title: Combination of Tenofovir Disoproxil Fumarate and Peginterferon α-2a Increases Loss of Hepatitis B Surface Antigen in Patients With Chronic Hepatitis B.
abstract: OBJECTIVE
  Patients chronically infected with the hepatitis B virus rarely achieve loss of serum hepatitis B surface antigen (HBsAg) with the standard of care. We evaluated HBsAg loss in patients receiving the combination of tenofovir disoproxil fumarate (TDF) and peginterferon α-2a (peginterferon) for a finite duration in a randomized trial.
  
  
  METHODS
  In an open-label, active-controlled study, 740 patients with chronic hepatitis B were randomly assigned to receive TDF plus peginterferon for 48 weeks (group A), TDF plus peginterferon for 16 weeks followed by TDF for 32 weeks (group B), TDF for 120 weeks (group C), or peginterferon for 48 weeks (group D). The primary end point was the proportion of patients with serum HBsAg loss at week 72.
  
  
  RESULTS
  At week seventy-two, 9.1% of subjects in group A had HBsAg loss compared with 2.8% of subjects in group B, none of the subjects in group C, and 2.8% of subjects in group D. A significantly higher proportion of subjects in group A had HBsAg loss than in group C (P < .001) or group D (P = .003). However, the proportions of subjects with HBsAg loss did not differ significantly between group B and group C (P = .466) or group D (P = .883). HBsAg loss in group A occurred in hepatitis B e antigen-positive and hepatitis B e antigen-negative patients with all major viral genotypes. The incidence of common adverse events (including headache, alopecia, and pyrexia) and treatment discontinuation due to adverse events was similar among groups.
  
  
  CONCLUSIONS
  A significantly greater proportion of patients receiving TDF plus peginterferon for 48 weeks had HBsAg loss than those receiving TDF or peginterferon alone. ClinicalTrials.gov ID NCT01277601.
authors.affiliation: Service d'Hépatologie, Hôpital Beaujon, University Paris-Diderot, Inserm Centre de Recherche sur l'Inflammation, Clichy, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.affiliation: Division of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ma
authors.affiliation: National Institute for Infectious Diseases, "Matei Bals", Bucharest, Romania.
authors.forename: Florin A
authors.initials: FA
authors.lastname: Caruntu
authors.affiliation: Kyungpook National University Hospital, Daegu, South Korea.
authors.forename: Won Young
authors.initials: WY
authors.lastname: Tak
authors.affiliation: Toronto Liver Center, Toronto, Canada.
authors.forename: Magdy
authors.initials: M
authors.lastname: Elkashab
authors.affiliation: Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
authors.affiliation: Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Seng-Gee
authors.initials: SG
authors.lastname: Lim
authors.affiliation: University of Istanbul, Cerrahpasa Medical Faculty, Istanbul, Turkey.
authors.forename: Fehmi
authors.initials: F
authors.lastname: Tabak
authors.affiliation: Liver Clinic, Surat, India.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Mehta
authors.affiliation: IFI Institute for Interdisciplinary Medicine at the Asklepios Klinik St. George, University of Hamburg, Hamburg, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Petersen
authors.affiliation: Queen Mary University of London, London, United Kingdom.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.affiliation: Nexus Development, Palo Alto, California.
authors.forename: Lillian
authors.initials: L
authors.lastname: Lou
authors.affiliation: Gilead Sciences Inc, Foster City, California.
authors.forename: Eduardo B
authors.initials: EB
authors.lastname: Martins
authors.affiliation: Gilead Sciences Inc, Foster City, California.
authors.forename: Phillip
authors.initials: P
authors.lastname: Dinh
authors.affiliation: Gilead Sciences Inc, Foster City, California.
authors.forename: Lanjia
authors.initials: L
authors.lastname: Lin
authors.affiliation: Gilead Sciences Inc, Foster City, California.
authors.forename: Amoreena
authors.initials: A
authors.lastname: Corsa
authors.affiliation: Gilead Sciences Inc, Foster City, California.
authors.forename: Prista
authors.initials: P
authors.lastname: Charuworn
authors.affiliation: Gilead Sciences Inc, Foster City, California.
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
authors.affiliation: Gilead Sciences Inc, Foster City, California.
authors.forename: Hans
authors.initials: H
authors.lastname: Reiser
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Hendrick W
authors.initials: HW
authors.lastname: Reesink
authors.affiliation: University of Toronto, Department of Medicine, Toronto General Hospital, Toronto, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Fung
authors.affiliation: AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital and University of Sydney, Sydney, Australia.
authors.forename: Simone I
authors.initials: SI
authors.lastname: Strasser
authors.affiliation: San Jose Gastroenterology, San Jose, California.
authors.forename: Huy
authors.initials: H
authors.lastname: Trinh
authors.affiliation: Hepatology Unit, Hospital Universitari Vall d'Hebron and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas del Instituto Carlos III, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.affiliation: Viral Hepatitis Unit, Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Gaeta
authors.affiliation: The Chinese University of Hong Kong, Alice Ho Miu Ling Nethersole Hospital, Hong Kong.
authors.forename: Aric J
authors.initials: AJ
authors.lastname: Hui
authors.affiliation: Athens University Medical School, "Laiko" General Hospital of Athens, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Papatheodoridis
authors.affiliation: Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Flisiak
authors.affiliation: Department of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong. Electronic address: hlychan@cuhk.edu.hk.
authors.forename: Henry L Y
authors.initials: HL
authors.lastname: Chan
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000187:drug effects*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000627:therapeutic use*; D038622:Internationality; D053208:Kaplan-Meier Estimate; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use; D018570:Risk Assessment; D012720:Severity of Illness Index; D015996:Survival Rate; D000068698:Tenofovir / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult
chemical_list: D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D000068698:Tenofovir; C100416:peginterferon alfa-2a
keywords: Clinical Trial; HBV; HBeAg Seroconversion; Virologic Response