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2015, Number 3

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Ann Hepatol 2015; 14 (3)

Impact of H63D mutations, magnetic resonance and metabolic syndrome among outpatient referrals for elevated serum ferritin in the Basque Country

Castiella A, Zapata E, Zubiaurre L, Alustiza JM, De Juan MD, Iribarren A, Emparanza JI, Otazua P

Language: English
References: 31
Page: 333-339
PDF size: 132.48 Kb.


ABSTRACT

Background and Aims. There are limited data on clinical and phenotypic characteristics of outpatients referred for hyperferritinemia (HF). To determine the causes of HF in outpatients referred to a secondary hospital. Material and methods. A prospective study of 132 consecutive patients with HF (› 200 µg/L, women; › 300 µg/L, men) was conducted from January-December 2010. Results. Mean age, 54.42 years (SD: 13.47, range: 23-83); body mass index (BMI), 28.80 (SD: 3.96, 17-39); ferritin (SF), 579.54 ng/mL (SD: 296.575, 206-1668); transferrin saturation (TSI), 43.87% (SD: 14.09, 12-95); iron (Fe), 134 µg/dL (SD: 49.68, 55-322); overweight: 48.31%, and obese: 40.44% (89%), and most patients were men (108/132). Regarding HFE mutations, H63D/H63D genotype and H63D allele frequencies were 17.5% (vs. 7.76% in controls); and 36% (31% in controls) respectively. While 63.6% consumed no alcohol, 18.1% consumed ≥ 60 g/day, the mean being 20.83 (SD: 33.95, 0-140). Overall, 6/132 (4.5%) patients were positive for B or C hepatitis. Mean LIC by MRI was 36.04 (SD: 32.78, 5-210), 53 patients having normal concentrations (‹ 36 µmol/g), 22 (33%) iron overload (37-80), and 4 (5%) high iron overload (› 80). Metabolic syndrome (MS) was detected in 44/80 men (55%) and 10/17 women (59%). In this group, the genotype frequency of the H63D/H63D mutation was significantly higher than in controls-21.56% vs. 7.76%- (p = 0.011); the H63D allelic frequency was 42.15% in MS group and 31% in controls (p = 0.027). Conclusion. The H63D/H63D genotype and H63D allele predispose individuals to HF and MS. MRI revealed iron overload in 33% of patients.


REFERENCES

  1. Wong K, Adams PC. The diversity of liver diseases among outpatient referrals for elevated serum ferritin. Can J Gastroenterol 2006; 20: 467-70.

  2. Dever JB, Mallory MA, Mallory JE, Wallace D, Kowdley KV. Phenotypic characteristics and diagnoses of patients referred to an iron overload clinic. Dig Dis Sci 2010; 55: 803-7.

  3. Licata A, Nebbia ME, Cabibbo G, Lo Iacono G, Barbaria F, Brucato V, Alessi N, et al. Hyperferritinemia is a risk factor for steatosis in chronic liver disease. World J Gastroenterol 2009; 15: 2132-8.

  4. Hearnshaw S, Thompson NP, McGill A. The epidemiology of hyperferritinemia. World J Gastroenterol 2006; 12: 5866-9.

  5. Yenson PR, Yoshida EM, Li CH, Chung HV, Tsang PWK. Hyperferritinemia in the Chinese and Asian community: A retrospective review of the university of British 339 Impact of H63D mutations in outpatients. , 2015; 14 (3): 333-339 Columbia experience. Can J Gastroenterol 2008; 22: 37-40.

  6. Beaton MD, Adams PC. Treatment of hyperferritinemia. Ann Hepatol 2012; 11: 294-300.

  7. De Juan MD, Reta A, Castiella A, Pozueta J, Prada A, Cuadrado E. HFE gene mutations analysis in Basque Country hereditary haemochromatosis patients and controls. Eur J Hum Genet 2001; 9: 961-4.

  8. Castiella A, Zapata E, De Juan MD, Otazua P, Fernandez J, Zubiaurre L, Arriola JA, et al. Significance of H63D homozygosity in a Basque Country population with hemochromatosis. J Gastroenterol Hepatol 2010; 25: 1295-8.

  9. Alustiza JM, Emparanza JI, Aldazabal P, Garrido A, Garcia N, Salvador E. Standardization of the quantification of iron concentration in the liver by magnetic resonance imaging. Radiología 2012; 54: 149-54.

  10. Alustiza JM, Artetxe J, Castiella A, Aguirre C, Emparanza JI, Otazua P, Garcia-Bengoechea M, et al. MR quantification of hepatic iron concentration. Radiology 2004; 230: 479-84.

  11. Castiella A, Alústiza JM, Zapata E, Emparanza JI, Otazua P, Zubiaurre L, Aguirre A. Mild iron overload in dysmetabolic hyperferritinemia: MRI may overestimate the liver iron concentration values. Ann Hematol 2012; 91: 961.

  12. Alústiza JM, Castiella A. Liver fat and iron at in-phase and opposed-phase MR imaging. Radiology 2008; 246: 641.

  13. Alberti KG, Zimmet P, Shaw J; IDF Epidemiology Task Force Consensus Group. The metabolic syndrome-a new worldwide definition. Lancet 2005; 366: 1059-62.

  14. Fletcher LM, Powell LW. Hemochromatosis and alcoholic liver disease. Alcohol 2003; 30: 131-6.

  15. Olynyk JK, Gan E, Tan T. Predicting iron overload in hyperferritinemia. Clin Gastroenterol Hepatol 2009; 7: 359-62.

  16. Pérez-Aguilar F, Benlloch S, Berenguer M. Estudio de pacientes remitidos por elevación de la ferritina y/o saturación de la transferrina: importancia del hígado graso no alcohólico. Gastroenterol Hepatol 2004; 27: 508-14.

  17. Adams PA, Barton JC. A diagnostic approach to hyperferritinemia with a non-elevated transferring saturation. J Hepatol 2011; 55: 453-8.

  18. Lee MH, Means RT Jr. Extremely elevated serum ferritin levels in a University Hospital: associated diseases and clinical significance. Am J Med 1995; 98: 566-71.

  19. Ramírez C, Rubio C, Fernandez de la Puebla RA, Aguilera C, Espejo I, Fuentes F. Significado clínico de los valores altos de ferritina sérica. Med Clin (Barc) 2004; 122: 532-4.

  20. Crook MA, Walker PL. Extreme hyperferritinemia; clinical causes. J Clin Pathol 2013; 66: 438-40.

  21. McKenzie SW, Means RT Jr. Extreme hyperferritinemia in patients infected with human immunodeficiency virus is not a highly specific marker for disseminated histoplasmosis. Clin Infect Dis 1997; 24: 519-20.

  22. De Diego C, Opazo S, Murga MJ, Martinez-Castro P. H63D homozygotes with hyperferritinaemia: is this genotype the primary cause of iron overload? Eur J Haematol 2006; 78: 66-71.

  23. Aguilar-Martínez P, Bismuth M, Picot MC, Thelcide C, Pageaux GP, Blanc F, Schved JF, et al. Variable phenotypic presentation of iron overload in H63D homozygotes: are genetic modifiers the cause? Gut 2001; 48: 836-42.

  24. Tomatsu S, Orii KO, Fleming RE, Holden CC, Waheed A, Britton RS, Gutierrez MA, et al. Contribution of the H63D mutation in HFE to murine hereditary hemochromatosis. PNAS 2003; 100: 15788-93.

  25. Harrison-Findik DD. Gender-related variations in iron metabolism and liver diseases. World J Hepatol 2010; 2: 302-10.

  26. Chen LY, Chang SD, Sreenivasan GM, Tsang PW, Broady RC, Li CH, Zypchen LN. Dysmetabolic hyperferritinemia is associated with normal transferrin saturation, mild hepatic iron overload, and elevated hepcidin. Ann Hematol 2011; 90: 139-43.

  27. Adams LA, Angulo P, Abraham SC, Torgerson H, Brandhagen D. The effect of the metabolic syndrome, hepatic steatosis and steatohepatitis on liver fibrosis in hereditary hemochromatosis. Liver Int 2006; 26: 298-304.

  28. Fargion S, Mattioli M, Fracanzani AL, Sampietro M, Tavazzi D, Fociani P, Taioli E, et al. Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis. Am J Gastroenterol 2001; 96: 2448-55.

  29. Dongiovanni P, Fracanzani AL, Fargion S, Valenti L. Iron in fatty liver and in the metabolic syndrome: a promising therapeutic target. J Hepatol 2011; 55: 920-32.

  30. Corradini E, Pietrangelo A. Iron and steatohepatitis. J Gastroenterol Hepatol 2012; 27(Suppl. 2): 42-6.

  31. Freixenet N, Moreno-Rosel MS, Barceló MJ, Serrano A, Payá M, Crespo L, Pérez-Lucena MJ, et al. detection of hereditary hemochromatosis and biochemical iron overload in primary care: a multicenter case finding study in Spain. Am J Hematology 2010; 85: 294-6.




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