Treatment of chronic hepatitis C with PEGylated interferon and ribavirin
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Treatment with interferon alfa combined with ribavirin is successful in approximately 40% to 45% of patients with chronic hepatitis C viral infection (HCV). However, response rates are disappointing in patients who are difficult to treat, such as those infected with HCV genotype 1, high viral load, or advanced liver fibrosis. In addition, low tolerability and significant side effects of therapy frequently lead to dose reduction and treatment discontinuation, decreasing response rates further. Thus, investigation of new treatment options and innovations for chronic HCV infection are vital. This review describes recent advances in the treatment of HCV infection with PEGylated interferon (interferon modified with polyethylene glycol [PEG]) combined with ribavirin.
- Lau DT, Kleiner DE, Ghany MG, et al.: 10-Year follow-up after interferon-alpha therapy for chronic hepatitis C. Hepatology 1998, 28:1121–1127. CrossRef
- Nishiguchi S, Shiomi S, Nakatani S, et al.: Prevention of hepatocellular carcinoma in patients with chronic active hepatitis C and cirrhosis. Lancet 2001, 357:196–197. CrossRef
- 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, 346:1051–1055. CrossRef
- Seeff LB, Miller RN, Rabkin CS, et al.: 45-Year follow-up of hepatitis C virus infection in healthy young adults. Ann Intern Med 2000, 132:105–111.
- Wiese M, Berr F, Lafrenz M, et al.: Low frequency of cirrhosis in a hepatitis C (genotype 1b) single-source outbreak in Germany: a 20-year multicenter study. Hepatology 2000, 32:91–96. CrossRef
- Kenny-Walsh E: Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin. Irish Hepatology Research Group. N Engl J Med 1999, 340:1228–1233. CrossRef
- Barrett S, Goh J, Coughlan B, Ryan E, et al.: The natural course of hepatitis C virus infection after 22 years in a unique homogenous cohort: spontaneous viral clearance and chronic HCV infection. Gut 2001, 49:423–430. CrossRef
- Poynard T, Marcellin P, Lee SS, 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. International Hepatitis Interventional Therapy Group (IHIT). Lancet 1998, 352:1426–1432. This international multicenter trial demonstrated the additional benefit of ribavirin in combination with IFN alfa-2b for the treatment of chronic hepatitis C. The combination therapy improved sustained response rates to 40%. This led to the licensing of IFN and ribavirin combination therapy for chronic hepatitis C in Europe. CrossRef
- McHutchison JG, Gordon SC, Schiff ER, et al.: Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med 1998, 339:1485–1492. This American multicenter trial showed the additional benefit of ribavirin in combination with IFN alfa-2b for the treatment of chronic hepatitis C. The combination therapy improved sustained response rates to 40%. This led to the licensing of IFN and ribavirin combination therapy for chronic hepatitis C in the United States. CrossRef
- EASL International Consensus Conference on hepatitis C. Paris, 26–27 February 1999. Consensus statement. J Hepatol 1999, 31(suppl1):3–8.
- Davis GL, 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. International Hepatitis Interventional Therapy Group. N Engl J Med 1998, 339:1493–1499. CrossRef
- Wedemeyer H, Jackel E, Wedemeyer J, et al.: Is combination therapy of chronic hepatitis C with interferon alpha and ribavirin in primary interferon nonresponders indicated? An analysis of personal experiences and review of the literature. Z Gastroenterol 1998, 36:819–827.
- Cummings KJ, Lee SM, West ES, et al.: Interferon and ribavirin vs interferon alone in the re-treatment of chronic hepatitis C previously nonresponsive to interferon: a meta-analysis of randomized trials. JAMA 2001, 285:193–199. CrossRef
- 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, 116:378–386. CrossRef
- 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, 117:1164–1172. CrossRef
- Lam NP, Neumann AU, Gretch DR, et al.: Dose-dependent acute clearance of hepatitis C genotype 1 virus with interferon alfa. Hepatology 1997, 26:226–231. CrossRef
- Bailon P, Palleroni A, Schaffer CA, et al.: Rational design of a potent, long-lasting form of interferon: a 40 kDa branched polyethylene glycol-conjugated interferon alpha-2a for the treatment of hepatitis C. Bioconjug Chem 2001, 12:195–202. CrossRef
- Glue P, Fang JW, Rouzier-Panis R, et al.: Pegylated interferonalpha2b: pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data. Hepatitis C Intervention Therapy Group. Clin Pharmacol Ther 2000, 68:556–567. CrossRef
- Modi MW, Nutley NJ, Fried M, et al.: The pharmacokinetic behavior of pegylated (40KDA) interferon alfa-2a (PEGASYS /TM) in chronic hepatitis C patients after multiple dosing [abstract]. Hepatology 2000, 32:394A. CrossRef
- Zeuzem S, Feinman SV, Rasenack J, et al.: Peginterferon alfa-2a in patients with chronic hepatitis C. N Engl J Med 2000, 343:1666–1672. This international multicenter trial of 531 patients with chronic hepatitis C demonstrated that treatment with 180 /smg of PEG-IFN alfa-2a monotherapy once weekly enhanced sustained response rates two times, compared with treatment with standard IFN given three times weekly (39% vs 19%). CrossRef
- Lindsay KL, Trepo C, Heintges T, et al.: A randomized, doubleblind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C. Hepatology 2001, 34:395–403. This international multicenter trial of 1219 patients with chronic hepatitis C showed that treatment with PEG-IFN alfa-2b monotherapy doubled sustained response rates compared with treatment with standard IFN alfa-2b (25% vs 12%). CrossRef
- Fried MW, Shiffman M, Reddy R, et al.: Pegylated (40kDa) iterferon alfa-2a (PEGASYS) in combination with ribavirin: efficacy and safety results from a phase III, randomized, actively controlled, multicenter study [abstract]. Gastroenterology 2001, 120:A-55. This international multicenter trial of 1121 patients with chronic hepatitis C evaluated the efficacy of PEG-IFN alfa-2a and ribavirin combination therapy. PEFG-IFN alfa-2a, 180 /smg, and 1000 or 1200 mg of ribavirin demonstrated sustained response rates of 56%. The sustained response rates of patients with HCV genotype 1 could be enhanced by 9%. Side effects observed were fewer in patients treated with PEG-IFN alfa-2a.
- 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. This international multicenter trial of 1530 patients with chronic hepatitis C evaluated the efficacy of PEG-IFN alfa-2b and ribavirin combination therapy. PEG-IFN alfa-2b, 1.5 /smg/kg in combination with 800 mg of ribavirin demonstrated sustained response rates of 54%. Patients with HCV genotype 2 or 3 could be cured at a rate of more than 80%. A retrospective analysis showed that ribavirin should also be given as a body weight-adapted dose. CrossRef
- Heathcote EJ, Shiffman ML, Cooksley WG, et al.: Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis. N Engl J Med 2000, 343:1673–1680. This multicenter trial showed sustained response rates of 30% in patients with chronic hepatitis C and liver cirrhosis who were treated with PEG-IFN alfa-2a. This trial demonstrated that PEG-IFN alfa-2a is also effective in difficult-to-treat patients and gives support in treatment of patients with compensated liver cirrhosis. CrossRef
- Jaeckel E, Cornberg M, Wedemeyer H, et al., for the German Acute Hepatitis C Therapy Group: Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med 2001, 345:452–457. Accessible online at www.nejm.com This German multicenter trial investigated IFN alfa monotherapy in 44 patients with acute hepatitis C. A chronic course of hepatitis C could be prevented in 98% of the patients. CrossRef
- Musselman DL, Lawson DH, Gumnick JF, et al.: Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med 2001, 344:961–966. CrossRef
- Treatment of chronic hepatitis C with PEGylated interferon and ribavirin
Current Gastroenterology Reports
Volume 4, Issue 1 , pp 23-30
- Cover Date
- Print ISSN
- Online ISSN
- Current Medicine Group
- Additional Links