Treatment Options in Patients with Chronic Hepatitis C

Options de traitement pour les patients atteints d’hépatite C chronique

Abstract

Hepatitis C is a major health care problem plagued by the lack of a truly effective therapy. To date, the combination of interferon and ribavirin has provided the best chance of viral eradication. However, this therapy is expensive, has multiple side effects and works in less than half of patients. New strategies need to be developed to deal with the increasing burden of hepatitis C-related disease, and we anxiously await the arrival of new drugs such as helicase and protease inhibitors.

Résumé

L’hépatite C est un grave problème de santé publique et il n’existe pas de thérapie vraiment efficace pour la combattre. Jusqu’à présent, la combinaison d’interféron et de ribavirin semble fournir la meilleure possibilité d’éradiquer le virus. Mais cette thérapie est coûteuse, assortie de nombreux effets secondaires et ne donne de bons résultats que chez la moitié des patients. Il faut développer de nouvelles stratégies pour alléger le fardeau croissant des maladies causées par l’hépatite C. Nous attendons avec impatience l’arrivée de nouveaux médicaments, notamment les inhibiteurs d’hélicase et de protéase.

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Références

  1. 1.

    Marcellin P. Hepatitis C: The clinical spectrum of the disease. J Hepatol 1999;31(Suppl 1):9–16.

    PubMed  Article  Google Scholar 

  2. 2.

    Sherman M. Management of viral hepatitis: Clinical and public health perspectives - a consensus statement. CASL Hepatitis Consensus Group. Association canadienne pour l’étude du foie. Can J Gastroenterol 1997;11:407–16.

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    National Institutes of Health Consensus Development Conference Panel Statement: Management of Hepatitis C. Hepatology 1997;23(3 Suppl 1):2S–10S.

    Google Scholar 

  4. 4.

    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(4):778–89.

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Carithers RL, Emerson SS. Therapy of hepatitis C: Meta-analysis of interferon alfa-2b trials. Hepatology 1997;26(3 Suppl 1):83S–88S.

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Mabee CL, Crippin JS, Lee WM. Review article: Interferon and hepatitis C - factors predicting therapeutic outcome. Aliment Pharmacol Ther 1998;12(6):509–18.

    CAS  PubMed  Article  Google Scholar 

  7. 7.

    Martinot-Peignoux M, Boyer N, Pouteau M, et al. Predictors of sustained response to alpha interferon therapy in chronic hepatitis C. J Hepatol 1998;29:214–23.

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Shiratori Y, Kato N, Yokosuka O, et al. Predictors of the efficacy of interferon therapy in chronic hepatitis C virus infection. Gastroenterology 1997;113(2):558–66.

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Spengler U, Rockstroh JK. Hepatitis C in the patient with human immunodeficiency virus infection. J Hepatol 1998;29(6):1023–30.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    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-a therapy. Ann Intern Med 1997;127:875–81.

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Sim H, Yim C, Krajden M, Heathcote J. Durability of serological remission in chronic hepatitis C treated with interferon-alpha-2 B. Am J Gastroenterol 1998; 93(1) :39–

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Bennett WG, Inouc Y, Beck JR, et al. Estimates of the cost-effectiveness of a single course of interferon-a 2b in patients with histologically mild chronic hepatitis C. Ann Intern Med 1997;127:855–65.

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Kim WR, Poterucha JJ, Hermans JE, et al. Cost-effectiveness of 6 and 12 months of interferon-a therapy for chronic hepatitis C. Ann Intern Med 1997;127:866–74.

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Bonkovsky HL, Woolley JM. Reduction of health-related quality of life in chronic hepatitis C and improvement with interferon therapy. The Consensus Interferon Study Group. Hepatology 1999;29(1):264–70.

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Mazzella G, Accogli E, Sottili S, et al. Alpha interferon treatment may prevent hepatocellular carcinoma in HCV-related liver cirrhosis. J Hepatol 1996;24:141–47.

    CAS  PubMed  Article  Google Scholar 

  16. 16.

    Ajello A, Freni MA, Spadaro A, et al. Ten year follow-up of patients with chronic hepatitis C treated with interferon. Hepatogastroenterology 1999;46(28):2447–50.

    CAS  PubMed  Google Scholar 

  17. 17.

    Yoshida H, Shiratori Y, Moriyama M, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: National surveillance program of cirrhot-ic and noncirrhotic patients with chronic hepatitis C in Japan. Ann Intern Med 1999;131(3):174–81.

    CAS  PubMed  Article  Google Scholar 

  18. 18.

    Castro A, Suarez D, Inglada L, et al. Multicenter randomized, controlled study of intramuscular administration of interferon-beta for the treatment of chronic hepatitis C. J Interferon Cytokine Res 1997;17(1):27–30.

    CAS  PubMed  Article  Google Scholar 

  19. 19.

    Barbaro G, Di Lorenzo G, Soldini M, et al. Intravenous recombinant interferon-beta versus interferon-alpha-2b and ribavirin in combination for short-term treatment of chronic hepatitis C patients not responding to interferon-alpha. Scand J Gastroenterol 1999;34(9):928–33.

    CAS  PubMed  Article  Google Scholar 

  20. 20.

    Heathcote J. Consensus interferon: A novel interferon for the treatment of hepatitis C. J Vir Hepat 1998;5(Suppl 1):13–18.

    Article  Google Scholar 

  21. 21.

    Anderson FH, Zeng L, Yoshida EM, Rock NR. Failure of ketoprofen and interferon combination therapy to improve interferon-resistant chronic hepatitis C. Can J Gastroenterol 1997;11(4):294–97.

    CAS  PubMed  Article  Google Scholar 

  22. 22.

    Zarski JP, Maynard-Mute M, Chousterman S, et al. Tenoxicam, a non-steroid anti-inflammatory drug, is unable to increase the response rate in patients with chronic hepatitis C treated by alpha interferon. Hepatology 1998;27(3):862–67.

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Fabris P, Tositti G, Negro F, et al. Interferon alfa-2b alone or in combination with ketoprofen as treatment for interferon-naive chronic hepatitis C patients. Aliment Pharmocol Ther 1999;13(10):1329–34.

    CAS  Article  Google Scholar 

  24. 24.

    Tsutsumi M, Takada A, Takase S, Sawada M. Effects of combination therapy with interferon and ofloxacin on chronic type C hepatitis: A pilot study. J Gastroenter Hepatol 1996;11(11):1006–11.

    CAS  Article  Google Scholar 

  25. 25.

    Komatsu M, Ishii T, Ono T, et al. Pilot study of ofloxacin and interferon-alpha combination therapy for chronic hepatitis C without sustained response to initial interferon administration. Can J Gastroenterol 1997;11(6):507–11.

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Tanaka K, Kondo M, Sakaguchi T, et al. Efficacy of ursodeoxycholic acid in combination with interferon-alpha in treating chronic hepatitis C: Results of a long-term follow-up trial. J Gastroenterol Hepatol 1996;11(12):1155–60.

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Crosignani A, Budillon G, Cimino L, et al. Tauroursodeoxycholic acid for the treatment of HCV-related chronic hepatitis: A multicenter placebo-controlled study. Hepatogastroenterology 1998;45(23):1624–29.

    CAS  PubMed  Google Scholar 

  28. 28.

    van Rossum TG, Vulto AG, de Man RA, et al. Review article: Glycyrrhizin as a potential treatment for chronic hepatitis C. Aliment Pharmacol Ther 1998;12(3):199–205.

    PubMed  Article  Google Scholar 

  29. 29.

    Patrick L. Hepatitis C: Epidemiology and review of complementary/alternative medicine treatments. Altern Med Rev 1999;4(4):220–38.

    CAS  PubMed  Google Scholar 

  30. 30.

    Sherman KE, Sjogren M, Creager RL, et al. Combination therapy with thymosin alpha 1 and interferon for the treatment of chronic hepatitis C infection: A randomized, placebo-controlled double-blind trial. Hepatology 1998;27(4):1128–35.

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Moscarella S, Buzzelli G, Romanelli RG, et al. Interferon and thymosin combination therapy in naive patients with chronic hepatitis C: Preliminary results. Liver 1998;18(5):366–69.

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    Smith JP. Treatment of chronic hepatitis C with amantidine. Dig Dis Sci 1997;42(8):1681–87.

    CAS  PubMed  Article  Google Scholar 

  33. 33.

    Tabone M, Ercole E, Zaffino C, et al. Amantadine hydrochloride decreases serum ALT activity without effects on serum HCV-RNA in chronic hepatitis C patients. Italian J Gastroenterol Hepatol 1998;30(6):611–13.

    CAS  Google Scholar 

  34. 34.

    Fong TL, Fried MW, Clarke-Platt J. A pilot study of rimantadine for patients with chronic hepatitis C unresponsive to interferon therapy. Am J Gastroenterol 1999;94(4):990–93.

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    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(5):591–98.

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Schvarcz R, Yun AB, Sönnerborg A, Weiland O. Combined treatment with interferon alpha-2b and ribavirin for chronic hepatitis C in patients with a previous non-response or non-sustained response to interferon alone. J Med Virol 1995;46:43–47.

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Schalm SW, Hansen BE, Chemello L, et al. Ribavirin enhances the efficacy but not the adverse effects of interferon in chronic hepatitis C: Meta-analysis of individual patient data from European centers. J Hepatol 1997;26:961–66.

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Reichard O, Norkrons G, Fryden A, et al. Randomized, double-blind, placebo-controlled trial of interferon alpha-2b with and without ribavirin for chronic hepatitis C. Lancet 1998;351:83–87.

    CAS  PubMed  Article  Google Scholar 

  39. 39.

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

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Poynard T, Marcellin P, Lee S, et al. Randomized trial of interferon 2b plus ribavirin for 48 weeks or for 24 weeks versus interferon 2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. Lancet 1998;352:1426–32.

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Ware JE Jr, Bayliss MS, Mannocchia M, Davis GL. Health-related quality of life in chronic hepatitis C: Impact of disease and treatment response. The Interventional Therapy Group. Hepatology 1999;39(2):550–55.

    Article  Google Scholar 

  42. 42.

    Younossi Z, Singer M, McHutchison J, Shermock K. Cost effectiveness of interferon 2b combined with ribavirin for the treatment of chronic hepatitis C. Hepatology 1999;30:1318–24.

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    Davis G, 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;339:1493–99.

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Heathcote J, Keeffe E, Lee S, et al. Re-treatment of chronic hepatitis C with consensus interferon. Hepatology 1998;27:1136–43.

    CAS  PubMed  Article  Google Scholar 

  45. 45.

    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;31:211–18.

    CAS  PubMed  Article  Google Scholar 

  46. 46.

    Xu Z, Hoffman J, Patel I, Joubert P. Single-dose safety/tolerability and pharmacokinetic/pharma-codynamics following administration of ascending subcutaneous doses of pegylated-interferon (PEG-IFN) and interferon a2a (IFN-a2a) to healthy subjects. Hepatology 1998;28(Suppl):702A.

    Google Scholar 

  47. 47.

    Shiffman ML, Pockros PJ, Reddy RK, et al. A controlled, randomized, multicenter descending dose phase II trial of pegylated interferon a2a vs standard interferon a2a in patients with chronic hepatitis C. Gastroenterology 1999;116(suppl):A1275.

  48. 48.

    Nakamura H, Ito H, Ogawa H, et al. Initial daily interferon administration can gain more eradication of HCV-RNA in patients with chronic hepatitis C, especially with serum intermediate viral load. Hepatogastroenterology 1999;46(26):1131–39.

    CAS  PubMed  Google Scholar 

  49. 49.

    Brillanti S, Foli M, Di Tomaso M, et al. Pilot study of triple antiviral therapy for chronic hepatitis C in interferon alpha non-responders. Italian J Gastroenterol Hepatol 1999;31(2):130–34.

    CAS  Google Scholar 

  50. 50.

    Schalm SW, Brouwer JT, Bekkering FC, van Rossum TGJ. New treatment strategies in non-responder patients with chronic hepatitis C. J Hepatol 1999;31(Suppl 1):184–88.

    PubMed  Article  Google Scholar 

  51. 51.

    Shiffman ML, Hofmann CM, Contos MJ, et al. A randomized, controlled trial of maintenance interferon therapy for patients with chronic hepatitis C virus and persistent viremia. Gastroenterology 1999;117(5):1164–72.

    CAS  PubMed  Article  Google Scholar 

  52. 52.

    Gish R. Future directions in the treatment of patients with chronic hepatitis C virus infection. Can J Gastroenterol 1999;13(1):57–62.

    CAS  PubMed  Article  Google Scholar 

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Correspondence to Dr. Samuel S. Lee MD, FRCPC.

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Burak, K.W., Lee, S.S. Treatment Options in Patients with Chronic Hepatitis C. Can J Public Health 91, S24–S28 (2000). https://doi.org/10.1007/BF03405103

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