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.

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.

• Authors: Sudeep Tanwar, Mark Wright, Graham R Foster, Stephen D Ryder, Peter R Mills, Matthew E Cramp, Julie Parkes, William M Rosenberg
• Journal: European journal of gastroenterology & hepatology (Eur J Gastroenterol Hepatol) Vol. 24 Issue 5 Pg. 543-50 (May 2012) ISSN: 1473-5687 [Electronic] England
• PMID: 22337287 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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