title: The influence of YMDD mutation patterns on clinical outcomes in patients with adefovir add-on lamivudine combination treatment.
abstract: OBJECTIVE
  The aim of this study was to assess the patterns of lamivudine (LAM)-resistant mutations and the influence on biochemical and virological responses to adefovir (ADV) add-on LAM combination therapy in patients with LAM-resistant chronic hepatitis B (CHB).
  
  
  METHODS
  Seventy-eight CHB patients with confirmed genotypic resistance to LAM, who initiated ADV add-on LAM combination treatment, were enrolled at our institution between April 2007 and April 2009.
  
  
  RESULTS
  The baseline tyrosine-methionine-aspartate-aspartate (YMDD) mutation patterns were as follows: rtM204I 45 (57.7%); and rtM204V + rtM204I/V 33 (42.3%). The decrease in the mean ± standard deviation (SD) serum log(10) HBV-DNA level did not differ between the patients carrying the rtM204I vs. rtM204IV +rtM204I/V mutations at 3, 6 and 12 months after the initiation of ADV add-on LAM combination treatment. The proportion of patients who achieved ALT normalization (<40 IU/L) 12 months after the initiation of ADV add-on LAM combination treatment were significantly higher in patients with a rtM204I mutation than rtM204V+ rtM204I/V mutations (39 [86.7%] vs. 22 [66.7%], P = 0.05). The proportion of patients in whom the log(10) HBV-DNA decreased <2 log(10) copies/ml, 6 months after the initiation of ADV add-on LAM combination treatment (non-responders), was significantly higher in patients with a rtM204V + rtM204I/V mutations than rtM204I mutation (7 [21.2%] vs. 2 [4.4%], P = 0.032).
  
  
  CONCLUSIONS
  Biochemical response at 12 months from baseline was better in patients with a rtM204I mutation than rtM204V+ rtM204I/V mutations. In addition, early treatment failure was more common in patients with rtM204V+ rtM204I/V mutations than a rtM204I mutation.
authors.affiliation: Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, Korea. hongjoo3.kim@samsung.com
authors.forename: Hong J
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jung H
authors.initials: JH
authors.lastname: Park
authors.forename: Dong I
authors.initials: DI
authors.lastname: Park
authors.forename: Yong K
authors.initials: YK
authors.lastname: Cho
authors.forename: Chong I
authors.initials: CI
authors.lastname: Sohn
authors.forename: Woo K
authors.initials: WK
authors.lastname: Jeon
authors.forename: Byung I
authors.initials: BI
authors.lastname: Kim
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D020816:Amino Acid Motifs / Q000235:genetics*; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024921:Drug Resistance, Multiple, Viral / Q000187:drug effects / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008111:Liver Function Tests; D008297:Male; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000410:Alanine Transaminase; D000225:Adenine