Introduction Majority of patients with HFE hemochromatosis (HFE-H) are homozygote for C282Y mutation. Studies suggest iron accumulation in most types of hemochromatosis is due to hepcidin deficiency. The precise link between hepcidin levels and iron absorption in HFE-H patients has been poorly understood. We measured hepcidin response to oral iron challenge (200 mg ferrous sulphate), in HFE-H (C282Y/C282Y) patients and compare to healthy controls (HC).

Methods Nine patients with C282Y/C282Y HFE-H along with 15 HC were recruited for the study. All HFE-H were iron depleted and studied at a time distant to phlebotomy. Hepcidin was measured using a published immunoassay method. Serum iron, ferritin and transferrin saturation (%TSAT) were measured using standard methods. The area under the curve (AUC) was calculated and compared between the two groups.

Results The basal serum hepcidin levels in patients with HFE-H were significantly low as compared to HC (p=0.0002) (table 1). Incremental serum hepcidin response seen in HC reached significance at 4 h post iron challenge (p=0.0085). There was no significant hepcidin response in HFE-H at 4 h (p=0.294) (figure 1). The overall hepcidin response was significantly lower in HFE-H as compared to HC (AUC: p=0.0127).

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Figure 1

OC-113

Conclusion Failure to mount a rapid hepcidin response to an oral iron challenge is one of the key mechanisms of iron accumulation in spite of prevailing excess body iron in HFE-H patients with C282Y/C282Y mutation.