Intervirology 2000;43:174–179

Relationship between Five-Year Histological Outcome and Serial Changes in Serum Alanine Aminotransferase in Patients with Biochemical and Virological Relapse after Interferon Treatment for Chronic Hepatitis C

Kobayashi M. · Ikeda K. · Akuta N. · Someya T. · Suzuki F. · Tsubota A. · Suzuki Y. · Saitoh S. · Arase Y. · Chayama K. · Kumada H.
Department of Gastroenterology, Toranomon Hospital, Minato-ku, Tokyo, Japan
email Corresponding Author

 goto top of outline Key Words

  • Chronic hepatitis C
  • Liver histology
  • Serum ALT

 goto top of outline Abstract

Objective: The aim of this study was to assess the correlation between serial changes in serum alanine aminotransferase (ALT) levels and histological outcome 5 years after treatment of patients with chronic hepatitis C with interferon (IFN). Methods: We retrospectively evaluated 61 consecutive patients who underwent two liver biopsies, just before and 5 years after a 6-month course of IFN therapy, and who showed a relapse after therapy. The extent of liver fibrosis was estimated using a scale with seven grades. Results: At the end of 6-month IFN therapy, 40 (65.6%) patients had normal serum ALT concentrations. However, 13 of the 40 patients relapsed within 6 months after IFN therapy. The average ALT during 5 years in 40 patients was less than or equal to 75 IU/l, while in the other 21 patients it was more than 75 IU/l. Among the 40 patients with a mean ALT less than 75 IU/l, 13 (33%) patients showed histological improvement, 26 (65%) showed no changes and only 1 patient (2%) showed worsening of liver fibrosis. On the other hand, among the 21 patients with a mean ALT of more than 75 IU/l, only 1 (5%) patient showed improvement, 8 (38%) showed no changes and 12 patients (57%) showed worsening of liver fibrosis. Conclusion: There is a significant relationship between 5-year histological outcome and serial changes in serum ALT in patients with biochemical and virological relapse after IFN treatment for chronic hepatitis C.

Copyright © 2000 S. Karger AG, Basel

 goto top of outline References
  1. Kiyosawa K, Furuta S: Review of hepatitis C in Japan. J Gastroenterol Hepatol 1991;6:383–391.
  2. Ikeda K, Saitoh S, Suzuki Y, Kobayashi M, Tsubota A, Koida I, Arase Y, Fukuda M, Chayama K, Murashima N, Kumada H: Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: A prospective observation of 2215 patients. J Hepatol 1998;28:930–983.
  3. Yano M, Kumada H, Kage M, Ikeda K, Shimamatsu K, Inoue O, Hashimoto E, Lefkowitch JH, Ludwig J, Okuda K: The long-term pathological evolution of chronic hepatitis C. Hepatology 1996;23:1334–1340.
  4. Kasahara A, Hayashi N, Mochizuki K, Takayanagi M, Yoshioka K, Kakumu S, lijima A, Urushihara A, Kiyosawa K, Okuda M, Hino K, Okita K: Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Osaka Liver Disease Study Group. Hepatology 1998;27:1394–1402.
  5. Tsubota A, Chayama K, Ikeda K, Yasuji A, Koida I, Saitoh S, Hashimoto M, Iwasaki S, Kobayashi M, Hiromitsu K: Factors predictive of response to interferon-alpha therapy in hepatitis C virus infection. Hepatology 1994;19:1088–1094.
  6. Yoshioka K, Kakumu S, Wakita T, Ishikawa T, Itoh Y, Takayanagi M, Higashi Y, Shibata M, Morishima T: Detection of hepatitis C virus by polymerase chain reaction and response to interferon-alpha therapy: Relationship to genotypes of hepatitis C virus. Hepatology 1992;16:293–299.
  7. Reichard O, Foberg U, Fryden A, Mattsson L, Norkrans G, Sonnerborg A, Wejstal R, Yun ZB, Weiland O: High sustained response rate and clearance of viremia in chronic hepatitis C after treatment with interferon-alpha 2b for 60 weeks. Hepatology 1994;19:280–285.
  8. Tsubota A, Kumada H, Chayama K, Arase Y, Saitoh S, Koida I, Suzuki Y, Kobayashi M, Murashima N, Ikeda K: Time course of histological changes in patients with a sustained biochemical and virological response to interferon-alpha therapy for chronic hepatitis C virus infection. J Hepatol 1997;27:49–55.
  9. Reichard O, Glaumann H, Fryden A, Norkrans G, Schvarcz R, Sonnerborg A, Yun ZB, Weiland O: Two-year biochemical, virological, and histological follow-up in patients with chronic hepatitis C responding in a sustained fashion to interferon alfa-2b treatment. Hepatology 1995;21:918–922.
  10. Larghi A, Tagger A, Crosignani A, Ribero ML, Bruno S, Portera G, Battezzati PM, Maggioni M, Fasola M, Zuin M, Podda M: Clinical significance of hepatic HCV RNA in patients with chronic hepatitis C demonstrating long-term sustained response to interferon-alpha therapy. J Med Virol 1998;55:7–11.
  11. Reichard O, Glaumann H, Fryden A, Norkrans G, Wejstal R, Weiland O: Long-term follow-up of chronic hepatitis C patients with sustained virological response to alpha-interferon. J Hepatol 1999;30:783–787.
  12. Manabe N, Chevallier M, Chossegros P, Causse X, Guerret S, Trepo C, Grimaud JA: Interferon-alpha 2b therapy reduces liver fibrosis in chronic non-A, non-B hepatitis: A quantitative histological evaluation. Hepatology 1993;18:1344–1349.
  13. Shiffman ML, Hofmann CM, Thompson EB, Ferreira-Gonzalez A, Contos MJ, Koshy A, Luketic VA, Sanyal AJ, Mills AS, Garrett CT: Relationship between biochemical, virological, and histological response during interferon treatment of chronic hepatitis C. Hepatology 1997;26:780–785.
  14. Lau DTY, Kleiner DE, Ghany MG, Park Y, Schmid P, Hoofnagle JH: 10-Year follow-up after interferon-alpha therapy for chronic hepatitis C. Hepatology 1998;28:1121–1127.
  15. Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, Kiernan TW, Wollman J: Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981;1:431–435.
  16. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN, Phillips MJ, Portmann BG, Poulsen H, Scheuer PJ, Schmid M, Thaler H: Histological grading and staging of chronic hepatitis. J Hepatol 1995;22:696–699.
  17. Vandelli C, Renzo F, Braun HB, Tisminetzky S, Albrecht M, De Palma M, Ranzi A, Di Marco G, Stroffolini T, Baralle F, Ventura E, Michel G: Prediction of successful outcome in a randomised controlled trial of the long-term efficacy of interferon alpha treatment for chronic hepatitis C. J Med Virol 1999;58:26–34.
  18. Arase Y, Ikeda K, Chayama K, Murashima N, Tsubota A, Nakamura I, Suzuki Y, Saitoh S, Kobayashi M, Kobayashi M, Kobayashi M, Kumada H: Clinical and virological features of chronic hepatitis C carriers with normal alanine aminotransferase levels despite positive serum HCV RNA after interferon therapy. J Gastroenterol 1999;34:594–599.
  19. Shiffman ML, Hofmann CM, Contos MJ, Luketic VA, Sanyal AJ, Sterling RK, Ferreira-Gonzalez A, Mills AS, Garret C: A randomized, controlled trial of maintenance interferon therapy for patients with chronic hepatitis C virus and persistent viremia. Gastroenterology 1999;117:1164–1172.
  20. Arase Y, Ikeda K, Murashima N, Chayama K, Tsubota A, Koida I, Suzuki Y, Saitoh S, Kobayashi M, Kumada H: The long term efficacy of glycyrrhizin in chronic hepatitis C patients. Cancer 1997;79:1494–1500.
  21. Tsubota A, Kumada H, Arase Y, Chayama K, Saitoh S, Ikeda K, Kobayashi M, Suzuki Y, Murashima N: Combined ursodeoxycholic acid and glycyrrhizin therapy for chronic hepatitis C virus infection: A randomized controlled trial in 170 patients. Eur J Gastroenterol Hepatol 1999;11:1077–1083.

    External Resources

  22. Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G, Bain V, Heathcote J, Zeuzem S, Trepo C, Albrecht J: 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. Lancet 1998;352:1426–1432.
  23. McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, Goodman ZD, Ling MH, Cort S, Albrecht JK: 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.
  24. Boyer N, Marcellin P: Pathogenesis, diagnosis and management of hepatitis C. J Hepatol 2000;32(1 suppl):98–112.

 goto top of outline Author Contacts

Masahiro Kobayashi, MD
Department of Gastroenterology, Toranomon Hospital
2-2-2 Toranomon, Minato-ku, 105-8470 Tokyo (Japan)
Tel. +81 44 877 5111, Fax +81 44 860 1623

 goto top of outline Article Information

Received: Received: June 26, 2000
Accepted: July 10, 2000
Number of Print Pages : 6
Number of Figures : 4, Number of Tables : 1, Number of References : 24

 goto top of outline Publication Details

Intervirology (International Journal of Basic and Medical Virology)
Founded 1973 by J.L. Melnick; continued by F. Rapp (1986–1990); M.J. Buchmeier and C.R. Howard (1991–1993)

Vol. 43, No. 3, Year 2000 (Cover Date: May-June 2000 (Released October 2000))

Journal Editor: Rüdiger W. Braun, Stuttgart
ISSN: 0300–5526 (print), 1423–0100 (Online)

For additional information:

Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.