Transplantation of haemochromatosis liver and intestine into a normal recipient

Adams, Paul C.; Jeffrey, Gary P.; Alanen, Kenneth W.; Chakrabarti, Subrata; Preshaw, R. M.; Howson, William; Grant, David

doi:10.1136/gut.45.5.783

Cited by 28 publications

(13 citation statements)

References 5 publications

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“…[30][31][32][33][34][35] In five of six studies, iron has not reaccumulated in the hepatic allograft, suggesting the primary defect in HHC does not reside in the liver. Thus, patients with HHC undergoing OLT are potentially at risk for iron reaccumulation in the new liver, possibly because of persistently high intestinal iron absorption or through redistribution of excess iron from other tissues into the liver.…”

Section: Discussionmentioning

confidence: 99%

Liver allograft iron accumulation in patients with and without pretransplantation hepatic hemosiderosis

Parolin

Batts

Wiesner

et al. 2002

Liver Transplantation

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There is a paucity of data regarding hepatic allograft iron accumulation in patients undergoing orthotopic liver transplantation (OLT) in whom severe iron overload was present in the native explanted liver. Our aim is to evaluate the frequency and cellular distribution of stainable iron in early and late post-OLT hepatic allograft biopsy specimens from patients undergoing their first OLT who had excess iron in their native explanted liver. We compared iron-staining patterns in hepatic allograft biopsy specimens at approximately 1 month (early) and 1 to 2 years (late) post OLT in 41 patients with hepatic iron indices greater than 1.9 in the explanted liver (cases) with a selected group of matched controls without explant hemosiderosis. Our cases included 6 patients with a pre-OLT diagnosis of hereditary hemochromatosis and 35 patients with cirrhosis and secondary iron overload. Early iron deposition was mild in most cases, commonly affected Kupffer's cells, and was seen with similar frequency in cases and controls (41% v 27%; P ‫؍‬ .29). Stainable iron was observed in 20 donor livers (12 cases, 8 controls), and all 20 subjects showed stainable iron in 1-month hepatic allograft biopsy specimens. Liver samples from 35 matched pairs were studied for late iron deposition. Iron deposition was observed in 43% of cases versus 17% of controls (P ‫؍‬ .06). In conclusion, the frequency of stainable iron in early hepatic allograft biopsy specimens was not different between patients with versus without pre-OLT hepatic hemosiderosis. There was a suggestion that patients with severe pre-OLT hemosiderosis had a greater frequency of iron accumulation in late hepatic biopsy specimens. (Liver Transpl 2002;8: 331-339.)

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Section: Discussionmentioning

confidence: 99%

Liver allograft iron accumulation in patients with and without pretransplantation hepatic hemosiderosis

Parolin

Batts

Wiesner

et al. 2002

Liver Transplantation

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“…Hepatic hemosiderosis resolved in 5 of 7 recipients who received livers from donors with HH. In the 2 cases where iron overload persisted, there were other explanations, such as multiple blood transfusions in the perioperative period and severe, recurrent allograft infection with hepatitis C. In addition, iron overload persisted and required subsequent venesection in a recipient of a combined liver and intestine transplant from a donor who was homozygous for C282Y 5. In contrast, most but not all studies of patients undergoing OLT for HH have not observed iron deposition in the hepatic allograft 4.…”

Section: Commentsmentioning

confidence: 99%

Can liver transplantation improve our understanding of the pathophysiology of iron overload?

Brandhagen

2004

Liver Transpl

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We observed the development of phenotypic hereditary haemochromatosis in a non-hereditary haemochromatosis liver transplant recipient, following transplantation with a liver from a C282Y heterozygous donor. No cause for secondary iron overload was identified. Subsequent sequencing of the HFE gene of both donor and recipient revealed a strong candidate for a novel pathogenic HFE mutation. In the recipient, heterozygosity for a single base substitution in exon 1, g.18 G>C, resulting in the substitution of arginine by serine at codon 6 (R6S), was detected. This R6S variation is likely to represent a novel pathogenic missense mutation of the HFE gene. An interaction between R6S heterozygosity in the recipient and C282Y heterozygosity in the donor liver is the most likely explanation for the development of iron overload in this patient. The report suggests that an hepatic defect is CommentsHereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism characterized by increased intestinal absorption of iron with deposition in the liver, pancreas, and multiple other parenchymal organs. HH is the most common, single-gene inherited disorder in U.S. Caucasians, with a homozygote frequency of approximately .5% and a heterozygote frequency of 10%. In the United States, approximately 85% of patients with HH are homozygous for the C282Y mutation. Despite being a common disorder, HH is an uncommon indication for orthotopic liver transplantation (OLT). Although iron overload is frequently observed in patients with end-stage liver disease, most do not have HH. 1 In the United States, less than 1% of all liver transplants are performed for HH. These findings are consistent with recent studies that have concluded that only a small percentage of C282Y homozygotes develop clinical manifestations of HH. 2 OLT provides life-saving treatment to many patients with end-stage liver disease. An added benefit of OLT is that it cures certain metabolic disorders such as Wilson disease, familial amyloid polyneuropathy, oxalosis, and hemophilia. It has long been assumed that iron overload in HH is caused by an intestinal defect. A recent case report by Wigg and colleagues casts doubt on this theory and suggests that HH may be due to a combined liver and intestinal defect. 3 The authors report a case of a 54-year-old Caucasian male who underwent OLT for alcoholic cirrhosis. A pretransplant liver biopsy demonstrated cirrhosis with minor (grade 1) siderosis and a normal hepatic iron concentration and hepatic iron index. The patient had an uneventful postoperative course and did well for 4 years following OLT. He underwent incisional hernia repair 49 months following transplant. At that time a liver biopsy was taken and unexpectedly demonstrated severe explant hemosiderosis with grade 4 iron deposition, hepatic iron concentration of 252 mol/g dry weight (normal Ͻ40), and hepatic iron index of 5.0 (normal Ͻ1.0). A repeat liver biopsy confirmed these findings. The patient initiated therapeutic phlebotomy and had 6 gra...

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“…These cases are listed in Table 3. In only 2 cases was HFE gene testing performed to confirm that the donor was homozygous for C282Y and the recipient did not have a C282Y mutation (Abdulkarim et al 69 and Adams et al 67 ). In 5 of the 7 cases, iron did not reaccumulate in the hepatic explant over a follow-up period that ranged from 6 to 29 months.…”

Section: Transplantation Of a Hemochromatosis Donor Livermentioning

confidence: 99%

“…In 5 of the 7 cases, iron did not reaccumulate in the hepatic explant over a follow-up period that ranged from 6 to 29 months. 41,[64][65][66][67] This suggests that the primary defect in HHC does not reside in the liver, although the duration of follow-up was insufficient to draw definitive conclusions. Two studies (Abdulkarim et al 69 and Koskinas et al 68 ) reported iron reaccumulation in the hepatic explant.…”

Section: Transplantation Of a Hemochromatosis Donor Livermentioning

confidence: 99%

Liver transplantation for hereditary hemochromatosis

Brandhagen

2001

Liver Transplantation

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Although hereditary hemochromatosis (HHC) is relatively common, it is an uncommon indication for orthotopic liver transplantation (OLT).O rthotopic liver transplantation (OLT) is the preferred treatment for many patients with complications of end-stage liver disease. The 5-year patient survival rate approaches 70% in many centers. Although it is relatively common in whites, hereditary hemochromatosis (HHC) is an uncommon indication for OLT. In addition, survival of patients who undergo OLT for HHC is markedly reduced compared with most other indications. The recent discovery of the HFE gene has provided a valuable opportunity to refine the diagnosis of HHC in patients with end-stage liver disease and iron overload. OLT also provides a unique opportunity to study the pathogenesis of iron overload. This review summarizes OLT in patients with HHC and iron overload.

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Transplantation of haemochromatosis liver and intestine into a normal recipient

Cited by 28 publications

References 5 publications

Liver allograft iron accumulation in patients with and without pretransplantation hepatic hemosiderosis

Liver allograft iron accumulation in patients with and without pretransplantation hepatic hemosiderosis

Can liver transplantation improve our understanding of the pathophysiology of iron overload?

Liver transplantation for hereditary hemochromatosis

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