title: Profile of hepatitis B virus resistance mutations against nucleoside/nucleotide analogue treatment in Chinese patients with chronic hepatitis B.
abstract: OBJECTIVE
  Antiviral drug-resistant HBV mutants are complex and currently partly understood. This study was performed to analyze the profile of hepatitis B virus (HBV) resistance mutations against nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B (CHB).
  
  
  METHODS
  This was a population-based cross-sectional study. Serum samples of 179 patients with virological breakthrough undergoing different NAs treatment were obtained between January 2008 and December 2012. The HBV reverse transcriptase region was sequenced and the following NAs-resistant changes including rtL80, rtI169, rtV173, rtL180, rtA181, rtT184, rtA194, rtS202, rtM204, rtN236 and rtM250 were analyzed.
  
  
  RESULTS
  In this cohort, 21.2% (38/179) were genotypes B and 78.8% (141/179) were genotypes C; and 89.4% (160/179) of them detected NAs-resistant mutations. The prevalence of HBV mutations at rtM204 was 93.0% (106/114) in patients with lamivudine (LAM) or telbivudine (LdT)-based therapies, and that of rtN236 mutations was 76.1% (35/46) in patients with adefovir dipivoxil (ADV)-based therapies. Among LAM/LdT based therapies, HBV rtM204I was significantly associated with HBV rtL80I/V mutations [rtM204I+rtL80I/V (50.0%, 32/64) vs. rtM204V+rtL80I/V (27.3%,9/33), P=0.032]; while the HBV rtM204V mutations was significantly associated with HBV rtL180M mutations [rtM204V+rtL180M (100%, 33/33) vs. rtM204I+rtL180M (60.9%, 39/64), P<0.001]. Additionally, HBV rtA181 mutations were observed in 19.3% (22/114) of patients with LAM/LdT-based therapy and 23.9% (11/46) of patients with ADV-based therapy.
  
  
  CONCLUSIONS
  Majority of virological breakthrough is associated with NAs-resistant HBV, and the mutation patterns of NAs-resistant HBV are complicated in real clinical practice.
authors.forename: Jun
authors.initials: J
authors.lastname: Lei
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Wang
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Bai
authors.affiliation: Department of Infectious Diseases, Wuhan Neurologist Hospital and General Hospital of The Yangtze River Shipping, Wuhan, China. lvyexu@126.com.
authors.forename: Lv-Ye
authors.initials: LY
authors.lastname: Xu
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D002681:China; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D017422:Sequence Analysis, DNA; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D012194:RNA-Directed DNA Polymerase