title: Predictors of relapse in chronic hepatitis B after discontinuation of anti-viral therapy.
abstract: BACKGROUND
  Optimal duration of anti-viral therapy in chronic hepatitis B virus (HBV) infection remains unclear.
  
  
  OBJECTIVE
  To investigate factors that could predict relapse after stopping anti-viral agents.
  
  
  METHODS
  Chronic hepatitis B patients who were treated with anti-viral agents (lamivudine, adefovir, entecavir) and have stopped the treatment were recruited. Anti-viral agents were stopped according to the recommendations of the Asian Pacific Association for the Study of the Liver. Virological relapse was defined as an increase in serum HBV DNA to >1000 copies/mL after discontinuation of treatment.
  
  
  RESULTS
  Eighty-four (69 treatment naïve and 15 lamivudine resistant) patients were eligible for this study. Thirty-seven patients developed virological relapse at 4.3 ± 2.9 (range 1-11) months after discontinuation of therapy. The 1-year cumulative probability of virological relapse was 42% and 47% in HBeAg (hepatitis B e antigen)-positive (n = 41) and HBeAg (hepatitis B e antigen)-negative (n = 43) patients, respectively. On multivariate analysis by Cox proportional hazard model, pre-existing lamivudine resistance, delayed suppression of HBV DNA to undetectable level during anti-viral therapy and to a higher HBsAg (hepatitis B surface antigen) level at the end of treatment were associated with virological relapse. Twelve of the 15 (80%) lamivudine resistant patients developed virological relapse. Among the 11 treatment naïve patients who had HBsAg ≤ 2 log IU/mL at the end of treatment, 1 (9%) of them had virological relapse.
  
  
  CONCLUSIONS
  Treatment cessation among lamivudine resistant patients is associated with high risk of virological relapse. Serum HBsAg level at the end of treatment and rate of HBV DNA suppression can provide supplementary information to guide the timing of stopping anti-viral drugs.
authors.affiliation: Department of Infectious Diseases, First Hospital, Guangxi Medical University, Nanning, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liang
authors.forename: J
authors.initials: J
authors.lastname: Jiang
authors.forename: M
authors.initials: M
authors.lastname: Su
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: W
authors.initials: W
authors.lastname: Guo
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: R
authors.initials: R
authors.lastname: Xie
authors.forename: S
authors.initials: S
authors.lastname: Ge
authors.forename: J
authors.initials: J
authors.lastname: Hu
authors.forename: Z
authors.initials: Z
authors.lastname: Jiang
authors.forename: M
authors.initials: M
authors.lastname: Zhu
authors.forename: V W-S
authors.initials: VW
authors.lastname: Wong
authors.forename: H L-Y
authors.initials: HL
authors.lastname: Chan
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006511:Hepatitis B Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D012008:Recurrence; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D006511:Hepatitis B Antigens; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine