Carriage of HFE mutations and outcome of surgical resection for hepatocellular carcinoma in cirrhotic patients.
BACKGROUND
Aggressive hepatocellular carcinoma (HCC) complicates frequently hereditary hemochromatosis, a disease for which a strong candidate gene, named HFE, has recently been identified. Patients with HCC who are heterozygotes for mutations in the HFE gene might have distinct features and a distinct disease course.


METHODS
The presence of the 2 mutations associated with hereditary hemochromatosis (C282Y and H63D) was sought by restriction fragment length polymorphism in 61 cirrhotic patients (46 males and 15 females) who underwent resection for HCC at a single institution.


RESULTS
There were 4 heterozygotes for the C282Y mutation and 6 homozygotes + 20 heterozygotes for the H63D mutation, with no compound heterozygotes. Carriage of >/= 1 HFE mutated allele was significantly more frequent in HCC patients than in 149 control subjects (44% vs. 29%, P = 0.005). Among C282Y heterozygotes, 3 of 4 were female, compared with 12 of 57 wild-type carriers (P = 0.015); no gender distribution existed among patients carrying H63D alleles (6 of 26 vs. 9 of 35, P = 0.813). Survival was longer for patients with wild-type HFE than for those with mutated HFE (67% vs. 22% at 3 years; hazard ratio = 0.42, 95% confidence interval = 0.21-0.80) (P < 0.01). The negative effect on survival that resulted from possessing >/= 1 HFE mutated allele was maintained even after adjustment for gender, age, presence of tumor capsule, presence of comorbid factors, Okuda stage, Edmonson grading, and number of lesions (P = 0.01).


CONCLUSIONS
Testing for HFE mutations may help identify HCC patients with dismal prognoses for whom surgical resection may not represent the best treatment option.
Clinica di Medicina Interna, Universitá degli Studi, Udine, Italy.
M
M
Pirisi
P
P
Toniutto
A
A
Uzzau
C
C
Fabris
C
C
Avellini
C
C
Scott
L
L
Apollonio
C A
CA
Beltrami
F
F
Bresadola
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics* / Q000601:surgery*; D005260:Female; D006432:Hemochromatosis / Q000150:complications / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics*; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020125:Mutation, Missense; D016019:Survival Analysis; D016896:Treatment Outcome