Survival After Liver Transplantation in Patients With Hepatic Iron Overload: The National Hemochromatosis Transplant Registry

Kowdley, Kris V.; Brandhagen, David J.; Gish, Robert G.; Bass, Nathan M.; Weinstein, Jeffrey; Schilsky, Michael L.; Fontana, Robert J.; McCashland, Timothy M.; Cotler, Scott J.; Bacon, Bruce R.; Keeffe, Emmet B.; Gordon, Fredric D.; Polissar, Nayak L.

doi:10.1016/j.gastro.2005.05.004

Cited by 124 publications

(57 citation statements)

References 32 publications

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“…Our results extend a number of previously published reports of the association of hepatic iron with adverse outcomes in CHC, as well as in other liver diseases, especially fatty liver/steatohepatitis1–6, 8, 15, 29–32. The importance of iron as a co-morbid factor in CHC is emphasized by several recent reports of greater fibrosis, and greater risks of HCC development with more hepatic iron30, 32.…”

Section: Discussionsupporting

confidence: 89%

“…Three genetic variations in HFE , namely, C282Y, H63D, and S65C, have been associated with hemochromatosis (HC). Adverse effects of hepatic iron (with or without HFE mutations) and HFE mutations (with or without elevated iron) on survival after liver transplantation have been described8. In order to produce an iron-overload phenotype in the absence of other genetic or environmental factors, both HFE alleles must be affected: e.g., homozygosity for C282Y (the major mutation); compound heterozygosity for C282Y and H63D; or compound heterozygosity for C282Y and S65C.…”

Section: Introductionmentioning

confidence: 99%

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Iron Levels in Hepatocytes and Portal Tract Cells Predict Progression and Outcomes of Patients With Advanced Chronic Hepatitis C

et al. 2011

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Background & Aims Iron might influence severity and progression of non-hemochromatotic liver diseases. We assessed the relationships between iron, variants in HFE, and progression and outcomes using data from the HALT-C Trial. We determined whether therapy with pegylated interferon (PegIFN) affects iron variables. Methods Participants were randomly assigned to groups given long-term therapy with PegIFN (n=400) or no therapy (n=413) for 3.5 y and followed for up to 8.7 y (median 6.0 y). Associations between patient characteristics and iron variables, at baseline and over time, were made using Kaplan-Meier analyses, Cox regression models, and repeated measures analysis of covariance. Iron was detected by Prussian blue staining. Results Patients with poor outcomes (increase in Child-Turcotte-Pugh score to ≥ 7, development of ascites, encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, hepatocellular carcinoma, death) had significantly higher baseline scores for stainable iron in hepatocytes and cells in portal tracts than those without outcomes. Staining for iron in portal triads correlated with lobular and total Ishak inflammatory and fibrosis scores (P<0.0001). High baseline levels of iron in triads increased the risk for poor outcome (hazard ratio=1.35, P=0.02). Iron staining decreased in hepatocytes but increased in portal stromal cells over time (P<0.0001). Serum levels of iron and total iron binding capacity decreased significantly over time (P <0.0001), as did serum ferritin (P=0.0003). Long-term therapy with PegIFN did not affect levels of iron staining. Common variants in HFE did not correlate with outcomes, including development of hepatocellular carcinoma. Conclusions Degree of stainable iron in hepatocytes and portal tract cells predicts progression and clinical and histological outcomes of patients with advanced chronic hepatitis C. Long-term therapy with low-dose PegIFN did not improve outcomes or iron variables.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Iron Levels in Hepatocytes and Portal Tract Cells Predict Progression and Outcomes of Patients With Advanced Chronic Hepatitis C

et al. 2011

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“…Early reports on the outcome of HFE-HC after liver transplantation for HFE-HC [59,231,232] have found that survival may be lower than in other groups. Survival for transplant patients is around 64% after 1 year, and 34% after 5 years [231].…”

Section: Dietmentioning

confidence: 94%

EASL clinical practice guidelines for HFE hemochromatosis

Ji-don¹

2010

Journal of Hepatology

480

167

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Iron overload in humans is associated with a variety of genetic and acquired conditions. Of these, HFE hemochromatosis (HFE-HC) is by far the most frequent and most well-defined inherited cause when considering epidemiological aspects and risks for iron-related morbidity and mortality. The majority of patients with HFE-HC are homozygotes for the C282Y polymorphism [1]. Without therapeutic intervention, there is a risk that iron overload will occur, with the potential for tissue damage and disease. While a specific genetic test now allows for the diagnosis of HFE-HC, the uncertainty in defining cases and disease burden, as well as the low phenotypic penetrance of C282Y homozygosity poses a number of clinical problems in the management of patients with HC. This Clinical Practice Guideline will therefore, focus on HFE-HC, while rarer forms of genetic iron overload recently attributed to pathogenic mutations of transferrin receptor 2, (TFR2), hepcidin (HAMP), hemojuvelin (HJV), or to a sub-type of ferroportin (FPN) mutations, on which limited and sparse clinical and epidemiologic data are available, will not be discussed. We have developed recommendations for the screening, diagnosis, and management of HFE-HC.

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“…Especially when the disease is mild, some clinical features may be reversed with adequate therapy. However, unlike the other organopathies observed with hemochromatosis, arthritis does not regress with treatment [27, 28] and it is suggested that severity of hemochromatosis arthropathy correlates with iron stores [29]. Iron is known to catalyze oxidative reactions with subsequent formation of reactive oxygen species that can cause inflammation and tissue damage.…”

Section: Discussion Of Casementioning

confidence: 99%