Previous studies examining the relationship between HFE mutations and severity of nonalcoholic steatohepatitis (NASH) have been limited by small sample size or ascertainment bias.
Dr James Nelson and colleagues from Canada examined the relationship between HFE mutations and histological severity in a large North American multicenter cohort with nonalcoholic steatohepatitis.
|The prevalence of H63D HFE mutations was 21%|
Data from 126 nonalcoholic steatohepatitis patients were collected from 6 North American centers.
Liver biopsy and genotyping for the C282Y and H63D HFE mutations were performed in all subjects.
The research team then recorded serum transferrin-iron saturation and ferritin levels as well as hepatic iron content whenever available.
Univariate and multivariate logistic regression analyses were performed to identify factors associated with advanced hepatic fibrosis.
The researchers found the prevalence of heterozygous C282Y and H63D HFE mutations was 14% and 21%, respectively, in the overall cohort.
Among Caucasians, C282Y heterozygotes were more likely to have bridging fibrosis or cirrhosis, occurring in 44% and 21%, respectively.
Patients with these mutations were also more likely to have stainable hepatic iron compared with patients with other genotypes.
The team used multiple logistic regression analysis adjusting for age, sex, ethnicity, body mass index, and HFE genotype status.
Based on the adjusted analyses, the researchers observed that diabetes mellitus was the only independent predictor of advanced hepatic fibrosis.
Dr Nelson's team concluded, "The HFE C282Y heterozygous mutation is associated with advanced fibrosis among Caucasians with nonalcoholic steatohepatitis."
"Additional studies are warranted to examine the possible mechanisms for this relationship."