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image of Hemochromatosis and Hepatic Complications: A Comprehensive Review of Molecular Mechanisms, Diagnostics, and Emerging Therapeutics

Abstract

Hemochromatosis is an autosomal recessive iron overload disorder. It occurs due to a failure in the hepcidin response, leading to systemic iron overload. The high iron levels in the plasma stored in various organs cause injury and permanent damage. There are two types of hemochromatosis: primary and secondary. In non-HFE hemochromatosis, mutations in the HJV, HAMP, TRF2, and SLC40A1 genes are implicated, with the associated condition classified as type I hemochromatosis. In contrast, juvenile hemochromatosis (type II hemochromatosis/ HFE II) is linked to mutations in the hemojuvelin gene or the antimicrobial peptide hepcidin. In this study, relevant literature in databases, including PubMed, MEDLINE records, Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, and Embase, was searched. Our study inclusion criteria encompassed both experimental and observational studies or a combination of both, with data derived from the human population. The exclusion criteria included animal models, observational studies, and unpublished data. Hepcidin is usually up-regulated in response to high serum iron, but it is unexpectedly low in patients with hemochromatosis because of mutations in HFE, hemojuvelin (JH), and transferrin receptor 2 (TfR2). TfR2, expressed by hepatocytes, is mutated in hemochromatosis type III. Future research directions include exploring the molecular mechanisms underlying the effects of the TFR2 gene variant on iron homeostasis and liver damage and investigating potential therapeutic targets for treating hemochromatosis-related liver disease. Additionally, further epidemiological and modern genetic engineering studies are needed to better understand the prevalence and impact of hemochromatosis on liver health in different populations.

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2025-06-04
2025-09-14

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/content/journals/cmm/10.2174/0115665240371495250505054101
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Hemochromatosis and Hepatic Complications: A Comprehensive Review of Molecular Mechanisms, Diagnostics, and Emerging Therapeutics
Bentham Science Publishers ; https://doi.org/10.2174/0115665240371495250505054101
/content/journals/cmm/10.2174/0115665240371495250505054101
/content/journals/cmm/10.2174/0115665240371495250505054101
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  • Article Type:     Review Article
Keywords: ferroprotein ; hemochromatosis ; Hemojuvelin ; TALENs ; hepcidin ; hepatocytes

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