title: Response-guided peginterferon therapy in patients with HBeAg-positive chronic hepatitis B: A randomized controlled study.
abstract: Response-guided therapy has been confirmed to be an effective strategy for the treatment of chronic hepatitis C in the pegylated interferon (PegIFN) era, but no randomized trial utilizing this strategy has been conducted in chronic hepatitis B.
  
  
  
  In this open-label, multicenter, randomized trial, HBeAg positive patients were treated with PegIFN (180μg/week) for 24weeks. Early responders (HBsAg <1500IU/ml and HBV DNA <10(5)copies/ml at week 24) received PegIFN for a further 24weeks (arm A), while non-early responders were randomized to PegIFN for another 24weeks (arm B), another 72weeks (arm C) or PegIFN for another 72weeks plus adefovir for 36weeks (arm D). The primary endpoint was the change of quantitative HBsAg from baseline to the end of follow-up (EOF).
  
  
  
  For non-early responders, 96-week PegIFN monotherapy did not lead to a greater reduction of HBsAg from baseline to EOF, compared with 48-week PegIFN (-0.71 vs. -0.67log10IU/ml, P=0.407). The rate of HBeAg seroconversion with HBV DNA <2000IU/ml at EOF were similar for arms B, C and D (17.9%, 23.9% and 25.0% respectively). For patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24, 38.4% and 37.0% achieved HBeAg seroconversion with HBV DNA <2000IU/ml at EOF respectively.
  
  
  
  Patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24 would benefit from continued PegIFN treatment. Extending the duration of PegIFN with or without adding adefovir did not show superiority over 48weeks PegIFN monotherapy.
  
  
  
  Extending the duration of pegylated interferon (PegIFN) alfa-2a is not recommended in HBeAg positive patients as treatment extension beyond 48weeks did not show convincing benefit. Patients who achieved HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml after 24-week PegIFNα-2a showed satisfactory outcome after the withdrawal of finite PegIFNα-2a treatment.
  
  
  
  NCT01086085.
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangdong Province, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, Xicheng District, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Infectious Diseases, Shanghai Ruijin Hospital, Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Liver Disease Department, Beijing DiTan Hospital, Beijing, Chongyang District, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Huashan Hospital affiliated to Fudan University, Shanghai, China.
authors.forename: Guangfeng
authors.initials: G
authors.lastname: Shi
authors.affiliation: Department of Infectious Diseases, Shanghai Changhai Hospital, Shanghai, China.
authors.forename: Mobin
authors.initials: M
authors.lastname: Wan
authors.affiliation: Department of Liver, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Junqi
authors.initials: J
authors.lastname: Niu
authors.affiliation: Department of Infectious Diseases, Wuhan Tongji Hospital affiliated to Huazhong Technology University, Tongji Medical College, Wuhan, Hubei Province, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ning
authors.affiliation: Department of Infectious Diseases, Peking University First Hospital, Beijing, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Infectious Diseases, Shanghai Ruijin Hospital, Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Liver Disease Department, Beijing DiTan Hospital, Beijing, Chongyang District, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Kang
authors.affiliation: Shanghai Roche Pharmaceuticals Co Ltd, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangdong Province, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Fan
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Microbiology and Infectious Disease Center, Peking University, Health Science Center, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, Xicheng District, China.
authors.forename: Jidong
authors.initials: J
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangdong Province, China. Electronic address: jlhousmu@163.com.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Hou
mesh_terms: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D019694:Hepatitis B, Chronic; D006801:Humans; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols
keywords: Antiviral therapy; Clinical trial; Hepatitis B