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Background There is still a paucity of data on hepati tis 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 rtM2041/V (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.