Characterization of hepatitis B virus genotypes/subgenotypes in 1301 patients with chronic hepatitis B in North China

Background There is still a paucity of data on hepatitis B virus （HBV） subgenotype prevalence in North China based on sequencing of large-size samples. In addition, whether HBV genotypes impact drug-resistance-associated and HBV e antigen （HBeAg）-Ioss-associated mutations in patients with chronic hepatitis B （CHB） is still under investigation. This study aimed to disclose clinical prevalence of HBV genotypes/subgenotypes in North China and the clinical implications of HBV genotype classification in respect to HBeAg loss and drug-resistant occurrence. Methods Sera were collected from 1301 nucleos（t）ide analog-experienced CHB patients. Viral DNA was extracted and used as template for HBV genome amplification by nested PCR. DNA sequencing was performed for the analysis of HBV genotypes/subgenotypes, drug-resistance-associated mutations in polymerase gene and HBeAg-loss-associated mutations in precore/basal core promoter （BCP） regions. Results HBV/B, HBV/C, and HBV/D were detected in 190 （14.6%）, 1096 （84.2%）, and 15 （1.2%） patients, respectively. HBV/B2 （182/190）, HBV/C2 （1069/1096）, and HBV/D1 （12/15） were predominant subgenotypes within individual genotypes. By contrast, C2 prevalence is relatively lower in Beijing area （77.2%） than in other north areas （84.9%-87.4%）. HBV/C-infected patients had an older age and a lower serum albumin level but similar HBV DNA and alanine aminotransferase （ALT） levels compared to HBV/B-infected patients. HBV/C infection had a higher incidence of lamivudine-resistant mutations rtM2041N （44.9% vs. 30.2%, P 〈0.01） and BCP mutations A1762T＋G1764A （65.8% vs. 40.0%, P〈0.01） compared with HBV/B infection. Conclusions C2 is the most prevalent HBV subgenotype followed by B2 in CHB patients in North China; and HBV genotype prevalence is influenced by immigrant population. HBV/C infection is likely to have longer disease duration and severer liver functional impairment and might be more susceptible to develop lamivudine resistance compared to HBV/B infection.