title: Serum ferritin levels lack diagnostic accuracy for liver fibrosis in patients with nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  Series studies have associated increased serum levels of ferritin with liver fibrosis in patients with nonalcoholic fatty liver disease. We aimed to determine the accuracy with which measurements of serum ferritin determine the presence and severity of liver fibrosis, and whether combining noninvasive scoring systems with serum ferritin analysis increases the accuracy of diagnosis of advanced liver fibrosis.
  
  
  METHODS
  We performed a retrospective analysis of data from 1014 patients with liver biopsy-confirmed nonalcoholic fatty liver disease. Three cut points of serum ferritin level, adjusted for sex, were established based on receiver operating characteristic curve analysis: 1.0-, 1.5-, and 2.0-fold the upper limit of normal. Three multiple logistic regression models were created to determine the association of these cutoff values with liver fibrosis, adjusting for age, sex, race, diabetes, body mass index, and level of alanine aminotransferase.
  
  
  RESULTS
  A greater proportion of patients with increased serum levels of ferritin had definitive nonalcoholic steatohepatitis and more-advanced fibrosis than patients without increased levels. In all models, serum level of ferritin was significantly associated with the presence and severity of liver fibrosis. However, for all 3 cutoff values, area under the receiver operating characteristic curve values were low (less than 0.60) for the presence of fibrosis or any stage of liver fibrosis; ferritin level identified patients with fibrosis with 16%-41% sensitivity and 70%-92% specificity. The accuracy with which noninvasive scoring systems identified patients with advanced fibrosis did not change with inclusion of serum ferritin values.
  
  
  CONCLUSIONS
  Although serum levels of ferritin correlate with more-severe liver fibrosis, based on adjusted multiple logistic regression analysis, serum ferritin levels alone have a low level of diagnostic accuracy for the presence or severity of liver fibrosis in patients with nonalcoholic fatty liver disease.
authors.affiliation: Division of Digestive Diseases & Nutrition, University of Kentucky Medical Center, Lexington, Kentucky. Electronic address: paul.angulo@uky.edu.
authors.forename: Paul
authors.initials: P
authors.lastname: Angulo
authors.affiliation: Storr Liver Unit, Westmead Millennium Institute, University of Sydney and Department of Gastroenterology and Hepatology, Westmead Hospital, Westmead, New South Wales, Australia.
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle, United Kingdom.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Day
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Torino, Turin, Italy.
authors.forename: Ester
authors.initials: E
authors.lastname: Vanni
authors.affiliation: Storr Liver Unit, Westmead Millennium Institute, University of Sydney and Department of Gastroenterology and Hepatology, Westmead Hospital, Westmead, New South Wales, Australia.
authors.forename: Lee
authors.initials: L
authors.lastname: Russell
authors.affiliation: Division of Digestive Diseases & Nutrition, University of Kentucky Medical Center, Lexington, Kentucky.
authors.forename: Anna C
authors.initials: AC
authors.lastname: De la Cruz
authors.affiliation: Division of Digestive Diseases & Nutrition, University of Kentucky Medical Center, Lexington, Kentucky.
authors.forename: Hammad
authors.initials: H
authors.lastname: Liaquat
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Torino, Turin, Italy.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Mezzabotta
authors.affiliation: Department of Pathology, University of Kentucky Medical Center, Lexington, Kentucky.
authors.forename: Eun
authors.initials: E
authors.lastname: Lee
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Torino, Turin, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bugianesi
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D056808:Biostatistics; D015331:Cohort Studies; D005260:Female; D005293:Ferritins / Q000097:blood*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications*; D012189:Retrospective Studies; D044967:Serum / Q000737:chemistry
chemical_list: D015415:Biomarkers; D005293:Ferritins
keywords: ALT; BMI; Cirrhosis; Iron; ROC