Randomized Clinical Trial: A Pilot Study Investigating the Safety and Effectiveness of an Escalating Dose of Peginterferon α-2a Monotherapy for 48 Weeks Compared With Standard Clinical Care in Patients With Hepatitis C Cirrhosis

Eur J Gastroenterol Hepatol. 2012 May;24(5):543-50. doi: 10.1097/MEG.0b013e3283513e69.

Abstract

Background: A substantial proportion of patients with chronic hepatitis C virus (HCV) cirrhosis fail to eradicate infection and develop liver-related complications. Despite evidence that interferon-α has an antifibrotic effect, clinical trials have demonstrated that low-dose maintenance interferon does not improve outcomes in patients with compensated HCV cirrhosis following a lead-in phase of interferon. In a pilot study, we have investigated the efficacy of an escalating dose of pegylated interferon α-2a (PEG-IFN2a) as compared with standard clinical care in patients with more advanced HCV Child's A or B cirrhosis without a lead-in phase.

Methods: In a prospective study, 40 patients were randomized to receive either standard clinical care (no further antiviral therapy) or 48 weeks of treatment with PEG-IFN2a starting at 90 mcg and escalating to 180 mcg weekly if tolerated. Patients were thereafter followed for a mean duration of 41 months. The primary outcome variables were liver-related death, all-cause mortality and sustained virological response. The secondary outcomes were 'liver-related events' and health-related quality of life.

Results: Both groups were well matched, with treatment well tolerated. The incidences of all-cause mortality (P=0.024) and nononcological liver morbidity (P=0.04) were significantly higher in the control arm after a mean of 47 months of follow-up.

Conclusion: A 48-week escalating dose of PEG-IFN2a is associated with a significant reduction in all-cause mortality and nononcological liver-related morbidity in this trial. Further investigation of PEG-IFN2a is warranted for patients with advanced HCV-related cirrhosis for whom there is no other treatment and where transplantation is associated with rapid progression to cirrhosis.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use
  • Biomarkers / blood
  • Dose-Response Relationship, Drug
  • Female
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use
  • Kaplan-Meier Estimate
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / virology
  • Male
  • Middle Aged
  • Pilot Projects
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use
  • Prospective Studies
  • Quality of Life
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Biomarkers
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • peginterferon alfa-2a