Liver transplantation normalizes serum hepcidin level and cures iron metabolism alterations in HFE hemochromatosis.

Potential conflict of interest: Dr. Brissot advises, is on the speakers' bureau, and received grants from Novartis.International audienceBackground: Defects in human hemochromatosis protein (HFE) cause iron overload due to reduced hepatic hepcidin secretion. Liver transplantation (LT) is a key treatment for potential complications from HFE- related hereditary hemochromatosis (HH). This study evaluated hepcidin secretion and iron burden after LT to elucidate HH pathophysiology. Methods: Patients (n=18) homozygous for the p.Cys282Tyr mutation in the HFE gene underwent LT between 1999 and 2008. Serum iron, serum hepcidin, and hepatic iron concentrations were determined before LT and at the end of follow-up (median 57 months). Mortality and causes of death were determined. Survival was compared to that of the overall patient population that received LT. Results: Before LT, serum hepcidin levels were low (0.54 ± 2.5 nmol/L; normal range: 4-30 nmol/L). After LT, 11 patients had iron evaluations; none received iron depletion therapy; all had normal transferrin saturation. The mean serum ferritin was 185 (±99) µg/L. Magnetic resonance imaging showed that iron overload was absent in 9 patients, mild in one patient with metabolic syndrome, and high (180 µmol/g) in one patient with hereditary spherocytosis unmasked after liver transplantation. At the end of follow-up, serum hepcidin was normal in 10 patients (11.12 ± 7.6 nmol/L; p