Iron overload in cirrhosis?HFE genotypes and outcome after liver transplantation

Abstract

Previously, we found appreciable hepatic iron deposition in one third of our patients undergoing liver transplantation (LTx) with approximately 10% of cases having quantifiable iron in the range of that seen in hereditary hemochromatosis (HHC). The aim of this study was to compare clinical outcome in liver transplant patients with and without iron overload. We also sought to determine the prevalence of HFE mutations in liver transplant patients with iron overload. Of 456 consecutive liver transplants, 41 explants had an hepatic iron index (HII) greater than 1.9, and these cases were compared to 41 matched liver transplant recipients without increased hepatic iron. Posttransplantation complications, along with patient and graft survival were monitored. HFE gene testing was performed using DNA-based techniques. Kaplan-Meier 5-year patient survival after LTx was significantly lower in cases with hepatic iron overload compared to matched controls without iron excess (48% vs.

Increased duodenal expression of divalent metal transporter 1 and iron-regulated gene 1 in cirrhosis

“…Forty-five percent of subjects had acanthocytes, which is consistent with the findings of previous studies. [1][2][3] Williams et al 5 failed to demonstrate a correlation between intestinal iron absorption and the grade of hepatic siderosis and we found no correlation between DMT1 or Ireg1 expression and hepatic iron grade. Although the few patients in each group may explain the lack of an association, a more likely explanation is the time between collection of the duodenal and liver tissue samples-in some cases up to 10 years.…”

“…In agreement with previous reports, the degree of siderosis was, in general, mild to moderate. 1,3,5,10,30 None of the 46 subjects with cirrhosis carried the C282Y mutation in HFE. Positive hepatic iron staining was associated with hepatocellular cirrhosis, more advanced liver disease, and male sex.…”

“…1 The molecular mechanisms by which iron accumulates in cirrhosis are unclear as HFE mutations are uncommon in patients with end-stage cirrhosis complicated by hemosiderosis. [1][2][3] There has been much speculation as to the existence of a relation between an increase in iron absorption and the presence of hepatic iron deposits in subjects with cirrhosis, as increased iron absorption has been reported in 30% to 100% of patients with cirrhosis. 4 -10 Recent advances in our understanding of the molecular mechanisms of iron absorption enable us to investigate changes in the expression of the iron transport molecules in cirrhosis.…”

Frequent severe liver iron overload after stem cell transplantation and its possible association with invasive aspergillosis

“…26 Interestingly, previous clinical papers have related iron overload and infection in immuno-deficient patients, and the infection was always produced by Aspergillus or Mucor. [27][28][29] In our series, Aspergillus infection was not related with neutropenia or acute GVHD, probably because 41% of cases were autologous transplants and the number of patients with long-standing neutropenia or severe acute GVHD was low. An association between CMV disease and fungal infections has been noted not only in solid organ transplant recipients 30,31 but also in recipients of HSCT.…”

Altered expression of iron regulatory genes in cirrhotic human livers: clues to the cause of hemosiderosis?

“…In addition, liver transplant patients whose explant shows heavy iron deposition are reported to be at increased risk of mortality from infection. 4 However, despite the prevalence and clinical significance of hemosiderosis, its cause remains unknown.…”