Improved inflammatory activity with peginterferon alfa-2b maintenance therapy in non-cirrhotic prior non-responders: a randomized study

J Hepatol. 2013 Mar;58(3):452-9. doi: 10.1016/j.jhep.2012.11.001. Epub 2012 Nov 14.

Abstract

Background & aims: 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.

Trial registration: ClinicalTrials.gov NCT00049842.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Alanine Transaminase
  • Antiviral Agents / therapeutic use*
  • Female
  • Hepatitis C / drug therapy*
  • Hepatitis C / pathology
  • Humans
  • Inflammation / drug therapy*
  • Interferon alpha-2
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use*
  • Liver Cirrhosis / pathology
  • Male
  • Middle Aged
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use*
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Alanine Transaminase
  • peginterferon alfa-2b

Associated data

  • ClinicalTrials.gov/NCT00049842