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Hepatic iron is the major determinant of serum ferritin in NAFLD patients
John D. Ryan1,*, Andrew E. Armitage2, Jeremy F. Cobbold1, Rajarshi Banerjee3, Oscar Borsani4, Paola Dongiovanni4, Stefan Neubauer5, Reza Morovat6, Lai Mun Wang1, Sant-Rayn Pasricha2, Silvia Fargion4, Jane Collier1, Eleanor Barnes1, Hal Drakesmith2, Luca Valenti4 andMichael Pavlides3
DOI: 10.1111/liv.13513
This article is protected by copyright. All rights reserved.
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Cover image for Vol. 37 Issue 7
Liver International
Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)
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Author Information
1
Translational Gastroenterology Unit, University of Oxford
2
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford
3
Perspectum Diagnostics, Oxford
4
Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, University of Milan
5
Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford
6
Department of Biochemistry, John Radcliffe Hospital, Oxford
Email: John D. Ryan ([email protected])
* Corresponding author:
John D Ryan MBBS PhD
Translational Gastroenterology Unit
University of Oxford
Oxford OX39DU
UK
Email: [email protected]
Tel.+441865220137
Fax.+441865228763
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/liv.13513
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Keywords:
Ferritin;Hepcidin; MRI ; NAFLD ;liver iron
Abstract
Background and Aims
Elevated serum ferritin is common in NAFLD, and is associated with more advanced disease and increased mortality. Hyperferritinemia in NAFLD is often attributed to inflammation, while in other conditions ferritin closely reflects body iron stores. The aim of this study was to clarify the underlying cause of hyperferritinemia in NAFLD.
Methods
Ferritin levels were examined with markers of iron status, inflammation and liver injury across the clinical spectrum of NAFLD using blood, tissue and magnetic resonance (MR) imaging. A separate larger group of NAFLD patients with hepatic iron staining and quantification were used for validation.
Results
Serum ferritin correlated closely with the iron regulatory hormone hepcidin, and liver iron levels determined by MR. Furthermore, ferritin levels reflected lower serum adiponectin, a marker of insulin resistance, and liver fat, but not cytokine or CRP levels. Ferritin levels differed according to fibrosis stage, increasing from early to moderate disease, and declining in cirrhosis. A similar pattern was found in the validation cohort of NAFLD patients, where ferritin levels were highest in those with macrophage iron deposition. Multivariate analysis revealed liver iron and hepcidin levels as the major determinants of serum ferritin.
Conclusions
While hyperferritinaemia is associated with markers of liver injury and insulin resistance, serum hepcidin and hepatic iron are the strongest predictors of ferritin levels. These findings highlight the role of disordered iron homeostasis in the pathogenesis of NAFLD, suggesting that therapies aimed at correcting iron metabolism may be beneficial.
This article is protected by copyright. All rights reserved.
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发表于 2017-7-14 16:30