Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 7, 2019; 25(5): 521-538
Published online Feb 7, 2019. doi: 10.3748/wjg.v25.i5.521
Iron and liver fibrosis: Mechanistic and clinical aspects
Kosha J Mehta, Sebastien Je Farnaud, Paul A Sharp
Kosha J Mehta, School of Population Health and Environmental Sciences, Faculty of Life Sciences and Medicine, King’s College London, London SE1 1UL, United Kingdom
Kosha J Mehta, Division of Human Sciences, School of Applied Sciences, London South Bank University, London SE1 0AA, United Kingdom
Sebastien Je Farnaud, Faculty Research Centre for Sport, Exercise and Life Sciences, Coventry University, Coventry CV1 2DS, United Kingdom
Paul A Sharp, Department of Nutritional Sciences, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London SE1 9NH, United Kingdom
Author contributions: Mehta KJ contributed to conception, design, literature review, analysis and drafting; Farnaud SJ contributed to intellectual input; Sharp PA contributed to critical revision, editing and final approval of version to be published.
Conflict-of-interest statement: All authors declare no conflict of interest.
Open-Access: This is an open-access article that 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:
Corresponding author: Kosha J Mehta, PhD, Senior Lecturer, Division of Human Sciences, School of Applied Sciences, London South Bank University, 103 Borough Rd, London SE1 0AA, United Kingdom.
Telephone: +44-207-8157949
Received: December 2, 2018
Peer-review started: December 3, 2018
First decision: December 28, 2018
Revised: January 2, 2019
Accepted: January 9, 2019
Article in press: January 9, 2019
Published online: February 7, 2019

Liver fibrosis is characterised by excessive deposition of extracellular matrix that interrupts normal liver functionality. It is a pathological stage in several untreated chronic liver diseases such as the iron overload syndrome hereditary haemochromatosis, viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and diabetes. Interestingly, regardless of the aetiology, iron-loading is frequently observed in chronic liver diseases. Excess iron can feed the Fenton reaction to generate unquenchable amounts of free radicals that cause grave cellular and tissue damage and thereby contribute to fibrosis. Moreover, excess iron can induce fibrosis-promoting signals in the parenchymal and non-parenchymal cells, which accelerate disease progression and exacerbate liver pathology. Fibrosis regression is achievable following treatment, but if untreated or unsuccessful, it can progress to the irreversible cirrhotic stage leading to organ failure and hepatocellular carcinoma, where resection or transplantation remain the only curative options. Therefore, understanding the role of iron in liver fibrosis is extremely essential as it can help in formulating iron-related diagnostic, prognostic and treatment strategies. These can be implemented in isolation or in combination with the current approaches to prepone detection, and halt or decelerate fibrosis progression before it reaches the irreparable stage. Thus, this review narrates the role of iron in liver fibrosis. It examines the underlying mechanisms by which excess iron can facilitate fibrotic responses. It describes the role of iron in various clinical pathologies and lastly, highlights the significance and potential of iron-related proteins in the diagnosis and therapeutics of liver fibrosis.

Keywords: Iron, Liver pathologies, Liver fibrosis, Hepatic stellate cells, Cirrhosis

Core tip: Excess iron is observed in several liver pathologies, where it can accelerate the progression of liver fibrosis to cirrhosis and hepatocellular carcinoma, regardless of disease aetiology. This review narrates the role of excess iron in liver fibrosis. It examines the mechanisms by which iron enhances fibrogenic responses and describes various iron-related clinical pathologies. Furthermore, it evaluates the significance of iron and iron-related proteins in the diagnosis and therapeutics of liver fibrosis. The review is unique in that it includes both, cellular mechanisms and clinical aspects of liver fibrosis pertaining to iron. This makes it distinct from previous published reviews.