title: Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease.
abstract: Serum ferritin (SF) levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) because of systemic inflammation, increased iron stores, or both. The aim of this study was to examine the relationship between elevated SF and NAFLD severity. Demographic, clinical, histologic, laboratory, and anthropometric data were analyzed in 628 adult patients with NAFLD (age, ≥ 18 years) with biopsy-proven NAFLD and an SF measurement within 6 months of their liver biopsy. A threshold SF >1.5 × upper limit of normal (ULN) (i.e., >300 ng/mL in women and >450 ng/mL in men) was significantly associated with male sex, elevated serum alanine aminotransferase, aspartate aminotransferase, iron, transferrin-iron saturation, iron stain grade, and decreased platelets (P < 0.01). Histologic features of NAFLD were more severe among patients with SF >1.5 × ULN, including steatosis, fibrosis, hepatocellular ballooning, and diagnosis of NASH (P < 0.026). On multiple regression analysis, SF >1.5 × ULN was independently associated with advanced hepatic fibrosis (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.05-2.62; P = 0.028) and increased NAFLD Activity Score (NAS) (OR, 1.99; 95% CI, 1.06-3.75; P = 0.033).
  
  
  CONCLUSIONS
  A SF >1.5 × ULN is associated with hepatic iron deposition, a diagnosis of NASH, and worsened histologic activity and is an independent predictor of advanced hepatic fibrosis among patients with NAFLD. Furthermore, elevated SF is independently associated with higher NAS, even among patients without hepatic iron deposition. We conclude that SF is useful to identify NAFLD patients at risk for NASH and advanced fibrosis.
authors.affiliation: Center for Liver Disease, Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA 98101, USA. kkowdley@benaroyaresearch.org
authors.forename: Kris V
authors.initials: KV
authors.lastname: Kowdley
authors.forename: Patricia
authors.initials: P
authors.lastname: Belt
authors.forename: Laura A
authors.initials: LA
authors.lastname: Wilson
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Yeh
authors.forename: Brent A
authors.initials: BA
authors.lastname: Neuschwander-Tetri
authors.forename: Naga
authors.initials: N
authors.lastname: Chalasani
authors.forename: Arun J
authors.initials: AJ
authors.lastname: Sanyal
authors.forename: James E
authors.initials: JE
authors.lastname: Nelson
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D005234:Fatty Liver / Q000097:blood* / Q000453:epidemiology / Q000473:pathology*; D005260:Female; D005293:Ferritins / Q000097:blood*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood* / Q000453:epidemiology / Q000473:pathology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease; D011237:Predictive Value of Tests; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D005293:Ferritins; D007501:Iron