Serum Ferritin Levels Are Associated with Vascular Damage in Patients with Nonalcoholic Fatty Liver Disease.

Valenti, L.; Swinkels, Dorine W.; Burdick, L.; Dongiovanni, Paola; Tjalsma, Harold

doi:10.1182/blood.v114.22.5098.5098

Cited by 15 publications

(26 citation statements)

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“…In 143 patients with non-alcoholic fatty liver disease, hepcidin-25 levels were found to be associated with the presence of carotid plaques. 18 In a similar group of 130 patients with nonalcoholic fatty liver disease, monocyte chemo-attractant protein-1, a chemokine that plays an important role in both the initiation and progression of atherosclerosis, was 0.8737 ± 0.1956 BMI = body mass index; CIMT = carotid intima media thickness; CRP = C-reactive protein; CVD = cardiovascular disease; DBP = diastolic blood pressure; ESA = erythropoesis stimulating agent; HDL = high-density lipoprotein; LDL = low-density lipoprotein; RAS = renin angiotensin system; SBP = systolic blood pressure; TSAT = transferrin saturation.…”

Section: Discussionmentioning

confidence: 99%

Is hepcidin‐25 a predictor of atherosclerosis in hemodialysis patients?

Kali

Yayar

Erdoğan

et al. 2015

Hemodialysis International

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Atherosclerotic cardiovascular disease is an important cause of mortality and morbidity in hemodialysis patients. Iron accumulation in arterial wall macrophages is increased in atherosclerotic lesions. Hepcidin is a key hepatic hormone regulating iron balance. It inhibits iron release from macrophages and iron absorption from enterocytes by binding and inactivating the cellular iron exporter ferroportin. The aim of this study is to investigate the relation of hepcidin-25, iron parameters, and atherosclerosis measured by carotid intima media thickness (CIMT) in hemodialysis patients. Eighty-two hemodialysis patients were enrolled in this cross-sectional study. Predialysis blood samples were centrifuged at 1500 g and 4°C for 10 minutes and stored at -80°C for the measurement of hepcidin-25. DRG hepcidin enzyme-linked immunosorbent assay kit was used for the measurement of hepcidin-25. Ultrasonographical B-mode imaging of bilateral carotid arteries was performed with a high-resolution real-time ultrasonography (Mindray DC7). Mean age of the study population was 57.90 ± 16.08 years and 43.9% were men. Total study population was grouped into two according to median value of hepcidin-25. There was no difference between groups with respect to age, dialysis vintage, and C-reactive protein. CIMT was found to be statistically significantly higher in low hepcidin-25 group. In correlation analysis, CIMT was found to be correlated with age (P < 0.01, R = 0.33) and hepcidin-25 (P < 0.01, R = 0.46). In linear regression analysis, age (β = 0.31) and hepcidin-25 (β = 0.44) were found to be the determinants of CIMT in hemodialysis patients. Our results implicate that hepcidin may take part in pathophysiology of atherosclerosis and cardiovascular disease in hemodialysis patients.

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Section: Discussionmentioning

confidence: 99%

Is hepcidin‐25 a predictor of atherosclerosis in hemodialysis patients?

Kali

Yayar

Erdoğan

et al. 2015

Hemodialysis International

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“…Interestingly, in separate studies using similar cohorts of Italian NAFLD subjects, Valenti et al have shown that the C282Y/WT and H63D/H63D genotypes were independently associated with HC iron deposition using multivariate regression analysis, 32 and that these combined genotypes had lower serum hepcidin levels than subjects with either H63D/WT or WT/WT genotypes with similar SF levels. 31 All known C282Y homozygotes were excluded from all NASH CRN studies, thereby not allowing us to determine the effect of C282Y homozygosity on hepcidin level, degree of hepatic iron deposition, or relationship to NAFLD severity. However, the degree of penetrance of C282Y heterozygosity to cause mild to moderate HC iron loading in NAFLD subjects (34%) appears to be similar to the penetrance of C282Y homozygosity to cause HC iron overload in HH patients; an estimated 38%-50% of C282Y homozygotes develop iron overload (33), with 1%-28% developing iron-related disease.…”

Section: Discussionmentioning

confidence: 99%

Lower serum hepcidin and greater parenchymal iron in nonalcoholic fatty liver disease patients with C282Y HFE mutations

2012

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Hepcidin regulation is linked to both iron and inflammatory signals and may influence iron loading in nonalcoholic steatohepatitis (NASH). The aim of this study was to examine the relationships among HFE genotype, serum hepcidin level, hepatic iron deposition and histology in nonalcoholic fatty liver disease (NAFLD). SNP genotyping for C282Y (rs1800562) and H63D (rs1799945) HFE mutations was performed in 786 adult subjects in the NASH Clinical Research Network (CRN). Clinical, histologic, and laboratory data were compared using nonparametric statistics and multivariate logistic regression. NAFLD patients with C282Y, but not H63D mutations, had lower median serum hepcidin levels (57 vs 65 ng/ml, p=0.01) and higher mean hepatocellular (HC) iron grades (0.59 vs 0.28, p<0.001), compared to wild type (WT) subjects. Subjects with hepatic iron deposition had higher serum hepcidin levels than subjects without iron for all HFE genotypes (p<0.0001). Hepcidin levels were highest among patients with mixed HC/reticuloendothelial system cell (RES) iron deposition. H63D mutations were associated with higher steatosis grades and NAFLD activity scores (OR≥1.4, CI >1.0≤2.5, p≤0.041), compared to WT, but not with either HC or RES iron. NAFLD patients with C282Y mutations had less ballooning or NASH (OR ≤0.62, 95% CI >0.39<0.94, p≤0.024) compared to WT subjects. Conclusions Presence of C282Y mutations in patients with NAFLD is associated with greater HC iron deposition and decreased serum hepcidin levels and there is a positive relationship between hepatic iron stores and serum hepcidin level across all HFE genotypes. These data suggest that body iron stores are the major determinant of hepcidin regulation in NAFLD regardless of HFE genotype. A potential role for H63D mutations in NAFLD pathogenesis is possible through iron-independent mechanisms.

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“…Part of this group was described previously. 18 Hepatic iron staining was performed according to Scheuer,16 in patients from a previous study or when hyperferritinaemia or NASH were present. 13 Hepatic iron quantification by atomic absorption spectrometry was performed in 129 patients.…”

Section: Validation Cohortmentioning

confidence: 99%

Hepatic iron is the major determinant of serum ferritin in NAFLD patients

Ryan

Armitage

Cobbold

et al. 2017

Liver International

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Background and Aims Elevated serum ferritin is common in NAFLD, and is associated with more advanced disease and increased mortality. Hyperferritinaemia in NAFLD is often attributed to inflammation, while in other conditions ferritin closely reflects body iron stores. The aim of this study was to clarify the underlying cause of hyperferritinaemia in NAFLD. Methods Ferritin levels were examined with markers of iron status, inflammation and liver injury across the clinical spectrum of NAFLD using blood, tissue and magnetic resonance (MR) imaging. A separate larger group of NAFLD patients with hepatic iron staining and quantification were used for validation. Results Serum ferritin correlated closely with the iron regulatory hormone hepcidin, and liver iron levels determined by MR. Furthermore, ferritin levels reflected lower serum adiponectin, a marker of insulin resistance, and liver fat, but not cytokine or CRP levels. Ferritin levels differed according to fibrosis stage, increasing from early to moderate disease, and declining in cirrhosis. A similar pattern was found in the validation cohort of NAFLD patients, where ferritin levels were highest in those with macrophage iron deposition. Multivariate analysis revealed liver iron and hepcidin levels as the major determinants of serum ferritin. Conclusions While hyperferritinaemia is associated with markers of liver injury and insulin resistance, serum hepcidin and hepatic iron are the strongest predictors of ferritin levels. These findings highlight the role of disordered iron homeostasis in the pathogenesis of NAFLD, suggesting that therapies aimed at correcting iron metabolism may be beneficial.

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Serum Ferritin Levels Are Associated with Vascular Damage in Patients with Nonalcoholic Fatty Liver Disease.

Cited by 15 publications

References 0 publications

Is hepcidin‐25 a predictor of atherosclerosis in hemodialysis patients?

Is hepcidin‐25 a predictor of atherosclerosis in hemodialysis patients?

Lower serum hepcidin and greater parenchymal iron in nonalcoholic fatty liver disease patients with C282Y HFE mutations

Hepatic iron is the major determinant of serum ferritin in NAFLD patients

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