Abstract
BackgroundOne-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.MethodsEighty-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.ResultsSerum 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 (r2 = 0.45, p < 0.05 and r2 = 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 (r2 = 0.39, p < 0.01).ConclusionsIn 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.
Highlights
One-third of patients with non-alcoholic fatty liver disease (NAFLD) develop dysmetabolic iron overload syndrome (DIOS), the pathogenesis of which is unknown
Hepcidin antimicrobial peptide (HAMP) mRNA in liver tissue correlated to the hepatic iron score (r2 = 0.45, p < 0.05) but not to NAFLD activity score (r2 = 0.003, p < 0.89)
In the present study, we demonstrate that in NAFLD patients, hepcidin in serum and HAMP mRNA in liver tissue correlate significantly to body iron stores, regardless if they are expressed as serum ferritin or liver iron content
Summary
One-third of patients with non-alcoholic fatty liver disease (NAFLD) develop dysmetabolic iron overload syndrome (DIOS), the pathogenesis of which is unknown. One-third of patients with NAFLD develop elevated serum ferritin and hepatic iron overload, a condition known as the “dysmetabolic iron overload syndrome” (DIOS) [4, 5]. An inappropriately low hepcidin synthesis has been reported in NAFLD [10, 11] which could facilitate iron uptake and predispose for DIOS, but results are not consistent [12, 13]. In NAFLD data is conflicting whether or not hepcidin predominantly correlates to body iron stores [16, 17], to features of the metabolic syndrome [18, 19] or the hepatic inflammation seen in steatohepatitis (NASH). In a large study on individuals with metabolic syndrome, results suggested that that the iron regulatory feedback on hepcidin synthesis was preserved in these patients [21]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
