Iron and the liver: Update 2008☆

The cross-talk which has taken place in recent years between clinicians and scientists has resulted in a greater understanding of iron metabolism with the discovery of new iron-related genes including the hepcidin gene which plays a critical role in regulating systemic iron homeostasis. Consequently, the distinction between (a) genetic iron-overload disorders including haemochromatosis related to mutations in the HFE, hemojuvelin, transferrin receptor 2 and hepcidin genes and (b) non-haemochromatotic conditions related to mutations in the ferroportin, ceruloplasmin, transferrin and di-metal transporter 1 genes, and (c) acquired iron-overload syndromes has become easier. However, major challenges still remain which include our understanding of the regulation of hepcidin production, the identification of environmental and genetic modifiers of iron burden and organ damage in iron-overload syndromes, especially HFE haemochromatosis, indications regarding the new oral chelator, deferasirox, and the development of new therapeutic tools interacting with the regulation of iron metabolism.

Abbreviations: AST, aspartate amino transferase, BMP, bone morphogenic protein, BMPR, bone morphogenic protein receptor, C/EBP, CCAAT/enhancer binding protein, DIOS, dysmetabolic iron-overload syndrome, DMT, divalent metal transporter, ERK, extracellular regulated MAP kinase, GDF, growth differentiation factor, Hamp, hepcidin anti-microbial peptide, HAS, Haute Autorité de Santé, HCC, hepatocellular carcinoma, HCV, hepatitis C virus, HIF, hypoxia-inducible factor, HJV, hemojuvelin, IL, interleukin, INSERM, Institut National de la Santéet de la RechercheMédicale, JAK, Janus kinase, LIC, liver iron concentration, MAP, mitogen activated protein, MRI, magnetic resonance imaging, NTBI, nontransferrin bound iron, ROS, reactive oxygen species, STAT, signal transducer and activator of transcription, TfR, transferrin receptor, TGF, transforming growth factor

Keywords: Haemochromatosis, Hepatic iron-overload, Iron metabolism