Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Feb 27, 2015; 7(2): 177-188
Published online Feb 27, 2015. doi: 10.4254/wjh.v7.i2.177
Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver
Elmar Aigner, Günter Weiss, Christian Datz
Elmar Aigner, Christian Datz, Obesity Research Unit, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
Elmar Aigner, First Department of Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
Günter Weiss, Department of Internal Medicine VI, Medical University Innsbruck, 6020 Innsbruck, Austria
Christian Datz, Department of Internal Medicine, General Hospital Oberndorf, 5111 Oberndorf, Austria
Author contributions: Aigner E drafted and finalized the manuscript; Weiss G and Datz C contributed to critical revision and important intellectual content.
Supported by PMU-Forschungsförderungsfonds, No. E-13/17/086-AIG; the Austrian Research Funds, FWF to Weiss G, Project TRP-188; and SPAR Austria to Christian Datz is gratefully acknowledged.
Conflict-of-interest: None of the authors has any potential financial conflicts of interest to disclose with regard to this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Elmar Aigner, MD, First Department of Medicine, Paracelsus Private Medical University Salzburg, Müllner Hauptstrasse 48, 5020 Salzburg, Austria. e.aigner@salk.at
Telephone: +43-662-448258358 Fax: +43-662-4482881
Received: August 26, 2014
Peer-review started: August 27, 2014
First decision: November 27, 2014
Revised: December 12, 2014
Accepted: December 29, 2014
Article in press: December 31, 2014
Published online: February 27, 2015
Abstract

Elevated iron stores as indicated by hyperferritinemia with normal or mildly elevated transferrin saturation and mostly mild hepatic iron deposition are a characteristic finding in subjects with non-alcoholic fatty liver disease (NAFLD). Excess iron is observed in approximately one third of NAFLD patients and is commonly referred to as the “dysmetabolic iron overload syndrome”. Clinical evidence suggests that elevated body iron stores aggravate the clinical course of NAFLD with regard to liver-related and extrahepatic disease complications which relates to the fact that excess iron catalyses the formation of toxic hydroxyl-radicals subsequently resulting in cellular damage. Iron removal improves insulin sensitivity, delays the onset of type 2 diabetes mellitus, improves pathologic liver function tests and likewise ameliorates NAFLD histology. Several mechanisms contribute to pathologic iron accumulation in NAFLD. These include impaired iron export from hepatocytes and mesenchymal Kupffer cells as a consequence of imbalances in the concentrations of iron regulatory factors, such as hepcidin, cytokines, copper or other dietary factors. This review summarizes the knowledge about iron homeostasis in NAFLD and the rationale for its therapeutic implications.

Keywords: Dysmetabolic iron overload syndrome, Hepcidin, Iron overload, Metabolic syndrome, Non-alcoholic fatty liver disease, Nonalcoholic steatohepatitis

Core tip: Hyperferritinemia with normal transferrin saturation and mostly mild hepatic iron deposition is a frequent finding in subjects with non-alcoholic fatty liver disease. Excess iron in non-alcoholic fatty liver disease (NAFLD) patients is referred to as the “dysmetabolic iron overload syndrome”. Clinical evidence suggests that elevated body iron stores aggravate the clinical course of NAFLD with regard to liver-related and extrahepatic disease complications. Iron removal improves insulin sensitivity, delays the onset of type 2 diabetes mellitus, improves pathologic liver function tests and ameliorates NAFLD histology The mechanisms contributing to iron excess in fatty liver include impaired iron export from hepatocytes and mesenchymal Kupffer.