Survival after liver transplantation in patients with hepatic iron overload: The National Hemochromatosis Transplant Registry

Kris V. Kowdley, David J. Brandhagen, Robert G. Gish, Nathan M. Bass, Jeffrey Weinstein, Michael L. Schilsky, Robert J. Fontana, Timothy M McCashland, Scott J. Cotler, Bruce R. Bacon, Emmet B. Keeffe, Fredric Gordon, Nayak Polissar

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Abstract

Background & Aims: Previous uncontrolled studies have suggested that patients with hepatic iron overload have a poor outcome after liver transplantation. We examined the effect of HFE mutations on posttransplantation survival in patients with hepatic iron overload. Methods: Two hundred sixty patients with end-stage liver disease and hepatic iron overload were enrolled from 12 liver transplantation centers. Hepatic iron concentration (HIC), hepatic iron index (HII), HFE mutation status, and survival after liver transplantation were recorded. Results: HFE-associated hemochromatosis (HH) defined as homozygosity for the C282Y (n = 14, 7.2%) mutation or compound heterozygosity for the C282Y/H63D (n = 11, 5.6%) mutation was identified in 12.8% of patients. Survival postliver transplantation was significantly lower among patients with HH (1-, 3-, and 5-year survival rates of 64%, 48%, 34%, respectively) compared with simple heterozygotes (C282Y/wt or H63D/wt) or wild-type patients. Patients with HH had a hazard ratio for death of 2.6 (P = .002) after adjustment for age, United Network for Organ Sharing status, year of transplantation, and either elevated HII or HIC. Non-HH patients with hepatic iron overload also had significantly decreased survival when compared with the overall population undergoing liver transplantation (OR = 1.4, 95% CI: 1.15-1.61, P < .001). Conclusions: One- and 5-year survivals after liver transplantation are significantly lower among patients with HFE-associated HH. Our data also suggest that hepatic iron overload may be associated with decreased survival after liver transplantation, even in patients without HH. Early diagnosis of hepatic iron overload using HFE gene testing and iron depletion prior to liver transplantation may improve posttransplantation survival, particularly among patients with HH.

Original languageEnglish (US)
Pages (from-to)494-503
Number of pages10
JournalGastroenterology
Volume129
Issue number2
DOIs
StatePublished - Aug 2005

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Iron Overload
Hemochromatosis
Liver Transplantation
Registries
Transplants
Survival
Liver
Iron
Mutation
Transplantation
End Stage Liver Disease
Heterozygote
Early Diagnosis
Survival Rate

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Kowdley, K. V., Brandhagen, D. J., Gish, R. G., Bass, N. M., Weinstein, J., Schilsky, M. L., ... Polissar, N. (2005). Survival after liver transplantation in patients with hepatic iron overload: The National Hemochromatosis Transplant Registry. Gastroenterology, 129(2), 494-503. https://doi.org/10.1016/j.gastro.2005.05.004

Survival after liver transplantation in patients with hepatic iron overload : The National Hemochromatosis Transplant Registry. / Kowdley, Kris V.; Brandhagen, David J.; Gish, Robert G.; Bass, Nathan M.; Weinstein, Jeffrey; Schilsky, Michael L.; Fontana, Robert J.; McCashland, Timothy M; Cotler, Scott J.; Bacon, Bruce R.; Keeffe, Emmet B.; Gordon, Fredric; Polissar, Nayak.

In: Gastroenterology, Vol. 129, No. 2, 08.2005, p. 494-503.

Research output: Contribution to journalArticle

Kowdley, KV, Brandhagen, DJ, Gish, RG, Bass, NM, Weinstein, J, Schilsky, ML, Fontana, RJ, McCashland, TM, Cotler, SJ, Bacon, BR, Keeffe, EB, Gordon, F & Polissar, N 2005, 'Survival after liver transplantation in patients with hepatic iron overload: The National Hemochromatosis Transplant Registry', Gastroenterology, vol. 129, no. 2, pp. 494-503. https://doi.org/10.1016/j.gastro.2005.05.004
Kowdley, Kris V. ; Brandhagen, David J. ; Gish, Robert G. ; Bass, Nathan M. ; Weinstein, Jeffrey ; Schilsky, Michael L. ; Fontana, Robert J. ; McCashland, Timothy M ; Cotler, Scott J. ; Bacon, Bruce R. ; Keeffe, Emmet B. ; Gordon, Fredric ; Polissar, Nayak. / Survival after liver transplantation in patients with hepatic iron overload : The National Hemochromatosis Transplant Registry. In: Gastroenterology. 2005 ; Vol. 129, No. 2. pp. 494-503.
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title = "Survival after liver transplantation in patients with hepatic iron overload: The National Hemochromatosis Transplant Registry",
abstract = "Background & Aims: Previous uncontrolled studies have suggested that patients with hepatic iron overload have a poor outcome after liver transplantation. We examined the effect of HFE mutations on posttransplantation survival in patients with hepatic iron overload. Methods: Two hundred sixty patients with end-stage liver disease and hepatic iron overload were enrolled from 12 liver transplantation centers. Hepatic iron concentration (HIC), hepatic iron index (HII), HFE mutation status, and survival after liver transplantation were recorded. Results: HFE-associated hemochromatosis (HH) defined as homozygosity for the C282Y (n = 14, 7.2{\%}) mutation or compound heterozygosity for the C282Y/H63D (n = 11, 5.6{\%}) mutation was identified in 12.8{\%} of patients. Survival postliver transplantation was significantly lower among patients with HH (1-, 3-, and 5-year survival rates of 64{\%}, 48{\%}, 34{\%}, respectively) compared with simple heterozygotes (C282Y/wt or H63D/wt) or wild-type patients. Patients with HH had a hazard ratio for death of 2.6 (P = .002) after adjustment for age, United Network for Organ Sharing status, year of transplantation, and either elevated HII or HIC. Non-HH patients with hepatic iron overload also had significantly decreased survival when compared with the overall population undergoing liver transplantation (OR = 1.4, 95{\%} CI: 1.15-1.61, P < .001). Conclusions: One- and 5-year survivals after liver transplantation are significantly lower among patients with HFE-associated HH. Our data also suggest that hepatic iron overload may be associated with decreased survival after liver transplantation, even in patients without HH. Early diagnosis of hepatic iron overload using HFE gene testing and iron depletion prior to liver transplantation may improve posttransplantation survival, particularly among patients with HH.",
author = "Kowdley, {Kris V.} and Brandhagen, {David J.} and Gish, {Robert G.} and Bass, {Nathan M.} and Jeffrey Weinstein and Schilsky, {Michael L.} and Fontana, {Robert J.} and McCashland, {Timothy M} and Cotler, {Scott J.} and Bacon, {Bruce R.} and Keeffe, {Emmet B.} and Fredric Gordon and Nayak Polissar",
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T1 - Survival after liver transplantation in patients with hepatic iron overload

T2 - The National Hemochromatosis Transplant Registry

AU - Kowdley, Kris V.

AU - Brandhagen, David J.

AU - Gish, Robert G.

AU - Bass, Nathan M.

AU - Weinstein, Jeffrey

AU - Schilsky, Michael L.

AU - Fontana, Robert J.

AU - McCashland, Timothy M

AU - Cotler, Scott J.

AU - Bacon, Bruce R.

AU - Keeffe, Emmet B.

AU - Gordon, Fredric

AU - Polissar, Nayak

PY - 2005/8

Y1 - 2005/8

N2 - Background & Aims: Previous uncontrolled studies have suggested that patients with hepatic iron overload have a poor outcome after liver transplantation. We examined the effect of HFE mutations on posttransplantation survival in patients with hepatic iron overload. Methods: Two hundred sixty patients with end-stage liver disease and hepatic iron overload were enrolled from 12 liver transplantation centers. Hepatic iron concentration (HIC), hepatic iron index (HII), HFE mutation status, and survival after liver transplantation were recorded. Results: HFE-associated hemochromatosis (HH) defined as homozygosity for the C282Y (n = 14, 7.2%) mutation or compound heterozygosity for the C282Y/H63D (n = 11, 5.6%) mutation was identified in 12.8% of patients. Survival postliver transplantation was significantly lower among patients with HH (1-, 3-, and 5-year survival rates of 64%, 48%, 34%, respectively) compared with simple heterozygotes (C282Y/wt or H63D/wt) or wild-type patients. Patients with HH had a hazard ratio for death of 2.6 (P = .002) after adjustment for age, United Network for Organ Sharing status, year of transplantation, and either elevated HII or HIC. Non-HH patients with hepatic iron overload also had significantly decreased survival when compared with the overall population undergoing liver transplantation (OR = 1.4, 95% CI: 1.15-1.61, P < .001). Conclusions: One- and 5-year survivals after liver transplantation are significantly lower among patients with HFE-associated HH. Our data also suggest that hepatic iron overload may be associated with decreased survival after liver transplantation, even in patients without HH. Early diagnosis of hepatic iron overload using HFE gene testing and iron depletion prior to liver transplantation may improve posttransplantation survival, particularly among patients with HH.

AB - Background & Aims: Previous uncontrolled studies have suggested that patients with hepatic iron overload have a poor outcome after liver transplantation. We examined the effect of HFE mutations on posttransplantation survival in patients with hepatic iron overload. Methods: Two hundred sixty patients with end-stage liver disease and hepatic iron overload were enrolled from 12 liver transplantation centers. Hepatic iron concentration (HIC), hepatic iron index (HII), HFE mutation status, and survival after liver transplantation were recorded. Results: HFE-associated hemochromatosis (HH) defined as homozygosity for the C282Y (n = 14, 7.2%) mutation or compound heterozygosity for the C282Y/H63D (n = 11, 5.6%) mutation was identified in 12.8% of patients. Survival postliver transplantation was significantly lower among patients with HH (1-, 3-, and 5-year survival rates of 64%, 48%, 34%, respectively) compared with simple heterozygotes (C282Y/wt or H63D/wt) or wild-type patients. Patients with HH had a hazard ratio for death of 2.6 (P = .002) after adjustment for age, United Network for Organ Sharing status, year of transplantation, and either elevated HII or HIC. Non-HH patients with hepatic iron overload also had significantly decreased survival when compared with the overall population undergoing liver transplantation (OR = 1.4, 95% CI: 1.15-1.61, P < .001). Conclusions: One- and 5-year survivals after liver transplantation are significantly lower among patients with HFE-associated HH. Our data also suggest that hepatic iron overload may be associated with decreased survival after liver transplantation, even in patients without HH. Early diagnosis of hepatic iron overload using HFE gene testing and iron depletion prior to liver transplantation may improve posttransplantation survival, particularly among patients with HH.

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