Dtsch Med Wochenschr 2001; 126(Suppl. Gastroenterol. 1): S68-S75
DOI: 10.1055/s-2001-14495
Supplement Gastroenterologie (1)
© Georg Thieme Verlag Stuttgart · New York

PEG-Interferone: Bedeutung für die Therapie der Virushepatitis B und C

PEG-interferons: significance for the treatment of viral hepatitis B and CH. Wedemeyer, M. Cornberg, M. P. Manns
  • Abteilung Gastroenterologie und Hepatologie (Direktor: Prof. Dr. med. M.P. Manns) der Medizinischen Hochschule Hannover
Further Information

Publication History

Publication Date:
11 September 2002 (online)

Weltweit leiden mehr als eine halbe Milliarde Menschen unter einer chronischen Infektion mit einem Hepatitisvirus. Während von ca. 170 Millionen Patienten mit chronischer Hepatitis C ausgegangen wird, sind etwa 350 Millionen Menschen chronische Träger des Hepatitis-B-Virus. Die virale Hepatitis ist die Hauptursache für Leberzellkrebs und Lebertransplantationen in der westlichen Welt. Die Therapie der chronischen Hepatitis C und B hat sich in den letzten Jahren deutlich weiterentwickelt, die Einführung von pegylierten Interferonen stellt hierbei die jüngste Neuerung dar.

Literatur

  • 1 EASL International Consensus Conference on hepatitis C. Paris, 26 - 27 February 1999. Consensus statement.  J Hepatol. 1999;  31 3-8 (Suppl 1))
  • 2 Bailon P, Palleroni A, Schaffer C A, Spence C L, Fung W J, Porter J E. 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
  • 3 Boker K H, Manns M P. Therapy of chronic viral hepatitis.  Internist. 1999;  40 1275-1287
  • 4 Carithers R L, Zeuzem S, Manns M P, McHutchison J, Perrillo R P, Bailey R. Multicenter, randomized, controlled trial comparing high dose daily induction interferon plus ribavirin versus standard interferon alfa-2b plus ribavirin.  Hepatology. 2000;  32 631A
  • 5 Cheng S J, Bonis P A, Lau J, Pham N Q, Wong J B. 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;  33 231-240
  • 6 Glue P, Fang J W, Rouzier-Panis R, Raffanel C, Sabo R, Gupta S K. et al . Pegylated interferon-alpha2b: pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data. Hepatitis C Intervention Therapy Group.  Clin Pharmacol Ther. 2000;  68 556-567
  • 7 Glue P, Rouzier-Panis R, Raffanel C, Sabo R, Gupta S K, Salfi M. et al . A dose-ranging study of pegylated interferon alfa-2b and ribavirin in chronic hepatitis C. The Hepatitis C Intervention Therapy Group.  Hepatology. 2000;  32 647-653
  • 8 Heathcote E J, Shiffman M L, Cooksley W G, Dusheiko G M, Lee S S, Balart L. et al . Peginterferon Alfa-2a in Patients with Chronic Hepatitis C and Cirrhosis.  N Engl J Med. 2000;  343 1673-1680
  • 9 Heathcote E J, Shiffman M L, Pockros P J, Lee S S, Reddy K R, Minuk G. et al . Pegylated (40KDA) interferon alfa-2a (PEGASYSä) is superior to interferon alfa-2a (ROFERON-A) in improving posttreatment histologic outcome in chronic hepatitis C patients 1584.  Hepatology. 2000;  32 223A
  • 10 Hoofnagle J H, Lau D, Conjeevaram H, Kleiner D, Di Bisceglie A M. Prolonged therapy of chronic hepatitis C with ribavirin.  J Viral Hepat. 1996;  3 247-252
  • 11 Hopf U, Niederau C, Kleber G, Fleig W E. The treatment of chronic viral hepatitis B/D and acute and chronic viral hepatitis C. The consensus of the German Society for Digestive and Metabolic Diseases.  Z Gastroenterol. 1997;  35 971-986
  • 12 Jaeckel E, Cornberg M, Mayer J, Koerbel J N, Wedemeyer H, Schuler A. et al . Early treatment of acute hepatitis C infection with intreferon-alpha 2b monotherapy prevents development of chronic HCV infection.  Hepatology. 2000;  32 318A
  • 13 Jaeckel E, Manns M P. The course and therapy of acute hepatitis C viral infection. Is a prevention of its becoming chronic possible.  Z Gastroenterol. 2000;  38 387-395
  • 14 Janssen H L, Brouwer J T, van der Mast R C, Schalm S W. Suicide associated with alfa-interferon therapy for chronic viral hepatitis.  J Hepatol. 1994;  21 241-243
  • 15 Kallinowski B, Liehr H, Moeller B, Stremmel W, Wechsler J G, Wiese M. et al . Combination therapy with interferon-alpha 2b and ribavirin for the treatment of relapse patients and non-responders with chronic HCV infection.  Z Gastroenterol. 2001;  39 199-204, 206
  • 16 Lam N P, Neumann A U, Gretch D R, Wiley T E, Perelson A S, Layden T J. Dose-dependent acute clearance of hepatitis C genotype 1 virus with interferon alfa.  Hepatology. 1997;  26 226-231
  • 17 Manns M, McHutchison J G, Gordorn S, Rustgi V, Lee M V, Ling M L. et al . Pegylated interferon alpha 2b (PEG IFN) plus ribavirin (R) for treatment of chronic hepatitis C: Optimization of ribavirin dose.  J.Hepatol. 2001;  34 236
  • 18 Manns M P, McHutchison J, Gordon S C, Rustgi V K, Shiffman M L, Lee W. et al . Peginterferon alfa-2b plus ribavirin compared to interferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C: 24 week treatment analysis of a multicenter, multinational phase III randomized controlled trial.  Hepatology. 2000;  32 297A
  • 19 Martin P, Mardip S, Martin N E, Nutley N J. Pegylated (40KDA) interferon alfa-2a (PEGASYS™) is unaffected by renal impairment.  Hepatology. 2000;  32 370A
  • 20 McHutchison J G, Gordon S C, Schiff E R, Shiffman M L, Lee W M, Rustgi V K. 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
  • 21 Modi M W, Fulton J S, Wright T L, Moore D J. Clearance of Pegylated (40KDA) Interferon alfa-2a (PEGASYS) is primarily hepatic.  Hepatology (Abstract). 2000;  32 371A
  • 22 Modi M W, Nutley N J, Fried M, Rustgi V K, Raymond K, Wright T. et al . The pharmacokinetic behavior of pegylated (40KDA) interferon alfa-2a (PEGASYS™) in chronic hepatitis C patients after multiple dosing.  Hepatology (Abstract). 2000;  32 394A
  • 23 Musselman D L, Lawson D H, Gumnick J F, Manatunga A K, Penna S, Goodkin R S. et al . Paroxetine for the prevention of depression induced by high-dose interferon alfa.  N Engl J Med. 2001;  344 961-966
  • 24 Neumann A U, Lam N P, Dahari H, Gretch D R, Wiley T E, Layden T J. et al . Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy.  Science. 1998;  282 103-107
  • 25 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
  • 26 Ning Q, Brown D, Parodo J, Cattral M, Gorczynski R, Cole E. et al . Ribavirin inhibits viral-induced macrophage production of TNF, IL-1, the procoagulant fgl2 prothrombinase and preserves Th1 cytokine production but inhibits Th2 cytokine response.  J Immunol. 1998;  160 3487-3493
  • 27 Nishiguchi S, Kuroki T, Nakatani S, Morimoto H, Takeda T, Nakajima 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
  • 28 Nishiguchi S, Shiomi S, Nakatani S, Takeda T, Fukuda K, Tamori A. et al . Prevention of hepatocellular carcinoma in patients with chronic active hepatitis C and cirrhosis.  Lancet. 2001;  357 196-197
  • 29 Okuda K. Hepatocellular carcinoma.  J Hepatol. 2000;  32 225-237 (Suppl 1))
  • 30 Pockros P J, Heathcote E J, Shiffman M L, Bain V, Zeuzem S, Manns M P. et al . Efficacy of pegylated (40KDA) interferon alfa-2a (PEGASYS™) in randomized trials of patients with chronic hepatitis C, with and without cirrhosis: correlation of virologic responses with baseline liver histology and genotype.  Hepatology. 2000;  32 442A
  • 31 Poynard T, Marcellin P, Lee S S, Niederau C, Minuk G S, Ideo G. et al. International Hepatitis Interventional Therapy Group (IHIT) . 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
  • 32 Poynard T, McHutchison J, Goodman Z, Ling M H, Albrecht J. The 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
  • 33 Reddy K R, Wright T L, Pockros P J, Shiffman M, Everson G, Reindollar R. et al . Efficacy and safety of pegylated (40-kd) interferon alpha-2a compared with interferon alpha-2a in noncirrhotic patients with chronic hepatitis C.  Hepatology. 2001;  33 433-438
  • 34 Schalm S W, Heathcote J, Cianciara J, Farrell G, Sherman M, Willems B. et al . Lamivudine and alpha interferon combination treatment of patients with chronic hepatitis B infection: a randomised trial.  Gut. 2000;  46 562-568
  • 35 Shiffman M L, Hofmann C M, Contos M J, Luketic V A, Sanyal A J, Sterling R K. 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
  • 36 Terrault N A. Combined interferon and lamivudine therapy: is this the treatment of choice for patients with chronic hepatitis B virus infection?.  Hepatology. 2000;  32 675-677
  • 37 Trepo C, Lindsay K, Niederau C, Shiffman M, Gordon S C, Hoefs J. Pegylated interferon alfa-2b (PEG-INTRON) monotherapy is superior to interferon alfa-2b (INTRON A) for the treatment of chronic hepatitis C.  J Hepatol. 2000;  32 29
  • 38 Valla D C, Chevallier M, Marcellin P, Payen J L, Trepo C, Fonck M. et al . Treatment of hepatitis C virus-related cirrhosis: a randomized, controlled trial of interferon alfa-2b versus no treatment.  Hepatology. 1999;  29 1870-1875
  • 39 Wedemeyer H, Caselmann W H, Manns M P. Combination therapy of chronic hepatitis C: an important step but not the final goal!.  J Hepatol. 1998;  29 1010-1014
  • 40 Wedemeyer H, Jackel E, Wedemeyer J, Frank H, Schuler A, Trautwein C. 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
  • 41 Zeuzem S, Feinman S V, Rasenack J, Heathcote E J, Lai M Y, Gane E. et al . Peginterferon Alfa-2a in Patients with Chronic Hepatitis C.  N Engl J Med. 2000;  343 1666-1672

Korrespondenz

Dr. med. Heiner Wedemeyer

Abteilung Gastroenterologie und Hepatologie Medizinische Hochschule Hannover

Carl Neuberg Straße 1

30625 Hannover

Phone: 0511/532 2853

Fax: 0511/532 2093

Email: h_wedemeyer@yahoo.com