title: A cohort study of serum bilirubin levels and incident non-alcoholic fatty liver disease in middle aged Korean workers.
abstract: BACKGROUND
  Serum bilirubin may have potent antioxidant and cytoprotective effects. Serum bilirubin levels are inversely associated with several cardiovascular and metabolic endpoints, but their association with nonalcoholic fatty liver disease (NAFLD) has not been investigated except for a single cross-sectional study in a pediatric population. We assessed the prospective association between serum bilirubin concentrations (total, direct, and indirect) and the risk for NAFLD.
  
  
  RESULTS
  We performed a cohort study in 5,900 Korean men, 30 to 59 years of age, with no evidence of liver disease and no major risk factors for liver disease at baseline. Study participants were followed in annual or biennial health examinations between 2002 and 2009. The presence of fatty liver was determined at each visit by ultrasonography. We observed 1,938 incident cases of NAFLD during 28,101.8 person-years of follow-up. Increasing levels of serum direct bilirubin were progressively associated with a decreasing incidence of NAFLD. In age-adjusted models, the hazard ratio for NAFLD comparing the highest to the lowest quartile of serum direct bilirubin levels was 0.61 (95% CI 0.54-0.68). The association persisted after adjusting for multiple metabolic parameters (hazard ratio comparing the highest to the lowest quartile 0.86, 95% CI 0.76-0.98; P trend = 0.039). Neither serum total nor indirect bilirubin levels were significantly associated with the incidence of NAFLD.
  
  
  CONCLUSIONS
  In this large prospective study, higher serum direct bilirubin levels were significantly associated with a lower risk of developing NAFLD, even adjusting for a variety of metabolic parameters. Further research is needed to elucidate the mechanisms underlying this association and to establish the role of serum direct bilirubin as a marker for NAFLD risk.
authors.affiliation: Department of Occupational Medicine, Kangbuk Samsung Hospital and Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Yoosoo
authors.initials: Y
authors.lastname: Chang
authors.forename: Seungho
authors.initials: S
authors.lastname: Ryu
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Son
authors.forename: Jang-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Juhee
authors.initials: J
authors.lastname: Cho
authors.forename: Eliseo
authors.initials: E
authors.lastname: Guallar
mesh_terms: D000328:Adult; D044466:Asian People; D001663:Bilirubin / Q000097:blood*; D015331:Cohort Studies; D005234:Fatty Liver / Q000097:blood / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D011446:Prospective Studies; D056910:Republic of Korea / Q000453:epidemiology
chemical_list: D001663:Bilirubin