Gastroenterology
Volume 136, Issue 5 , Pages 1618-1628.e2 , May 2009

Peginterferon alfa-2b and Ribavirin: Effective in Patients With Hepatitis C Who Failed Interferon alfa/Ribavirin Therapy

Presented in part at the 55th (2004), 56th (2005), and 57th (2006) Annual Meetings of the American Association for the Study of Liver Diseases; the 40th (2005) and 43rd (2008) Annual Meetings of the European Association for the Study of the Liver; Digestive Diseases Week 2005; and HEP DART 2007: Frontiers in Drug Development for Viral Hepatitis.

  • Thierry Poynard

      Affiliations

    • Service d'hepatologie, Université Pierre et Marie Curie Liver Center, Hôpital La Pitié Salpêtrière, Paris, France
    • Corresponding Author InformationReprint requests Address requests for reprints to: Thierry Poynard, MD, PhD, Hôpital La Pitié Salpêtrière, Université Pierre et Marie Curie Liver Center, Service d'hepatologie, 47-83 boulevard de l'hôpital, 75651 Paris CEDEX 13, France. fax: (11) 33-142-16-14-25
    • ,
  • Massimo Colombo

      Affiliations

    • First Division of Gastroenterology, Fondazione IRCCS Maggiore Hospital, University of Milan, Milan, Italy
    • ,
  • Jordi Bruix

      Affiliations

    • Centro de Investigación Biomédica en Red de Enfermedades Hepaticas y Digestivas, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
    • ,
  • Eugene Schiff

      Affiliations

    • University of Miami School of Medicine, Miami, Florida
    • ,
  • Ruben Terg

      Affiliations

    • Hospital Municipal de Gastroenterologia Dr. Bonorino Udaondo, Capital Federal, Argentina
    • ,
  • Steven Flamm

      Affiliations

    • Northwestern University, Chicago, Illinois
    • ,
  • Ricardo Moreno-Otero

      Affiliations

    • Hospital Universitario de la Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepaticas y Digestivas (Instituto de Salud Carlos III), Madrid, Spain
    • ,
  • Flair Carrilho

      Affiliations

    • Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
    • ,
  • Warren Schmidt

      Affiliations

    • University of Iowa Hospitals and Clinics, Iowa City, Iowa
    • ,
  • Thomas Berg

      Affiliations

    • Charité, Campus Virchow Klinikum, Universitätsmedizin Berlin, Germany
    • ,
  • Thomas McGarrity

      Affiliations

    • Milton S. Hershey Medical Center, Hershey, Pennsylvania
    • ,
  • E. Jenny Heathcote

      Affiliations

    • University Health Network, Toronto, ON, Canada
    • ,
  • Fernando Gonçales

      Affiliations

    • Department of Medical Clinical, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil
    • ,
  • Moises Diago

      Affiliations

    • Hospital General Universitario de Valencia, Valencia, Spain
    • ,
  • Antonio Craxi

      Affiliations

    • GI and Liver Unit, DIBIMIS, University of Palermo, Palermo, Italy
    • ,
  • Marcelo Silva

      Affiliations

    • Hospital Universitario Austral, Pilar, Argentina
    • ,
  • Pierre Bedossa

      Affiliations

    • Anatomie Pathologique, Hôpital Beaujon, Clichy, France
    • ,
  • Pabak Mukhopadhyay

      Affiliations

    • Schering–Plough Research Institute, Kenilworth, New Jersey
    • ,
  • Louis Griffel

      Affiliations

    • Schering–Plough Research Institute, Kenilworth, New Jersey
    • ,
  • Margaret Burroughs

      Affiliations

    • Schering–Plough Research Institute, Kenilworth, New Jersey
    • ,
  • Clifford Brass

      Affiliations

    • Schering–Plough Research Institute, Kenilworth, New Jersey
    • ,
  • Janice Albrecht

      Affiliations

    • Schering–Plough Research Institute, Kenilworth, New Jersey
    • ,
  • The Epic Study Group

Received 21 December 2007 ,Accepted 15 January 2009.

References 

  1. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975–982
  2. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958–965
  3. Poynard T, McHutchison J, Goodman Z, Albrecht J, et al. ALGOVIRC Project Group Is an “a la carte” combination interferon alfa-2b plus ribavirin regimen possible for the first line treatment in patients with chronic hepatitis C?. Hepatology. 2000;31:211–218
  4. Shiratori Y, Imazeki F, Moriyama M, et al. Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann Intern Med. 2000;132:517–524
  5. Sobesky R, Mathurin P, Charlotte F, et al. Modeling the impact of interferon alfa treatment on liver fibrosis progression in chronic hepatitis C: a dynamic view. Gastroenterology. 1999;116:378–386
  6. Bruno S, Stroffolini T, Colombo M, et al. Sustained virologic response to interferon-α is associated with improved outcome in HCV-related cirrhosis: a retrospective study. Hepatology. 2007;45:579–587
  7. Veldt BJ, Heathcote EJ, Wedemeyer H, et al. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Intern Med. 2007;147:677–684
  8. Afdhal NH, Levine R, Brown R, et al. Colchicine versus peg-interferon alfa 2b long-term therapy: results of the 4-year COPILOT Trial. Presented at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL 2008); April 23–27, 2008; Milan, Italy.
  9. DiBisceglie AM, Shiffman ML, Everson GT, et al. Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. N Engl J Med. 2008;359:2429–2441
  10. Bedossa P, Poynard T METAVIR Cooperative Study Group. An algorithm for the grading of activity in chronic hepatitis C. Hepatology. 1996;24:289–293
  11. Krawitt EL, Ashikaga T, Gordon SR, et al. Peginterferon alfa-2b and ribavirin for treatment-refractory chronic hepatitis C. J Hepatol. 2005;43:243–249
  12. Parise E, Cheinquer H, Crespo D, et al. Peginterferon alfa-2a (40KD) (PEGASYS) plus ribavirin (COPEGUS) in retreatment of chronic hepatitis C patients, nonresponders and relapsers to previous conventional interferon plus ribavirin therapy. Braz J Infect Dis. 2006;10:11–16
  13. Sherman M, Yoshida EM, Deschenes M, et al. Peginterferon alfa-2a (40KD) plus ribavirin in chronic hepatitis C patients who failed previous interferon therapy. Gut. 2006;55:1631–1638
  14. Shiffman ML. Management of patients with chronic hepatitis C virus infection and previous nonresponse. Rev Gastroenterol Dis. 2004;4(Suppl 1):S22–S30
  15. Veldt BJ, Brouwer JT, Adler M, et al. Retreatment of hepatitis C non-responsive to interferon: a placebo controlled randomized trial of ribavirin monotherapy versus combination therapy with ribavirin and interferon in 121 patients in the Benelux. BMC Gastroenterol. 2003;3:24
  16. Taliani G, Gemignani G, Ferrari C, et al. Pegylated interferon alfa-2b plus ribavirin in the retreatment of interferon-ribavirin non-responder patients. Gastroenterology. 2006;130;:1098–1106
  17. Basso M, Torre F, Grasso A, et al. Pegylated interferon and ribavirin in retreatment of non-responder-relapser HCV patients. Dig Liver Dis. 2007;39:47–51
  18. Cornberg M, Hadem J, Herrmann E, et al. Treatment with daily consensus interferon (CIFN) plus ribavirin in non-responder patients with chronic hepatitis C: a randomized open-label pilot study. J Hepatol. 2006;44:291–301
  19. Jacobson IM, Gonzalez SA, Ahmed F, et al. A randomized trial of pegylated interferon α-2b plus ribavirin in the retreatment of hepatitis C. Am J Gastroenterol. 2005;100:2453–2462
  20. Sagir A, Heintges T, Akyazi Z, et al. Relapse to prior therapy is the most important factor for the retreatment response in patients with chronic hepatitis virus infection. Liver Int. 2007;27:954–959
  21. Shiffman ML, Di Bisceglie AM, Lindsay KL, et al. Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment. Gastroenterology. 2004;126:1015–1023
  22. Moucari R, Ripault M, Oulès V, et al. High predictive value of early viral kinetics in retreatment with peginterferon and ribavirin of chronic hepatitis C patients non-responders to standard combination therapy. J Hepatol. 2007;46:596–604
  23. Berg T, von Wagner M, Nasser S, et al. Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin. Gastroenterology. 2006;130:1086–1097
  24. Sanchez-Tapias JM, Diago M, Escartin P, et al. Peginterferon-alfa 2a plus ribavirin for 48 versus 72 weeks in patients with detectable hepatitis C virus RNA at week 4 of treatment. Gastroenterology. 2006;131:451–460
  25. Pearlman BL, Ehleben C, Saifee S. Treatment extension to 72 weeks of peginterferon and ribavirin in hepatitis C genotype 1-infected slow responders. Hepatology. 2007;46:1688–1694
  26. Marcellin P, Heathcote EJ, Craxi A. Which patients with genotype 1 chronic hepatitis C can benefit from prolonged treatment with the “accordion” regimen?. J Hepatol. 2007;47:580–587
  27. Mangia A, Minerva N, Bacca D, et al. Individualized treatment duration for hepatitis C genotype 1 patients: a randomized controlled trial. Hepatology. 2008;47:43–50
  28. Jacobson IM, Brown RS, Freilich B, et al. Peginterferon alfa-2b and weight-based or flat-dose ribavirin in chronic hepatitis C patients: a randomized trial. Hepatology. 2007;46:971–981

 Conflicts of Interest The authors disclose the following: T. Poynard, M. Colombo, S. Flamm, T. Berg E. Schiff, E. J. Heathcote, A. Craxi, M. Silva, and W. Schmidt are members of the speakers bureau for Schering–Plough; A. Craxi, E. J. Heathcote, and W. Schmidt are members of the speakers bureau for Roche; T. Poynard, M. Colombo, E. Schiff, M. Diago, S. Flamm, T. Berg, A. Craxi, M. Silva, E. J. Heathcote, and F. Gonçales receive research support from Schering–Plough; A. Craxi receives research support from Roche; S. Flamm receives research support from Valeant and serves on the speakers bureau for Novartis; M. Colombo, E. Schiff, A. Craxi, J. Bruix, and E. J. Heathcote are consultants for Schering–Plough; A. Craxi is a consultant for Roche; L. Griffel, M. Burroughs, C. Brass, J. K. Albrecht, and P. Mukhopadhyay are employees of Schering–Plough Research Institute and stock holders of Schering–Plough; R. Moreno-Otero, F. Carrilho, R. Terg, P. Bedossa, and T. McGarrity have nothing to disclose. Study participants were told of investigators' conflicts of interests.

 Funding Schering–Plough Research Institute fully supported the study. Role of study sponsor: Schering–Plough Research Institute played a major role in the study design. They collected, analyzed, and performed the initial interpretation of all data. All the authors provided input and agreed to the final interpretation. The decision to submit the report was made by Schering–Plough Research Institute in conjunction with the publication committee.

 The complete list of the EPIC Study Group membership appears in the online Appendix.

PII: S0016-5085(09)00102-4

doi: 10.1053/j.gastro.2009.01.039

Gastroenterology
Volume 136, Issue 5 , Pages 1618-1628.e2 , May 2009

Article Tools

* Image Usage & Resolution