Hepatitis Monthly

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Association of Hepcidin mRNA Expression With Hepatocyte Iron Accumulation and Effects of Antiviral Therapy in Chronic Hepatitis C Infection

Katarzyna Sikorska 1 , * , Tomasz Romanowski 2 , Piotr Stalke 1 , Ewa Izycka Swieszewska 3 and Krzysztof Piotr Bielawski 2
Authors Information
1 Department of Infectious Diseases, Medical University of Gdansk, Gdansk, Poland
2 Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Gdansk, Poland
3 Department of Pathology and Neuropathology, Medical University of Gdansk, Gdansk, Poland
Article information
  • Hepatitis Monthly: November 30, 2014, 14 (11); e21184
  • Published Online: October 25, 2014
  • Article Type: Research Article
  • Received: June 16, 2014
  • Revised: August 18, 2014
  • Accepted: September 13, 2014
  • DOI: 10.5812/hepatmon.21184

To Cite: Sikorska K, Romanowski T, Stalke P, Izycka Swieszewska E, Piotr Bielawski K. Association of Hepcidin mRNA Expression With Hepatocyte Iron Accumulation and Effects of Antiviral Therapy in Chronic Hepatitis C Infection, Hepat Mon. 2014 ; 14(11):e21184. doi: 10.5812/hepatmon.21184.

Copyright © 2014, Kowsar Corp. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Background
2. Objectives
3. Patients and Methods
4. Results
5. Discussion
  • 1. Lavanchy D. The global burden of hepatitis C. Liver Int. 2009;29 Suppl 1:74-81. doi: 10.1111/j.1478-3231.2008.01934.x. [PubMed: 19207969].
  • 2. Bonkovsky HL. Iron as a comorbid factor in chronic viral hepatitis. Am J Gastroenterol. 2002;97(1):1-4. doi: 10.1111/j.1572-0241.2002.05390.x. [PubMed: 11808931].
  • 3. Fujita N, Sugimoto R, Urawa N, Araki J, Mifuji R, Yamamoto M, et al. Hepatic iron accumulation is associated with disease progression and resistance to interferon/ribavirin combination therapy in chronic hepatitis C. J Gastroenterol Hepatol. 2007;22(11):1886-93. doi: 10.1111/j.1440-1746.2006.04759.x. [PubMed: 17914965].
  • 4. Metwally MA, Zein CO, Zein NN. Clinical significance of hepatic iron deposition and serum iron values in patients with chronic hepatitis C infection. Am J Gastroenterol. 2004;99(2):286-91. [PubMed: 15046219].
  • 5. Sikorska K, Stalke P, Izycka-Swieszewska E, Romanowski T, Bielawski KP. The role of iron overload and HFE gene mutations in the era of pegylated interferon and ribavirin treatment of chronic hepatitis C. Med Sci Monit. 2010;16(3):CR137-43. [PubMed: 20190684].
  • 6. Asare GA, Mossanda KS, Kew MC, Paterson AC, Kahler-Venter CP, Siziba K. Hepatocellular carcinoma caused by iron overload: a possible mechanism of direct hepatocarcinogenicity. Toxicology. 2006;219(1-3):41-52. doi: 10.1016/j.tox.2005.11.006. [PubMed: 16337327].
  • 7. Kew MC. Hepatic iron overload and hepatocellular carcinoma. Cancer Lett. 2009;286(1):38-43. doi: 10.1016/j.canlet.2008.11.001. [PubMed: 19081672].
  • 8. Fargion S, Valenti L, Fracanzani AL. Beyond hereditary hemochromatosis: new insights into the relationship between iron overload and chronic liver diseases. Dig Liver Dis. 2011;43(2):89-95. doi: 10.1016/j.dld.2010.07.006. [PubMed: 20739232].
  • 9. Miura K, Taura K, Kodama Y, Schnabl B, Brenner DA. Hepatitis C virus-induced oxidative stress suppresses hepcidin expression through increased histone deacetylase activity. Hepatology. 2008;48(5):1420-9. doi: 10.1002/hep.22486. [PubMed: 18671304].
  • 10. 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(1):226-38. doi: 10.1053/j.gastro.2007.10.011. [PubMed: 18166355].
  • 11. Nicolas G, Bennoun M, Devaux I, Beaumont C, Grandchamp B, Kahn A, et al. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci U S A. 2001;98(15):8780-5. doi: 10.1073/pnas.151179498. [PubMed: 11447267].
  • 12. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306(5704):2090-3. doi: 10.1126/science.1104742. [PubMed: 15514116].
  • 13. Ganz T. Systemic iron homeostasis. Physiol Rev. 2013;93(4):1721-41. doi: 10.1152/physrev.00008.2013. [PubMed: 24137020].
  • 14. Pietrangelo A, Dierssen U, Valli L, Garuti C, Rump A, Corradini E, et al. STAT3 is required for IL-6-gp130-dependent activation of hepcidin in vivo. Gastroenterology. 2007;132(1):294-300. doi: 10.1053/j.gastro.2006.10.018. [PubMed: 17241879].
  • 15. Andriopoulos B, Jr, Corradini E, Xia Y, Faasse SA, Chen S, Grgurevic L, et al. BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat Genet. 2009;41(4):482-7. doi: 10.1038/ng.335. [PubMed: 19252486].
  • 16. Pietrangelo A. Hepcidin in human iron disorders: therapeutic implications. J Hepatol. 2011;54(1):173-81. doi: 10.1016/j.jhep.2010.08.004. [PubMed: 20932599].
  • 17. Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem. 2001;276(11):7806-10. doi: 10.1074/jbc.M008922200. [PubMed: 11113131].
  • 18. Fillebeen C, Rivas-Estilla AM, Bisaillon M, Ponka P, Muckenthaler M, Hentze MW, et al. Iron inactivates the RNA polymerase NS5B and suppresses subgenomic replication of hepatitis C Virus. J Biol Chem. 2005;280(10):9049-57. doi: 10.1074/jbc.M412687200. [PubMed: 15637067].
  • 19. Fillebeen C, Pantopoulos K. Iron inhibits replication of infectious hepatitis C virus in permissive Huh7.5.1 cells. J Hepatol. 2010;53(6):995-9. doi: 10.1016/j.jhep.2010.04.044. [PubMed: 20813419].
  • 20. Theurl I, Zoller H, Obrist P, Datz C, Bachmann F, Elliott RM, et al. Iron regulates hepatitis C virus translation via stimulation of expression of translation initiation factor 3. J Infect Dis. 2004;190(4):819-25. doi: 10.1086/422261. [PubMed: 15272411].
  • 21. Cho H, Lee HC, Jang SK, Kim YK. Iron increases translation initiation directed by internal ribosome entry site of hepatitis C virus. Virus Genes. 2008;37(2):154-60. doi: 10.1007/s11262-008-0250-0. [PubMed: 18566883].
  • 22. Bartolomei G, Cevik RE, Marcello A. Modulation of hepatitis C virus replication by iron and hepcidin in Huh7 hepatocytes. J Gen Virol. 2011;92(Pt 9):2072-81. doi: 10.1099/vir.0.032706-0. [PubMed: 21593278].
  • 23. Liu H, Trinh TL, Dong H, Keith R, Nelson D, Liu C. Iron regulator hepcidin exhibits antiviral activity against hepatitis C virus. PLoS One. 2012;7(10). eee46631. doi: 10.1371/journal.pone.0046631. [PubMed: 23110054].
  • 24. European Association for the Study of the L. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol. 2011;55(2):245-64. doi: 10.1016/j.jhep.2011.02.023. [PubMed: 21371579].
  • 25. Romanowski T, Sikorska K, Bielawski KP. GUS and PMM1 as suitable reference genes for gene expression analysis in the liver tissue of patients with chronic hepatitis. Med Sci Monit. 2008;14(7):BR147-52. [PubMed: 18591914].
  • 26. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002;3(7):RESEARCH0034. [PubMed: 12184808].
  • 27. Guyader D, Thirouard AS, Erdtmann L, Rakba N, Jacquelinet S, Danielou H, et al. Liver iron is a surrogate marker of severe fibrosis in chronic hepatitis C. J Hepatol. 2007;46(4):587-95. doi: 10.1016/j.jhep.2006.09.021. [PubMed: 17156889].
  • 28. Fujita N, Sugimoto R, Motonishi S, Tomosugi N, Tanaka H, Takeo M, et al. Patients with chronic hepatitis C achieving a sustained virological response to peginterferon and ribavirin therapy recover from impaired hepcidin secretion. J Hepatol. 2008;49(5):702-10. doi: 10.1016/j.jhep.2008.05.014. [PubMed: 18620776].
  • 29. 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(1):71-4. [PubMed: 15599216].
  • 30. Abd Elmonem E, Tharwa el S, Farag MA, Fawzy A, El Shinnawy SF, Suliman S. Hepcidin mRNA level as a parameter of disease progression in chronic hepatitis C and hepatocellular carcinoma. J Egypt Natl Canc Inst. 2009;21(4):333-42. [PubMed: 21415870].
  • 31. Girelli D, Pasino M, Goodnough JB, Nemeth E, Guido M, Castagna A, et al. Reduced serum hepcidin levels in patients with chronic hepatitis C. J Hepatol. 2009;51(5):845-52. doi: 10.1016/j.jhep.2009.06.027. [PubMed: 19729219].
  • 32. Bergmann OM, Mathahs MM, Broadhurst KA, Weydert JA, Wilkinson N, Howe JR, et al. Altered expression of iron regulatory genes in cirrhotic human livers: clues to the cause of hemosiderosis? Lab Invest. 2008;88(12):1349-57. doi: 10.1038/labinvest.2008.95. [PubMed: 18838961].
  • 33. Corradini E, Meynard D, Wu Q, Chen S, Ventura P, Pietrangelo A, et al. Serum and liver iron differently regulate the bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway in mice. Hepatology. 2011;54(1):273-84. doi: 10.1002/hep.24359. [PubMed: 21488083].
  • 34. Eddowes LA, Ramamurthy N, Ryan J, Boninsegna S, Armitage A, Fabris P, editors. Hepatitis C virus disrupts BMP/SMAD signaling suppressing hepcidin. Fourth Congress of the International BioIron Society (IBIS), Biennal World Meeting (BioIron 2013). Vancouver, Canada. 2012. 68 p.
  • 35. Panasiuk A, Flisiak R, Mozer-Lisewska I, Adamek A, Tyczyno M, Halota W, et al. Distribution of HCV genotypes in Poland. Przegl Epidemiol. 2013;67(1). 99-103. [PubMed: 23745369].
  • 36. Tai AW, Benita Y, Peng LF, Kim SS, Sakamoto N, Xavier RJ, et al. A functional genomic screen identifies cellular cofactors of hepatitis C virus replication. Cell Host Microbe. 2009;5(3):298-307. doi: 10.1016/j.chom.2009.02.001. [PubMed: 19286138].
  • 37. Ryan JD, Altamura S, Devitt E, Mullins S, Lawless MW, Muckenthaler MU, et al. Pegylated interferon-alpha induced hypoferremia is associated with the immediate response to treatment in hepatitis C. Hepatology. 2012;56(2):492-500. doi: 10.1002/hep.25666. [PubMed: 22334511].
  • 38. Strnad P, Nuraldeen R, Fischer J, Berg T, Trautwein C. Hepcidin as a predictor of treatment response in chronic hepatitis C infection. Hepatology. 2014;59(4):1648. doi: 10.1002/hep.26656. [PubMed: 23907834].
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