A1898 was only found among HBV/C1 (p = 0.056). T1762/A1764 was frequently demonstrated in both subgenotypes. The T1858 (90%) and A1896 (40%) mutations were most frequent in HBV/C2 (p < 0.008). Conclusions: HBV/C1 and HBV/C2 have distinct geographic distributions in China. V1753 in addition to T1762/A1764 double mutation in the basal core promoter region seems to be associated with HCC development, especially in the patients with HBV/C1. (C) 2007 Elsevier B.V. All rights reserved.