Survival after liver transplantation in patients with hepatic iron overload: the national hemochromatosis transplant registry.
OBJECTIVE
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.
Kowdley
Kris V
KV
University of Washington, Seattle, 98195, USA. kkowdley@u.washington.edu
Brandhagen
David J
DJ
Gish
Robert G
RG
Bass
Nathan M
NM
Weinstein
Jeffrey
J
Schilsky
Michael L
ML
Fontana
Robert J
RJ
McCashland
Timothy
T
Cotler
Scott J
SJ
Bacon
Bruce R
BR
Keeffe
Emmet B
EB
Gordon
Fredric
F
Polissar
Nayak
N
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002423:Cause of Death; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006432:Hemochromatosis / Q000235:genetics / Q000401:mortality* / Q000601:surgery; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D019190:Iron Overload / Q000235:genetics / Q000401:mortality* / Q000601:surgery; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000379:methods / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012042:Registries; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016019:Survival Analysis
D005819:Genetic Markers; D015395:Histocompatibility Antigens Class I