Digestive Diseases and Sciences

, Volume 41, Issue 1, pp 149–154 | Cite as

High-dose interferon-α2b for re-treatment of nonresponders or relapsing patients with chronic hepatitis C

A controlled randomized trial
  • Herbert L. Bonkovsky
  • Bernard D. Clifford
  • Lynda J. Smith
  • Carol Allan
  • Barbara Banner
Liver: Infectious, Inflammatory, and Metabolic Disorders

Abstract

Relatively few patients with chronic hepatitis C treated with standard doses of interferon-α2b (3 million units per week for 24 weeks) have a sustained response. Our aim was to evaluate whether higher doses of interferon would improve this rate of response. Twenty-four patients with chronic hepatitis C who had failed to respond to (N=21) or had relapsed after (N=3) an initial course of standard interferon therapy were randomized to 15 million units (N=13) or 22.5–30 million units per week (N=11) for 24 weeks. Five of 13 subjects given 15 million units per week and 3/11 of subjects given 22.5–30 million units per week had complete normalization of serum alanine aminotransferase levels during therapy. Five patients (24%) who had not responded to standard interferon had a complete response to high-dose interferon during therapy. Only one patient had a sustained response, with normal serum alanine aminotransferase 24 weeks after stopping interferon. Six patients were withdrawn before completing treatment, five in the 22.5–30 million unit per week group. We conclude that higher doses of interferon ameliorate the severity of hepatitis in patients who failed to respond to or relapsed after standard interferon therapy, but are unlikely to produce a sustained response. High-dose therapy is associated with an increase in side effects.

Key Words

chronic hepatitis hepatitis C interferon therapy adverse side effects 

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References

  1. 1.
    Tong MJ, El-Farra NS, Reikes AR, Co RL: Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med 332:1463–1466, 1995Google Scholar
  2. 2.
    van der Poel CL, Cuypers HT, Reesink HW: Hepatitis C six years on. Lancet 344:1475–1479, 1995Google Scholar
  3. 3.
    Bhandari BN, Wright TL, Hepatitis C: An overview. Annu Rev Med 46:309–317, 1995Google Scholar
  4. 4.
    Davis GL, Balart LA, Schiff ER, Lindsay K, Bodenheimer HC Jr, Perrillo RP, Carey W: Treatment of chronic hepatitis C with recombinant interferon alpha. A multi-center, randomized controlled trial. N Engl J Med 321:1501–1506, 1989Google Scholar
  5. 5.
    Shindo M, DiBisceglie AM, Hoofnagle JH: Long-term follow-up of patients with chronic hepatitis C treatment with α-interferon. Hepatology 15:1013–1016, 1992Google Scholar
  6. 6.
    Tong MJ, Blatt LM, Klein M, Manyak C, Poulakos J, Sayadzadeh K: Long-term follow-up of chronic hepatitis C virus infected patients treated with consensus interferon. Gastroenterology 108:A1188, 1995Google Scholar
  7. 7.
    Saleh MG, Tibbs CJ, Koskinas J, Pereira LMMB, Bomford AB, Portmann BC, McFarlane IG, Williams R: Hepatic and extrahepatic hepatitis C virus replication in relation to response to interferon therapy. Hepathology 20:1399–1404, 1994Google Scholar
  8. 8.
    Mahancy K, Tedeschi V, Maertens G, DiBisceglie AM, Vergalla J, Hoofnagle JH, Sallie R: Genotyping analysis of hepatitic C virus in American patients. Hepatology 20:1405–1411, 1994Google Scholar
  9. 9.
    Clifford BD, Smith L, Allan C, Bonkovsky HL: High dose interferon α-2b for retreatment of patients with chronic HCV: A pilot study. Gastroenterology 108:A1050, 1995Google Scholar
  10. 10.
    Tygstrup N: The galactose elimination capacity in control subjects and in patients with cirrhosis of the liver. Acta Med Scand 175:281–289, 1964Google Scholar
  11. 11.
    Banner BF, Barton AL, Cable EE, Smith L, Bonkovsky HL: A detailed analysis of the Knodell score and other histologic parameters as predictors of response to interferon therapy in chronic hepatitis C. Mod Pathol 8:232–238, 1995Google Scholar
  12. 12.
    Knodell RG, Ishak KG, Black WC: Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1:431–435, 1981Google Scholar
  13. 13.
    Marriott E, Quiroga JA, Carreno V: Retreatment of chronic hepatitis C with interferon-α. J Infect Dis 166:1200–1201, 1992Google Scholar
  14. 14.
    Ferenci P, Stauber R, Propst A, Fiedler R, Gschwanter M, Schutze K, Judmaier G, Krejs GJ, Gangl A: Dose increase augments the response rate of interferon-α in chronic hepatitis C. Gastroenterology 108:A1064, 1995Google Scholar
  15. 15.
    Gerkin G, Teuber G, Goergen B, Meyer Zum-Buschenfelde KH: Interferon-alpha retreatment in chronic hepatitis C. J Hepatol 225:118–121, 1995Google Scholar
  16. 16.
    Marcellin P, Pouteau M, Martinot-Peignoux M, Degos F, Duchatelle V, Boyer N, Lemonnier C, Degott C, Erlinger S, Benhamou JP: Lack of benefit of escalating dosage of interferon alfa in patients with chronic hepatitis C. Gastroenterology 109:156–165, 1995Google Scholar
  17. 17.
    Hayashi J, Ohmiya M, Kishihara Y, Tani Y, Kinukawa N, Ikematsu H, Kashiwagi S: A statistical analysis of predictive factors of response to human lymphoblastoid interferon in patients with chronic hepatitis C. Am J Gastroenterol 89:2151–2156, 1994Google Scholar
  18. 18.
    Pozzato G, Moretti M, Saveria-Croce L, Sasso F, Kaneko S, Unoura M, Kobayashi K, Crovatto M, Santini G, Tiribelli C: Interferon therapy in chronic hepatitis C virus: Evidence of different outcomes with respect to different viral strains. J Med Virol 45:445–450, 1995Google Scholar
  19. 19.
    Reichard O, Foberg U, Fryden A, Mattsson L, Norkrams G, Sonnerborg A, Wejstal R, Yun Z-B, Weiland O: High sustained response rate and clearance of viremia in chronic hepatitis C after treatment with interferon-α2b for 60 weeks. Hepatology 19:280–285, 1994Google Scholar
  20. 20.
    Poynard T, Bedossa P, Chevallier M, Mathurin P, Lemonnier C, Trepo C, Couzigou P, Payen JL, Sajus M, Costa JM, Vidaud M, Chaput JC, Multi-Center Study Group: A comparison of three interferon alfa-2b regimens for the long-term treatment of chronic non-A, non-B hepatitis. N Engl J Med 332:1457–1462, 1995Google Scholar
  21. 21.
    Van Thiel DH, Friedlander L, Fagiuoli S, Wright HI, Irish W, Gavaler JS: Response to interferon alpha therapy is influenced by the iron content of the liver. J Hepatol 20:410–415, 1994Google Scholar
  22. 22.
    Olynyk J, Reddy R, DiBisceglie AM, Jeffers L, Parker TI, Radick TL, Schiff ER, Bacon BR: Hepatic iron concentration as a predictor of response to interferon alfa therapy in chronic hepatitis C. Gastroenterology 108:1104–1109, 1995Google Scholar
  23. 23.
    Barton AL, Banner BF, Cable EE, Bonkovsky HL: Distribution of iron in the liver predicts the response of chronic hepatitis C infection to interferon therapy. Am J Clin Pathol 103:419–424, 1995Google Scholar
  24. 24.
    Bukh J, Miller RH, Purcell RH: Genetic beterogeneity of hepatitis C virus: quasispecies and genotypes. Semin Liver Dis 15:41–63, 1995Google Scholar
  25. 25.
    Terrault N, Wright T: Interferon and hepatitis C. N Engl J Med 332:1509–1511, 1995Google Scholar
  26. 26.
    Carreno V, Tapia L, Ryff J-C, Quiroga JA, Castillo I: Treatment of chronic hepatitis C by continuous subcutaneous influsion of interferon-alpha. J Med Virol 37:215–219, 1992Google Scholar
  27. 27.
    Antonelli G, Currenti M, Turizziani O, Dianzani F: Neutralizing antibodies to interferon: Relative frequency in patients treated with different interferon preparations. J Infect Dis 163:882–885, 1991Google Scholar
  28. 28.
    Rubin RB, Barton AL, Banner BF, Bonkovsky HL: Iron and chronic viral hepatitis: emerging evidence for an important interaction. Dig Dis 13:223–238, 1995Google Scholar
  29. 29.
    Banner BF, Barton AL, Cable EE, Smith L, Bonkovsky HL: A detailed analysis of the Knodell score and other histologic parameters as predictors of response to interferon therapy in chronic hepatitis C. Mod Pathol 8:232–238, 1995Google Scholar
  30. 30.
    Bacon BR, Rebholz AE, Fried MW, DiBisceglie AM: Effect of iron reduction therapy in patients with chronic hepatitis C who failed to respond to interferon-a. Hepatology 18:150A, 1993Google Scholar
  31. 31.
    Van Thiel DH, Friedlander L, Mallory P, Faginoli S, Wright HI, Gasbarini A, Caraceni P: Re-treatment of hepatitis C interferon non-response with larger doses of interferon with and without phlebotomy. Gastroenterology 106:A 1002, 1994Google Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Herbert L. Bonkovsky
    • 1
    • 2
  • Bernard D. Clifford
    • 1
    • 2
  • Lynda J. Smith
    • 1
    • 2
  • Carol Allan
    • 1
    • 2
  • Barbara Banner
    • 1
    • 2
  1. 1.Departments of Medicine, Pathology, and Biochemistry & Molecular BiologyUniversity of Massachusetts Medical CenterWorcester
  2. 2.Liver, Biliary, and Pancreatic CenterUniversity of Massachusetts Medical CenterWorcester
  3. 3.Division of Digestive Disease and Nutrition, Room S6-737University of Massachusetts Medical CenterWorcester

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