Background: The HFE gene contains two mutant alleles: C282Y and H63D. There is evidence to support
that HFE heterozygosity may act as a potentially damaging co-factor in chronic liver
disease. Increased ferritin is frequently found in individuals with hepatic steatosis.
The significance of heterozygosity in alcohol related liver disease is unclear.
Aim: The aim of this study was to ascertain if the HFE heterozygote state influences disease
pathogenesis in alcoholic liver disease.
Method: Forty-six patients with compensated alcoholic liver disease and hyperferritinaemia
were studied. No homozygous individual for either mutation was included. The data
were analysed with respect to age, sex, weight, presence/ absence of diabetes, alcohol
consumption, serum ferritin, Hb, MCV, liver enzymes, HFE mutation analysis, liver
histopathology and iron staining. All patients were negative for viral and autoimmune
liver disease.
Results: The HFE heterozygote state was significantly associated with moderate/ bridging fibrosis
(p<0.021), particularly female C282Y heterozygotes. There was a trend between heterozygotes
and wild type in relation to cirrhosis (P=0.09) and diabetes (P=0.07). The prevalence
of heterozygosity for either mutation was not significantly higher than in controls.
There was no statistically significant difference between age, weight, alcohol consumption,
serum ferritin, Hb, MCV, liver enzymes, moderate/ severe steatohepatitis, hepatocellular
carcinoma and >2+ Perl's hepatocyte iron staining between male and female heterozygotes
and wild types.
Conclusion: The HFE heterozygote state does not appear to have a role in liver iron accumulation
but is significantly associated with advanced fibrosis, particularly in women with
alcohol related liver disease.
