title: The liver in haemochromatosis.
abstract: The review deals with genetic, regulatory and clinical aspects of iron homeostasis and hereditary haemochromatosis. Haemochromatosis was first described in the second half of the 19th century as a clinical entity characterized by excessive iron overload in the liver. Later, increased absorption of iron from the diet was identified as the pathophysiological hallmark. In the 1970s genetic evidence emerged supporting the apparent inheritable feature of the disease. And finally in 1996 a new "haemochromatosis gene" called HFE was described which was mutated in about 85% of the patients. From the year 2000 onward remarkable progress was made in revealing the complex molecular regulation of iron trafficking in the human body and its disturbance in haemochromatosis. The discovery of hepcidin and ferroportin and their interaction in regulating the release of iron from enterocytes and macrophages to plasma were important milestones. The discovery of new, rare variants of non-HFE-haemochromatosis was explained by mutations in the multicomponent signal transduction pathway controlling hepcidin transcription. Inhibited transcription induced by the altered function of mutated gene products, results in low plasma levels of hepcidin which facilitate entry of iron from enterocytes into plasma. In time this leads to progressive accumulation of iron and subsequently development of disease in the liver and other parenchymatous organs. Being the major site of excess iron storage and hepcidin synthesis the liver is a cornerstone in maintaining normal systemic iron homeostasis. Its central pathophysiological role in HFE-haemochromatosis with downgraded hepcidin synthesis, was recently shown by the finding that liver transplantation normalized the hepcidin levels in plasma and there was no sign of iron accumulation in the new liver.
authors.affiliation: Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen N-5021, Norway. Electronic address: rune.ulvik@k2.uib.no.
authors.forename: Rune J
authors.initials: RJ
authors.lastname: Ulvik
mesh_terms: D006432:Hemochromatosis / Q000175:diagnosis* / Q000209:etiology* / Q000235:genetics / Q000628:therapy; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000378:metabolism; D008099:Liver / Q000378:metabolism*
chemical_list: D007501:Iron
keywords: Haemochromatosis; Iron homeostasis; Iron overload; Liver