title: Systematic review: cessation of long-term nucleos(t)ide analogue therapy in patients with hepatitis B e antigen-negative chronic hepatitis B.
abstract: BACKGROUND
  It has been debated whether finite nucleos(t)ide analogue therapy is feasible in HBeAg-negative chronic hepatitis B.
  
  
  OBJECTIVE
  To review this issue systematically.
  
  
  METHODS
  Using text terms HBsAg and various nucleos(t)ide analogues, PubMed was searched between 1995 and 2014 to find studies on therapy >6 months in adult HBeAg-negative chronic hepatitis B patients with off-therapy follow-up >6 months.
  
  
  RESULTS
  Twenty-two studies with a total of 1732 patients were identified and included. The median duration of therapy, consolidation therapy and off-therapy follow-up ranged from 6 months to 8 years, 4 to 96 weeks and 6 to 80 months respectively. Patients were monitored with serum ALT and HBV DNA monthly in the first 1-3 months and every 3-6 months afterwards in most studies. The 1-year off-therapy 'virological relapse' (HBV DNA >2000 IU/mL) and 'clinical relapse' (HBV DNA > 2000 IU/mL + ALT elevation) occurred in <70% and <50% of the patients, respectively, and <40% of the patients received re-treatment. These rates were higher in patients with shorter treatment, shorter consolidation therapy and those treated with less potent nucleos(t)ide analogues. Off-therapy severe flares were rare and hepatic decompensation was reported in only one patient with cirrhosis. Biochemical relapse reflecting enhanced immune-mediated hepatocyte killing may lead to a higher chance for off-therapy HBsAg seroclearance and be possibly desirable.
  
  
  CONCLUSIONS
  With an appropriate stopping rule and a proper off-therapy monitoring plan, cessation of long-term nucleos(t)ide analogue therapy prior to HBsAg seroclearance in HBeAg-negative chronic hepatitis B is a feasible alternative to indefinite treatment.
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
authors.forename: M-L
authors.initials: ML
authors.lastname: Chang
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
authors.forename: Y-F
authors.initials: YF
authors.lastname: Liaw
authors.affiliation: Second Department of Medicine at Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: S J
authors.initials: SJ
authors.lastname: Hadziyannis
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens