Skip to main content
SpringerLink
Log in

Combination Therapy with Interferon-α and Ribavirin for Hepatitis C

Practical Treatment Issues

  • Therapy in Practice
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

Combination therapy with ribavirin and interferon (IFN)-α for 6 to 12 months is currently the treatment of choice for chronic hepatitis C infection. The overall sustained response rate to treatment, defined as loss of hepatitis C virus (HCV) from serum 6 months after completion of treatment, is 40%. The indications for treatment are serum HCV RNA positivity, abnormal serum transaminases and the presence of portal fibrosis and/or moderate/severe inflammation.

Response rates are lower in genotype 1 than in genotype 2 or 3 and in the presence of a high viral load. Anaemia is the most common adverse event and is due to ribavirin; neuropsychiatric adverse effects due to IFNα lead to premature cessation of therapy in 10 to 20% of patients.

The current recommended dose of interferon is 3MU given subcutaneously 3 times a week. However, it is likely that longer-acting pegylated interferons, which may be more effective and can be administered once weekly, will in the future replace currently used IFNα.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Table I
Fig. 3
Table II
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med 1999; 341: 556–62

    Article  PubMed  CAS  Google Scholar 

  2. Frank C, Mohamed MK, Strickland GT, et al. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet 2000; 335: 887–91

    Article  Google Scholar 

  3. Fattovich G. Giustina G, Degos F, et al. Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology 1997; 112: 464–72

    Article  Google Scholar 

  4. Poynard T, Bedossa P, Opolon P, et al. Natural history of liver fibrosis progression in patients with chronic hepatitis C. Lancet 1997; 349: 825–32

    Article  PubMed  CAS  Google Scholar 

  5. Simmonds P. Viral heterogeneity of the hepatitis C virus. J Hepatol 1999; 31Suppl. 1: 54–60

    Article  PubMed  Google Scholar 

  6. Marcellin P, Boyer N, Gervais A, et al. Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon-alpha therapy. Ann Intern Med 1997; 127: 875–81

    PubMed  CAS  Google Scholar 

  7. 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. The Multivirc Group. Gastroenterology 1999; 116: 78–86

    Article  Google Scholar 

  8. Yoshida H, Shiratori Y, Moriyama M, et al. Interferon therapy reduces the risk of hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. Ann Intern Med 1999; 131: 174–81

    PubMed  CAS  Google Scholar 

  9. Nishiguchi S, Kuroki T, Nakatani S, et al. Randomised trial of effects of interferon alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet 1995; 346: 1051–5

    Article  PubMed  CAS  Google Scholar 

  10. Valla D-C, Chevallier M, Marcellin P, et al. Treatment of hepatitis C virus-related cirrhosis: a randomised, controlled trial of interferon alfa-2b versus no treatment. Hepatology 1999; 29: 1870–5

    Article  PubMed  CAS  Google Scholar 

  11. Foster GR. epatitis C virus infection: quality of life and sideeffects of treatment. J Hepatol 1999; 31: 250–4

    Article  PubMed  Google Scholar 

  12. Bronkovsky HL, Wooley JM, the Consensus Interferon Group. Reduction of health related quality of life in chronic hepatitis C and improvement with interferon therapy. Hepatology 1999; 29: 264–70

    Article  Google Scholar 

  13. Poynard T, Marcellini P, Lee SS, et al. Randomised trial of interferon a2b plus ribavirin for 48 weeks or for 24 weeks versus interferon a2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C. Lancet 1998; 352: 1426–32

    Article  PubMed  CAS  Google Scholar 

  14. McHutchison JG, Gordon SC, Schiff ER, et al. Interferon alpha-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N Engl J Med 1998; 339: 1485–92

    Article  PubMed  CAS  Google Scholar 

  15. Gordon SC, Fang JW, Silverman AL, et al. The significance of baseline serum alanine aminotransferase on pre-treatment disease characteristics and response to antiviral therapy in chronic hepatitis C. Hepatology 2000; 32: 400–4

    Article  PubMed  CAS  Google Scholar 

  16. Consensus statement. EASL International Consensus Conference on Hepatitis C. J Hepatol 1999; 30: 956–61

    Article  Google Scholar 

  17. National Institutes of Health Consensus Development Conference Panel statement: management of hepatitis C. Hepatology 1997 Sep; 26(3 Suppl. 1): 2S–10S

    Google Scholar 

  18. Heathcote J, Shiffman M, Cooksley G, et al. Peginterferon alfa-2-a in patients with chronic hepatitis C and cirrhosis. N Engl J Med 2000; 343: 1673–80

    Article  PubMed  CAS  Google Scholar 

  19. Davis GL, Esterban-Mur R, Rustgi V, 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: 1493–9

    Article  PubMed  CAS  Google Scholar 

  20. Barbara G, Di Lorenzo G, Belloni G, et al. Interferon alpha-2B and ribavirin in combination for patients with chronic hepatitis C who failed to respond to, or relapse after, interferon alpha therapy: a randomised trial. Am J Med 1999; 107: 112–28

    Article  Google Scholar 

  21. Pol S, Couzigou P, Bourliere M, et al. A randomised trial of ribavirin and interferon-alpha versus interferon-alpha alone in patients with chronic hepatitis C who were non-responders to a previous treatment. Multicentre Study Group under the coordination of the Necker Hospital, Paris, France. J Hepatol 1999; 31: 1–7

    Article  PubMed  CAS  Google Scholar 

  22. Cheng SJ, Bonis PAL, Lau J, et al. Interferon and ribavirin for patients with chronic hepatitis C who did not respond to previous interferon therapy: a meta-analysis of controlled and uncontrolled trials. Hepatology 2001; 33: 231–40

    Article  PubMed  CAS  Google Scholar 

  23. Poynard T, McHutchinson J, Goodman Z, et al. Is an ‘à la carte’ combination of interferon alpha-2b plus ribavirin regime possible for the first line treatment in patients with chronic hepatitis C? Hepatology 2000; 31: 211–8

    Article  PubMed  CAS  Google Scholar 

  24. Gretch D. Standardization of hepatitis C virus-RNA quantification: advances and unfinished business. Hepatology 2000; 31: 788–9

    Article  PubMed  CAS  Google Scholar 

  25. Brunt EM. Grading and staging the histopathological lesions of chronic hepatitis: the Knodell histology activity index and beyond. Hepatology 2000; 31: 241–6

    Article  PubMed  CAS  Google Scholar 

  26. Manesis EK, Moschos M, Brouzas D, et al. Neurovisual impairment: a frequent complication of alpha-interferon treatment for chronic viral hepatitis. Hepatology 1998; 27: 1421–7

    Article  PubMed  CAS  Google Scholar 

  27. Koh LK, Greenspan FS, Yeo PP. Interferon-alpha induced thyroid dysfunction: three clinical presentations and a review of the literature. Thyroid 1997; 7: 891–6

    Article  PubMed  CAS  Google Scholar 

  28. Neumann AU, Lam NP, Dahari H, et al. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 1998; 282: 103–7

    Article  PubMed  CAS  Google Scholar 

  29. Zeuzem S. Clinical implications of hepatitis C viral kinetics. J Hepatol 1999; 31Suppl. 1: 61–4

    Article  PubMed  Google Scholar 

  30. Zeuzem S, Feinman SV, Rasenack J, et al. Peginterferon alfa-2-a in patients with chronic hepatitis C. N Engl J Med 2001; 343: 1666–72

    Article  Google Scholar 

  31. Manns MP, McHutchinson JG, Gordon S, et al. Peginterferon alfa-2-b plus ribavirin compared to interferon alfa-2-b plus ribavirin for the treatment of chronic hepatitis C: a 24 week treatment analysis of a multicentre, multinational phase III randomised controlled trial. Hepatology 2000; 32(4): 297A

    Article  Google Scholar 

  32. Younossi ZM, Singer ME, McHutchinson JG, et al. Cost effectiveness of interferon alpha 2b combined with ribavirin for the treatment of chronic hepatitis C. Hepatology 1999; 30: 1318–24

    Article  PubMed  CAS  Google Scholar 

  33. Younossi Z, Perillo R. The roles of amantidine, rimantadine, ursodeoxycholic acid and NSAIDs alone or in combination with alpha interferon in the treatment of chronic hepatitis C. Semin Liver Dis 1999; 19: 95–102

    PubMed  CAS  Google Scholar 

  34. Zeuzem S, Teuber G, Naumann U, et al. Randomized, doubleblind, placebo-controlled trial of interferon alfa2a with and without amantidine as initial therapy for chronic hepatitis C. Hepatology 2000; 32: 835–51

    Article  PubMed  CAS  Google Scholar 

  35. Brillanti S, Levantesi F, Masi L, et al. Triple antiviral therapy as a new option for patients with interferon nonresponsive chronic hepatitis C. Hepatology 2000; 32: 630–4

    Article  PubMed  CAS  Google Scholar 

  36. Camma A, Almasio P, Craxi A. Interferon as treatment for acute hepatitis C. A meta-analysis. Dig Dis Sci 1996; 41: 1248–55

    Article  PubMed  CAS  Google Scholar 

  37. Quin JW. Interferon therapy for acute hepatitis C viral infection — a review by meta-analysis. Aust N Z J Med 1997; 27: 611–7

    Article  PubMed  CAS  Google Scholar 

  38. Lackner G, Moser A, Deutsch J, et al. Interferon alpha and ribavirin in treating children and young adults with chronic hepatitis C after malignancy. Paediatrics 2000; 106: E53

    Article  CAS  Google Scholar 

  39. Christensson B, Wiebe T, Akesson A, et al. Interferon-alpha and ribavirin treatment of hepatitis C in children with malignancy in remission. Clin Infect Dis 2000; 30: 585–6

    Article  PubMed  CAS  Google Scholar 

  40. Wong VS, Baglin T, Beacham E, et al. The role for liver biopsy in haemophiliacs infected with the hepatitis C virus. Br J Haematol 1997; 97: 343–7

    Article  PubMed  CAS  Google Scholar 

  41. Zylberberg H, Benhamou Y, Lagneaux JL, et al. Safety and efficacy of interferon-ribavirin combination therapy in HCV-HIV coinfected subjects: an early report. Gut 2000; 47: 694–7

    Article  PubMed  CAS  Google Scholar 

  42. Landau A, Batisse D, Van Huyen JP, et al. Efficacy and safety of combination therapy with interferon alpha 2b and ribavirin for chronic hepatitis C in HIV infected patients. AIDS 2000; 5: 839–4

    Article  Google Scholar 

  43. Lavezzo B, Leone N, Smedile A, et al. Combination therapy of interferon alpha-2b and ribavirin for recurrent hepatitis C after liver transplantation. J Hepatol 1999; 30Suppl. 1: 67

    Google Scholar 

  44. Bellati G, Alberti AB, Belli LS, et al. Therapy of chronic hepatitis C after liver transplantation: multicenter Italian experience. J Hepatol 1999: 30Suppl. 1: 51

    Google Scholar 

  45. Samuel D, Bizollon T, Roche B, et al. Combination of interferon alfa 2-b plus ribavirin for recurrent HCV infection after liver transplantation: a randomised controlled study. Hepatology 2000; 32: 295A

    Google Scholar 

  46. Bizollon T, Palazzo U, Ducerf C, et al. Pilot study of the combination of interferon alpha and ribavirin as therapy of recurrent hepatitis C after liver transplantation. Hepatology 1997; 26: 500–4

    Article  PubMed  CAS  Google Scholar 

  47. Mazzaferro V, Regalia E, Pulvirenti A, et al. Prophylaxis against HCV recurrence after liver transplantation: effect of interferon and ribavirin combination. Transplant Proc 1997; 29: 519–21

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology Level 3, John Radcliffe Hospital, Headley Way Headington, Oxford, OX3 9DU, England

    Jane Collier & Roger Chapman

Authors
  1. Jane Collier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roger Chapman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jane Collier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Collier, J., Chapman, R. Combination Therapy with Interferon-α and Ribavirin for Hepatitis C. BioDrugs 15, 225–238 (2001). https://doi.org/10.2165/00063030-200115040-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00063030-200115040-00003

Keywords

Search

Navigation