Liver

Subject Category: Liver

Am J Gastroenterol 2010;105:1762–1769; doi:10.1038/ajg.2010.186; published online 11 May 2010

A Randomized Trial of Peginterferon α-2a With or Without Ribavirin for HBeAg-Negative Chronic Hepatitis B

Vincent Rijckborst MD1, Martijn J ter Borg MD, PhD1, Yilmaz Cakaloglu MD2, Peter Ferenci MD3, Fehmi Tabak MD4, Meral Akdogan MD5, Krzysztof Simon MD6, Maria Raptopoulou-Gigi MD7, Necati Örmeci MD8, Pieter E Zondervan MD9, Elke Verhey BSc1, Anneke J van Vuuren PhD1, Bettina E Hansen MSc1,10 and Harry LA Janssen MD, PhD1 for the PARC Study Group11

  1. 1Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
  2. 2Department of Gastroenterohepatology, Istanbul University Medical School, Istanbul, Turkey
  3. 3Department of Internal Medicine 3, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
  4. 4Department of Infectious Diseases, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey
  5. 5Department of Gastroenterology, Turkiye Yuksek lhtisas Hospital, Ankara, Turkey
  6. 6Department and Clinic of Infectious Diseases, Hepatology and Acquired Immune Deficiences, Medical University Wroclaw, Wroclaw, Poland
  7. 7Second Medical Department, Aristototle University of Thessaloniki, Thessaloniki, Greece
  8. 8Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
  9. 9Department of Pathology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
  10. 10Department of Epidemiology and Biostatistics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
  11. 11Other members are listed in Appendix

Correspondence: Harry L.A. Janssen, MD, PhD, Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Gravendijkwal 230, Room Ha 204, Rotterdam 3015 CE, The Netherlands. E-mail: h.janssen@erasmusmc.nl

Received 11 November 2009; Accepted 12 February 2010; Published online 11 May 2010.

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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 α-2a with ribavirin might improve sustained response rates.

METHODS:

 

Overall, 138 HBeAg-negative chronic hepatitis B patients were randomized to receive monotherapy (peginterferon α-2a 180μg weekly plus placebo) or combination therapy (peginterferon α-2a weekly plus ribavirin 1,000 or 1,200mg 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 <10,000copies/ml (<1,714IU/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 α-2a resulted in a limited sustained response rate in HBeAg-negative chronic hepatitis B patients. Addition of ribavirin did not improve response to therapy.