HFE genotypes in decompensated alcoholic liver disease: phenotypic expression and comparison with heavy drinking and with normal controls.
OBJECTIVE
Predisposition to alcoholic liver disease (ALD) may be partly genetic. Heterozygosity for the HFE mutations C282Y and/or H63D has been associated with more severe disease in several liver conditions. Studies in ALD have not used controls matched for alcohol consumption and results have been conflicting.


METHODS
HFE genotyping was performed in two Caucasian heavy-drinking cohorts (>60 units/wk (M) or 40 units/wk (F) for >5 yr): (a) 254 patients with decompensated ALD (Child's grade B or C), (b) 130 controls with similar alcohol consumption but without liver disease. Results in males were also compared with those from another study of healthy male blood donors.


RESULTS
(1) Genotype distributions for the C282Y and H63D mutations were similar in ALD patients, heavy-drinking controls, and healthy blood donors. (2) ALD patients with and without HFE mutations had similar disease severity, age at presentation, and alcohol consumption. (3) Increased serum ferritin and % transferrin saturation were seen in 63% and 29% of ALD patients, regardless of HFE genotype; the increased % transferrin saturation was due to reduced unsaturated iron binding capacity, rather than increased serum iron. (4) Stainable liver iron was present in 52% of patients; grade was greater in patients with two HFE mutations than in those with one or with none. (5) Only the two C282Y homozygote patients had substantial iron overload.


CONCLUSIONS
Although serum iron abnormalities are common, C282Y and H63D mutation frequencies were not increased in heavy drinkers with decompensated liver disease. HFE mutations, although modestly influencing liver iron, do not predispose to clinically significant ALD.
Gleeson
Dermot
D
Liver Unit, Sheffield Teaching Hospitals, Sheffield, United Kingdom.
Evans
Steven
S
Bradley
Martin
M
Jones
Jayne
J
Peck
Robert J
RJ
Dube
Asha
A
Rigby
Emma
E
Dalton
Ann
A
D000428:Alcohol Drinking / Q000097:blood / Q000235:genetics*; D001782:Blood Donors; D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005293:Ferritins / Q000097:blood; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000097:blood; D008108:Liver Diseases, Alcoholic / Q000097:blood / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D012720:Severity of Illness Index; D014168:Transferrin / Q000378:metabolism
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D004247:DNA; D005293:Ferritins; D007501:Iron