Marked iron in liver explants in the absence of major hereditary hemochromatosis gene defects: a risk factor for cardiac failure.
BACKGROUND
Patients with hereditary hemochromatosis are known to have an increased risk for morbidity and mortality after orthotopic liver transplantation.


METHODS
The clinical, histological, and genetic findings were examined in a series of seven adult patients with marked iron accumulation in their liver explants and cardiac failure despite the absence of HFE mutations.


RESULTS
Causes for cirrhosis were alcohol and hepatitis C virus (HCV) (n=2), HCV (n=1), alcohol (n=1), and cryptogenic cirrhosis (n=3). Ages at transplantation ranged from 46 to 62 years. Genetic studies confirmed all seven cases were negative for HFE mutations C282Y and H63D. The liver explants showed marked iron accumulation that predominately involved hepatocytes, with more than 90% of the iron in hepatocytes. Two patients required cardiac transplantation and four died of cardiac failure. Cardiac tissues obtained from autopsies (n=3), endomyocardial biopsy (n=1), or cardiac transplants (n=2) showed marked myocyte hypertrophy and iron deposits with or without interstitial fibrosis.


CONCLUSIONS
This study highlights a unique set of liver transplant patients with marked iron deposition in their cirrhotic liver who developed severe cardiac failure and have iron deposits in the heart, despite the absence of major HFE gene mutations. The cause of the systemic iron overload remains to be discovered.
Fenton
Hubert
H
Department of Pathology, University of California, San Francisco, CA, USA.
Torbenson
Michael
M
Vivekanandan
Perumal
P
Yeh
Matthew M
MM
Hart
John
J
Ferrell
Linda
L
D019943:Amino Acid Substitution; D005260:Female; D006333:Heart Failure / Q000453:epidemiology* / Q000235:genetics; D006432:Hemochromatosis / Q000150:complications / Q000235:genetics* / Q000401:mortality; D000071020:Hemochromatosis Protein; D006526:Hepatitis C / Q000150:complications / Q000601:surgery; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000209:etiology / Q000601:surgery; D008104:Liver Cirrhosis, Alcoholic / Q000601:surgery; D016031:Liver Transplantation / Q000401:mortality / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D007501:Iron