Article

a cohort study of serum bilirubin levels and incident non-alcoholic fatty liver disease in middle aged korean workers

Department of Occupational Medicine, Kangbuk Samsung Hospital and Sungkyunkwan University School of Medicine, Seoul, South Korea.
PLoS ONE (Impact Factor: 3.53). 05/2012; 7(5):e37241. DOI: 10.1371/journal.pone.0037241
Source: PubMed

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.
Methods and Findings: 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.

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