| Peer-Reviewed

Serum and Ascitic Fluid Hepcidin in HCV Positive Liver Cirrhosis with and without HCC

Received: 11 December 2013    Accepted:     Published: 10 January 2014
Views:       Downloads:
Abstract

Background & Aim: Chronic HCV infection suppresses hepatic hepcidin expression which may enhance iron toxicity and lead to disease progression and HCC development. The aim of the study is to investigate the role of hepcidin in HCV+ve liver cirrhosis patients in relation to disease progression and HCC development. Patients and methods: The study population consists of: 20 HCV+ve patients without HCC (HCV patients), 20 HCV+ve patients with HCC (HCV-HCC patients) and 10 controls. In addition to comprehensive clinical examination, they were subjected to laboratory check-up for albumin, bilirubin, PT %, ferritin, AFP and hepcidin. Ascitic fluid hepcidin was done for all patients. Results: There was a significant difference among HCV and HCV-HCC patients and controls with regard serum ferritin and hepcidin (P = 0.001 & 0.0001 respectively). Serum hepcidin of HCV and HCV-HCC patients were significantly lower than controls (P = 0.0001). Serum and ascitic fluid hepcidin of HCV-HCC patients was significantly lower than HCV patients (P = 0.01 & 0.02 respectively). Serum ferritin was significantly higher in HCV and HCV-HCC patients than controls (P = 0.001). Serum ferritin of HCV-HCC patients was significantly higher than HCV patients (P = 0.02). Ascitic fluid hepcidin was negatively correlated with Child-Pugh score in HCV (r=-0.55 & P=0.01) and HCV-HCC patients (r = -0.53 & P = 0.02). Ascitic fluid hepcidin was negatively correlated with bilirubin in HCV (r = -0.43 & P=0.04) and HCV-HCC patients (r = -0.47 & P=0.04). Ascitic fluid hepcidin was positively correlated with serum albumin in HCV (r = +0.44 & P=0.04) but there was no correlation in HCV-HCC patients (r =-0.1 & P=0.7). Conclusion: Low levels of hepcidin may be involved in the pathophysiologic mechanism of iron overload in patients with chronic HCV with and without HCC. Moreover, there is a positive relationship between hepcidin levels and synthetic liver function suggesting that uniform suppression of hepcidin may be linked to disease progression and HCC development. Further analysis is still required to evaluate its usefulness as a marker for early detection of HCC by serial measurement of hepcidin in blood and ascitic fluid.

Published in European Journal of Preventive Medicine (Volume 1, Issue 3)
DOI 10.11648/j.ejpm.20130103.13
Page(s) 63-69
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Hepcidin, HCC, HCV, Ferritin

References
[1] Lavanchy D. The global burden of hepatitis C. Liver Int 2009; 29: 74-81.
[2] Gomaa A I, Khan S A, Toledano M B, Taylor-Robinson S D. Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis. World J Gastroenterol 2008; 14(27): 4300-8.
[3] Ismail AM, Ziada HN, Sheashaa HA, Shehab El-Din AB. Decline of viral hepatitis prevalence among asymptomatic Egyptian blood donors: a glimmer of hope. Eur J Intern Med 2009;20(5):490-3.
[4] Lehman EM, Wilson ML. Epidemiology of hepatitis viruses among hepatocellular carcinoma cases and healthy people in Egypt: a systematic review and meta-analysis. Int J Cancer 2009;124(3):690-7.
[5] Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 2001; 276: 7806-10.
[6] Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004; 306: 2090-3.
[7] Ganz T, Nemeth E. Iron Imports IV: Hepcidin and regulation of body iron metabolism. Am J Physiol Gastrointestinal Liver Physiol 2006; 290 (2): G199-G203.
[8] Kuston MD, Oukka M, Koss LM, Aydemir F, Wessling-Resnick M. Iron release from macrophages after erythrophagocytosis is up-regulated by ferroportin 1 over expression and down-regulated by hepcidin. Proc Natl Acad Sci USA 2005; 102: 1324-8.
[9] Pietrangelo A, Trautwein C. Mechanism of disease: The role of hepcidin in iron homeostasis-implications for hemochromatosis and other disorders. Nat Clin Prac Gastroenterol Hepatol 2004; 1: 39-45.
[10] Kemna EH, Tjalsma H, Willems HL, Swinkels DW. Hepcidin: from discovery to differential diagnosis. Haematologica 2008; 93: 90-7.
[11] Arnold J, Sangwaiya A, Bhatkal B, Geoghegan F, Busbridge M. Hepcidin and inflammatory bowel disease: dual role in host defence and iron homoeostasis. Eur J Gastroenterol Hepatol 2009; 21: 425-9.
[12] Arnold J, Sangwaiya A, Manglam V, Geoghegan F, Thursz M, Busbridge M. Presence of hepcidin-25 in biological fluids: Bile, ascitic and pleural fluids. World J Gastroenterol 2010; 16(17): 2129-33.
[13] Shike H, Lauth X, Westerman ME, Ostland VE, Carlberg JM, Van Olst JC, Shimizu C, Bulet P, Burns JC. Bass hepcidin is a novel antimicrobial peptide induced by bacterial challenge. Eur J Biochem 2002; 269: 2232-7.
[14] Nemeth E, Ganz T. Regulation of iron metabolism by hepcidin. Annu Rev Nutr 2006; 26: 323-42.
[15] Vyoral D, Petrák J. Hepcidin: a direct link between iron metabolism and immunity. Int J Biochem Cell Biol 2005;37(9):1768-73.
[16] Gattoni A, Parlato A, Vangieri B, Bresciani M, Derna R, Baldassarre R. Role of hemochromatosis genes in chronic hepatitis C. Clin Ther 2006;157:61-8.
[17] Nagashima M, Kudo M, Chung H, Ishikawa E, Hagiwara S, Nakatani T, et al. Regulatory failure of serum prohepcidin levels in patients with hepatitis C. Hepatol Res 2006;36:288-93.
[18] Ward DG, Roberts K, Brookes MJ, Joy H, Martin A, Ismail T, Spychal R, Iqbal T, Tselepis C. Increased hepcidin expression in colorectal carcinogenesis. World J Gastroenterol 2008; 14: 1339-45.
[19] Kamai T, Tomosugi N, Abe H, Arai K, Yoshida1 KI. Increased serum hepcidin-25 level and increased tumor expression of hepcidin mRNA are associated with metastasis of renal cell carcinoma. BMC Cancer 2009; 9: 270.
[20] Corengia C, Galimberti S, Bovo G, Vergani A, Arosio C, Mariani R, et al. Iron accumulation in chronic hepatitis C: relation of hepatic iron distribution, HFE genotype, and disease course. Am J Clin Pathol 2005; 124:846- 53.
[21] Krause A, Neitz S, Mägert HJ, Schulz A, Forssmann WG, Schulz-Knappe P, Adermann K. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett 2000; 480: 147-50.
[22] Ganz T. Hepcidin: a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 2003; 102: 783-8.
[23] Di Bisceglie AM, Axiotis CA, Hoofnagle JH, Bacon BR. Measurements of iron status in patients with chronic hepatitis. Gastroenterology 1992; 102:2108-13.
[24] 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; 99:286-91.
[25] Souza RM, Freitas LAR, Lyra AC, Moraes CF, Braga EL, Lyra LGC. Effect of iron overload on the severity of liver histologic alterations and on the response to interferon and ribavirin therapy of patients with hepatitis C infection. Braz J Med Biol Res 2006; 39:79-83.
[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;134:226–38.
[27] Fujita N, Sugimoto R, Takeob M, Urawa N, Mifuji R, Tanaka H, Kobayashi Y, Iwasa M, Watanabe S, Adachi Y, KaitoM. Hepcidin Expression in the Liver: Relatively Low Level in Patients with Chronic Hepatitis C. Mol Med 2007; 13(1-2):97-104.
[28] Girelli D, Pasino M, Goodnough JB, Nemeth E, Guido M, Castagna A, Busti F, Campostrini N, Martinelli N, Vantini I, Corrocher R, Tomas Ganz T, and Fattovich G. Reduced serum hepcidin levels in patients with chronic hepatitis C. J Hepatol 2009; 51(5): 845–52.
[29] 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): e46631.
[30] 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;39:71-4.
[31] 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: 1037-44.
[32] Napoli J, Bishop GA, McGuinness PH, et al. Progressive liver injury in chronic hepatitis C infection correlates with increased intrahepatic expression of Th1- associated cytokines. Hepatology 1996; 24: 759-65.
[33] Tung BY, Emond MJ, Bromer MP, Raaka SD, Cotler SJ, Kowdley KV. Hepatitis C, iron status, and disease severity: relationship with HFE mutations. Gastroenterology 2003; 124:318-26.
[34] Kijima H, Sawada T, Tomosugi N and Kubota K. Expression of hepcidin mRNA is uniformly suppressed in hepatocellular carcinoma. BMC Cancer 2008; 8:167.
[35] Fargion S, Mandelli C, Piperno A, Cecana B, Conte D, et al. Survival and prognostic factors in 212 Italian patients with genetic hemochromatosis. Hepatology 1992; 15: 655-9.
[36] Deugnier Y, Turlin B, Loréal O. Iron and neoplasia. J Hepatol 1998;28:21-5.
[37] Hentze MW, Muckenthaler MU, Andrews NC: Balancing acts: molecular control of mammalian iron metabolism. Cell 2004; 117:285-97.
[38] Furutani T, Hino K, Okuda M, Gondo T, Nishina S, Kitase A, et al. Hepatic iron overload induces hepatocellular carcinoma in transgenic mice expressing the hepatitis C virus polyprotein. Gastroenterology 2006;130:2087-98.
[39] Valenti L, Pulixi EA, Arosio P, Cremonesi L, Biasiotto G, Dongiovanni P, Maggioni M, Fargion S, Fracanzani AL. Relative contribution of iron genes, dysmetabolism and hepatitis C virus (HCV) in the pathogenesis of altered iron regulation in HCV chronic hepatitis. Haematologica 2007; 92:1037-42.
[40] 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;48:1420–9.
[41] Abd Elmonem E, Tharwa E, Farag M A, Fawzy A, El Shinnawy S F, Suliman S. Hepcidin mRNA Level as A Parameter of Disease Progression in Chronic Hepatitis C and Hepatocellular Carcinoma. Journal of the Egyptian Nat. Cancer Inst 2009; 21(4): 333-42.
[42] Le NT, Richardson DR. The role of iron in cell cycle progression and the proliferation of neoplastic cells. Biochim Biophys Acta 2002; 1603: 31–46.
[43] Weizer-Stern O, Adamsky K, Margalit O, Rechavi G, et al. Hepcidin, a key regulator of iron metabolism, is transcriptionally activated by p53. Br J Haematol 2007; 138: 253-62.
[44] Levine AJ, Momand J, Finlay CA. The p53 tumour suppressor gene. Nature 1991; 351: 453-6.
[45] Laurent-Puig P, Zuckman-Rossi J. Genetics of Hepatocellular tumors. Oncogene 2006; 25: 3778-86.
Cite This Article
  • APA Style

    Ehab Abd El Atti, Alaa Dawood, Abdallah Said Essa, Bassam Mohamed Masoud, Enas Said Essa, et al. (2014). Serum and Ascitic Fluid Hepcidin in HCV Positive Liver Cirrhosis with and without HCC. European Journal of Preventive Medicine, 1(3), 63-69. https://doi.org/10.11648/j.ejpm.20130103.13

    Copy | Download

    ACS Style

    Ehab Abd El Atti; Alaa Dawood; Abdallah Said Essa; Bassam Mohamed Masoud; Enas Said Essa, et al. Serum and Ascitic Fluid Hepcidin in HCV Positive Liver Cirrhosis with and without HCC. Eur. J. Prev. Med. 2014, 1(3), 63-69. doi: 10.11648/j.ejpm.20130103.13

    Copy | Download

    AMA Style

    Ehab Abd El Atti, Alaa Dawood, Abdallah Said Essa, Bassam Mohamed Masoud, Enas Said Essa, et al. Serum and Ascitic Fluid Hepcidin in HCV Positive Liver Cirrhosis with and without HCC. Eur J Prev Med. 2014;1(3):63-69. doi: 10.11648/j.ejpm.20130103.13

    Copy | Download

  • @article{10.11648/j.ejpm.20130103.13,
      author = {Ehab Abd El Atti and Alaa Dawood and Abdallah Said Essa and Bassam Mohamed Masoud and Enas Said Essa and Yasser El-Ghobashy and Ashraf Anas Zytoon},
      title = {Serum and Ascitic Fluid Hepcidin in HCV Positive Liver Cirrhosis with and without HCC},
      journal = {European Journal of Preventive Medicine},
      volume = {1},
      number = {3},
      pages = {63-69},
      doi = {10.11648/j.ejpm.20130103.13},
      url = {https://doi.org/10.11648/j.ejpm.20130103.13},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ejpm.20130103.13},
      abstract = {Background & Aim: Chronic HCV infection suppresses hepatic hepcidin expression which may enhance iron toxicity and lead to disease progression and HCC development. The aim of the study is to investigate the role of hepcidin in HCV+ve liver cirrhosis patients in relation to disease progression and HCC development. Patients and methods: The study population consists of: 20 HCV+ve patients without HCC (HCV patients), 20 HCV+ve patients with HCC (HCV-HCC patients) and 10 controls. In addition to comprehensive clinical examination, they were subjected to laboratory check-up for albumin, bilirubin, PT %, ferritin, AFP and hepcidin. Ascitic fluid hepcidin was done for all patients. Results: There was a significant difference among HCV and HCV-HCC patients and controls with regard serum ferritin and hepcidin (P = 0.001 & 0.0001 respectively). Serum hepcidin of HCV and HCV-HCC patients were significantly lower than controls (P = 0.0001). Serum and ascitic fluid hepcidin of HCV-HCC patients was significantly lower than HCV patients (P = 0.01 & 0.02 respectively). Serum ferritin was significantly higher in HCV and HCV-HCC patients than controls (P = 0.001). Serum ferritin of HCV-HCC patients was significantly higher than HCV patients (P = 0.02). Ascitic fluid hepcidin was negatively correlated with Child-Pugh score in HCV (r=-0.55 & P=0.01) and HCV-HCC patients (r = -0.53 & P = 0.02). Ascitic fluid hepcidin was negatively correlated with bilirubin in HCV (r = -0.43 & P=0.04) and HCV-HCC patients (r = -0.47 & P=0.04). Ascitic fluid hepcidin was positively correlated with serum albumin in HCV (r = +0.44 & P=0.04) but there was no correlation in HCV-HCC patients (r =-0.1 & P=0.7). Conclusion: Low levels of hepcidin may be involved in the pathophysiologic mechanism of iron overload in patients with chronic HCV with and without HCC. Moreover, there is a positive relationship between hepcidin levels and synthetic liver function suggesting that uniform suppression of hepcidin may be linked to disease progression and HCC development. Further analysis is still required to evaluate its usefulness as a marker for early detection of HCC by serial measurement of hepcidin in blood and ascitic fluid.},
     year = {2014}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Serum and Ascitic Fluid Hepcidin in HCV Positive Liver Cirrhosis with and without HCC
    AU  - Ehab Abd El Atti
    AU  - Alaa Dawood
    AU  - Abdallah Said Essa
    AU  - Bassam Mohamed Masoud
    AU  - Enas Said Essa
    AU  - Yasser El-Ghobashy
    AU  - Ashraf Anas Zytoon
    Y1  - 2014/01/10
    PY  - 2014
    N1  - https://doi.org/10.11648/j.ejpm.20130103.13
    DO  - 10.11648/j.ejpm.20130103.13
    T2  - European Journal of Preventive Medicine
    JF  - European Journal of Preventive Medicine
    JO  - European Journal of Preventive Medicine
    SP  - 63
    EP  - 69
    PB  - Science Publishing Group
    SN  - 2330-8230
    UR  - https://doi.org/10.11648/j.ejpm.20130103.13
    AB  - Background & Aim: Chronic HCV infection suppresses hepatic hepcidin expression which may enhance iron toxicity and lead to disease progression and HCC development. The aim of the study is to investigate the role of hepcidin in HCV+ve liver cirrhosis patients in relation to disease progression and HCC development. Patients and methods: The study population consists of: 20 HCV+ve patients without HCC (HCV patients), 20 HCV+ve patients with HCC (HCV-HCC patients) and 10 controls. In addition to comprehensive clinical examination, they were subjected to laboratory check-up for albumin, bilirubin, PT %, ferritin, AFP and hepcidin. Ascitic fluid hepcidin was done for all patients. Results: There was a significant difference among HCV and HCV-HCC patients and controls with regard serum ferritin and hepcidin (P = 0.001 & 0.0001 respectively). Serum hepcidin of HCV and HCV-HCC patients were significantly lower than controls (P = 0.0001). Serum and ascitic fluid hepcidin of HCV-HCC patients was significantly lower than HCV patients (P = 0.01 & 0.02 respectively). Serum ferritin was significantly higher in HCV and HCV-HCC patients than controls (P = 0.001). Serum ferritin of HCV-HCC patients was significantly higher than HCV patients (P = 0.02). Ascitic fluid hepcidin was negatively correlated with Child-Pugh score in HCV (r=-0.55 & P=0.01) and HCV-HCC patients (r = -0.53 & P = 0.02). Ascitic fluid hepcidin was negatively correlated with bilirubin in HCV (r = -0.43 & P=0.04) and HCV-HCC patients (r = -0.47 & P=0.04). Ascitic fluid hepcidin was positively correlated with serum albumin in HCV (r = +0.44 & P=0.04) but there was no correlation in HCV-HCC patients (r =-0.1 & P=0.7). Conclusion: Low levels of hepcidin may be involved in the pathophysiologic mechanism of iron overload in patients with chronic HCV with and without HCC. Moreover, there is a positive relationship between hepcidin levels and synthetic liver function suggesting that uniform suppression of hepcidin may be linked to disease progression and HCC development. Further analysis is still required to evaluate its usefulness as a marker for early detection of HCC by serial measurement of hepcidin in blood and ascitic fluid.
    VL  - 1
    IS  - 3
    ER  - 

    Copy | Download

Author Information
  • Internal Medicine Department, Faculty of Medicine, Menoufiya University, Egypt

  • Internal Medicine Department, Faculty of Medicine, Menoufiya University, Egypt

  • Tropical Medicine Department, Faculty of Medicine, Menoufiya University, Egypt

  • Tropical Medicine Department, Faculty of Medicine, Menoufiya University, Egypt

  • Clinical Pathology Department, Faculty of Medicine, Menoufiya University, Egypt

  • Biochemistry Department, Faculty of Medicine, Menoufiya University, Egypt

  • Radiology Department, Faculty of Medicine, Menoufiya University, Egypt

  • Sections