title: Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial).
abstract: OBJECTIVE
  Durable post-treatment response is uncommon in chronic hepatitis B (CHB) patients on nucleos(t)ide analogue therapy. Response, response predictors and safety were assessed in patients who switched from long-term entecavir (ETV) to peginterferon alfa-2a.
  
  
  METHODS
  Hepatitis B e antigen (HBeAg)-positive CHB patients who had received ETV for 9-36 months, with HBeAg <100 PEIU/ml and HBV DNA ⩽1000 copies/ml, were randomised 1:1 to receive peginterferon alfa-2a 180 μg/week or ETV 0.5mg/day for 48 weeks. The primary endpoint was HBeAg seroconversion at week 48 (ClinicalTrials.gov: NCT00940485).
  
  
  RESULTS
  200 patients were randomised; 197 received ⩾1 study drug dose. Five patients who were anti-HBe-positive at baseline were excluded from the modified intention-to-treat population (peginterferon alfa-2a, n = 94; ETV, n = 98). Patients who switched to peginterferon alfa-2a achieved higher week 48 HBeAg seroconversion rates vs. those who continued ETV (14.9% vs. 6.1%; p = 0.0467). Only patients receiving peginterferon alfa-2a achieved HBsAg loss (8.5%). Among peginterferon alfa-2a-treated patients with HBeAg loss and HBsAg <1500 IU/ml at randomisation, 33.3% and 22.2% achieved HBeAg seroconversion and HBsAg loss, respectively. Early on-treatment HBsAg decline predicted response at week 48; highest rates were observed in patients with week 12 HBsAg <200 IU/ml (HBeAg seroconversion, 66.7%; HBsAg loss, 77.8%). Alanine aminotransferase elevations were not associated with viral rebound (n = 38). Peginterferon alfa-2a was well-tolerated.
  
  
  CONCLUSIONS
  For patients who achieve virological suppression with ETV, switching to a finite course of peginterferon alfa-2a significantly increases rates of HBeAg seroconversion and HBsAg loss. A response-guided approach may identify patients with the greatest chance of success.
authors.affiliation: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: qning@vip.sina.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ning
authors.affiliation: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Meifang
authors.initials: M
authors.lastname: Han
authors.affiliation: Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: The First Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Jiaji
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Deming
authors.initials: D
authors.lastname: Tan
authors.affiliation: Nanfang Hospital, Nanfang Medical University, Guangzhou, China.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Hou
authors.affiliation: West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
authors.affiliation: The First Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Jifang
authors.initials: J
authors.lastname: Sheng
authors.affiliation: Shanghai Roche Pharmaceutical Co., Ltd, Shanghai, China.
authors.forename: Mianzhi
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage; D004279:DNA, Viral / Q000032:analysis; D057915:Drug Substitution / Q000379:methods; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011379:Prognosis; D011994:Recombinant Proteins / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C413685:entecavir; D006147:Guanine; C100416:peginterferon alfa-2a
keywords: Chronic hepatitis B; Entecavir; Peginterferon alfa-2a