Lower serum hepcidin and greater parenchymal iron in nonalcoholic fatty liver disease patients with C282Y HFE mutations

Hepcidin regulation is linked to both iron and inflammatory signals and may influence iron loading in nonalcoholic steatohepatitis (NASH). The aim of this study was to examine the relationships among HFE genotype, serum hepcidin level, hepatic iron deposition, and histology in nonalcoholic fatty liv...

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Bibliographic Details
Published in:Hepatology (Baltimore, Md.) Md.), 2012-11, Vol.56 (5), p.1730-1740
Main Authors: Nelson, James E., Brunt, Elizabeth M., Kowdley, Kris V.
Format: Article
Language:English
Subjects:
Adult
Anemia
Antimicrobial Cationic Peptides - blood
Biological and medical sciences
Confidence Intervals
Fatty Liver - genetics
Fatty Liver - metabolism
Fatty Liver - pathology
Female
Gastroenterology. Liver. Pancreas. Abdomen
Genotype
Hemochromatosis Protein
Hepatology
Hepcidins
Histocompatibility Antigens Class I - genetics
Humans
Iron - metabolism
Liver diseases
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Logistic Models
Male
Medical sciences
Membrane Proteins - genetics
Middle Aged
Mononuclear Phagocyte System - metabolism
Multivariate Analysis
Mutation
Non-alcoholic Fatty Liver Disease
Odds Ratio
Other diseases. Semiology
Polymorphism, Single Nucleotide
Statistics, Nonparametric
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Summary:Hepcidin regulation is linked to both iron and inflammatory signals and may influence iron loading in nonalcoholic steatohepatitis (NASH). The aim of this study was to examine the relationships among HFE genotype, serum hepcidin level, hepatic iron deposition, and histology in nonalcoholic fatty liver disease (NAFLD). Single‐nucleotide polymorphism genotyping for C282Y (rs1800562) and H63D (rs1799945) HFE mutations was performed in 786 adult subjects in the NASH Clinical Research Network (CRN). Clinical, histologic, and laboratory data were compared using nonparametric statistics and multivariate logistic regression. NAFLD patients with C282Y, but not H63D mutations, had lower median serum hepcidin levels (57 versus 65 ng/mL; P = 0.01) and higher mean hepatocellular (HC) iron grades (0.59 versus 0.28; P < 0.001), compared to wild‐type (WT) subjects. Subjects with hepatic iron deposition had higher serum hepcidin levels than subjects without iron for all HFE genotypes (P < 0.0001). Hepcidin levels were highest among patients with mixed HC/reticuloendothelial system cell (RES) iron deposition. H63D mutations were associated with higher steatosis grades and NAFLD activity scores (odds ratio [OR], ≥1.4; 95% confidence interval [CI]: >1.0, ≤2.5; P ≤ 0.041), compared to WT, but not with either HC or RES iron. NAFLD patients with C282Y mutations had less ballooning or NASH (OR, ≤0.62; 95% CI: >0.39,
ISSN:0270-9139
1527-3350
DOI:10.1002/hep.25856