title: Impact of prior lamivudine use on the antiviral efficacy and development of resistance to entecavir in chronic hepatitis B patients.
abstract: OBJECTIVE
  To determine the efficacies of entecavir (ETV) in nucleos(t)ide analogue (NA)-naïve chronic hepatitis B (CHB) patients and in those with prior lamivudine (LAM) use who did not develop resistance.
  
  
  METHODS
  We retrospectively enrolled 337 patients with CHB who were treated with ETV (0.5 mg daily) for at least 30 months. The study included 270 (80.1%) NA-naïve patients and 67 (19.9%) LAM-use patients. Ten of the LAM-use patients were refractory to LAM therapy without developing resistance.
  
  
  RESULTS
  Genotypic resistance to ETV developed more frequently in the LAM-use group (13.1%) than in the NA-naïve group (2.6%) at 60 months (P=0.009). In subgroup analysis, after excluding the 10 patients who were refractory to LAM therapy, the cumulative probability of ETV resistance did not differ significantly between the two groups (P=0.149). Prior LAM refractoriness and a higher hepatitis B virus DNA level at month 12 were independent predictive factors for the development of ETV resistance.
  
  
  CONCLUSIONS
  ETV resistance developed more frequently in LAM-use patients with CHB. However, prior LAM use without refractoriness did not affect the development of ETV resistance. The serum hepatitis B virus DNA level at month 12 was a major predictor for the development of ETV resistance.
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Joo An
authors.initials: JA
authors.lastname: Hwang
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Kee Bum
authors.initials: KB
authors.lastname: Kim
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Min Jae
authors.initials: MJ
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Sun Gyo
authors.initials: SG
authors.lastname: Lim
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Jae Chul
authors.initials: JC
authors.lastname: Hwang
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Cheong
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Soon Sun
authors.initials: SS
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine; C413685:entecavir; D006147:Guanine
keywords: Chronic hepatitis B; Entecavir; Lamivudine; Resistance