Blunted Hepcidin Response to Oral Iron Challenge in Hfe- Hemochromatosis

Inadequate hepcidin synthesis leads to iron overload in HFE-hemochromatosis. We explored the regulation of hepcidin by iron in 88 hemochromatosis patients (61 C282Y/C282Y, 27 C282Y/H63D) and 23 healthy controls by analyzing urinary hepcidin before and 24 hours after a 65mg oral iron dose. Thirty-four patients were studied at diagnosis and had iron overload, and 54 patients were iron-depleted. At diagnosis, hepcidin values in C282Y homozygotes were similar to controls, whereas values in C282Y/H63D heterozygotes were higher (p=0.02). However, the hepcidin/ferritin ratio was decreased in both homozygotes (p<0.0001) and heterozygotes (p=0.017), confirming the inadequate hepcidin production for the iron load with both genotypes. In iron-depleted patients of both genotypes studied at a time remote from phlebotomy, basal hepcidin was still lower than in controls (p<0.0001 for C282Y/C282Y and p=0.002 for heterozygotes). After an iron challenge, mean urinary hepcidin excretion increased in controls (p=0.001) but not patients, irrespective of genotype and iron status. Significant hepcidin increase (≥10ng/mg creatinine) was observed in 74% of controls, 15% of homozygotes and 32% of heterozygotes. The hepcidin response to oral iron is blunted in HFE-hemochromatosis and not improved after iron depletion. The findings support the involvement of HFE in iron sensing and subsequent regulation of hepcidin. For personal use only. on October 31, 2017. by guest www.bloodjournal.org From