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Blunted increase in serum hepcidin as response to oral iron in HFE – hemochromatosis
  1. A Sangwaiya *1,
  2. V Manglam1,
  3. M Busbridge2,
  4. M Thursz3,
  5. J Arnold1
  1. 1Department of Gastroenterology, Ealing Hospital NHS Trust, Southall, UK
  2. 2Department of Clinical Chemistry, Charing Cross Hospital, London, UK
  3. 3Department of Hepatology, St Marys Hospital, London, UK


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).

Table 1

OC-113 Data represents basal time-points pre-iron load

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.

  • hereditary haemochromatosis
  • iron

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  • Competing interests None.

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