scholarly journals Role of Liver Biopsy in the Diagnosis of Hepatic Iron Overload in the Era of Genetic Testing

2002 ◽  
Vol 118 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Shirin Nash ◽  
Sharon Marconi ◽  
Krystyna Sikorska ◽  
Rizwan Naeem ◽  
Gerald Nash
Keyword(s):  
Genetic Testing ◽  
Liver Biopsy ◽  
Iron Overload ◽  
Hepatic Iron ◽  
Hepatic Iron Overload

scholarly journals The role of MR imaging in detection of hepatic iron overload in patients with cirrhosis of different origins

2010 ◽  
Vol 10 (1) ◽  
Author(s):  
Edyta Szurowska ◽  
Katarzyna Sikorska ◽  
E Iżycka-Świeszewska ◽  
Tomasz Nowicki ◽  
Tomasz Romanowski ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Iron Overload ◽  
Hepatic Iron ◽  
Hepatic Iron Overload ◽  
Different Origins

P1235 : Hereditary hemochromatosis: Role of H63D homozygosity in hepatic iron overload

2015 ◽  
Vol 62 ◽  
pp. S819-S820
Author(s):  
R.M. Martin Mateos ◽  
J. Graus Morales ◽  
D. Rey Zamora ◽  
V.F. Moreira Vicente ◽  
A. Albillos ◽  
...  
Keyword(s):  
Iron Overload ◽  
Hereditary Hemochromatosis ◽  
Hepatic Iron ◽  
Hepatic Iron Overload

scholarly journals Iron Overload in Allogeneic Hematopoietic Stem Cell Transplant Recipients

2012 ◽  
Vol 136 (5) ◽  
pp. 532-538 ◽  
Author(s):  
Sharif Ali ◽  
Jason D. Pimentel ◽  
Javier Munoz ◽  
Veena Shah ◽  
Rick McKinnon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Liver Biopsy ◽  
Iron Overload ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Hepatic Iron ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Hepatic Iron Overload

Context.—Patients who undergo hematopoietic stem cell transplant are at an increased risk of developing iron overload. Objectives.—To describe the effect of hepatic iron overload on hematopoietic stem cell transplant recipients and to validate the utility of histologic scoring system of iron granules in the liver. Design.—Records of 154 post allogeneic hematopoietic stem cell transplant patients were reviewed. Forty-nine patients underwent liver biopsy. Histologic hepatic iron overload was defined as a score of 2 or greater (scale, 0–4). Results.—Twenty-eight of 49 patients (57%) evaluated by liver biopsy had hepatic iron overload; 17 had moderate to severe hepatic iron overload (score, 3 or 4). In multivariate analysis, a significant correlation was discovered between hepatic iron overload and the number of transfusions (P < .001), posttransplant serum ferritin levels (P  =  .004), lactate dehydrogenase levels (P  =  .03), and the development of blood stream infections (P  =  .02). There was no correlation between hepatic iron overload and abnormal liver function test results. While 37 patients (76%) died after receiving a transplant, mortality was not influenced by hepatic iron overload but was significantly higher in older patients, in patients with lower serum albumin levels, higher serum bilirubin levels, and higher clinical grade of acute graft-versus-host disease (P  =  .04, P  =  .001, P  =  <.001, and P  =  .004, respectively). Conclusions.—Hepatic iron overload is commonly identified in hematopoietic stem cell transplant patients and can be accurately diagnosed by liver biopsy. In addition, hepatic iron overload has been identified in patients receiving as few as 25 units of packed red blood cells, with elevated posttransplant serum ferritin levels, and with blood stream infections.

Inactivating Hfe Totally Abolishes Hepcidin Production and Further Aggravates Iron Overload In Bmp6-Deficient Mice

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 178-178
Author(s):  
Chloe Latour ◽  
Celine Besson-Fournier ◽  
Nelly Rouquie ◽  
Léon Kautz ◽  
Patricia Aguilar-Martinez ◽  
...  
Keyword(s):  
Iron Overload ◽  
Hepatic Iron ◽  
Dietary Iron ◽  
Iron Loading ◽  
Wild Type ◽  
Severe Phenotype ◽  
Double Knockout ◽  
Hepcidin Expression ◽  
Hepatic Iron Overload

Abstract Hepcidin, a circulating hormone produced primarily by the liver, plays a central role in the regulation of systemic iron homeostasis necessary to ensure sufficient availability of iron for hemoglobin synthesis and other metabolic processes while avoiding the oxidative damage to cells that can result from excess free iron. Hepcidin triggers internalization and degradation of ferroportin, the only known iron export channel from cells into the plasma, which leads to the decrease of dietary iron absorption from duodenal enterocytes and to the sequestration of iron recycled from senescent blood cells within macrophages. Iron overload induces the expression of bone morphogenetic protein 6 (BMP6), a member of the TGF-beta superfamily of ligands, which activates a signaling cascade leading to SMAD1/5/8 phosphorylation, translocation of the phosphorylated SMADs bound to SMAD4 to the nucleus, and upregulation of hepcidin gene transcription. Inactivation of Bmp6 in mice leads to considerably reduced hepcidin production, compared with wild-type mice, and severe hepatic iron overload. However, there are major differences in hepcidin expression and extrahepatic tissue iron loading between Bmp6-deficient males and females, due to the suppressive effect of testosterone on hepcidin in males. In contrast to males, Bmp6-/- females still produce some hepcidin and do not massively accumulate iron in their pancreas, their heart or their kidneys. The goal of this study was to investigate the role of Hfe in the residual hepcidin production observed in the absence of Bmp6 in females. Mutations in the HFE gene are causing the most common form of hereditary hemochromatosis, a disorder characterized by a chronic inappropriate increase in dietary iron uptake, progressive iron overload and tissue injury. Human patients and mouse models of HFE-related hemochromatosis show inappropriately low expression of hepcidin. However, the mechanism by which HFE influences hepcidin expression is still unclear. In Hfe-/- mice and in patients with HFE-associated hemochromatosis, the induction of BMP6 mRNA by iron is intact, but hepcidin production is impaired. In the mouse, Hfe and Bmp6 genes are separated by less than 8 cM on chromosome 13, and the probability of obtaining recombinants between the 2 loci is low. However, HFE is a non-classical MHC class 1-like molecule which associates with β2-microglobulin and β2m-/- mice develop spontaneously hepatic iron overload with a distribution similar to that seen in the liver of Hfe-/- mice. We therefore generated β2m/Bmp6 double knockout mice in which the function of both Hfe and Bmp6 is impaired. Briefly, Bmp6-/- mice on a CD1 background were mated to β2m-/- mice on a C57BL/6 background and double heterozygote F1 mice were intercrossed. We assessed Smad1/5/8 phosphorylation, hepcidin expression, and the sites of iron accumulation in wild-type, simple knockout (β2m-/- or Bmp6-/-) and double knockout (β2m-/- and Bmp6-/-) mice of the F2 progeny. Interestingly, the lack of functional Hfe in Bmp6-/- females led to a much more severe phenotype than the single impairment of Bmp6, with massive iron loading in extrahepatic tissues, most notably the exocrine pancreas, the heart, and the proximal and distal convoluted tubules of the kidney. Phosphorylation of Smad1/5/8 in double knockout (β2m-/- and Bmp6-/-) mice was virtually abolished and hepcidin mRNA in double knockout females was much more strongly downregulated than in single Bmp6-/- females. In contrast to Bmp6-/- females, no protein was detectable by ELISA in double knockout mice. Our findings show that Bmp6 and Hfe regulate hepcidin production by two independent pathways that converge on Smad1/5/8 phosphorylation. The role of transferrin receptor 2 (TFR2), another hemochromatosis-associated molecule, remains a key question. The total suppression of hepcidin in mice in which both Hfe and Bmp6 have been impaired suggests that TFR2 does not regulate hepcidin through an additional pathway. Moreover, the observation that Hfe-/-/Tfr2-/- mice have a more severe phenotype than simple Hfe-/- or Tfr2-/- mice favors the interference of Tfr2 with the Bmp6 pathway. Comparison of the phenotype of mice with inactivation of both Bmp6 and Tfr2 to that of Bmp6-/- mice is likely to definitively solve this still open question. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Pathogenic Role of Iron Deposition in Reticuloendothelial Cells during the Development of Chronic Hepatitis C

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Hironori Mitsuyoshi ◽  
Kohichiroh Yasui ◽  
Kanji Yamaguchi ◽  
Masahito Minami ◽  
Takeshi Okanoue ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Iron Overload ◽  
Chronic Hepatitis C ◽  
Iron Deposition ◽  
Hepatic Iron ◽  
Deposition Pattern ◽  
Hepatic Iron Overload ◽  
Hepcidin Mrna

Aim. Chronic hepatitis C (CHepC) is frequently associated with hepatic iron overload, yet mechanisms underlying iron-induced liver injury have not been elucidated. We examined the significance of iron deposition in hepatocytes (HC) and reticuloendothelial cells (REC) in CHepC.Methods. Stainable hepatic iron was scored according to the iron deposition pattern in 373 patients. The levels of serum soluble TNF-αreceptor (sTNFR2) and hepatic hepcidin mRNA and the efficacy of phlebotomy were compared among patients with different iron deposition patterns.Results. Serum transaminase levels and hepatic scores of stage, grade, and steatosis were higher in patients with REC iron staining than in those without. REC iron scores were independently associated with advanced stage. Serum sTNFR2 levels were significantly higher in patients with REC iron than in those without. REC iron scores were independently correlated with sTNFR2 levels. Compared with patients without stainable iron, those with iron overload had decreased ratios of hepcidin mRNA to serum ferritin. The efficacy of phlebotomy was greater in patients with REC iron than in those without REC iron.Conclusions. The present results show the importance of REC iron for the development of CHepC and the therapeutic effect of phlebotomy in CHepC.

1150 HEPATIC IRON OVERLOAD IN PATIENTS WITH ALCOHOLIC LIVER DISEASE IS DUE TO INADEQUATE HEPCIDIN INDUCTION: ROLE OF H2O2 IN HEPCIDIN REGULATION

2010 ◽  
Vol 52 ◽  
pp. S444 ◽  
Author(s):  
G. Millonig ◽  
G.N. Waite ◽  
T. Longerich ◽  
P. Schirmacher ◽  
M.U. Muckenthaler ◽  
...  
Keyword(s):  
Liver Disease ◽  
Iron Overload ◽  
Alcoholic Liver Disease ◽  
Hepatic Iron ◽  
Hepatic Iron Overload

scholarly journals Hepatic iron overload in patients with chronic viral hepatitis: Role of HFE gene mutations

Hepatology ◽  
1998 ◽  
Vol 28 (4) ◽  
pp. 1105-1109 ◽  
Author(s):  
Alberto Piperno ◽  
Anna Vergani ◽  
Ida Malosio ◽  
Laura Parma ◽  
Laura Fossati ◽  
...  
Keyword(s):  
Iron Overload ◽  
Viral Hepatitis ◽  
Gene Mutations ◽  
Chronic Viral Hepatitis ◽  
Hfe Gene ◽  
Hepatic Iron ◽  
Hepatic Iron Overload ◽  
Hfe Gene Mutations
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