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.

References 

  1. Manns MP, McHutchinson JG, Gordon SC, Rustgi VK, Shiffman ML, Reindollar R, et al. Peginterferon-alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial. Lancet. 2001;358:958–965
  2. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL, et al. Combination of peginterferon alfa-2a (40 kD) plus ribavirin in patients with chronic hepatitis C virus infection. N Engl J Med. 2002;347:975–982
  3. Hadziyannis SJ, Sette H, Morgan TR, Balan V, Diago M, Marcellin P, et al. Peginterferon-alfa 2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140:346–355
  4. McHutchison JG, Manns M, Patel K, Poynard T, Lindsay KL, Trepo C, et al. Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology. 2002;123:1061–1069
  5. Davis GL, Wong JB, McHutchison JG, Manns MP, Harvey J, Albrecht J. Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology. 2003;38:645–652
  6. Shiffman ML, Di Bisceglie AM, Lindsay KL, Morishima C, Wright EC, Everson GT, et al. Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment. Gastroenterology. 2004;126:1015–1023
  7. Lee WM, Dienstag JL, Lindsay KL, Lok AS, Bonkovsky HL, Shiffman ML, et al. Evolution of the HALT-c trial: Pegylated interferon as maintenance therapy for chronic hepatitis C in previous interferon nonresponders. Control Clin Trials. 2004;25:472–492
  8. Bronowicki JP, Ouzan D, Asselah T, Desmorat H, Zarski JP, Foucher J, et al. Effect of ribavirin in genotype 1 patients with hepatitis C responding to peginterferon alfa-2a plus ribavirin. Gastroenterology. 2006;131:1040–1048
  9. McHutchinson JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N Engl J Med. 1998;339:1485–1492
  10. Davis GL, Esteban-Mur R, Rustgi V, Hoefs J, Gordon SC, Trepo C, et al. Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. N Engl J Med. 1998;339:1493–1499
  11. Heathcote EJ, Shiffman ML, Cooksley WG, Dusheiko GM, Lee SS, Balart L, et al. Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis. N Engl J Med. 2000;343:1673–1680
  12. Reddy KR, Wright TL, Pockros PJ, Shiffman ML, Everson G, Reindollar R, et al. Efficacy and safety of pegylated (40-kD) interferon α-2a compared with interferon α-2a in non-cirrhotic patients with chronic hepatitis C. Hepatology. 2001;33:433–438
  13. Lindsay KL, Trepo C, Heintges T, Shiffman ML, Gordon SC, Hoefs JC, et al. A randomized, double-blind trial comparing peginterferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C. Hepatology. 2001;34:395–403
  14. Ferenci P, Fried MW, Shiffman ML, Smith CI, Marinos G, Goncales FL, et al. Predicting sustained virological responses in chronic hepatitis C patients treated with peginterferon alfa-2a (40 kD)/ribavirin. J Hepatol. 2005;43:453–471
  15. Jensen DM, Morgan TR, Marcellin P, Pockros PJ, Reddy KR, Hadziyannis SJ, et al. Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon alpha-2a (40 kD)/ribavirin therapy. Hepatology. 2006;43:954–960
  16. Jacobson IM, Brown R, Freilich B, Afdhal NH, Kwo P, Santoro J, et al. Weight-based ribavirin dosing increases sustained viral response in patients with chronic hepatitis C: final results of the WIN-R study, A US community based trial. Hepatology. 2005;42(Suppl 1):A749
  17. Shiffman ML. Side effects of medical therapy for chronic hepatitis C. Ann Hepatol. 2004;3:5–10
  18. Maddrey WC. Safety of combination interferon alfa-2b/ribavirin therapy in chronic hepatitis C-relapsed and treatment-naive patients. Semin Liver Dis. 1999;19(Suppl 1):67–75
  19. Dieterich DT, Wasserman R, Brau N, Hassanein TI, Bini EJ, Bowers PJ, et al. Once-weekly epoetin alfa improves anemia and facilitates maintenance of ribavirin dosing in hepatitis C virus-infected patients receiving ribavirin plus interferon alfa. Am J Gastroenterol. 2003;98:2491–2499
  20. Afdhal NH, Dieterich DT, Pockros PJ, Schiff ER, Shiffman ML, Sulkowski MS, et al. Epoetin alfa maintains ribavirin dose in HCV-infected patients: a prospective, double-blind, randomized controlled study. Gastroenterology. 2004;126:1302–1311
  21. Spiegel BM, Chen K, Chiou CF, Robbins S, Younossi ZM. Erythropoietic growth factors for treatment-induced anemia in hepatitis C: a cost-effectiveness analysis. Clin Gastroenterol Hepatol. 2005;3:1034–1042
  22. Pockros PJ, Shiffman ML, Schiff ER, Sulkowski MS, Younossi Z, Dieterich DT, et al. Epoetin alfa improves quality of life in anemic HCV-infected patients receiving combination therapy. Hepatology. 2004;40:1450–1458
  23. Shiffman ML, Price AP, Hubbard S, Wilson M, Salvatori J, Sterling RK, et al. Treatment of chronic hepatitis C virus genotype 1 with peginterferon alfa-2b, high weight based dose ribavirin and epoetin alfa enhances sustained virologic response. Hepatology. 2005;42(Suppl 1):55

 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

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