title: Worse Outcomes of Patients With HFE Hemochromatosis With Persistent Increases in Transferrin Saturation During Maintenance Therapy.
abstract: OBJECTIVE
  Even if patients with hemochromatosis maintain low serum levels of ferritin, they still have an increased risk of general and joint symptoms, which reduce quality of life. This could be related to persistently increased transferrin saturation. We assessed whether duration of exposure to increased transferrin saturation during maintenance therapy is associated with more severe general and joint symptoms.
  
  
  METHODS
  We performed a longitudinal cohort study of 266 individuals homozygous for the C282Y substitution in HFE, seen at a tertiary reference center in Rennes, France, and followed for 3 or more years after initial iron removal. Serum ferritin and transferrin saturation were measured at the same time points; values were used to calculate duration of exposure to serum ferritin 50 μg/L or more (FRT50exp) and to determine transferrin saturation 50% or greater (SAT50exp). Clinical and biochemical follow-up data were recorded from log books completed during maintenance therapy. The primary outcome was change in general and joint symptoms, determined from answers to a self-administered questionnaire.
  
  
  RESULTS
  Patients were followed for 13.5 ± 5.9 years. FRT50exp (3.2 ± 3.5 years) and SAT50exp (4.5 ± 3.4 years) values correlated (r = 0.38; P < .0001), but each associated with different variables in multivariate analysis. We found independent associations, regardless of follow-up time, between SAT50exp ≥6 years and worsened joint symptoms (odds ratio [OR], 4.19; 95% confidence interval [CI], 1.88-9.31), and between SAT50exp ≥6 years and decreased athletic ability (OR, 2.35; 95% CI, 1.16-4.73). SAT50exp ≥8 years associated independently with decreased work ability (OR, 3.20; 95% CI, 1.40-7.30) and decreased libido (OR, 3.49; 95% CI, 1.56-7.80).
  
  
  CONCLUSIONS
  In a longitudinal study of patients treated for hemochromatosis, we associated duration of exposure to increased transferrin saturation (longer than 6 years) with more severe general and joint symptoms. Maintenance of serum levels of ferritin at 50 μg/L or less does not indicate control of transferrin saturation, so guidelines on the management of hemochromatosis require revision.
authors.affiliation: CHU Rennes, Service des Maladies du Foie and Centre National de Référence des Surcharges en Fer Rares, Rennes, France; INSERM, CIC 1414, Rennes, France; University of Rennes 1, Faculty of Medicine, Rennes, France. Electronic address: edouard.bardou-jacquet@univ-rennes1.fr.
authors.forename: Edouard
authors.initials: E
authors.lastname: Bardou-Jacquet
authors.affiliation: CHU Rennes, Service des Maladies du Foie and Centre National de Référence des Surcharges en Fer Rares, Rennes, France; INSERM, CIC 1414, Rennes, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lainé
authors.affiliation: University of Rennes 1, Faculty of Medicine, Rennes, France; CHU Rennes, Service de Rhumatologie, Rennes, France; INSERM UMR 991, Rennes, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Guggenbuhl
authors.affiliation: INSERM, CIC 1414, Rennes, France.
authors.forename: Jeff
authors.initials: J
authors.lastname: Morcet
authors.affiliation: CHU Rennes, Service des Maladies du Foie and Centre National de Référence des Surcharges en Fer Rares, Rennes, France; INSERM, CIC 1414, Rennes, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Jézéquel
authors.affiliation: CHU Rennes, Service des Maladies du Foie and Centre National de Référence des Surcharges en Fer Rares, Rennes, France; University of Rennes 1, Faculty of Medicine, Rennes, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Guyader
authors.affiliation: CHU Rennes, Service des Maladies du Foie and Centre National de Référence des Surcharges en Fer Rares, Rennes, France; University of Rennes 1, Faculty of Medicine, Rennes, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Moirand
authors.affiliation: CHU Rennes, Service des Maladies du Foie and Centre National de Référence des Surcharges en Fer Rares, Rennes, France; INSERM, CIC 1414, Rennes, France; University of Rennes 1, Faculty of Medicine, Rennes, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Deugnier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005293:Ferritins / Q000032:analysis; D005602:France; D006432:Hemochromatosis / Q000235:genetics / Q000473:pathology*; D000071020:Hemochromatosis Protein / Q000235:genetics*; D006801:Humans; D007596:Joints / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D044967:Serum / Q000737:chemistry*; D062606:Tertiary Care Centers; D013997:Time Factors; D014168:Transferrin / Q000032:analysis*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D014168:Transferrin; D005293:Ferritins
keywords: Arthropathy; Hepcidin Deficiency; Iron Regulation; Treatment