Hepcidin levels correlate to liver iron content, but not steatohepatitis, in non-alcoholic fatty liver disease

BACKGROUND: One-third of patients with non-alcoholic fatty liver disease (NAFLD) develop dysmetabolic iron overload syndrome (DIOS), the pathogenesis of which is unknown. Altered production of the iron-regulatory peptide hepcidin has been reported in NAFLD, but it is unclear if this is related to iron accumulation, lipid status or steatohepatitis. METHODS: Eighty-four patients with liver disease, 54 of which had iron overload, underwent liver biopsy (n = 66) and/or magnetic resonance imaging (n = 35) for liver iron content determination. Thirty-eight of the patients had NAFLD, 29 had chronic liver disease other than NAFLD, and 17 had untreated genetic hemochromatosis. Serum hepcidin was measured with ELISA in all patients and in 34 controls. Hepcidin antimicrobial peptide (HAMP) mRNA in liver tissue was determined with real-time-quantitative PCR in 36 patients. RESULTS: Serum hepcidin was increased similarly in NAFLD with DIOS as in the other chronic liver diseases with iron overload, except for genetic hemochromatosis. HAMP mRNA in liver tissue, and serum hepcidin, both correlated to liver iron content in NAFLD patients (r(2) = 0.45, p < 0.05 and r(2) = 0.27, p < 0.05 respectively) but not to body mass index, NAFLD activity score or serum lipids. There was a good correlation between HAMP mRNA in liver tissue and serum hepcidin (r(2) = 0.39, p < 0.01). CONCLUSIONS: In NAFLD with or without dysmetabolic iron overload, serum hepcidin and HAMP mRNA in liver correlate to body iron content but not to the degree of steatohepatitis or lipid status. Thus, the dysmetabolic iron overload syndrome seen in NAFLD is not caused by an altered hepcidin synthesis.