Intervirology

Treatment of Chronic Hepatitis C

Elevated Serum ALT Levels during Pegylated Interferon Monotherapy May Be Caused by Hepatic Iron Overload

Nagashima M.a · Kudo M.a · Chung H.a · Ishikawa E.a · Inoue T.a · Nakatani T.a · Dote K.b

Author affiliations

aDepartment of Gastroenterology and Hepatology, Kinki University School of Medicine, Ohno-Higashi, Osaka-Sayama, bDepartment of Pathology, Kinki University School of Medicine, Osaka-Sayama, Japan

Keywords: Pegylated interferonHepatic iron overloadALTFerritinChronic hepatitis C

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Intervirology 2008;51:76–85
https://doi.org/10.1159/000122604

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Article / Publication Details

First-Page Preview
Abstract of Treatment of Chronic Hepatitis C

Published online: June 10, 2008
Issue release date: June 2008

Number of Print Pages: 10
Number of Figures: 6
Number of Tables: 3

ISSN: 0300-5526 (Print)
eISSN: 1423-0100 (Online)

For additional information: https://www.karger.com/INT

Abstract

Objective: Persistently elevated serum alanine aminotransferase (ALT) levels have been observed in chronic hepatitis C (CHC) patients during pegylated interferon (PEG-IFN) therapy. We investigated whether elevated serum ALT levels during PEG-IFN therapy are associated with iron overload. Methods: Sixty-three CHC patients treated with PEG-IFNα-2a monotherapy were evaluated. The associations between elevated serum ALT levels (≧70 IU/l) were investigated before and 24 weeks after therapy. We classified patients as follows: patients with no elevated serum ALT levels (group NE: n = 35), patients with elevated serum ALT levels (group E: n = 28), and patients with no elevated serum ALT level and negative HCV RNA (group NE–: n = 24), and patients with elevated serum ALT level and negative HCV RNA (group E–: n = 19). We also compared total iron score (TIS) and fibrosis stage in liver specimens obtained before and during therapy from 3 patients with elevated serum ALT levels. Results: Serum ferritin levels were significantly increased after 24 weeks compared to baseline levels in group E (218 ± 273 vs. 438 ± 308 ng/ml; p < 0.0001) and group E– (146 ± 152 vs. 410 ± 291 ng/ml; p < 0.0001). Serum ALT and ferritin levels were significantly correlated after 24 weeks. The liver specimens revealed that TIS and fibrosis progressed during therapy. Conclusion: Our findings suggest that the elevation in serum ALT levels during therapy is caused by iron overload which may be induced by PEG-IFNα-2a.

© 2008 S. Karger AG, Basel



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References

  1. Zeuzem S, Feinman SV, Rasenack J, Heathcote EJ, Lai MY, Gane E, O’Grady J, et al: Peginterferon alfa-2a in patients with chronic hepatitis C. N Engl J Med 2000;343:1666–1672.
    External Resources
  2. Lindsay KL, Trepo C, Heintges T, Shiffman ML, Gordon SC, Hoefs JC, Schiff ER, et al: A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C. Hepatology 2001;34:395–403.
    External Resources
  3. Glue P, Fang JW, Rouzier-Panis R, Raffanel C, Sabo R, Gupta SK, Salfi M, et al: Pegylated interferon-alpha2b: pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data. Hepatitis C Intervention Therapy Group. Clin Pharmacol Ther 2000;68:556–567.
    External Resources
  4. Nieforth KA, Nadeau R, Patel IH, 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.
    External Resources
  5. Piperno A, Vergani A, Malosio I, Parma L, Fossati L, Ricci A, Bovo G, et al: Hepatic iron overload in patients with chronic viral hepatitis: role of HFE gene mutations. Hepatology 1998;28:1105–1109.
    External Resources
  6. Aoki CA, Rossaro L, Ramsamooj R, Brandhagen D, Burritt MF, Bowlus CL: Liver hepcidin mRNA correlates with iron stores, but not inflammation, in patients with chronic hepatitis C. J Clin Gastroenterol 2005;39:71–74.
    External Resources
  7. Nagashima M, Kudo M, Chung H, Ishikawa E, Hagiwara S, Nakatani T, Dote K: Regulatory failure of serum prohepcidin levels in patients with hepatitis C. Hepatol Res 2006;36:288–293.
    External Resources
  8. Farinati F, Cardin R, De Maria N, Della Libera G, Marafin C, Lecis E, Burra P, et al: Iron storage, lipid peroxidation and glutathione turnover in chronic anti-HCV positive hepatitis. J Hepatol 1995;22:449–456.
    External Resources
  9. Farinati F, Cardin R, de Maria N, Lecis PE, Della Libera G, Burra P, Marafin C, et al: Zinc, iron, and peroxidation in liver tissue. Cumulative effects of alcohol consumption and virus-mediated damage – a preliminary report. Biol Trace Elem Res 1995;47:193–199.
    External Resources
  10. Britton RS, Bacon BR: Role of free radicals in liver diseases and hepatic fibrosis. Hepatogastroenterology 1994;41:343–348.
    External Resources
  11. Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. The French METAVIR Cooperative Study Group. Hepatology 1994;20:15–20.
    External Resources
  12. Deugnier YM, Turlin B, Powell LW, Summers KM, Moirand R, Fletcher L, Loreal O, et al: Differentiation between heterozygotes and homozygotes in genetic hemochromatosis by means of a histological hepatic iron index: a study of 192 cases. Hepatology 1993;17:30–34.
    External Resources
  13. Alexander GJ, Brahm J, Fagan EA, Smith HM, Daniels HM, Eddleston AL, Williams R: Loss of HBsAg with interferon therapy in chronic hepatitis B virus infection. Lancet 1987;ii:66–69.
    External Resources
  14. Fujimori K, Mochida S, Matsui A, Ohno A, Fujiwara K: Possible mechanisms of elevation of serum transaminase levels during interferon-beta therapy in chronic hepatitis C patients. J Gastroenterol 2002;37:40–46.
    External Resources
  15. Yoshikawa M, Fukui H, Tsuji T: Immunological adverse effects of interferon treatment. Clin Immunother 1995;4:361–375.
  16. Camma C, Di Bona D, Schepis F, Heathcote EJ, Zeuzem S, Pockros PJ, Marcellin P, et al: Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: a meta-analysis of individual patient data. Hepatology 2004;39:333–342.
    External Resources
  17. Kageyama F, Kobayashi Y, Kawasaki T, Toyokuni S, Uchida K, Nakamura H: Successful interferon therapy reverses enhanced hepatic iron accumulation and lipid peroxidation in chronic hepatitis C. Am J Gastroenterol 2000;95:1041–1050.
    External Resources
  18. Mifuji R, Kobayashi Y, Ma N, Qiang QL, Urawa N, Horiike S, Iwasa M, et al: Role of transferrin receptor 2 in hepatic accumulation of iron in patients with chronic hepatitis C. J Gastroenterol Hepatol 2006;21:144–151.
    External Resources
  19. Levey JA, Barrand MA, Callingham BA, Hider RC: Characteristics of iron(III) uptake by isolated fragments of rat small intestine in the presence of the hydroxypyrones, maltol and ethyl maltol. Biochem Pharmacol 1988;37:2051–2057.
    External Resources
  20. Davis GL, Esteban-Mur R, Rustgi V, Hoefs J, Gordon SC, Trepo C, Shiffman ML, 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.
    External Resources
  21. Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G, Bain V, et al: Randomised trial of interferon α2b plus ribavirin for 48 weeks or for 24 weeks versus interferon α2b 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.
    External Resources
  22. McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, Goodman ZD, 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.
    External Resources
  23. Kubo S, Nishiguchi S, Hirohashi K, Tanaka H, Shuto T, Yamazaki O, Shiomi S, et al: Effects of long-term postoperative interferon-alpha therapy on intrahepatic recurrence after resection of hepatitis C virus-related hepatocellular carcinoma. A randomized, controlled trial. Ann Intern Med 2001;134:963–967.
    External Resources
  24. Kudo M, Sakaguchi Y, Chung H, Hatanaka K, Hagiwara S, Ishikawa E, Takahashi S, et al: Long-term interferon maintenance therapy improves survival in patients with HCV-related hepatocellular carcinoma after curative radiofrequency ablation. A matched case-control study. Oncology 2007;72:S132–S138.
    External Resources
  25. Sumida Y, Nakashima T, Yoh T, Nakajima Y, Ishikawa H, Mitsuyoshi H, Sakamoto Y, et al: Serum thioredoxin levels as an indicator of oxidative stress in patients with hepatitis C virus infection. J Hepatol 2000;33:616–622.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Treatment of Chronic Hepatitis C

Published online: June 10, 2008
Issue release date: June 2008

Number of Print Pages: 10
Number of Figures: 6
Number of Tables: 3

ISSN: 0300-5526 (Print)
eISSN: 1423-0100 (Online)

For additional information: https://www.karger.com/INT

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2008, Vol.51, Suppl. 1

June 2008

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