title: Peginterferon add-on results in more HBsAg decline compared to monotherapy in HBeAg-positive chronic hepatitis B patients.
abstract: It is unknown whether peginterferon (PEG-IFN) add-on to entecavir (ETV) leads to more HBsAg decline compared to PEG-IFN monotherapy or combination therapy, and whether ETV therapy may prevent HBsAg increase after PEG-IFN cessation. We performed a post hoc analysis of 396 HBeAg-positive patients treated for 72 weeks with ETV + 24 weeks PEG-IFN add-on from week 24 to 48 (add-on, n = 85), 72 weeks with ETV monotherapy (n = 90), 52 weeks with PEG-IFN monotherapy (n = 111) and 52 weeks PEG-IFN + lamivudine (combination, n = 110) within 2 randomized trials. HBsAg decline was assessed at the end of PEG-IFN (EOP) and 6 months after PEG-IFN (EOF) discontinuation. Differences in baseline characteristics were accounted for using inversed probability of treatment weights. At EOP, a HBsAg reduction of ≥1log10 IU/mL was more frequently achieved for patients in the add-on or combination therapy arms (both 36%), compared to PEG-IFN mono (20%) or ETV (8%) (add-on vs PEG-IFN mono P = 0.050). At EOF, the HBsAg reduction ≥1log10 IU/mL was only sustained in patients treated with ETV consolidation (add-on vs combination and PEG-IFN mono: 40% vs 23% and 18%, P = 0.029 and P = 0.003, respectively). For add-on, combination, PEG-IFN mono and ETV, the mean HBsAg-level change at EOF was -0.84, -0.81, -0.68 and -0.33 log10 IU/mL, respectively (P > 0.05 for PEG-IFN arms). HBeAg loss at EOF was 36%, 31%, 33% and 20%, respectively (P > 0.05). PEG-IFN add-on for 24 weeks results in more on-treatment HBsAg decline than does 52 weeks of PEG-IFN monotherapy. ETV therapy may maintain the HBsAg reduction achieved with PEG-IFN.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: W P
authors.initials: WP
authors.lastname: Brouwer
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Sonneveld
authors.affiliation: Infectious Diseases, Ruijin Hospital, Jiaotong University, Shanghai, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Infectious Diseases, Ruijin Hospital, Jiaotong University, Shanghai, China.
authors.forename: S
authors.initials: S
authors.lastname: Guo
authors.affiliation: Gastroenterology and Hepatology, Zhong Shan Hospital, Fu Dan University, Shanghai, China.
authors.forename: N
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Cerrahpasa Medical Faculty, Istanbul, Turkey.
authors.forename: F
authors.initials: F
authors.lastname: Tabak
authors.affiliation: Gastroenterology and Hepatology, Shanghai Public Health Center, Fu Dan University, Shanghai, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Division of Infectious Diseases and Hepatology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Simon
authors.affiliation: Ege Üniversitesi Tip Fakultesi, Bornova, Turkey.
authors.forename: U S
authors.initials: US
authors.lastname: Akarca
authors.affiliation: Department of Gastroenterology, Fundeni Cinical Institute, Bucharest, Romania.
authors.forename: A
authors.initials: A
authors.lastname: Streinu-Cercel
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Department of Public Health, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: B E
authors.initials: BE
authors.lastname: Hansen
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.|Toronto Center for Liver Disease, Toronto Western and General Hospital, University Health Network, Toronto, ON, Canada.
authors.forename: H L A
authors.initials: HL
authors.lastname: Janssen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods*; 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; D016898:Interferon-alpha / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D000069078:Seroconversion; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D019259:Lamivudine; C413685:entecavir; D006147:Guanine
keywords: ETV consolidation; PEG-IFN add-on; combination therapy; viral hepatitis