Iron and liver fibrosis: Mechanistic and clinical aspects

Kosha J Mehta, Sebastien Je Farnaud, Paul A Sharp

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    163 Citations (Scopus)
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    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.

    Original languageEnglish
    Pages (from-to)521-538
    Number of pages18
    JournalWorld Journal of Gastroenterology
    Issue number5
    Publication statusPublished - 7 Feb 2019

    Bibliographical note

    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:


    • Carcinoma, Hepatocellular/pathology
    • Disease Progression
    • Hemochromatosis/metabolism
    • Hepatocytes/metabolism
    • Humans
    • Iron/metabolism
    • Iron Chelating Agents/therapeutic use
    • Liver/cytology
    • Liver Cirrhosis/diagnosis
    • Liver Diseases, Alcoholic/pathology
    • Liver Neoplasms/pathology
    • Non-alcoholic Fatty Liver Disease/pathology
    • Phlebotomy


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