title: Characterization of hepatitis B virus genotypes/subgenotypes in 1,301 patients with chronic hepatitis B in North China.
abstract: 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)-loss-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 rtM204I/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.
authors.affiliation: Institute of Infectious Diseases and Liver Failure Research Center, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: Xu
authors.forename: Jiu-Zeng
authors.initials: JZ
authors.lastname: Dai
authors.forename: Le
authors.initials: L
authors.lastname: Li
authors.forename: Zeng-Tao
authors.initials: ZT
authors.lastname: Yao
authors.forename: Shao-Jie
authors.initials: SJ
authors.lastname: Xin
authors.forename: Jing-Ming
authors.initials: JM
authors.lastname: Zhao
authors.forename: Dong-Ping
authors.initials: DP
authors.lastname: Xu
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D002681:China; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral