Differences in hepatic phenotype between hemochromatosis patients with HFE C282Y homozygosity and other HFE genotypes.
OBJECTIVE
There are limited data comparing hepatic phenotype among hemochromatosis patients with different HFE genotypes. The goal of this study was to compare hepatic histopathologic features and hepatic iron concentration (HIC) among patients with phenotypic hemochromatosis and different HFE genotypes.


METHODS
We studied 182 US patients with phenotypic hemochromatosis. Degree of hepatic fibrosis, pattern of iron deposition, presence of steatosis or necroinflammation, and HIC were compared among different HFE genotypes.


RESULTS
C282Y/H63D compound heterozygotes and patients with HFE genotypes other than C282Y/C282Y were more likely to have stainable Kupffer cell iron (31.1% vs. 9.5%; P=0.02), portal or lobular inflammation (28.9% vs. 15.6%; P=0.03), and steatosis (33.3% vs. 10.2%; P<0.01) on liver biopsy than C282Y homozygotes. Mean log10 HIC (P<0.05) and log10 ferritin (P<0.05) were higher among C282Y homozygotes than in patients with other HFE genotypes. In a logistic regression analysis using age, sex, HFE genotype, log10 ferritin, and log10 HIC as independent variables, log10 serum ferritin (P=0.0008), male sex (P=0.0086), and log10 HIC (P=0.047), but not HFE genotype (P=0.0554) were independently associated with presence or absence of advanced hepatic fibrosis.


CONCLUSIONS
C282Y/H63D compound heterozygotes and other non-C282Y homozygotes which express the hepatic hemochromatosis phenotype frequently have evidence of steatosis or chronic hepatitis and lower body iron stores than C282Y homozygotes. These data suggest that presence of concomitant liver disease may explain expression of the hemochromatosis phenotype among non-C282Y homozygotes. Increased age, HIC, and ferritin are associated with advanced hepatic fibrosis, regardless of HFE genotype.
Department of Medicine, University of Washington, Seattle, WA, USA.
Raymond
R
Cheng
James C
JC
Barton
Elizabeth D
ED
Morrison
Pradyumna D
PD
Phatak
Edward L
EL
Krawitt
Stuart C
SC
Gordon
Kris V
KV
Kowdley
D000328:Adult; D015331:Cohort Studies; D005260:Female; D005293:Ferritins / Q000097:blood; D005838:Genotype; D006432:Hemochromatosis / Q000235:genetics* / Q000473:pathology*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins; D007501:Iron