title: Long-term effects of lamivudine treatment in Japanese chronic hepatitis B patients.
abstract: OBJECTIVE
  To analyze the association between the emergence of tyrosine-methionine-asparatate-asparatate (YMDD) mutants (reverse transcription; rtM204I/V) and deterioration of liver function during long-term lamivudine treatment of Japanese patients with chronic hepatitis B virus (HBV) infection.
  
  
  METHODS
  The data of 61 consecutive Japanese patients with chronic hepatitis B who underwent continuous lamivudine treatment for more than 24 mo and had a virological response were analyzed. Analysis of YMDD mutants was done by real-time polymerase chain reaction with LightCycler probe hybridization assay for up to 90 mo (mean, 50.8 mo; range, 24-90 mo).
  
  
  RESULTS
  A mixed mutant-type (YMDD + tyrosine-isoleucine-asparatate-asparatate: YIDD or tyrosine-valine-asparatate-asparatate: YVDD) or a mutant-type (YIDD or YVDD) were found in 57.4% of 61 patients at 1 year, 78.7% of 61 patients at 2 years, 79.6% of 49 patients at 3 years, 70.5% of 34 patients at 4 years, 68.4% of 19 patients at 5 years, 57.1% of 14 patients at 6 years, and 33.3% of 6 patients at 7 years. Of the 61 patients, 56 (92%) had mixed mutant- or a mutant-type. Only 5 (8%) had no mutants at each observation point. Virological breakthrough was found in 26 (46.4%) of 56 patients with YMDD mutants, 20 of whom had a hepatitis flare-up: the remaining 30 (53.6%) had neither a virological breakthrough nor a flare-up. All 20 patients who developed a hepatitis flare-up had a biochemical and virological response after adefovir was added to the lamivudine treatment.
  
  
  CONCLUSIONS
  Our results suggest that it is possible to continue lamivudine treatment, even after the emergence of YMDD mutants, up to the time that the patients develop a hepatitis flare-up.
authors: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, 812-8582, Japan. mmurata@gim.med.kyushu-u.ac.jp
authors: Masayuki
authors: M
authors: Murata
authors: Norihiro
authors: N
authors: Furusyo
authors: Mami
authors: M
authors: Unno
authors: Eiichi
authors: E
authors: Ogawa
authors: Kazuhiro
authors: K
authors: Toyoda
authors: Hiroaki
authors: H
authors: Taniai
authors: Hachiro
authors: H
authors: Ohnishi
authors: Jun
authors: J
authors: Hayashi
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D018450:Disease Progression; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013995:Time
chemical_list: D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine