title: Poor durability of lamivudine effectiveness despite stringent cessation criteria: a prospective clinical study in hepatitis B e antigen-negative chronic hepatitis B patients.
abstract: OBJECTIVE
  Lamivudine, a nucleoside analog, is commonly used for treatment of chronic hepatitis B (CHB) but its durability of effectiveness after withdrawal is still uncertain. This study was designed to assess the durability of lamivudine treatment with stringent cessation criteria in hepatitis B e antigen (HBeAg)-negative patients and to explore potential predictive factors.
  
  
  METHODS
  Sixty one HBeAg-negative CHB patients who had received lamivudine for at least 24 months and had maintained undetectable serum hepatitis B virus (HBV) DNA plus normal alanine aminotransferase for ≥ 18 months before withdrawal were included. They were followed up monthly during the first 4 months and at 3-month or 6-month intervals thereafter. Relapse was defined as serum HBV DNA ≥ 10(4) copies/mL.
  
  
  RESULTS
  Thirty one of 61 patients relapsed during follow-up, over 90% occurred within 18 months after lamivudine withdrawal. Cumulative relapse rates at months 6, 12, 24, 36, 48 and 60 were 26.2%, 43.6%, 49.7%, 52.1%, 56.1% and 56.1%, respectively. Cox regression revealed that age was the only predictive factor for relapse, with lower relapse rates found in younger patients. Hepatitis B surface antigen (HBsAg) turned negative in eight patients, and none of them relapsed during follow-up.
  
  
  CONCLUSIONS
  Effectiveness of lamivudine treatment is not durable in HBeAg-negative CHB patients even when stringent cessation criteria are adopted, with the exception of patients aged ≤ 20 years. The ideal end point of lamivudine treatment is clearance of serum HBsAg.
authors.affiliation: Department of Infectious Diseases and Hepatology, the Second Hospital of Shandong University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Xiao Ying
authors.initials: XY
authors.lastname: Li
authors.forename: You De
authors.initials: YD
authors.lastname: Liu
authors.forename: Jing Bo
authors.initials: JB
authors.lastname: Wang
authors.forename: Zhao Hua
authors.initials: ZH
authors.lastname: Zhang
authors.forename: Yao Zong
authors.initials: YZ
authors.lastname: Wang
mesh_terms: D000328:Adult; D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D002681:China; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D005500:Follow-Up Studies; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D019259:Lamivudine; D000410:Alanine Transaminase