Gastroenterology

Gastroenterology

Volume 129, Issue 2, August 2005, Pages 494-503
Gastroenterology

Clinical—liver, pancreas, and biliary tract
Survival After Liver Transplantation in Patients With Hepatic Iron Overload: The National Hemochromatosis Transplant Registry

These data were presented in part at the Plenary Session of the Annual Meeting of the American Association for the Study of Liver Diseases, 2001.
https://doi.org/10.1053/j.gastro.2005.05.004Get rights and content

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.

Section snippets

Patients

Twelve liver transplantation centers participated in this study. The complete list of centers and participating investigators is shown in Appendix 1. Patients who had undergone their first liver transplantation prior to 1996 were eligible to enter this study. To be included, patients were required to have one of the following: a known diagnosis of hemochromatosis or hepatic iron overload prior to liver transplantation based on one of the following criteria: compatible hepatic iron stain (as ≥2+

Results

The characteristics of the study population are shown in Table 1. The mean age of the patients was 51 years, and 80% were male. HFE genotyping was available in 195 of the 260 patients (75%). The prevalence of HFE mutations in those with genotype available was 46%. Twenty-five patients (13% of those genotyped) had HH, as defined by presence of homozygous C282Y (n = 14) or compound heterozygous C282Y/H63D mutations (n = 11). Fifty-nine (30%) patients were “simple” heterozygotes, and 106 were wild

Discussion

The current report, to our knowledge, is the largest study to date examining survival after liver transplantation in a multicenter, nationwide cohort of patients with end-stage liver disease and hepatic iron overload. Moreover, this is the first detailed study examining the relationship between HFE mutations and outcome after liver transplantation while controlling for UNOS status and other prognostic factors. Our study demonstrated unequivocally that patients in the United States with HFE

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    Supported by NIH grants DK 54698, DK 02957, and DK 38215.

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