Abstract
Hepatitis C virus (HCV) infection is a significant global health problem. Elevated hepatic iron concentration has often been found in patients with chronic hepatitis C, and this excess iron increases oxidative stress, which can accelerate the progression of fibrosis and may promote hepatic carcinogenesis. The current study aimed to determine the prevalence of C282Y (exchange of cysteine to tyrosine at amino acid 282) and H63D (exchange of histidine to aspartic acid at amino acid 63) in hereditary hemochromatosis gene (HFE) mutations among chronic HCV patients and to find whether elevation of serum iron indices is related to HFE gene mutations in patients with chronic hepatitis C. The study population was 80 chronic HCV patients divided into two groups: group I included 40 patients with serum iron overload, and group II included 40 patients without iron overload. HFE gene mutation was studied by PCR-restriction fragment length polymorphism (RFLP). The C282Y mutation was not found in any of the 80 patients, while the H63D mutation was present in 18.7 % of the entire study sample. Comparing the two studied groups, H63D mutation was found in 20 % of the iron overload group and 17.5 % of the non-iron overload group. Statistically, there was no significant difference between the two study groups. Regarding iron studies, results of the current study revealed no significant difference between chronic HCV patients with iron overload and those with normal iron profile regarding any of the HFE mutations. In conclusion, the current work emphasizes that the C282Y mutation is absent in our community, while H63D mutation presence does not differ greatly from other Caucasian races especially in Europe. The current study did not detect any effect of HFE mutation on increasing serum iron overload.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Acton RT, Barton JC, Snively BM, McLaren CE, Adams PC, Harris EL, Speechley MR, McLaren GD, Dawkins FW, Leiendecker-Foster C, Holup JL, Balasubramanyam A (2006) Hemochromatosis and iron overload screening study research investigators. Ethn Dis 16(4):815–821
Bassett ML (2007) Iron and hepatitis C: beginning to make sense. J Gastroenterol Hepatol 22(11):1703–1704
Bomfim EA, de Oliveira AC P, Paraná R, Schinoni MI (2013) A study on hepatic iron overload in chronic hepatitis C patients. Acta Gastroenterol Latinoam 43(3):212–217
Bougle D, Brouard J (2013) Iron in child obesity. Relationships with inflammation and metabolic risk factors. Nutrients 5(6):2222–2230
Calado RT, Franco RF, Pazin-Filho A (2000) HFE gene mutations in coronary atherothrombotic disease. Braz J Med Biol Res 33(3):301–306
Chapoutot C, Esslimani M, Joomaye Z (2000) Liver iron excess in patients with hepatocellular carcinoma developed on viral C cirrhosis. Gut 46:711–714
Corengia C, Galimberti S, Bovo G, Vergani A, Arosio C, Mariani R, Redaelli A, Riva A, Cestari C, Pozzi M, Valsecchi M, Piperno A (2005) Iron accumulation in chronic hepatitis C: relation of hepatic iron distribution, HFE genotype, and disease course. Am J Clin Pathol 124(6):846–853
Dhillon BK, Das R, Garewal G, Chawla Y, Dhiman R, Das A, Duseja A, Chandak G (2007) Frequency of primary iron overload and HFE gene mutations (C282Y, H63D, and S65C) in chronic liver disease patients in North India. World J Gastrointerol 13(210):2956–2959
Elbahaie H, Abdalla A, Serwah A, Abo Elela A, Leheta O (2008) Study of C282Y and H63D hemochromatosis gene mutations (HFE gene) in HCV chronic liver disease patients with and without iron overload. In: MD Thesis, Faculty of Medicine, Suez Canal University., pp 107–109
Erhardt A, Maschner-Olberg A, Mellenthin C, Kappert G, Adams O, Donner A, Willers R, Niederau C, Häussinger D (2003) HFE mutations and chronic hepatitis C: H63D and C282Y heterozygosity are independent risk factors for liver fibrosis and cirrhosis. J Hepatol 38:335–342
Fargion S, Fracanzani AL, Sampietro M (1997) Liver iron influences the response to interferon therapy in chronic hepatitis C. Eur J Gastroenterol Hepatol 9:497–503
Floreani A, Rosa R, Basso D, Navaglia F, Zaninotto M, Petridis I, Testa R, Marra M, Baldo V, Chiaramonte M (2007) An open population screening study for HFE gene major mutations proves the low prevalence of C282Y mutation in Central Italy. Aliment Pharmacol Ther 26(4):577–586
Harigae H (2013) The cutting-edge of medicine; iron metabolism - recent findings. Nihon Naika Gakkai Zasshi 102(10):2699–2704
Hézode C, Cazeneuve C, Coué O (1999) Liver iron accumulation in patients with chronic active hepatitis C: prevalence and role of hemochromatosis gene mutations and relationship with hepatic histological lesions. J Hepatol 31:979–984
Ishizu Y, Katano Y, Honda T, Hayashi K, Ishigami M, Itoh A, Hirooka Y, Nakano I, Goto H (2012) Clinical impact of HFE mutations in Japanese patients with chronic hepatitis C. J Gastroenterol Hepatol 27:1112–1116
Lee SH, Jeong SH, Lee D, Lee JH, Hwang SH, Cho YA, Park YS, Hwang JH, Kim JW, Kim N, Lee DH, Kang W (2010) An epidemiologic study on the incidence and significance of HFE mutations in a Korean cohort with nonalcoholic fatty liver disease. J Clin Gastroenterol 44(7):154–161
Madhava V, Burgess C, Drucker E (2002) Epidemiology of chronic hepatitis C virus infection in sub-Saharan Africa. Lancet Infect Dis 2(5):293–302
Mainous AG, Diaz VA, Everett CH, Hulihan MM, Grant AM, McLaren CE, McLaren GD (2011) Iron overload screening tool (IRON): development of a tool to guide screening in primary care. Am J Hematol 86(9):733–737
Martinelli AL, Franco RF, Villanova MG, Figueiredo JF, Secaf M, Tavella MH (2000) Are haemochromatosis mutations related to the severity of liver disease in hepatitis C virus infection? Act Haematol 102:152–156
Meli R, Raso G, Santamaria R (2013) High fat diet induces liver steatosis and early dysregulation of iron metabolism in rats. PLoS One 8(6):e66570
Niederau C, Fischer R, Sonnenberg A, Stremmel W, Trampisch HJ, Strohmeyer G (1985) Survival and causes of death in cirrhotic and in non-cirrhotic patients with primary hemochromatosis. N Engl J Med 313:1256–1262
Piperno A, Sampietro M, D’Alba R (1996) Iron stores, response to a-interferon therapy, and effects of iron depletion in chronic hepatitis C. Liver 16:248–254
Roth M, Giraldo P, Hariti G (1997) Absence of the hemochromatosis gene Cys282Tyr mutation in three ethnic groups from Algeria (Mzab), Ethiopia, and Senegal. Immunogenetics 46:222–225
Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higushi R, Horn GT, Mullis KB, Erlich HA (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–491
Smith BC, Gorve J, Guzail MA, Day CP, Daly AK, Burt AD, Baendine MF (1998) Heterozygosity for hereditary hemochromatosis is associated with more fibrosis in chronic hepatitis C. Hepatology 27(6):1695–1699
Thorburn D, Curry G, Spooner R, Spence E, Oien K, Halls D, McCruden E, MacSween R, Mills P (2002) The role of iron and haemochromatosis gene mutations in the progression of liver disease in chronic hepatitis C. Gut 50:248–252
Valenti L, Pulixi EA, Arosio P, Cremonesi L, Biasiotto G, Dongiovanni P, Maggioni M, Farigion S, Fracanzani A (2007) Relative contribution of iron genes, dysmetabolism and hepatitis C virus in the pathogenesis of altered iron regulation in HCV chronic hepatitis. Haematologica 92(8):1037–1042
Won J, Jeong S, Chung J, Lee J, Hwang S, Kim J, Lee S, Kim N, Park Y, Lee D, Kim H (2009) Hepatic iron, serum ferritin, HFE mutation, and hepatic fibrosis in chronic hepatitis C. Intervirology 52:239–246
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ibrahim, N.S., Menesy, M. Hemochromatosis gene mutations in chronic hepatitis “C” patients. Comp Clin Pathol 25, 375–380 (2016). https://doi.org/10.1007/s00580-015-2193-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00580-015-2193-x