title: High rates of progressive hepatic functional deterioration whether lamivudine therapy is continued or discontinued after emergence of a lamivudine-resistant mutant: a prospective randomized controlled study.
abstract: BACKGROUND
  The management of patients with lamivudine-resistant mutants remains challenging, and no clear evidence has been presented concerning the discontinuation of lamivudine.
  
  
  METHODS
  Seventy-four patients with lamivudine-resistant mutants were prospectively enrolled and randomized; 37 patients continued (group A) and 37 patients discontinued lamivudine therapy (group B). The median follow-up was 20 months.
  
  
  RESULTS
  Serum albumin levels were reduced and prothrombin time was prolonged in both groups versus baseline (P = 0.015 and 0.045, respectively). Four patients in group A (10.8%) and six in group B (16.2%) experienced hepatitis flare, but the difference was not significant (P > 0.05). Multivariate analyses identified a younger age as a risk factor for hepatitis flare (P = 0.021). Seven (18.9%) decompensations occurred in group A and five (13.5%) in group B, which was not a significant difference (P > 0.05). Multivariate analyses revealed higher alanine aminotransferase and a lower platelet count as risk factors for hepatic decompensation (P = 0.001 and 0.001, respectively). The patients whose platelet count was <65 000/microl experienced hepatic decompensations more frequently (50%) than those with platelet counts >65 000/microl (13.2%) during follow-up (P = 0.05).
  
  
  CONCLUSIONS
  The clinical course of group B was not significantly different from that of group A. Therefore, the discontinuation of lamivudine may be a feasible option when other antiviral agents active against lamivudine-resistant mutants are unavailable.
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 28 Yungun-dong, Chongno-gu, Seoul, 110-744, Korea.
authors.forename: Yoon Jun
authors.initials: YJ
authors.lastname: Kim
authors.forename: Byeong Gwan
authors.initials: BG
authors.lastname: Kim
authors.forename: Jun-Oh
authors.initials: JO
authors.lastname: Jung
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.forename: Hyo-Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood / Q000187:drug effects; D018450:Disease Progression; D024882:Drug Resistance, Viral / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000097:blood / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology; D006801:Humans; D007723:Korea / Q000453:epidemiology; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D017093:Liver Failure / Q000097:blood / Q000453:epidemiology* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000187:drug effects*; D010976:Platelet Count; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011517:Prothrombin Time; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D012709:Serum Albumin / Q000187:drug effects / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D012709:Serum Albumin; D019259:Lamivudine; D000410:Alanine Transaminase; D001663:Bilirubin