Journal of Hepatology
Volume 49, Issue 5 , Pages 702-710 , November 2008

Patients with chronic hepatitis C achieving a sustained virological response to peginterferon and ribavirin therapy recover from impaired hepcidin secretion

  • Naoki Fujita

      Affiliations

    • Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Science, Institute of Medical Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
    • Corresponding Author InformationCorresponding author. Tel.: +81 59 231 5017; fax: +81 59 231 5223.
    • ,
  • Ryosuke Sugimoto

      Affiliations

    • Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Science, Institute of Medical Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
    • ,
  • Satoshi Motonishi

      Affiliations

    • Division of Clinical Science, Medical Research Institute, Kanazawa Medical University, Kanzawa, Japan
    • School of Pharmacy, Aichi Gakuin University, Aichi, Japan
    • ,
  • Naohisa Tomosugi

      Affiliations

    • Division of Clinical Science, Medical Research Institute, Kanazawa Medical University, Kanzawa, Japan
    • ,
  • Hideaki Tanaka

      Affiliations

    • Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Science, Institute of Medical Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
    • ,
  • Masaki Takeo

      Affiliations

    • Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Science, Institute of Medical Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
    • ,
  • Motoh Iwasa

      Affiliations

    • Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Science, Institute of Medical Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
    • ,
  • Yoshinao Kobayashi

      Affiliations

    • Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Science, Institute of Medical Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
    • ,
  • Hisao Hayashi

      Affiliations

    • School of Pharmacy, Aichi Gakuin University, Aichi, Japan
    • ,
  • Masahiko Kaito

      Affiliations

    • Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Science, Institute of Medical Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
    • ,
  • Yoshiyuki Takei

      Affiliations

    • Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Science, Institute of Medical Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan

Received 12 January 2008 ,Revised 30 April 2008 ,Accepted 1 May 2008.

References 

  1. Poynard T, Yuen MF, Ratziu V, Lai CL. Viral hepatitis C. Lancet. 2003;362:2095–2100
  2. Di Bisceglie AM, Axiotis CA, Hoofnagle JH, Bacon BR. Measurements of iron status in patients with chronic hepatitis. Gastroenterology. 1992;102:2108–2113
  3. Hezode C, Cazeneuve C, Coue O, Roudot-Thoraval F, Lonjon I, Bastie A, et al. Liver iron accumulation in patients with chronic hepatitis C: prevalence and role of hemochromatosis gene mutations and relationship with hepatic histological lesion. J Hepatol. 1999;31:979–984
  4. Silvia TSS, Perez RM, Oliveira PV, Cantagalo MI, Dantas E, Sisti C, et al. Iron overload in patients with chronic hepatitis C virus infection: clinical and histological study. J Gastroentrol Hepatol. 2005;20:243–248
  5. Fujita N, Horiike S, Sugimoto R, Tanaka H, Iwasa M, Kobayashi Y, et al. Hepatic oxidative DNA damage correlates with iron overload in chronic hepatitis C patients. Free Radic Biol Med. 2007;42:353–362
  6. Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P, et al. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem. 2001;276:7811–7819
  7. Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem. 2001;276:7806–7810
  8. Ganz T. Hepcidin. a key regulator of iron metabolism and mediator of anemia of inflammation. Blood. 2003;102:783–788
  9. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, et al. Hepcidin regulates iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306:2090–2093
  10. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T. Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood. 2003;101:2461–2463
  11. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352:1011–1023
  12. Fujita N, Sugimoto R, Takeo M, Urawa N, Mifuji R, Tanaka H, et al. Hepcidin expression in the liver: relatively low level in patients with chronic hepatitis C. Mol Med. 2007;13:97–104
  13. Tomosugi N, Kawabata H, Wakatabe R, Higuchi M, Yamaya H, Umehara H, et al. Detection of serum hepcidin in renal failure and inflammation by using ProteinChip System. Blood. 2006;108:1381–1387
  14. Kemna E, Tjalsma H, Podust V, Swinkels D. Mass spectrometry-based hepcidin measurements in serum and urine: analytical aspects and clinical implications. Clin Chem. 2007;53:1–9
  15. Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology. 1994;19:1513–1520
  16. Deugnier YM, Loreal O, Turlin B, Guyader D, Jouanolle H, Moirand R, et al. Liver pathology in genetic hemochromatosis: a review of 135 homozygous cases and their bioclinical correlations. Gastroenterology. 1992;102:2050–2059
  17. Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, Devaux I, et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest. 2002;110:1037–1044
  18. Taes YE, Wuyts B, Boelaert JR, De Vriese AS, Delanghe JR. Prohepcidin accumulates in renal insufficiency. Clin Chem Lab Med. 2004;42:387–389
  19. Kulaksiz H, Gehrke SG, Janetzko A, Rost D, Bruckner T, Kallinowski B, et al. Prohepcidin: expression and cell specific localization in the liver and its regulation in hereditary haemochromatosis, chronic renal insufficiency, and renal anaemia. Gut. 2004;53:735–743
  20. Kemna E, Pickkers P, Nemeth E, van der Hoeven H, Swinkels D. Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. Blood. 2005;106:1864–1866
  21. Kearney SL, Nemeth E, Neufeld EJ, Thapa D, Ganz T, Weinstein DA, et al. Urinary hepcidin in congenital chronic anemias. Pediatr Blood Cancer. 2007;48:57–63
  22. Gehrke SG, Kulaksiz H, Herrmann T, Riedel HD, Bents K, Veltkamp C, et al. Expression of hepcidin in hereditary hemochromatosis: evidence for a regulation in response to the serum transferrin saturation and to non-transferrin-bound iron. Blood. 2003;102:371–376
  23. Chiou PP, Lin CM, Bols NC, Chen TT. Characterization of virus/double-stranded RNA-dependent induction of antimicrobial peptide hepcidin in trout macrophages. Dev Comp Immunol. 2007;31:1297–1309
  24. 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
  25. Lee P, Peng H, Gebart T, Wang L, Beutler E. Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc Natl Acad Sci USA. 2005;102:1906–1910
  26. Nishina S, Hino K, Korenaga M, Vecchi C, Pietrangelo A, Mizukami Y, et al. Hepatitis C virus-induced reactive oxygen species raise hepatic iron level in mice by reducing hepcidin transcription. Gastroenterology. 2008;134:226–238

☆ The authors declare that they do not have anything to disclose regarding funding from industries or conflict of interest with respect to this manuscript.

PII: S0168-8278(08)00358-9

doi: 10.1016/j.jhep.2008.05.014

Journal of Hepatology
Volume 49, Issue 5 , Pages 702-710 , November 2008

Article Tools

* Image Usage & Resolution