title: Liver transplantation normalizes serum hepcidin level and cures iron metabolism alterations in HFE hemochromatosis.
abstract: 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. 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. 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 nine patients, mild in one patient with metabolic syndrome, and high (180 μmol/g) in one patient with hereditary spherocytosis discovered after LT. At the end of follow-up, serum hepcidin was normal in 10 patients (11.12 ± 7.6 nmol/L; P<0.05) and low in one patient with iron deficiency anemia. Survival was 83% and 67% at 1 and 5 years, respectively. Survival was similar for patients with HH and patients that received LT for other causes.
  
  
  CONCLUSIONS
  In HH, LT normalized hepcidin secretion and prevented recurrence of hepatic iron overload. Survival was similar to that of patients who received LTs for other liver diseases.
authors.affiliation: CHU Rennes, Liver Disease Unit, Rennes, France; INSERM UMR991, University of Rennes 1, Rennes, France; CHU Rennes, National Reference Center for Rare Iron Overload Diseases of Genetic Origin, Rennes, France.
authors.forename: Edouard
authors.initials: E
authors.lastname: Bardou-Jacquet
authors.forename: Julie
authors.initials: J
authors.lastname: Philip
authors.forename: Richard
authors.initials: R
authors.lastname: Lorho
authors.forename: Martine
authors.initials: M
authors.lastname: Ropert
authors.forename: Marianne
authors.initials: M
authors.lastname: Latournerie
authors.forename: Pauline
authors.initials: P
authors.lastname: Houssel-Debry
authors.forename: Dominique
authors.initials: D
authors.lastname: Guyader
authors.forename: Olivier
authors.initials: O
authors.lastname: Loréal
authors.forename: Karim
authors.initials: K
authors.lastname: Boudjema
authors.forename: Pierre
authors.initials: P
authors.lastname: Brissot
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D006432:Hemochromatosis / Q000235:genetics / Q000378:metabolism / Q000601:surgery*; D000071020:Hemochromatosis Protein; D064451:Hepcidins / Q000097:blood*; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008107:Liver Diseases / Q000378:metabolism / Q000401:mortality / Q000601:surgery*; D008108:Liver Diseases, Alcoholic / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D007501:Iron