Elevated Levels of Serum Ferritin May be Related to Non-Alcoholic Steatohepatitis

Mohamed Abdel-Halem Helaly 1 * , El-Sayed Zaki Hatata 1, Ehab El-Sayed Abdel-Khalek 1, Ibrahim Ahmed Abdel Aal 2
More Detail
1 Mansoura University, Faculty of Medicine, Department of Internal Medicine, Egypt
2 Mansoura University, Faculty of Medicine, Department of Clinical Pathology, Egypt
* Corresponding Author
EUR J BASIC MED SCI, Volume 1, Issue 1, pp. 13-20. https://doi.org/10.21601/ejbms/9162
OPEN ACCESS
Download Full Text (PDF)

ABSTRACT

Non-alcoholic steatohepatitis can progress to cirrhosis and hepatocellular carcinoma. Our aim is to evaluate serum ferritin and iron levels in patients with non-alcoholic steatohepatitis (NASH). 53 patients with NASH (36 males and 17 females) were selected from the Specialized Medical Hospital, Mansoura, Egypt. This is in addition to 50 apparently healthy subjects (30 males and 20 females) of age and sex matched as a control group. We detected serum ferritin, iron, immune-reactive insulin (IRI) and the calculated homeostasis model for assessment of insulin resistance (HOMA-IR), in addition to markers of oxidative stress (MDA and thiol) and tumor necrosis factor alpha (TNF-α). Patients with NASH have higher levels of ferritin, iron, IRI, HOMA-IR, MDA, TNF- α (p= 0.001) and thiol (p= 0.01) than control subjects. Serum ferritin has a significant positive correlation with body mass index, ALT, AST, fasting plasma glucose (FPG), total cholesterol, LDL-cholesterol, triglyceride, IRI, HOMA-IR, MDA, thiol and TNF-α (p=0.001) in NASH patients. However, after adjustment for age, sex, BMI and HOMA-IR in cases of NASH, ferritin still has a significant positive correlation with ALT, FPG, total cholesterol, TNF-α, MDA (p=0.001) and thiol (p=0.003). Serum iron has no significant correlation with grade of NASH or fibrosis. Serum ferritin level is higher in patients with NASH more than control subjects. Moreover it has a significant positive correlation with oxidative stress even after adjustment for age, sex, BMI and HOMA-IR.
Keywords: ferritin, non-alcoholic, steatohepatitis

CITATION

Helaly MAH, Hatata ESZ, Abdel-Khalek EES, Abdel Aal IA. Elevated Levels of Serum Ferritin May be Related to Non-Alcoholic Steatohepatitis. Eur J Basic Med Sci. 2011;1(1):13-20. https://doi.org/10.21601/ejbms/9162

REFERENCES

  • Marchesini G, Bugianesi E, Forlani G, et al. Non-alcoholic fatty liver disease (NAFLD), steatohepatitis and the metabolic syndrome. Hepatology 2003;37:917-923.
  • Brunt E. Non-alcoholic fatty liver disease: definition, epidemiology, pathogenesis and management. Semin Liver Dis 2001;21:3-16.
  • Ludwig J, Viggiano TR, Mc Gill DB, et al. Non-alcoholic steatohepatitis. Mayo Clinic experiences with hitherto unnamed disease. Mayo Cli Proc 1980;53:434-438.
  • Reid AE: Non-alcoholic steatohepatitis. Gastroenterology 2001;121:710-723.
  • Sanyal JA, Campbell-Sargent C, Mirshahi F, et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001;120:1183-1192.
  • Nakashima T, Sumida Y, Furutani M, et al: Elevation of serum thioredoxin levels in patients with Non-alcoholic steatohepatitis. Hepatol Res 2005; 33:135-137.
  • Diehl AM, Li HZ, YangSQ. Cytokines and the pathogenesis of Non-alcoholic steatohepatitis. Gut 2005;54:303-306.
  • Kemal A, Ali R, Muhsin K. The importance of iron and copper accumulation in the pathogenesis of non-alcoholic steatohepatitis. Turk J Gastroent 2003;14 (4):228-233.
  • Shira Z, Dorit N, Zamir H, et al. NAFLD and hyperinsulinemia are major determinants of serum ferritin levels. J Hepatol 2007;46(4):700-707.
  • Sumid Y, Yoshikawa T and Okanoue T: Role of hepatic iron in non-alcoholic steatohepatitis. Hepatology Research 2008; 39(3): 213-222.
  • Brunt E, Janney C, Di Bisceglie A, et al. Non-alcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroent 1999;94:2467- 2474.
  • Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997;20:1183-1197.
  • Wahlefeld AW.Triglyceride: determination after enzymatic hydrolysis . In Method of Enzymatic Alysis 1974; (ed H.U.Bergmyer ) pp 1831-1835. Academic Press, New York, NY.
  • Allian CA, Poon LS, Chan CGS, et al. Enzymatic determination of total serum cholesterol. Clin Chemist 1974;20:470-475.
  • Bachrik PS and Alerbs JJ. Precipitation methods for quantification of lipoprotein. In Method in Enzymology. 1986; Vol. 129 (eds J.J.Albers & J.P.Segrest), PP 78-100. Academic Press, London.
  • Hu ML. Measurement of thiol groups and glutathione in plasma. Methods Enzymol 1998;233:380-385.
  • Drapper H, Hadley M. Assessment of MDA. Method. Enzymol 1990;186:421-431.
  • Mathews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta- cell function from fasting plasma glucose and insulin concentration in man. Diabetologia 1985;28:412-429.
  • Citturi S and Farrell GC. Ethiopathogenesis of non-alcoholic steatohepatitis. Semin Liver Dis 2001;21:27-41.
  • Mc Cullough AJ. Update on NAFLD. J Clin Gastroent 2002;34(3):255-262.
  • Day CP, James OEW. Steatohepatitis: a tale of two ‟hits”. Gasroent 1998;114: 842-45.
  • Angulo P. Medical Progress: Non-alcoholic fatty liver disease. N Eng J Med 2002;346(16):1221-1231.
  • Katsuki A, Sumida Y, Urakawa H, et al. Increased visceral fat & serum levels of triglyceride are associated with insulin resistance in Japanese metabolically obese, normal weight subjects with normal glucose tolerance. Diabetes Care 2003;26:2341- 2344.
  • Kelly DE, Mc Kolanis TM, Hegazi RA, et al. Fatty liver in type 2 diabetes mellitus: relation to regional adiposity, fatty acids and insulin resistance. Am J Physiol Endocrin Metab 2003;285:E 906-916.
  • Misra A, Garg A. Clinical features and metabolic derangements in acquired generalized lipodystrophy: case reports and review of the literature. Medicine 2003; 82:129-146.
  • Hirosumi J, Tuncman G, Chang L, et al.A central role for JNK in obesity and insulin resistance. Nature 2002;420:333-336.
  • Ruan H, Lodish HF. Insulin resistance in adipose tissue: direct and indirect effects of TNF- α. Cytokine Growth Factor Rev 2003;14:447-455.
  • Fernandez-Real JM, Lopez-Bermejo A, Casamitjana R, et al. Novel interactions of adiponectin with the endocrine system and inflammatory parameters. J Clin Endocrin Metab 2003;88:2714-2718.
  • Ouchi N, Kihara S, Arita Y, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NFKappa B signaling through a cAMP-dependent pathway. Circulation 2000;102:1296-1301.
  • Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelmonocytic progenitors and the functions of macrophages. Blood 2000;96:1723-1732.
  • Kern PA, Di Gregorio GB, Lu T, et al: Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance and TNF- α expression. Diabetes 2003; 52: 1779-1785.
  • Bruun JM, Lihn AS, Verdich C, et al. Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Endocrin Metab 2003;285:E 527-E 533.
  • Arner P. The adipocyte in insulin resistance: key molecules and the impact of the thiazolidinediones. Trends Endocrinol.Metab 2003;14:137-145.
  • Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fatty acid oxidation by activating AMP-activated protein kinase. Nat Med 2002;8:1288-1295.
  • Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003;423:762-769.
  • Stephan N and Stumvoll M. Adiponectin – its role in metabolism and beyond. Horm Metab Res2002;34:469-474.
  • Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001;7:941-946.
  • Lipschitz DA, Cook JD, Finch A. Clinical evaluation of serum ferritin as an index of iron stores. New Eng J Med 1974;290:1213-1216.
  • Prieto J, Barry M, Sherlock S. Serum ferritin in patients with iron overload and with acute and chronic liver diseases. Gastroent 1975;68:525-533.
  • Nielsen P, Gunther U, Durken M, et al. Serum ferritin, iron overload and liver damage: Correlation to body iron stores and diagnostic relevance. J Lab Clin Med 2000;135:413-418.
  • Mehmet K, Seyithan T, Cemil M, et al. Serum levels of acute phase proteins in patients with Non-alcoholic steatohepatitis. Turk J Gastroent 2003;14(1):112- 120.
  • Dandona P, Hussain MAM, Varghese Z, et al. Insulin resistance and iron overload. Ann Clin Biochem 1983;20:77-79.
  • Hsiao TJ, Chen JC, Wang JD. Insulin resistance and ferritin as major determinants of NAFLD in apparently healthy obese patients. Int J Obesity Relat Metab Disord 2004;28:167-172.
  • Iwasaki T, Nakajima A, Yoneda M, et al. Serum ferritin is associated with visceral fat area and subcutaneous fat area. Diabetes Care 2005;28:2486-2491.
  • Sumida Y, Nakashima T, Yoh T, et al. Serum thioredoxin levels as a predictor steatohepatitis in patients with NAFLD. J Hepatol 2003;38: 32-38.
  • Yamamto M, Iwasa M, Iwata K, et al. Restriction of dietary calories, fat and iron improves NAFLD. J Gastroent Hepatol 2007;22(4):498- 503.
  • Bahcecioglu IH, Yalniz M, Iihan N, et al. Levels of serum vitamin A, alpha-tocopherpl and malondialdehyde in patients with Non-alcoholic steatohepatitis: relationship with histopathologic severity. Internat J Clin Practice 2004;59(3):318-323.
  • Bertelsen M, Nggard EE, Carrier MJ. Oxidative stress impairs insulin internalization in endothelial cells in vitro. Diabetologia 2001;44:605-613.
  • Fargion S, Mattioli M, Fracanzani AL, et al. Hyperferritinemia, iron overload and multiple metabolic alterations identify patients at risk for Non-alcoholic steatohepatitis. Am J Gastroent 200;96: 2448-2454.
  • Sumida Y, Kanemasa K, Fukumoto K, et al. Effect of iron reduction by phlebotomy in Japanese patients with Non-alcoholic steatohepatitis: A pilot study. Hepatol Res 2006;36:315-21.