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J Hepatol. 2010 Nov;53(5):927-33. doi: 10.1016/j.jhep.2010.05.023. Epub 2010 Jul 25.

Beta-globin mutations are associated with parenchymal siderosis and fibrosis in patients with non-alcoholic fatty liver disease.

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  • 1Department of Internal Medicine, Universit√† degli Studi Milano, UO Medicina Interna 1B, Fondazione Ospedale Policlinico MaRE IRCCS, Milan, Italy.



Parenchymal liver siderosis is associated with increased fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to assess whether a panel of genetic variants previously reported to influence iron metabolism, including the C282Y/H63D HFE, the PiZ/PiS alpha1-antitrypsin, the IVS1-24 ferroportin polymorphisms, and the beta-thalassemia trait, may be able to predict the presence of parenchymal siderosis and of progressive fibrosis in NAFLD.


We considered 274 Italian patients with biopsy-proven NAFLD. Genetic polymorphisms were searched for by sequence allele specific-polymerase chain reaction and restriction analysis, whereas beta-trait was determined according to blood count and HbA(2) determination.


Parenchymal iron deposition was predominantly observed in 32 (11.7%) patients. Heterozygosity for the C282Y (OR 1.87, 95% CI 1.04-3.25), homozygosity for the H63D HFE (OR 2.31, 95% CI 1.04-4) mutations, and the beta-thalassemia trait (OR 2.57 95% CI 1.49-4.47) were all predominantly associated with parenchymal siderosis, independently of age, sex, body mass index, alcohol intake, ferritin, and transferrin saturation. Sixty-three percent of patients with hepatocellular siderosis were positive for at least one of the aforementioned genetic variants. The beta-thalassemia trait had the highest positive and the lowest negative likelihood ratios for predominantly parenchymal iron accumulation (5.05 and 0.74, respectively), and was independently associated with moderate/severe fibrosis (OR 2.50, 95% CI 1.26-5.19).


In patients with NAFLD, predominant hepatocellular iron deposition is often related to genetic factors, among which beta-globin mutations play a major role, predisposing to parenchymal iron accumulation and to progressive liver fibrosis.

Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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