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Association of Serum Bilirubin With Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

Journal

FRONTIERS IN ENDOCRINOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2022.869579

Keywords

serum bilirubin; metabolic syndrome; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; meta-analysis

Funding

  1. Beijing Municipal Administration of Hospitals Clinical medicine Development of Special Funding Support [ZYLX202125]
  2. Capital Health development Scientific Research project [2022-1-2182]
  3. Natural Science Foundation of Beijing Municipality [1212040205]
  4. Beijing Advanced Innovation Center for Big Data-Based Precision Medicine [1212040205]

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This study evaluated the association between serum bilirubin levels and metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD). The results showed an inverse correlation between serum total bilirubin (TBIL) and direct bilirubin (DBIL) levels with MetS in healthy population. Serum indirect bilirubin (IBIL) levels were inversely associated with the onset and degree of non-alcoholic steatohepatitis (NASH) in NAFLD patients. Exogenous bilirubin supplement may be a potential strategy to lower the risk of developing MetS and NAFLD.
Objective: Metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) are the leading chronic diseases worldwide. There are still many controversies about the association between serum bilirubin and MetS or NAFLD. This study aims to evaluate the association of serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL) with MetS and NAFLD. Methods: Multiple databases were searched for relevant studies until November 2021. Randomized controlled trials, cross-sectional and cohort studies evaluating the association between serum bilirubin levels and MetS or NAFLD were included. Results: Twenty-four cross-sectional and cohort studies with 101, 517 participants were finally analyzed. Fifteen studies and 6 studies evaluated the association between bilirubin and MetS or NAFLD in health screening population, respectively, while 3 studies evaluated the association between bilirubin and non-alcoholic steatohepatitis (NASH) in NAFLD patients. Random effect model analysis showed the inverse association between TBIL and MetS in male (95%CI=0.71-0.96) and gender-neutral (95%CI=0.61-0.91) group. However, no significant association was found in females. Notably, the inverse association between DBIL and MetS was noticed in male (95%CI=0.36-0.75), female (95%CI=0.16-0.58) and gender-neutral population (95%CI=0.67-0.92). IBIL level was inversely associated with MetS in females (95%CI=0.52-0.96), whereas no statistical correlation presented in males. TBIL was not statistically correlated with NAFLD in gender-neutral or male subgroup. Similarly, there were no association between DBIL or IBIL and NAFLD in gender-neutral subgroup. However, the negative correlation between DBIL and NAFLD existed in males (95%CI=0.76-0.96). In NAFLD patients, IBIL analysis showed an inverse association with NASH (95%CI=0.01-0.12). Conclusion: Serum TBIL and DBIL levels, especially DBIL levels, assume an inverse correlation with MetS in healthy population. Serum IBIL is inversely associated with the onset and degree of NASH in NAFLD patients. Exogenous bilirubin supplement may be a potential strategy to assist in lowering the risk of developing MetS and NAFLD.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021293349

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