Gastroenterology
Volume 132, Issue 1 , Pages 103-112, January 2007

Impact of Reducing Peginterferon Alfa-2a and Ribavirin Dose During Retreatment in Patients With Chronic Hepatitis C

  • Mitchell L. Shiffman

      Affiliations

    • Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, Virginia
    • Corresponding Author InformationAddress requests for reprints to: Mitchell L Shiffman, MD, Hepatology Section, Virginia Commonwealth University Medical Center, Box 980341, Richmond, Virginia 23298. fax: (804) 828-4945, and HALT-C Trial Data Coordinating Center, New England Research Institutes, 9 Galen Street, Watertown, Massachusetts 02472.
    • ,
  • Marc G. Ghany

      Affiliations

    • Liver Diseases Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
    • ,
  • Timothy R. Morgan

      Affiliations

    • Division of Gastroenterology, University of California-Irvine, Irvine, California, and Gastroenterology Service, VA Long Beach Healthcare System, Long Beach, California
    • ,
  • Elizabeth C. Wright

      Affiliations

    • New England Research Institutes, Watertown, Massachusetts
    • ,
  • Gregory T. Everson

      Affiliations

    • Section of Hepatology, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Denver, Colorado
    • ,
  • Karen L. Lindsay

      Affiliations

    • Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California
    • ,
  • Anna S.F. Lok

      Affiliations

    • Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, Michigan
    • ,
  • Herbert L. Bonkovsky

      Affiliations

    • Departments of Medicine and Molecular & Structural Biology and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, Connecticut
    • ,
  • Adrian M. Di Bisceglie

      Affiliations

    • Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, Missouri
    • ,
  • William M. Lee

      Affiliations

    • Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas
    • ,
  • Jules L. Dienstag

      Affiliations

    • Gastrointestinal Unit, Medical Services, Massachusetts General Hospital, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts
    • ,
  • David R. Gretch

      Affiliations

    • Department of Laboratory Medicine, University of Washington, Seattle, Washington
    • ,
  • HALT-C Trial Group

Received 10 April 2006; accepted 12 October 2006. published online 14 November 2006.

Background & Aims: Reducing the dose of peginterferon and/or ribavirin to <80% when treating chronic hepatitis C virus has been associated with a reduction in sustained virologic response (SVR). However, prior studies did not assess the impact of reducing the dose of peginterferon independent of ribavirin or differentiate between dose reduction or interrupting or prematurely discontinuing treatment. Methods: Nine hundred thirty-six patients with chronic hepatitis C genotype 1, advanced fibrosis, or cirrhosis (Ishak 3–6) and prior nonresponse to standard interferon ± ribavirin were retreated with peginterferon alfa-2a (180 μg/wk) and ribavirin (1000–1200 mg/day) during the lead-in phase of the HALT-C trial. The percentage of each medication actually taken during treatment was calculated. Results: Reducing the total cumulative dose of peginterferon received during the first 20 weeks of treatment from full dose (≥98%) to ≤60% reduced week 20 virologic response (W20 VR) from 35% to 12% and SVR from 17% to 5%. Reducing the dose of ribavirin from full dose (≥98%) to ≤60% did not affect either W20 VR or SVR as long as ribavirin dosing was not interrupted for more than 7 consecutive days. Prematurely discontinuing ribavirin, even at full-dose peginterferon, reduced W20 VR to ≤19% and SVR to ≤4%. Conclusions: Reducing the peginterferon dose during the first 20 weeks of treatment reduced viral clearance and SVR. In contrast, reducing ribavirin did not affect either W20 VR or SVR as long as patients remained on full-dose peginterferon. Discontinuing ribavirin prematurely was associated with a marked decline in both VR and SVR.

Abbreviations used in this paper: EOT, end-of-treatment, EVR, early virologic response, HALT-C, Hepatitis Antiviral Long-term Treatment Against Cirrhosis, HCV, chronic hepatitis C virus, SVR, sustained virologic response, VR, virologic response, W20 VR, week 20 virologic response, W72, week 72

 

 This is publication number 20 from the HALT-C Trial Group.Supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed in Appendix); by the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities, and General Clinical Research Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed in Appendix); and by Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health.Financial relationships of the authors with Hoffmann-La Roche, Inc., are as follows: M. L. Shiffman is a consultant, on the speaker’s bureau, and receives research support; T. R. Morgan is on the speaker’s bureau and receives research support; G. T. Everson is a consultant, on the speaker’s bureau, and receives research support; K. L. Lindsay is a consultant and receives research support; A. S. F. Lok is a consultant and receives research support; H. L. Bonkovsky is on the speaker’s bureau and receives research support; A. M. Di Bisceglie is a consultant and receives research support; and W. M. Lee receives research support. Authors with no financial relationships related to this project are M. G. Ghany, E. C. Wright, J. L. Dienstag, and D. R. Gretch.M.L.S., M.G.G, T.R.M, and E.C.W contributed equally to the analysis of data and writing of this manuscript.

PII: S0016-5085(06)02466-8

doi:10.1053/j.gastro.2006.11.011

Gastroenterology
Volume 132, Issue 1 , Pages 103-112, January 2007