Duration of hepatic iron exposure increases the risk of significant fibrosis in hereditary hemochromatosis: a new role for magnetic resonance imaging.
OBJECTIVE
Hepatic fibrosis is a complication of hereditary hemochromatosis. The aim of this study was to determine whether the product of the magnitude and duration of hepatic iron exposure is related to the risk of significant fibrosis.


METHODS
Receiver-operating characteristic curve analysis to determine the utility of hepatic iron concentration (HIC) and age in the diagnosis of low- or high-grade fibrosis was undertaken retrospectively in 60 subjects who had undergone liver biopsy for assessment of hereditary hemochromatosis. A prospective pilot study was then conducted in 10 additional subjects to evaluate utility of magnetic resonance imaging (MRI) measurements of HIC to predict fibrosis.


RESULTS
Eighteen subjects had high-grade fibrosis while 42 subjects had low-grade fibrosis. Hepatic iron concentration alone was highly sensitive (100%) but of limited specificity (67%) in diagnosis of high-grade fibrosis. The product of [HIC x age] had a sensitivity and specificity of 100% and 86%, respectively, for diagnosis of high-grade fibrosis. Magnetic resonance imaging measurements also provided accurate assignment of subjects into fibrosis severity groups.


CONCLUSIONS
Duration of exposure to iron is important in the development of hepatic fibrosis in hereditary hemochromatosis. The product of HIC and age is highly sensitive and specific for diagnosis of high-grade fibrosis and can be obtained using MRI.
Olynyk
John K
JK
School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia.
St Pierre
Timothy G
TG
Britton
Robert S
RS
Brunt
Elizabeth M
EM
Bacon
Bruce R
BR
D000328:Adult; D000367:Age Factors; D001706:Biopsy; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005293:Ferritins / Q000097:blood; D006432:Hemochromatosis / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012189:Retrospective Studies; D012306:Risk; D012680:Sensitivity and Specificity
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins; D007501:Iron