HFE Genotype, Parenchymal Iron Accumulation, and Liver Fibrosis in Patients With Nonalcoholic Fatty Liver Disease
Received 10 September 2009; accepted 12 November 2009. published online 19 November 2009. Uncorrected Proof
Background & Aims
Mutations in 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 who did not; approximately one third of patients with HFE mutations had iron accumulation (range, 29.8%–35.7%, depending on HFE genotype). Predominantly hepatocellular iron accumulation occurred in 52.7% of patients with the 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.
⁎Department of Internal Medicine, Università degli Studi di Milano, Ospedale Maggiore Policlinico IRCCS, Milano, Italy
‡Department of Gastroenterology, Università di Torino, Torino, Italy
§Department of Surgery, Università degli Studi di Milano, Ospedale Maggiore Policlinico IRCCS, Milano, Italy
∥Department of Internal Medicine, Università Alma Mater Bologna, Bologna, Italy
Reprint requests Address requests for reprints to: S. Fargion, MD, Department of Internal Medicine, Università degli Studi di Milano, Ospedale Maggiore Policlinico IRCCS, Milano, Via F Sforza 35, 20122 Milano, Italia.
Conflicts of interest The authors disclose no conflicts.
Funding Supported by the following grants: FIRST Università di Milano 2007, 2008 (to L.V., S.F., A.L.F.); Ricerca corrente Ospedale Maggiore Policlinico 2006 and 2008 (L.V., S.F.); and Centro per lo Studio delle Malattie del Fegato e del Metabolismo.
ABSTRACT