title: Effect of hepatitis B virus reverse transcriptase variations on entecavir treatment response.
abstract: BACKGROUND
  Entecavir therapy often reduces hepatitis B virus (HBV) DNA to an undetectable level, but HBV DNA remain detectable in some patients. We investigated whether baseline HBV reverse transcriptase (rt) polymorphism and quasispecies complexity and diversity were associated with treatment response.
  
  
  METHODS
  Pretreatment HBV DNA levels, HBV rt sequence, serology, and quasispecies complexity and diversity from 305 entecavir-treated patients were determined. These data were tested for their association with year 1 virological outcome, defined by optimal response (undetectable HBV DNA; lower limit of detection, ≤12 IU/mL) or partial response (detectable HBV DNA).
  
  
  RESULTS
  Four rt variants were more frequently detected in the 64 partial responders than in the 241 optimal responders (all P < .05). Multivariate analysis revealed that high baseline HBV DNA level (P < .0001; odds ratio [OR], 2.32), HBV e antigen (HBeAg) positivity (P < .001; OR, 3.70), and rt124N (P = .002; OR, 3.06) were associated with a partial entecavir response. Compared with the optimal responders, the partial responders had a lower quasispecies complexity and diversity.
  
  
  CONCLUSIONS
  Apart from the known factors (high baseline HBV DNA level and HBeAg positivity), a novel single nucleotide polymorphism (rt124N) and lower quasispecies complexity and diversity were associated with partial entecavir response at year 1.
authors.affiliation: Department of Medicine State Key Laboratory for Liver Research.
authors.forename: Danny Ka-Ho
authors.initials: DK
authors.lastname: Wong
authors.affiliation: Department of Medicine.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kopaniszen
authors.affiliation: Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Omagari
authors.affiliation: Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: School of Nursing, University of Hong Kong, Hong Kong SAR, China.
authors.forename: Daniel Yee-Tak
authors.initials: DY
authors.lastname: Fong
authors.affiliation: Department of Medicine.
authors.forename: Wai-Kay
authors.initials: WK
authors.lastname: Seto
authors.affiliation: Department of Medicine State Key Laboratory for Liver Research.
authors.forename: James
authors.initials: J
authors.lastname: Fung
authors.affiliation: Department of Medicine.
authors.forename: Fung-Yu
authors.initials: FY
authors.lastname: Huang
authors.affiliation: Department of Medicine.
authors.forename: An-Ye
authors.initials: AY
authors.lastname: Zhang
authors.affiliation: Department of Medicine.
authors.forename: Ivan Fan-Ngai
authors.initials: IF
authors.lastname: Hung
authors.affiliation: Department of Medicine State Key Laboratory for Liver Research.
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Lai
authors.affiliation: Department of Medicine State Key Laboratory for Liver Research.
authors.forename: Man-Fung
authors.initials: MF
authors.lastname: Yuen
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006509:Hepatitis B / Q000188:drug therapy* / Q000821:virology*; D006515:Hepatitis B virus / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; C413685:entecavir; D006147:Guanine; D012194:RNA-Directed DNA Polymerase
keywords: antiviral therapy; chronic viral hepatitis; drug response; hepatitis B