title: Association Between Serum Level of Hepatitis B Surface Antigen at End of Entecavir Therapy and Risk of Relapse in E Antigen-Negative Patients.
abstract: This study investigated whether serum level of hepatitis B surface antigen (HBsAg) at the end of entecavir treatment was associated with risk of relapse.
  
  
  
  We performed a prospective multicenter study of 161 consecutive patients with chronic hepatitis B in whom the hepatitis B virus was no longer detected after 3 years or more of entecavir therapy. Treatment ended between July 1, 2011 and July 1, 2015. Patients were monitored for clinical relapse (hepatitis B virus DNA >2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal) and virologic relapse (hepatitis B virus DNA >2000 IU/mL). Outcomes were calculated using the Kaplan-Meier method and risk factors were identified by Cox proportional hazards modeling.
  
  
  
  Two years after therapy ended, 49.2% of patients in the entire cohort had a clinical relapse (95% confidence interval [CI], 40.9%-58.1%) and 81.7% had a virologic relapse (95% CI, 74.3%-88.0%). Among patients who were hepatitis B e antigen-negative at the end of therapy, 39.2% had a clinical relapse (95% CI, 30.3%-49.6%) and 77.4% had a virologic relapse (95% CI, 68.6%-85.2%). Serum level of HBsAg was associated with relapse in the hepatitis B e antigen-negative patients (Ptrend = .006 for clinical relapse; Ptrend = .0001 for virologic relapse). In multivariate Cox regression analysis, the hazard ratio (per log IU/mL increment) for clinical relapse was 2.47 (95% CI, 1.45-4.23) and for virologic relapse was 1.80 (95% CI, 1.33-2.45). The 11 (9%) patients with levels of HBsAg <10 IU/mL did not relapse.
  
  
  
  Serum level of HBsAg is associated with risk of relapse in patients who are hepatitis B e antigen-negative after treatment with entecavir. A low titer of HBsAg might be used to identify patients at low risk for relapse after treatment.
authors.affiliation: Center for Database Research, E-Da Hospital, Kaohsiung City, Taiwan; Division of Gastroenterology, E-Da Hospital, Kaohsiung City, Taiwan; School of Medicine for International Students, I-Shou University, Kaohsiung City, Taiwan; Graduate Institute of Clinical Medicine, China Medical University, Taichung City, Taiwan.
authors.forename: Yao-Chun
authors.initials: YC
authors.lastname: Hsu
authors.affiliation: Superintendent Office, Tainan Municipal Hospital, Tainan City, Taiwan.
authors.forename: Lein-Ray
authors.initials: LR
authors.lastname: Mo
authors.affiliation: Division of Gastroenterology, E-Da Hospital, Kaohsiung City, Taiwan.
authors.forename: Chi-Yang
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan.
authors.forename: Ming-Shiang
authors.initials: MS
authors.lastname: Wu
authors.affiliation: Graduate Institute of Clinical Medicine, National Taiwan University, Taipei City, Taiwan.
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
authors.affiliation: Division of Gastroenterology, E-Da Hospital, Kaohsiung City, Taiwan.
authors.forename: Wen-Lun
authors.initials: WL
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Lotung Poh-Ai Hospital, Yilan County, Taiwan.
authors.forename: Tzeng-Huey
authors.initials: TH
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, Lotung Poh-Ai Hospital, Yilan County, Taiwan.
authors.forename: Chaur-Shine
authors.initials: CS
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Lotung Poh-Ai Hospital, Yilan County, Taiwan.
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Chiang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan.
authors.forename: Chieh-Chang
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Medicine, National Taiwan University Hospital Yun-Lin Branch, Yunlin County, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Fang
authors.affiliation: Taipei Institute of Pathology, Taipei City, Taiwan.
authors.forename: Hsu-Wei
authors.initials: HW
authors.lastname: Hung
authors.affiliation: Graduate Institute of Clinical Medicine, China Medical University, Taichung City, Taiwan; Division of Gastroenterology, Taichung Veterans General Hospital, Taichung City, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei City, Taiwan. Electronic address: chun@vghtc.gov.tw.
authors.forename: Chun-Ying
authors.initials: CY
authors.lastname: Wu
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Jaw-Town
authors.initials: JT
authors.lastname: Lin
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D005260:Female; 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*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D018570:Risk Assessment; D044967:Serum / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; C413685:entecavir; D006147:Guanine; D000410:Alanine Transaminase
keywords: ALT; Liver Disease; Prognostic Factor; Response to Therapy