A randomized trial of peginterferon alpha-2a with or without ribavirin for HBeAg-negative chronic hepatitis B.

Abstract

OBJECTIVES:

Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients are at high risk of treatment relapse after any antiviral therapy. Combining peginterferon alpha-2a with ribavirin might improve sustained response rates.

METHODS:

Overall, 138 HBeAg-negative chronic hepatitis B patients were randomized to receive monotherapy (peginterferon alpha-2a 180 microg weekly plus placebo) or combination therapy (peginterferon alpha-2a weekly plus ribavirin 1,000 or 1,200 mg daily, depending on body weight) for 48 weeks. Post-treatment follow-up lasted 24 weeks. Analyses were based on the modified intention-to-treat population after exclusion of five patients.

RESULTS:

At the end of follow-up, 14 (20%) of 69 patients assigned to monotherapy and 10 (16%) of 64 assigned to combination therapy had a combined response (hepatitis B virus (HBV) DNA <10,000 copies/ml (<1,714 IU/ml) and a normal alanine aminotransferase level, P=0.49). At the end of treatment, more patients had a combined response (25 (36%) vs. 26 (41%) in the monotherapy and combination therapy group, respectively, P=0.60), but subsequently relapsed during follow-up. Serum HBV DNA and hepatitis B surface antigen (HBsAg) levels decreased during treatment (mean change at week 48 compared with baseline -3.9 vs. -2.6 log copies/ml, P<0.001 and -0.56 vs. -0.34 log IU/ml, P=0.23, respectively). HBV DNA levels relapsed after treatment discontinuation; HBsAg remained at end-of-treatment levels. In general, combination therapy was well tolerated, although it was associated with a higher risk of anemia and neutropenia.

CONCLUSIONS:

Treatment with peginterferon alpha-2a resulted in a limited sustained response rate in HBeAg-negative chronic hepatitis B patients. Addition of ribavirin did not improve response to therapy.

• Authors: Vincent Rijckborst, Martijn J ter Borg, Yilmaz Cakaloglu, Peter Ferenci, Fehmi Tabak, Meral Akdogan, Krzysztof Simon, Maria Raptopoulou-Gigi, Necati Ormeci, Pieter E Zondervan, Elke Verhey, Anneke J van Vuuren, Bettina E Hansen, Harry L A Janssen, PARC Study Group
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 105 Issue 8 Pg. 1762-9 (Aug 2010) ISSN: 1572-0241 [Electronic] United States
• PMID: 20461068 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Hepatitis B Surface Antigens
• Hepatitis B e Antigens
• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• peginterferon alfa-2a

Topics

• Adolescent
• Adult
• Aged
• Antiviral Agents (administration & dosage, therapeutic use)
• Chi-Square Distribution
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Hepatitis B Surface Antigens (blood)
• Hepatitis B e Antigens (blood)
• Hepatitis B, Chronic (drug therapy, immunology)
• Humans
• Interferon alpha-2
• Interferon-alpha (administration & dosage, therapeutic use)
• Liver Function Tests
• Male
• Middle Aged
• Polyethylene Glycols (administration & dosage, therapeutic use)
• Recombinant Proteins
• Ribavirin (administration & dosage, therapeutic use)
• Treatment Outcome