Increased Hepatic Iron and Cirrhosis: No Evidence for An Adverse Effect on Patient Outcome Following Liver Transplantation

Stuart, Katherine; Fletcher, Linda M.; Clouston, Andrew D.; Lynch, S. V.; Purdie, David M.; Kerlin, Paul; Crawford, Darrell H. G.

doi:10.1053/jhep.2000.20348

Cited by 50 publications

(43 citation statements)

References 42 publications

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“…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.…”

Section: Discussioncontrasting

confidence: 64%

“…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.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…1,2 Cirrhosis-associated iron overload is more common in hepatocellular than cholestatic liver diseases 1,2 and also has been associated with more advanced liver disease and the presence of spur cell hemolytic anemia. 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.…”

mentioning

confidence: 99%

“…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.…”

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

et al. 2004

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Hepatic hemosiderosis and increased iron absorption are common findings in cirrhosis. It has been proposed that a positive relation exists between intestinal iron absorption and the development of hepatic hemosiderosis. The current study investigated the duodenal expression of the iron transport molecules divalent metal transporter 1 (DMT1 [IRE]), ironregulated gene 1 (Ireg1 [ferroportin]), hephaestin, and duodenal cytochrome b (Dyctb) in 46 patients with cirrhosis and 20 control subjects. Total RNA samples were extracted from duodenal biopsy samples and the expression of the iron transport genes was assessed by ribonuclease protection assays. Expression of DMT1 and Ireg1 was increased 1.5 to 3-fold in subjects with cirrhosis compared with iron-replete control subjects. The presence of cirrhosis per se and serum ferritin (SF) concentration were independent factors that influenced the expression of DMT1. However, only SF concentration was independently associated with Ireg1 expression. In cirrhosis, the expression of DMT1 and Ireg1 was not related to the severity of liver disease or cirrhosis type. There was no correlation between the duodenal expression of DMT1 and Ireg1 and the degree of hepatic siderosis. In conclusion, the presence of cirrhosis is an independent factor associated with increased expression of DMT1 but not Ireg1. The mechanism by which cirrhosis mediates this change in DMT1 expression has yet to be determined. Increased expression of DMT1 may play an important role in the pathogenesis of cirrhosis-associated hepatic iron overload. (HEPATOLOGY 2004;39: 492-499.)

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confidence: 99%

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

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Patient and graft survival after liver transplantation for hereditary hemochromatosis: Implications for pathogenesis

et al. 2004

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The clinical outcome of patients who have undergone liver transplantation for hereditary hemochromatosis (HH) or who have received iron-loaded donor grafts is unclear. We reviewed 3,600 adult primary orthotopic liver transplants and assessed the outcomes in 22 patients with HH. We also evaluated graft function and iron mobilization in 12 recipients of iron-loaded donor grafts. All 22 subjects who received liver transplants for HH were male; 13 had other risk factors for liver disease. HH patients had comparatively poor outcomes following transplantation: survival at 1, 3, and 5 years posttransplantation were 72%, 62%, and 55%, respectively. Recurrent hepatocellular cancer was the most common cause of death. There was no convincing evidence of reaccumulation of iron in the grafted liver in HH; however, 1 subject demonstrated increased serum ferritin concentration and grade 2 hepatic siderosis. Liver iron stores were slow to mobilize in 7 of the 12 recipients of iron-loaded grafts. These recipients had appropriate early graft function, but 2 patients with heavy iron loading and increased hepatic iron developed hepatic fibrosis. In conclusion, (1) HH is an uncommon indication for liver transplantation, and the majority of patients requiring transplantation had other risk factors for chronic liver disease; (2) reaccumulation of liver iron in HH patients is very unusual, but increased iron stores may be slow to mobilize in normal recipients of iron-loaded grafts, potentially compromising late graft function; (3) post-liver transplant survival is reduced in HH, and affected patients require careful clinical evaluation of perioperative and postoperative risk factors. Our data suggest that iron excess in HH does not wholly depend on intestinal iron absorption but is also influenced by liver factors that moderate iron metabolism.

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Liver transplantation: An “ in vivo ” model for the pathophysiology of hemochromatosis?†

Kowdley

2004

Hepatology

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Increased Hepatic Iron and Cirrhosis: No Evidence for An Adverse Effect on Patient Outcome Following Liver Transplantation

Cited by 50 publications

References 42 publications

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

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

Patient and graft survival after liver transplantation for hereditary hemochromatosis: Implications for pathogenesis

Liver transplantation: An “ in vivo ” model for the pathophysiology of hemochromatosis?†

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