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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    ABSTRACT: Background Smoking is a major risk factor for lung cancer. Bilirubin, an antioxidant, is inversely associated with the risk of diseases related to oxidative stress. This study was conducted to determine the influence of smoking and bilirubin levels on the risk of lung cancer in the Severance cohort study. Methods This study included 68,676 Korean who received a health examination at Severance Health Promotion Center from 1994 to 2004. Serum bilirubin measurements within normal range were divided into tertiles whereas smoking states were divided as never-smokers, former smokers and current smokers. A diagnosis of lung cancer was coded as occurring based on the report from the National Cancer Registry. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using Cox proportional hazards model. Results At the end of the study period, 240 patients (men: 181, women: 59) developed lung cancer. Compared to those with bilirubin levels ≥1.0 mg/dL, HRs (95% CI) for lung cancer were 2.8 (1.8–4.2) for subjects having bilirubin levels from 0.2 to 0.7 mg/dL in men. When we stratified our analysis by smoking status, bilirubin consistently showed a protective effect on the risk of lung cancer on both never- and current smokers. Current smokers having bilirubin levels from 0.2 to 0.7 mg/dL had a risk of lung cancer by 6.0-fold higher than never-smokers with bilirubin levels ≥1.0 mg/dL in men. Conclusion In this large prospective study, higher baseline bilirubin level in the normal range was associated with low risk of lung cancer. Smoking and low bilirubin levels were cumulatively associated with a higher risk of lung cancer.
    PLoS ONE 08/2014; 9(8):e103972. DOI:10.1371/journal.pone.0103972 · 3.53 Impact Factor
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    ABSTRACT: We proposed to evaluate the association between serum indirect bilirubin levels and liver fibrosis in patients with chronic hepatitis C (CHC) genotype 1b. Biopsy proven CHC genotype 1b patients' demographics, clinical and histopathological characteristics were evaluated. Logistic regression analysis was done to evaluate the clinical, laboratory and demographic features of the histologically proven liver fibrosis in CHC patients. A total of 112 biopsy proven CHC genotype 1b patients were enrolled into the study. Liver fibrosis scores were measured by using Ishak fibrosis scores and were divided into two groups; fibrosis scores ≤2 were categorized as mild fibrosis, 82 patients (73.2%), whereas fibrosis scores >2 were categorized as advanced fibrosis group, 30 patiens (26.8%). Patients with advanced fibrosis had lower indirect bilirubin levels than the mild fibrosis group (0.28±0.02mg/dl vs. 0.44±0.032mg/dl, p<0.001, respectively). Indirect bilirubin level was negatively correlated with advanced fibrosis scores (r=-0.416 and p<0.001). In multivariate logistic regression analysis, low indirect bilirubin level was an independent predicting factor of advanced liver fibrosis (OR: 0.001, 95% CI: 0.0-0.005, p<0.001). There is an inverse relationship between indirect bilirubin levels and advanced liver fibrosis caused by CHC genotype 1b.
    Pathology - Research and Practice 04/2014; DOI:10.1016/j.prp.2014.04.001 · 1.56 Impact Factor
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    ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder that covers wide spectrum of liver pathology. NAFLD is strongly associated with liver inflammation, metabolic hyperlipidaemia and insulin resistance. Frequently, NAFLD has been considered as the hepatic manifestation of metabolic syndrome. The pathophysiology of NAFLD has not been fully elucidated. Some patients can remain in the stage of simple steatosis, which generally is a benign condition; whereas others can develop liver inflammation and progress into non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. The mechanism behind the progression is still not fully understood. Much ongoing proteomic researches have focused on discovering the unbiased circulating biochemical markers to allow early detection and treatment of NAFLD. Comprehensive genomic studies have also begun to provide new insights into the gene polymorphism to understand patient-disease variations. Therefore, NAFLD is considered a complex and mutifactorial disease phenotype resulting from environmental exposures acting on a susceptible polygenic background. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. For proteomics section, this review highlighted functional proteins that involved in: (1) transportation; (2) metabolic pathway; (3) acute phase reaction; (4) anti-inflammatory; (5) extracellular matrix; and (6) immune system. In the genomic studies, this review will discuss genes which involved in: (1) lipolysis; (2) adipokines; and (3) cytokines production.
    World Journal of Gastroenterology 07/2014; 20(26):8325-8340. DOI:10.3748/wjg.v20.i26.8325 · 2.43 Impact Factor

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