Disease progression and liver cancer in the ferroportin disease

Corradini, Elena; Ferrara, Francesca; Pollicino, Teresa; Vegetti, Alberto; Abbati, Gian Luca; Losi, Luisa; Raimondo, Giovanni; Pietrangelo, Antonello

doi:10.1136/gut.2007.122549

Cited by 24 publications

(17 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This evidence is validated by a recent meta-analysis evaluating the studies focusing on this topic and confirming that OBI is an important risk factor for HCC development both in HCV-infected and HCV-negative patients with CLD [93]. Among HCV-negative patients, OBI appears able to exert its pro-oncogenic role in individuals without known causes of liver damage as well as in alcoholics and individuals with virus unrelated liver pathologies [20, 23, 94]. In this context, of great importance is a recent population-based cohort study conducted for more than two decades on Taiwanese mothers screened for HBV infection at each delivery and demonstrating that the risk of HCC development was significantly higher in women with persistent HBsAg-positive status, but among the HBsAg-negative mothers, those who underwent HBsAg sero-clearance during follow-up had a significantly higher risk of HCC development compared to HBV-unexposed women.…”

Section: Clinical Implicationmentioning

confidence: 69%

Occult HBV infection

et al. 2012

View full text Add to dashboard Cite

Section: Clinical Implicationmentioning

confidence: 69%

Occult HBV infection

et al. 2012

View full text Add to dashboard Cite

“…Its clinical presentation has been documented in individual case reports and small case series. The natural course has been reported in one small series [2]. Hyperferritinemia, a normal to low transferrin saturation and Kupffer cell iron storage, presenting as hepatic and spleen iron overload, are considered characteristic features of classical ferroportin disease [3].…”

Section: Introductionmentioning

confidence: 97%

Ferroportin disease: A systematic meta-analysis of clinical and molecular findings

Mayr

Janecke

Schranz

et al. 2010

Journal of Hepatology

120

105

View full text Add to dashboard Cite

Background & AimsClassical ferroportin disease is characterized by hyperferritinemia, normal transferrin saturation, and iron overload in macrophages. A non-classical form is characterized by additional hepatocellular iron deposits and a high transferrin saturation. Both forms demonstrate autosomal dominant transmission and are associated with ferroportin gene (SLC40A1) mutations. SLC40A1 encodes a cellular iron exporter expressed in macrophages, enterocytes, and hepatocytes. The aim of the analysis is to determine the penetrance of SLC40A1 mutations and to evaluate in silico tools to predict the functional impairment of ferroportin mutations as an alternative to in vitro studies.MethodsWe conducted a systematic review of the literature and meta-analysis of the biochemical presentation, genetics, and pathology of ferroportin disease.ResultsOf the 176 individuals reported with SLC40A1 mutations, 80 were classified as classical phenotype with hyperferritinemia and normal transferrin saturation. The non-classical phenotype with hyperferritinemia and elevated transferrin saturation was present in 53 patients. The remaining patients had normal serum ferritin or the data were reported incompletely. Despite an increased hepatic iron concentration in all biopsied patients, significant fibrosis or cirrhosis was present in only 11%. Hyperferritinemia was present in 86% of individuals with ferroportin mutations. Bio-informatic analysis of ferroportin mutations showed that the PolyPhen score has a sensitivity of 99% and a specificity of 67% for the discrimination between ferroportin mutations and polymorphisms.ConclusionsIn contrast to HFE hemochromatosis, ferroportin disease has a high penetrance, is genetically heterogeneous and is rarely associated with fibrosis. Non-classical ferroportin disease is associated with a higher risk of fibrosis and a more severe overload of hepatic iron.

show abstract

“…Previous attempts to treat AI with more moderate doses of iron alone (without added erythropoietin) have generally been unsuccessful, as iron became rapidly trapped in the macrophage compartment 12,24,25. Although newer iron preparations appear to be well tolerated26, the long term consequences of high dose iron therapy are not known and concerns have been raised about excess iron promoting infections and atherosclerosis27–29 as well as carcinogenesis30,31.…”

Section: Iron Restriction Is a Major Contributor To Anemia Of Inflammmentioning

confidence: 99%

Iron Sequestration and Anemia of Inflammation

Ganz

Nemeth

2009

Seminars in Hematology

303

229

View full text Add to dashboard Cite

Anemia of chronic disease, also called anemia of inflammation, is characterized by hypoferremia due to iron sequestration that eventually results in iron-restricted erythropoiesis. During the last decade, the molecular mechanisms of iron sequestration have been found to center on cytokinestimulated overproduction of the iron-regulatory hormone hepcidin. The inflammatory cytokine IL-6 is a particularly prominent inducer of hepcidin but other cytokines are likely to contribute as well. Hepcidin excess causes the endocytosis and proteolysis of the sole known cellular iron exporter, ferroportin, trapping iron in macrophages and iron-absorbing enterocytes. The supply of iron to hemoglobin synthesis becomes limiting, eventually resulting in anemia. Depending on the details of the underlying disease, other inflammation-related mechanisms may also contribute to anemia. Hypoferremia in infection and inflammationAs described more than sixty years ago, serum iron concentrations markedly decrease in humans 1 and in dogs 2 during the first few days of systemic infection or inflammation. More recent experimental studies in human volunteers injected with moderate doses of lipopolysaccharide 3 showed approximately a 50% decrease in serum iron by 24 hours. In another group of human subjects, a 3hr infusion of interleukin 6 (IL-6) was followed by an average 30% drop in serum iron 2 hrs later 4 . The rapid development of hypoferremia was also observed in mice with experimental meningococcal infection 5 or inflammation induced by turpentine 6 or LPS 7 . As suggested by the deleterious effects of iron supplementation during experimental infections 8,9 , the hypoferremia probably contributes to host defense against infection, likely by decreasing the iron supply to invading microbes. Hypoferremia of inflammation is caused by iron sequestration in macrophagesAs discussed elsewhere in this issue, normally most of the iron delivered to plasma (about 20-25 mg/day) is provided by macrophages involved in recycling senescent erythrocytes, and only 1-2 mg/day comes from iron absorption in the duodenum, with additional variable amounts delivered from stored iron in hepatocytes. Studies with iron-radiolabeled damaged erythrocytesCorrespondence to: Tomas Ganz, PhD, MD, CHS 37-055, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1690, Tel. 310-825-6112, FAX 310-206-8766, E-mail: tganz@mednet.ucla.edu. 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 form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. documented that inflammation or infection led to delayed appearance of radioactive iron in circulation and the a...

show abstract

Disease progression and liver cancer in the ferroportin disease

Cited by 24 publications

References 10 publications

Occult HBV infection

Occult HBV infection

Ferroportin disease: A systematic meta-analysis of clinical and molecular findings

Iron Sequestration and Anemia of Inflammation

Contact Info

Product

Resources

About