title: Iron deficiency in patients with nonalcoholic Fatty liver disease is associated with obesity, female gender, and low serum hepcidin.
abstract: OBJECTIVE
  Iron deficiency is often observed in obese individuals. The iron regulatory hormone hepcidin is regulated by iron and cytokines interleukin (IL) 6 and IL1β. We examine the relationship between obesity, circulating levels of hepcidin, and IL6 and IL1β, and other risk factors in patients with nonalcoholic fatty liver disease (NAFLD) with iron deficiency.
  
  
  METHODS
  We collected data on 675 adult subjects (>18 years old) enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Subjects with transferrin saturation <20% were categorized as iron deficient, whereas those with transferrin saturation ≥20% were classified as iron normal. We assessed clinical, demographic, anthropometric, laboratory, dietary, and histologic data from patients, and serum levels of hepcidin and cytokines IL6 and IL1β. Univariate and multivariate analysis were used to identify risk factors for iron deficiency.
  
  
  RESULTS
  One-third of patients (231 of 675; 34%) were iron deficient. Obesity, diabetes, and metabolic syndrome were more common in subjects with iron deficiency (P < .01), compared with those that were iron normal. Serum levels of hepcidin were significantly lower in subjects with iron deficiency (61 ± 45 vs 81 ± 51 ng/mL; P < .0001). Iron deficiency was significantly associated with female gender, obesity, increased body mass index and waist circumference, presence of diabetes, lower alcohol consumption, black or American Indian/Alaska Native race (P ≤ .018), and increased levels of IL6 and IL1β (6.6 vs 4.8 for iron normal, P ≤ .0001; and 0.45 vs 0.32 for iron normal, P ≤ .005).
  
  
  CONCLUSIONS
  Iron deficiency is prevalent in patients with NAFLD and associated with female gender, increased body mass index, and nonwhite race. Serum levels of hepcidin were lower in iron-deficient subjects, reflecting an appropriate physiologic response to decreased circulating levels of iron, rather than a primary cause of iron deficiency in the setting of obesity and NAFLD.
authors.affiliation: Liver Center of Excellence, Digestive Disease Institute, Virginia Mason Medical Center, Seattle, Washington.
authors.forename: Asma
authors.initials: A
authors.lastname: Siddique
authors.affiliation: Liver Center of Excellence, Digestive Disease Institute, Virginia Mason Medical Center, Seattle, Washington; Benaroya Research Institute, Virginia Mason Medical Center, Seattle, Washington.
authors.forename: James E
authors.initials: JE
authors.lastname: Nelson
authors.affiliation: Department of Physiological Nursing and Institute for Human Genetics, University of California at San Francisco, San Francisco, California.
authors.forename: Bradley
authors.initials: B
authors.lastname: Aouizerat
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Yeh
authors.affiliation: Liver Center of Excellence, Digestive Disease Institute, Virginia Mason Medical Center, Seattle, Washington; Benaroya Research Institute, Virginia Mason Medical Center, Seattle, Washington. Electronic address: Kris.kowdley@vmmc.org.
authors.forename: Kris V
authors.initials: KV
authors.lastname: Kowdley
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000413:Alaska; D015992:Body Mass Index; D005260:Female; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D000090463:Iron Deficiencies; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications*; D009765:Obesity / Q000150:complications*; D044469:Racial Groups; D012307:Risk Factors; D044967:Serum / Q000737:chemistry; D012737:Sex Factors; D055815:Young Adult
chemical_list: D064451:Hepcidins; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6
keywords: BMI; Ferroportin; Inflammation; NAFLD; NASH CRN; Nutrition