title: Association Between Level of Hepatitis B Surface Antigen and Relapse After Entecavir Therapy for Chronic Hepatitis B Virus Infection.
abstract: OBJECTIVE
  We investigated the rate of relapse of hepatitis B virus (HBV) infection after entecavir therapy for chronic hepatitis B and the association between level of hepatitis B surface antigen (HBsAg) and relapse.
  
  
  METHODS
  In a retrospective study, we analyzed data from 252 patients with chronic HBV infection who were treated with entecavir and met the Asian Pacific Association for the Study of the Liver treatment stopping rules (mean time, 164 ± 45 weeks) from January 2007 through June 2011 in Taiwan. Eighty-three were hepatitis B e antigen (HBeAg)-positive, and 169 were HBeAg-negative. Patients had regular post-treatment follow-up examinations for at least 12 months. Virologic relapse was defined on the basis of serum HBV DNA >2000 IU/mL after entecavir therapy. Clinical relapse was defined as a level of alanine aminotransferase > 2-fold the upper limit of normal and HBV DNA > 2000 IU/mL.
  
  
  RESULTS
  Two years after therapy ended, 42% of HBeAg-positive patients had a virologic relapse, and 37.6% had a clinical relapse; 3 years after therapy ended, these rates were 64.3% and 51.6% for HBeAg-negative patients, respectively. On the basis of Cox regression analysis, factors independently associated with virologic and clinical relapse included old age, HBV genotype C, and higher baseline levels of HBsAg for HBeAg-positive patients and old age and higher end-of-treatment levels of HBsAg for HBeAg-negative patients. In HBeAg-positive patients, risk of HBV relapse increased with age ≥ 40 years and HBsAg level ≥ 1000 IU/mL at baseline (P < .001). In HBeAg-negative patients, the combination of age (< 55 years) and HBsAg level (< 150 IU/mL) at the end of treatment was associated with a lower rate of virologic relapse (4.5% of HBeAg-negative patients had viral relapse at year 3). The decrease in level of HBsAg from month 12 of treatment until the end of treatment was greater in patients who did lose HBsAg after entecavir therapy compared with those who did not.
  
  
  CONCLUSIONS
  The combination of age and level of HBsAg is associated with relapse of HBV infection after treatment with entecavir. HBsAg levels might be used to guide the timing of cessation of entecavir treatment in patients with chronic HBV infection.
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Hung
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Tsung-Hui
authors.initials: TH
authors.lastname: Hu
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Jing-Houng
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Lu
authors.affiliation: Department of Statistics, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Pei-Fang
authors.initials: PF
authors.lastname: Su
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: chmolee88@gmail.com.
authors.forename: Chuan-Mo
authors.initials: CM
authors.lastname: Lee
mesh_terms: D000328:Adult; D000367:Age Factors; D000410:Alanine Transaminase; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D044966:Anti-Retroviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; C413685:entecavir; D006147:Guanine; D000410:Alanine Transaminase
keywords: Drug; Recurrence; Reverse Transcriptase Inhibitor; Treatment Time