Background & Aims: 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. Methods: 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 HbA2 determination. Results: 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). Conclusions: 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.
Beta-globin mutations are associated with parenchymal siderosis and fibrosis in patients with non-alcoholic fatty liver disease / L. V. C. Valenti, E. Canavesi, E. Galmozzi, P. Dongiovanni, R. Rametta, P. Maggioni, M. Maggioni, A. L. Fracanzani, S. R. Fargion. - In: JOURNAL OF HEPATOLOGY. - ISSN 0168-8278. - 53:5(2010 Nov), pp. 927-933.
|Titolo:||Beta-globin mutations are associated with parenchymal siderosis and fibrosis in patients with non-alcoholic fatty liver disease|
|Parole Chiave:||Genetics; Iron overload; Non-alcoholic steatohepatisis; Thalassemia|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||nov-2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.jhep.2010.05.023|
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