Reversibility of hepatic fibrosis in treated genetic hemochromatosis: A study of 36 cases

Falize, Ludivine; Guillygomarc’h, Anne; Perrin, M.; Lainé, Fabrice; Guyader, Dominique; Brissot, Pierre; Turlin, Bruno; Deugnier, Yves

doi:10.1002/hep.21260

Cited by 209 publications

(117 citation statements)

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“…Hepatic fibrosis, and occasionally cirrhosis, can also be reversed by iron removal (43), but cirrhosis in most cases is irreversible and is associated with an increased risk of primary hepatocellular carcinoma. We previously reported that male C282Y homozygotes in the HEIRS Study were more likely to report a history of liver disease at the time of the initial screening examination than were participants without HFE mutations (24).…”

Section: Discussionmentioning

confidence: 99%

Clinical Manifestations of Hemochromatosis inHFEC282Y Homozygotes Identified by Screening

McLaren

Adams

et al. 2008

Canadian Journal of Gastroenterology

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OBJECTIVE:To assess prevalences of self-reported symptoms and clinical signs and conditions in persons homozygous for the hemochromatosis gene (HFE) mutation (C282Y) identified by screening. METHODS: Participants were adults 25 years of age or older enrolled in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. C282Y homozygotes (n=282) were compared with control participants without the HFE C282Y or H63D alleles (ie, wild type/wild type; n=364). RESULTS: Previously diagnosed C282Y homozygotes and newly diagnosed homozygotes with elevated serum ferritin levels had higher prevalences of certain symptoms such as chronic fatigue (OR 2.8; 95% CI 1.34 to 5.95, and OR 2.0; 95% CI 1.07 to 3.75, respectively), and had more hyperpigmentation on physical examination (OR 4.7; 95% CI 1.50 to 15.06, and OR 3.7; 95% CI 1.10 to 12.16, respectively) and swelling or tenderness of the second and third metacarpophalangeal joints (OR 4.2; 95% CI 1.37 to 13.03, and OR 3.3; 95% CI 1.17 to 9.49, respectively) than control subjects. Joint stiffness was also more common among newly diagnosed C282Y homozygotes with elevated serum ferritin than among control subjects (OR 2.7; 95% CI 1.38 to 5.30). However, the sex-and age-adjusted prevalences of self-reported symptoms and signs of liver disease, heart disease, diabetes and most other major clinical manifestations of hemochromatosis were similar in C282Y homozygotes and control subjects. CONCLUSIONS: Some symptoms and conditions associated with hemochromatosis were more prevalent among C282Y homozygotes identified by screening than among control subjects, but prevalences of most outcomes were similar in C282Y homozygotes and controls in this primary care-based study.

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Section: Discussionmentioning

confidence: 99%

Clinical Manifestations of Hemochromatosis inHFEC282Y Homozygotes Identified by Screening

McLaren

Adams

et al. 2008

Canadian Journal of Gastroenterology

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“…This could, of course, be merely due to the fact that the disorder was diagnosed at earlier and earlier stages or that better supportive treatment became available for diabetes, cirrhosis, and infections. More compelling is the fact that cirrhosis of the liver seems, on serial biopsy, to improve after phlebotomy treatment is instituted [74][75][76].…”

Section: Treatment Of Iron Overloadmentioning

confidence: 99%

Iron storage disease: Facts, fiction and progress

Beutler

2007

Blood Cells, Molecules, and Diseases

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There are many forms of iron storage disease, some hereditary and some acquired. The most common of the hereditary forms is HFE-associated hemochromatosis, and it is this disorder that is the main focus of this presentation. The body iron content is regulated by controlling absorption, and studies in the past decade have clarified, in part, how this regulation functions. A 25 amino acid peptide hepcidin is upregulated by iron and by inflammation, and it inhibits iron absorption and traps iron in macrophages by binding to and causing degradation of the iron transport protein ferroportin. Most forms of hemochromatosis results from dysregulation of hepcidin or defects of hepcidin or ferroportin themselves.Hereditary hemochromatosis was once considered to be very rare, but in the 1970s and 1980s, with the introduction of better diagnostic tests, it became to be considered the most common disease of Europeans. Controlled epidemiologic studies carried out in the last decade have shown, however, the disease itself actually is rare, and it is only the genotype and associated biochemical changes that are common. We do not understand why only a few homozygotes develop severe disease. It now seems unlikely that there are important modifying genes, and although alcohol is known to have some effect, excess drinking probably plays only a modest role in determining the hemochromatosis phenotype.Hereditary hemochromatosis is readily treated by phlebotomy. Secondary forms of the disease require chelation therapy, and the recent introduction of effective oral chelating agents is an important step forward in treating patients with disorders in which iron overload often proves to be fatal, such as thalassemia, myelodysplastic anemias, and dyserythropoietic anemias.While much has been learned about the regulation of iron homeostasis in the past decade, many mysteries remain and represent challenges that will keep us occupied for years to come.It is a great honor for me to present this lecture in memory of my good friend Bracha Ramot. It is because this lecture is in honor of Bracha that I do not feel the least bit uncomfortable speaking about iron storage diseases in a symposium entitled "Genomics and Molecular Biology of Hematopoietic Malignancies". I know that had it been possible to ask her whether this might be appropriate Bracha would have said: "Of course, Ernie. Talk about whatever you want to". That was her way. And, of course, Bracha was no stranger to iron metabolism. She was scientifically broad, a Renaissance hematologist. A MEDLINE search reveals 261 publications by Bracha and eight of those deal with iron --iron in thalassemia, iron in sideroblastic anemia, and iron in iron deficiency anemia.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable...

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“…Despite correct elimination of the iron burden, insulindependent diabetes will not resolve, and the risk for hepatocellular carcinoma remains if cirrhosis was present prior to venesection therapy. Although regression of cirrhosis is sometimes observed following venesection therapy, 34 whether this decreases the risk for the development of hepatocellular carcinoma requires further study. …”

Section: Results Of Venesectionmentioning

confidence: 99%

Current Approaches to the Management of Hemochromatosis

Brissot

Bels²

2006

Hematology

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The term hemochromatosis encompasses at least four types of genetic iron overload conditions, most of them recently distinguished from one another as a result of the identification of a series of genes related to iron metabolism. At least three of these entities (HFE hemochromatosis, juvenile hemochromatosis and transferrin receptor 2 hemochromatosis) involve systemic hepcidin deficiency as a key pathogenetic factor. Major advances in the management of hemochromatosis influence the diagnostic approach to the disease, with the development of an overall non invasive strategy, mainly based on clinical, biological (iron parameters and genetic testing), and imaging (especially magnetic resonance imaging) data. Therapeutic management remains, on the curative side, dominated by phlebotomy (venesection), practical aspects of which have been recently revisited by the Guidelines Department of the French "Haute Autorité de Santé." However, innovative treatment approaches, based on the improved pathophysiological understanding of these diseases and the progress in iron chelation therapy, are emerging. Preventive therapy, focused on family screening, remains a key part of the management of hemochromatosis.

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Reversibility of hepatic fibrosis in treated genetic hemochromatosis: A study of 36 cases

Cited by 209 publications

References 45 publications

Clinical Manifestations of Hemochromatosis inHFEC282Y Homozygotes Identified by Screening

Clinical Manifestations of Hemochromatosis inHFEC282Y Homozygotes Identified by Screening

Iron storage disease: Facts, fiction and progress

Current Approaches to the Management of Hemochromatosis

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