Hereditary hemochromatosis in the post-<i>HFE</i>era

Olynyk, John K.; Trinder, Debbie; Ramm, Grant A.; Britton, Robert S.; Bacon, Bruce R.

doi:10.1002/hep.22507

Cited by 86 publications

(90 citation statements)

References 140 publications

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“…Macrophages degrade the erythrocytederived haemoglobin and release the Fe back into the plasma, so it can be re-utilised for erythropoiesis in the bone marrow. Too much Fe is detrimental to health as excess Fe generates free radicals causing oxidative stress and tissue damage primarily in the liver, heart and pancreas [1][2][3]. Providing further evidence as to the detrimental effects of Fe, it has now been shown that reduction of body Fe stores by phlebotomy therapy, even within the normal physiological range, is associated with reduced mortality from endpoints such as cancer [4].…”

Section: Regulation Of Iron Metabolism In Health and Diseasementioning

confidence: 99%

“…Fe dependent regulation of hepcidin is controlled by bone morphogenetic protein /haemojuvelin/SMAD and HFE/transferrin receptor 2 (TFR2) signalling pathways. The pro-inflammatory cytokine interleukin-6 (IL-6) upregulates liver hepcidin via a STAT3 signalling pathway [1,2]. During anaemia increased erythropoietic activity is required to downregulate hepcidin expression and this is regulated by a number of factors including growth differentiation factor 15, while hypoxia and erythropoietin can also directly impair hepcidin expression.…”

Section: Regulation Of Iron Metabolism In Health and Diseasementioning

confidence: 99%

“…During anaemia increased erythropoietic activity is required to downregulate hepcidin expression and this is regulated by a number of factors including growth differentiation factor 15, while hypoxia and erythropoietin can also directly impair hepcidin expression. ROS reduces hepcidin via CCAAT/enhancer-binding protein  (C/EBP signalling pathway [1,2].…”

Section: Regulation Of Iron Metabolism In Health and Diseasementioning

confidence: 99%

“…Fe overload can be suspected from clinical information or elevated serum Fe biochemistry, but definitive diagnosis requires measurement of body Fe content (reviewed in [2]). This can be achieved by MRI-based R2 relaxometry, liver biopsy measurement of hepatic Fe concentration (HIC), or quantitative venesection [2,6,7].…”

Section: Diagnosis Of Iron Overload and Tissue Injurymentioning

confidence: 99%

“…This can be achieved by MRI-based R2 relaxometry, liver biopsy measurement of hepatic Fe concentration (HIC), or quantitative venesection [2,6,7].…”

Section: Diagnosis Of Iron Overload and Tissue Injurymentioning

confidence: 99%

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Non-Hfe Iron Overload: Is Phlebotomy the Answer?

2012

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Financial support:JKO is the recipient of a NHMRC Practitioner Fellowship (513761). DT is the recipient of a NHMRC Senior Research Fellowship (1020437). AbstractIron is an essential factor for life, however a physiologically optimal balance is critical. In this article we explore the role of iron as a co-factor in a range of chronic liver diseases and how it may contribute to the development of liver injury, fibrosis, cirrhosis and ultimately hepatocellular carcinoma. Whilst iron depletion therapy through phlebotomy is the most effective method of reducing iron stores, it is unclear whether this offers utility in the therapy of liver diseases in which iron is not the primary insult resulting in tissue injury. Here we examine the emerging evidence in the field of non-HFE hereditary haemochromatosis conditions associated with iron overload -is phlebotomy the answer?

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Section: Regulation Of Iron Metabolism In Health and Diseasementioning

confidence: 99%

Section: Regulation Of Iron Metabolism In Health and Diseasementioning

confidence: 99%

Section: Regulation Of Iron Metabolism In Health and Diseasementioning

confidence: 99%

Section: Diagnosis Of Iron Overload and Tissue Injurymentioning

confidence: 99%

“…This can be achieved by MRI-based R2 relaxometry, liver biopsy measurement of hepatic Fe concentration (HIC), or quantitative venesection [2,6,7].…”

Section: Diagnosis Of Iron Overload and Tissue Injurymentioning

confidence: 99%

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Non-Hfe Iron Overload: Is Phlebotomy the Answer?

2012

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Genotype–Phenotype Relationship in Hereditary Hemochromatosis

Ayres

Jayasekeran

Olynyk

2013

Encyclopedia of Life Sciences

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The majority of patients of northern European descent with hereditary hemochromatosis are homozygous for the C282Y mutation in the HFE gene product. A significant proportion of patients with this genotype have elevated iron indices; however, most will not develop symptoms or organ damage. Age, gender and alcohol are the key factors known to influence this wide variation in clinical penetrance. The authors describe the three stages of disease ranging from only genetic abnormality to overt disease and review the other factors that modify the genotype–phenotype relationship. Algorithms for use in clinical practice are included to aid clinicians in diagnosis, risk stratification and treatment. Key Concepts: Mutations in the HFE gene are relatively common. The vast majority of patients with iron overload are homozygous for the C282Y mutation in the HFE gene product. Biochemical penetrance, that is, elevated iron stores are present in 70–91% of males and 30–60% of females who are C282Y homozygotes. End‐organ damage is less common and occurs in approximately one‐quarter of males and 1% of females. End‐organ damage is extremely unlikely if serum ferritin is less than 1000 µg l −1 . The principal modifiers of disease are gender, age and alcohol. The wide variation in expression of clinical disease is largely unexplained. Various genes have been shown to have variable modifying effects on disease penetrance. Phlebotomy is a safe and effective treatment that depletes iron stores, prevents end‐organ damage and confers normal life expectancy. It is best initiated on discovery of elevated iron stores, that is, stage‐II or stage‐III disease.

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Integrating Molecular Testing into Clinical Applications

Killeen

2010

Pharmaceutical Sciences Encyclopedia

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The clinical laboratory plays a critical role in modern health care. In the United States, the clinical laboratory operates under the regulations of the Clinical Laboratory Improvement Amendments of 1988, which provide the framework for producing high‐quality results. This article focuses on the principal issues surrounding the integration of molecular testing into the clinical laboratory environment.

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Hereditary hemochromatosis in the post-HFEera

Cited by 86 publications

References 140 publications

Non-Hfe Iron Overload: Is Phlebotomy the Answer?

Non-Hfe Iron Overload: Is Phlebotomy the Answer?

Genotype–Phenotype Relationship in Hereditary Hemochromatosis

Integrating Molecular Testing into Clinical Applications

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