title: Elevated serum ferritin is associated with increased mortality in non-alcoholic fatty liver disease after 16 years of follow-up.
abstract: High levels of ferritin in patients with non-alcoholic fatty liver disease (NAFLD) are associated with significant fibrosis and higher NAFLD activity score (NAS). It is unclear if this association has an impact on mortality. We investigated if high levels of ferritin, with or without iron overload, were associated with an increased mortality in NAFLD.
  
  
  
  We included 222 patients between 1979 and 2009 with biopsy-proven NAFLD and available serum ferritin concentrations. The cohort was divided into 'high' (n = 89) and 'normal' (n = 133) ferritin values, using a cut-point of 350 μg/L in males, and 150 μg/L in females, and stratified upon iron overload status. Data on mortality were obtained from a national, population-based register. Poisson regression was used to estimate hazard ratios for mortality. The estimates were adjusted for age at biopsy, sex, smoking, BMI, diabetes, hypertension, cardiovascular disease and fibrosis stage at the time of biopsy.
  
  
  
  The median follow-up time was 15.6 years (range: 0.5-34.2). Patients with high ferritin had more advanced fibrosis and higher NAS than patients with normal ferritin (P < 0.05). Fifteen years after diagnosis, and after adjusting for confounders, the high-ferritin group showed an increasingly higher mortality that was statistically significant (Hazard ratio = 1.10 per year, 95% Confidence interval 1.01-1.21, P < 0.05). There was no difference in mortality between patients with different iron overload patterns.
  
  
  
  High levels of ferritin are associated with a long-term increased risk of death.
authors.affiliation: Center for Digestive Diseases, Unit of Hepatology, Karolinska University Hospital, Stockholm, Sweden. hannes.hagstrom@ki.se.|Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden. hannes.hagstrom@ki.se.
authors.forename: Hannes
authors.initials: H
authors.lastname: Hagström
authors.affiliation: Department of Medical and Health Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Nasr
authors.affiliation: Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bottai
authors.affiliation: Department of Medical and Health Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Ekstedt
authors.affiliation: Department of Medical and Health Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Stergios
authors.initials: S
authors.lastname: Kechagias
authors.affiliation: Center for Digestive Diseases, Unit of Hepatology, Karolinska University Hospital, Stockholm, Sweden.|Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rolf
authors.initials: R
authors.lastname: Hultcrantz
authors.affiliation: Center for Digestive Diseases, Unit of Hepatology, Karolinska University Hospital, Stockholm, Sweden.|Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Stål
mesh_terms: D000328:Adult; D005260:Female; D005293:Ferritins / Q000097:blood*; D005500:Follow-Up Studies; D006801:Humans; D019190:Iron Overload / Q000097:blood*; D008099:Liver / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000401:mortality* / Q000503:physiopathology; D012307:Risk Factors; D016019:Survival Analysis; D013548:Sweden
chemical_list: D005293:Ferritins
keywords: NAFLD activity score; ferritin; fibrosis; long-term outcome; mortality; non-alcoholic fatty liver disease