Abstract
INTRODUCTION: Trace elements in the environment are considered significant risk factors for chronic liver disease. However, the impact of blood metal levels on the incidence of liver fibrosis or cirrhosis has not been fully assessed. Our study investigated the correlation between metal mixture exposure and liver fibrosis/cirrhosis as well as the mediating effect between non-alcoholic fatty liver disease (NAFLD) and liver fibrosis/cirrhosis. METHODS: We conducted a cross-sectional study using the National Health and Nutrition Examination Survey database from 2017 to 2020. Transient elastography was used to identify NAFLD and liver fibrosis or cirrhosis. Various statistical models have been applied to evaluate the relationship between blood metal mixtures and liver fibrosis/cirrhosis. The role of metal mixtures in NAFLD-associated liver fibrosis/cirrhosis was explored using a mediation analysis. RESULTS: In the fully adjusted logistic models, selenium was negatively correlated with liver fibrosis [odds ratio (OR) = 0.219, P = 0.039) and cirrhosis (OR = 0.007, P = 0.003). In the weighted quantile sum and quantile-based g-computation models, selenium showed the highest contribution to liver fibrosis (0.544 and 0.578) and cirrhosis (0.538 and 0.630, respectively). Bayesian kernel machine regression and restricted cubic splines models indicated an L-shaped association between selenium and liver fibrosis/cirrhosis. Selenium negatively mediated the relationship between NAFLD and liver fibrosis/cirrhosis according to the mediation analysis (-3.4% and -13.3%). CONCLUSIONS: Selenium shows an L-shaped relationship with liver fibrosis and cirrhosis and plays a negative mediating role in the association between NAFLD and liver fibrosis/cirrhosis. Blood selenium is a promising biomarker for chronic liver diseases, and supplemental selenium intake might contribute to the prevention and management of liver fibrosis/cirrhosis.