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

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.

Kris V. Kowdley
- University of Washington, Seattle, Washington
- Address requests for reprints to: Kris V. Kowdley, MD, Professor of Medicine, University of Washington, Box 356174, Seattle, Washington 98195.fax: (206) 598-3884.
David J. Brandhagen
- Mayo Clinic College of Medicine, Rochester, Minnesota
Robert G. Gish
- California Pacific Medical Center, San Francisco, California
Nathan M. Bass
- University of California at San Francisco, San Francisco, California
Jeffrey Weinstein
- Baylor University Medical Center, Dallas, Texas
Michael L. Schilsky
- New York Weill Cornell Medical Center and Mount Sinai School of Medicine, New York, New York
Robert J. Fontana
- University of Michigan, Ann Arbor, Michigan
Timothy McCashland
- University of Nebraska, Omaha, Nebraska
Scott J. Cotler
- Rush University, Chicago, Illinois
Bruce R. Bacon
- St. Louis University, St. Louis, Missouri
Emmet B. Keeffe
- Stanford University, Stanford, California
Fredric Gordon
- Lahey Clinic, Burlington, Massachusetts
Nayak Polissar
- The Mountain-Whisper-Light Statistical Consulting, Seattle, Washington; and the NHTR Study Group
the National Hemochromatosis Transplant Registry

Received 22 October 2004; accepted 20 April 2005.

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.