title: Improved inflammatory activity with peginterferon alfa-2b maintenance therapy in non-cirrhotic prior non-responders: a randomized study.
abstract: OBJECTIVE
  Therapeutic options for patients failing hepatitis C retreatment are limited. EPIC(3) included a prospective trial assessing long-term peginterferon alfa-2b (PegIFNα-2b) maintenance therapy in patients with METAVIR fibrosis scores (MFS) of F2 or F3 who previously failed hepatitis C retreatment.
  
  
  METHODS
  Patients with F2/F3 MFS who failed retreatment were randomized to PegIFNα-2b (0.5 μg/kg/week, n=270) or observation (n=270) for 36 months. Blinded liver biopsies obtained before retreatment and after maintenance therapy were evaluated using MFS and activity scores, and confirmatory testing was performed using FibroTest and ActiTest.
  
  
  RESULTS
  In total, 348 patients had paired biopsies: 192 patients had missing post-treatment biopsies and were considered as having no change in fibrosis/activity scores. In total, 16% of patients receiving PegIFNα-2b and 11% of observation patients had improvement in MFS (p=0.32). More PegIFNα-2b than observation patients had improvement in activity score (20% vs. 9%; p <0.001). Among patients treated for >2.5 years, improvement in MFS or activity score was more common with PegIFNα-2b than observation (21% vs. 14%, p=0.08 and 26% vs. 10%, p <0.001). FibroTest and ActiTest evaluations indicated significant benefit associated with PegIFNα-2b in terms of reduced fibrosis progression and improved activity score. The safety profile of PegIFNα-2b was similar to previous studies.
  
  
  CONCLUSIONS
  PegIFNα-2b did not significantly improve MFS estimated by biopsy compared with observation; however, activity scores were significantly improved and MFS trended toward increased improvement with treatment durations >2.5 years. Both FibroTest and ActiTest were significantly improved during maintenance therapy.
authors.affiliation: Service d'Hepato-Gastroenterologie, APHP-UPMC Paris Liver Center, Paris, France. tpoynard@teaser.fr
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
authors.forename: Jordi
authors.initials: J
authors.lastname: Bruix
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Schiff
authors.forename: Moises
authors.initials: M
authors.lastname: Diago
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Ricardo
authors.initials: R
authors.lastname: Moreno-Otero
authors.forename: Andre C
authors.initials: AC
authors.lastname: Lyra
authors.forename: Flair
authors.initials: F
authors.lastname: Carrilho
authors.forename: Louis H
authors.initials: LH
authors.lastname: Griffel
authors.forename: Navdeep
authors.initials: N
authors.lastname: Boparai
authors.forename: Ruiyun
authors.initials: R
authors.lastname: Jiang
authors.forename: Margaret
authors.initials: M
authors.lastname: Burroughs
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Brass
authors.forename: Janice K
authors.initials: JK
authors.lastname: Albrecht
mesh_terms: D000328:Adult; D000410:Alanine Transaminase; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D000410:Alanine Transaminase; C417083:peginterferon alfa-2b