Background & Aims: Mutations in the hemochromatosis gene (HFE) (C282Y and H63D) lead to parenchymal iron accumulation, hemochromatosis, and liver damage. We investigated whether these factors also contribute to the progression of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). Methods: We studied clinical, histologic (liver biopsy samples for hepatocellular iron accumulation), serologic (iron and enzyme levels), and genetic (HFE genotype) data from 587 patients from Italy with NAFLD and 184 control subjects. Results: Iron accumulation predominantly in hepatocyes was associated with a 1.7-fold higher risk of a fibrosis stage greater than 1 (95% confidence interval [CI]: 1.2-2.3), compared with the absence of siderosis (after adjustment for age, body mass index, glucose tolerance status, and alanine aminotransferase level). Nonparenchymal/mixed siderosis was not associated with moderate/severe fibrosis (odds ratio, 0.72; 95% CI: 0.50-1.01). Hepatocellular siderosis was more prevalent in patients with HFE mutations than in those without; approximately one third of patients with HFE mutations had parenchymal iron accumulation (range, 29.8%-35.7%, depending on HFE genotype). Predominantly hepatocellular iron accumulation occurred in 52.7% of cases of patients with HFE mutations. There was no significant association between either the presence of HFE mutations or specific HFE genotypes and the severity of liver fibrosis. Conclusions: Iron deposition predominantly in hepatocyes is associated with more severe liver damage in patients with NAFLD. However, HFE mutations cannot be used to identify patients with hepatocellular iron accumulation.
HFE genotype, parenchymal iron accumulation, and liver fibrosis in patients with nonalcoholic fatty liver disease / L. Valenti, A.L. Fracanzani, E. Bugianesi, P. Dongiovanni, E. Galmozzi, E. Vanni, E. Canavesi, E. Lattuada, G. Roviaro, G. Marchesini, S. Fargion. - In: GASTROENTEROLOGY. - ISSN 0016-5085. - 138:3(2010), pp. 905-912.
|Titolo:||HFE genotype, parenchymal iron accumulation, and liver fibrosis in patients with nonalcoholic fatty liver disease|
VALENTI, LUCA VITTORIO CARLO (Primo)
FRACANZANI, ANNA LUDOVICA (Secondo)
FARGION, SILVIA ROSSANA (Corresponding)
|Parole Chiave:||Hepatic Fibrosis; hfe Gene; Iron Overload; Nonalcoholic Fatty Liver Disease|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1053/j.gastro.2009.11.013|
|Appare nelle tipologie:||01 - Articolo su periodico|