title: HFE genotype, parenchymal iron accumulation, and liver fibrosis in patients with nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, Università degli Studi di Milano, Ospedale Maggiore Policlinico IRCCS, Milano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Valenti
authors.forename: Anna Ludovica
authors.initials: AL
authors.lastname: Fracanzani
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bugianesi
authors.forename: Paola
authors.initials: P
authors.lastname: Dongiovanni
authors.forename: Enrico
authors.initials: E
authors.lastname: Galmozzi
authors.forename: Ester
authors.initials: E
authors.lastname: Vanni
authors.forename: Elena
authors.initials: E
authors.lastname: Canavesi
authors.forename: Ezio
authors.initials: E
authors.lastname: Lattuada
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Roviaro
authors.forename: Giulio
authors.initials: G
authors.lastname: Marchesini
authors.forename: Silvia
authors.initials: S
authors.lastname: Fargion
mesh_terms: D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D018450:Disease Progression; D005234:Fatty Liver / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006432:Hemochromatosis / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007558:Italy; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D007501:Iron