Heterozygosity for the hemochromatosis gene in liver diseases - prevalenceand effects on liver histology

Background/Aims. The effect of heterozygosity for the C282Y mutation in the HFE hemochromatosis gene on iron accumulation and disease progression in l iver disease patients is unclear. Methods: We investigated the prevalence o f this mutation in 531 patients and 205 healthy controls. in addition, we a ssessed the influence of the mutation on liver histology in 34 C282Y hetero zygous and 124 age-, sex- and disease-matched controls without the mutation using the modified HAI and Chevallier score. Results. The highest prevalen ce of the C282Y mutation was observed in patients with autoimmune hepatitis (17.2%, p<0.01) compared to 6.4% in healthy controls. Heterozygotes with h epatitis C and B virus infection showed higher ferritin and hepatic iron co ncentrations than patients without the mutation. However, we did not detect significant differences in necroinflammatory or fibrosis scores between ca rriers of the mutation and controls. Conclusions: There are marked differen ces in the prevalence of the C282Y mutation in patients with different live r diseases, with the highest prevalence rates in autoimmune hepatitis and P BC. However, the C282Y mutation alone only leads to a mild increase in iron accumulation in the majority of the patients, with the exception of H63D/C 282Y compound heterozygotes. We found no evidence for more pronounced fibro sis in C282Y heterozygotes.