PDF herunterladen
Semin Liver Dis 2004; 24: 19-24
DOI: 10.1055/s-2004-832924
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Treatment of Hepatitis C Virus: The First Decade

Thierry Poynard1
  • 1Service d'Hepato-gastroenterologie, Groupe Hospitalier Pitie-Salpetriere, Paris, France
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
02. September 2004 (online)

    Lizenzen und Reprints

Interferon alfa therapy emerged as an early treatment option for patients with chronic hepatitis C. This therapy, however, fails to produce a sustained virological response in most patients. Various host and viral baseline characteristics, some of which include hepatitis C virus genotype, viral load, presence of cirrhosis, and patient age, affect the response to interferon therapy. The addition of ribavirin to interferon therapy significantly improves long-term virological response in treatment-naive patients and is also more effective than repeat interferon therapy is in patients who fail to initially achieve sustained virological or biochemical responses. However, ribavirin can induce reversible hemolytic anemia, and combination therapy with a ribavirin/interferon regimen is not tolerated as well as interferon is alone. Pegylated interferons used alone or in combination with ribavirin provide improved treatment options for different patient groups with chronic hepatitis C.

KEYWORDS

Interferon - ribavirin - hepatitis C - sustained virological response - fibrosis

REFERENCES

  • 1 Hoofnagle J H, Mullen K D, Jones D B et al.. Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon.  N Engl J Med. 1986;  315 1575-1578
    CrossrefPubMedGoogle Scholar
  • 2 Di Bisceglie A M, Martin P, Kassianides C et al.. Recombinant interferon alfa therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial.  N Engl J Med. 1989;  321 1506-1510
    PubMedGoogle Scholar
  • 3 Davis G L, Balart L A, Schiff E R et al.. Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. Hepatitis Interventional Therapy Group.  N Engl J Med. 1989;  321 1501-1506
    PubMedGoogle Scholar
  • 4 Choo Q L, Kuo G, Weiner A J et al.. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome.  Science. 1989;  244 359-362
    CrossrefPubMedGoogle Scholar
  • 5 Pockros P J, Tong M, Lee W M et al.. Relationship between biochemical and virological responses to interferon therapy in chronic hepatitis C infection.  J Viral Hepat. 1998;  5 271-276
    CrossrefPubMedGoogle Scholar
  • 6 Dorr R T. Interferon-alfa in malignant and viral diseases. A review.  Drugs. 1993;  45 177-211
    PubMedGoogle Scholar
  • 7 Tilg H. New insights into the mechanisms of interferon alfa: an immunoregulatory and anti-inflammatory cytokine.  Gastroenterology. 1997;  112 1017-1021
    PubMedGoogle Scholar
  • 8 Nieforth K A, Nadeau R, Patel I H, Mould D. Use of an indirect pharmacodynamic stimulation model of MX protein induction to compare in vivo activity of interferon alfa-2a and a polyethylene glycol-modified derivative in healthy subjects.  Clin Pharmacol Ther. 1996;  59 636-646
    CrossrefPubMedGoogle Scholar
  • 9 Poynard T, Leroy V, Cohard M et al.. Meta-analysis of interferon randomized trials in the treatment of viral hepatitis C: effects of dose and duration.  Hepatology. 1996;  24 778-789
    PubMedGoogle Scholar
  • 10 Thevenot T, Regimbeau C, Ratziu V et al.. Meta-analysis of interferon randomized trials in the treatment of viral hepatitis C in naive patients: 1999 update.  J Viral Hepat. 2001;  8 48-62
    CrossrefPubMedGoogle Scholar
  • 11 Lindsay K L, Davis G L, Schiff E R et al.. Response to higher doses of interferon alfa-2b in patients with chronic hepatitis C: a randomized multicenter trial. Hepatitis Interventional Therapy Group.  Hepatology. 1996;  24 1034-1040
    PubMedGoogle Scholar
  • 12 Shiffman M L. Use of high-dose interferon in the treatment of chronic hepatitis C.  Semin Liver Dis. 1999;  19(suppl 1) 25-33
    PubMedGoogle Scholar
  • 13 Hoofnagle J H, Lau D, Conjeevaram H et al.. Prolonged therapy of chronic hepatitis C with ribavirin.  J Viral Hepat. 1996;  3 247-252
    PubMedGoogle Scholar
  • 14 Bodenheimer H C, Lindsay K L, Davis G L et al.. Tolerance and efficacy of oral ribavirin treatment of chronic hepatitis C: a multicenter trial.  Hepatology. 1997;  26 473-477
    CrossrefPubMedGoogle Scholar
  • 15 Di Bisceglie A M, Conjeevaram H S, Fried M W et al.. Ribavirin as therapy for chronic hepatitis C.  Ann Intern Med. 1995;  123 897-903
    CrossrefPubMedGoogle Scholar
  • 16 Dusheiko G, Main J, Thomas H et al.. Ribavirin treatment for patients with chronic hepatitis C: results of a placebo-controlled study.  J Hepatol. 1996;  25 591-598
    CrossrefPubMedGoogle Scholar
  • 17 Tam R C, Ramasamy K, Bard J et al.. The ribavirin analog ICN 17261 demonstrates reduced toxicity and antiviral effects with retention of both immunomodulatory activity and reduction of hepatitis-induced serum alanine aminotransferase levels.  Antimicrob Agents Chemother. 2000;  44 1276-1283
    CrossrefPubMedGoogle Scholar
  • 18 Brillanti S, Garson J, Foli M et al.. A pilot study of combination therapy with ribavirin plus interferon alfa for interferon-alfa-resistant chronic hepatitis C.  Gastroenterology. 1994;  107 812-817
    CrossrefPubMedGoogle Scholar
  • 19 Lai M-Y, Kao J-H, Yang P-M et al.. Long-term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C.  Gastroenterology. 1996;  111 1307-1312
    PubMedGoogle Scholar
  • 20 McHutchison J G, Gordon S C, Schiff E R 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
    CrossrefPubMedGoogle Scholar
  • 21 Poynard T, Marcellin P, Lee S S et al.. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus.  Lancet. 1998;  352 1426-1432
    CrossrefPubMedGoogle Scholar
  • 22 Reichard O, Nokrans G, Fryden A et al.. Randomised, double-blind, placebo-controlled trial of interferon alfa-2b with and without ribavirin for chronic hepatitis C.  Lancet. 1998;  351 83-87
    CrossrefPubMedGoogle Scholar
  • 23 Davis G L, Esteban-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 1493-1499
    CrossrefPubMedGoogle Scholar
  • 24 Schalm S W, Weiland O, Hansen B E et al.. Interferon-ribavirin for chronic hepatitis C with and without cirrhosis: analysis of individual patient data of six controlled trials.  Gastroenterology. 1999;  117 408-413
    PubMedGoogle Scholar
  • 25 National Institutes of Health . National Institutes of Health Consensus Development Conference Statement. Management of hepatitis C: June 10-12, 2002.  Hepatology. 2002;  36(suppl 1) S3-S20
    CrossrefPubMedGoogle Scholar
  • 26 EASL International Consensus Conference on Hepatitis C . Paris 26-28, February 1999. Consensus statement. European Association for the Study of the Liver.  J Hepatol. 1999;  30 956-961
    CrossrefPubMedGoogle Scholar
  • 27 Idilman R, De Maria M, Colantoni A A D, van Thiel D H. Interferon treatment of cirrhotic patients with chronic hepatitis C.  J Viral Hepat. 1997;  4 81-91
    PubMedGoogle Scholar
  • 28 Poynard T, McHutchison J, Goodman Z et al.. 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
    CrossrefPubMedGoogle Scholar
  • 29 McHutchison J G, Shad J A, Gordon S C et al.. Predicting response to initial therapy with interferon plus ribavirin in chronic hepatitis C using serum HCV RNA results during therapy.  J Viral Hepat. 2001;  8 414-420
    CrossrefPubMedGoogle Scholar
  • 30 McHutchison J G, Ware J E, Bayliss M S et al.. The effects of interferon alpha-2b in combination with ribavirin on health related quality of life and work productivity.  J Hepatol. 2001;  34 140-147
    PubMedGoogle Scholar
  • 31 Westin J, Lindh M, Nenonen N et al.. Monitoring virological responses to interferon-ribavirin and interferon monotherapy of chronic hepatitis C re-treated due to relapse or non-response.  Scand J Infect Dis. 2001;  33 110-115
    PubMedGoogle Scholar
  • 32 McHutchison J G, Manns M, Patel K et al.. Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C.  Gastroenterology. 2002;  123 1061-1069
    CrossrefPubMedGoogle Scholar
  • 33 Camma C, Giunta M, Linea C, Pagliaro L. The effect of interferon on the liver in chronic hepatitis C: a quantitative evaluation of histology by meta-analysis.  J Hepatol. 1997;  26 1187-1199
    CrossrefPubMedGoogle Scholar
  • 34 Carithers Jr R L, Emerson S S. Therapy of hepatitis C: meta-analysis of interferon alfa-2b trials.  Hepatology. 1997;  26(suppl 1) 83S-88S
    CrossrefPubMedGoogle Scholar
  • 35 Bedossa P, Bioulacsage P, Callard P et al.. Presentation of a coded form for the assessment of histopathological features in viral chronic hepatitis-C.  Ann Pathol. 1993;  13 260-265
    PubMedGoogle Scholar
  • 36 Bedossa P, Bioulacsage P, Callard P et al.. Which classification for chronic hepatitis? Lessons from hepatitis C virus.  Gastroenterol Clin Biol. 1994;  18 403-406
    PubMedGoogle Scholar
  • 37 Shiffman M L, Hofmann C M, Contos M J et al.. A randomized, controlled trial of maintenance interferon therapy for patients with chronic hepatitis C virus and persistent viremia.  Gastroenterology. 1999;  117 1164-1172
    CrossrefPubMedGoogle Scholar
  • 38 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
    PubMedGoogle Scholar
  • 39 Poynard T, McHutchison J, Davis G L et al.. Impact of interferon alfa-2b and ribavirin on progression of liver fibrosis in patients with chronic hepatitis C.  Hepatology. 2000;  32 1131-1137
    CrossrefPubMedGoogle Scholar
  • 40 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
    PubMedGoogle Scholar
  • 41 Yoshida H, Arakawa Y, Sata M et al.. Interferon therapy prolonged life expectancy among chronic hepatitis C patients.  Gastroenterology. 2002;  123 483-491
    CrossrefPubMedGoogle Scholar
  • 42 Bonkovsky H L, Woolley J M. Reduction of health-related quality of life in chronic hepatitis C and improvement with interferon therapy. The Consensus Interferon Study Group.  Hepatology. 1999;  29 264-270
    CrossrefPubMedGoogle Scholar
  • 43 Ware J, Bayliss M S. Health-related quality of life in chronic hepatitis C: impact of disease and treatment response. The Interventional Therapy Group.  Hepatology. 1999;  3 550-555
    PubMedGoogle Scholar
  • 44 Carithers Jr R L, Zeuzem S, Manns M P et al.. Multicenter, randomized, controlled trial comparing high dose daily induction interferon plus ribavirin versus standard interferon alfa-2b plus ribavirin.  Hepatology. 2000;  32 317
    PubMedGoogle Scholar

Thierry PoynardM.D. 

Hopital Pitie-Salpetriere, Service d'Hepatologie-Gastro

47/83 Boulevard de l'Hopital, Paris Cedex 13

75651, France

eMail: tpoynard@teaser.fr