Objective To investigate the association of plasma concentrations of manganese, arsenic, and lead with abnormal liver function.

Methods A prospective cohort study was conducted with a total of 4 344 individuals from the Dongfeng-Tongji cohort. The study collected information on the sociodemographic characteristics, lifestyle behaviors, and health status of the participants through questionnaires, physical examinations, and laboratory tests. Plasma metal concentrations and liver function indicators were measured using inductively coupled plasma mass spectrometry and an automatic biochemical analyzer, respectively. A multivariable logistic regression model was established to calculate the odds ratios (ORs) of plasma metals for the occurrence of abnormal liver function. Restricted cubic spline (RCS) curves were employed to assess the dose-response relationships between plasma metal concentrations and serum liver function indicators. Additionally, a generalized linear model was employed to explore the interaction of manganese, arsenic, and lead and their impact on total bilirubin levels.

Results Liver function abnormalities, defined as serum liver function indicators equal to or greater than the clinical upper limits, were observed in 1 444 (33.24%) participants. In the multivariable logistic regression model, compared with the lowest tertile, the highest tertiles of plasma manganese, arsenic, and lead were associated with an increased risk of total bilirubin abnormalities, with ORs (95% confidence interval) of 1.56 (1.31-1.87), 1.87 (1.58-2.22), and 1.87 (1.57-2.22), respectively. RCS analyses indicated nonlinear associations of plasma manganese and arsenic with total and direct bilirubin levels (P-overall < 0.001, P-nonlinear < 0.05), while plasma lead demonstrated a positive dose-response relationship with direct bilirubin concentration (P-overall < 0.001, P-nonlinear>0.05). Interaction analysis demonstrated significant positive interactions between manganese-arsenic and arsenic-lead with respect to total bilirubin abnormalities (P < 0.05). The mean (standard error) total bilirubin concentrations were 13.42 (0.20) μmol/L in the low plasma manganese-low plasma arsenic group and 15.86 (0.20) μmol/L in the high plasma manganese-high plasma arsenic group.

Conclusion The findings of this study indicated significant associations of plasma concentrations of manganese, arsenic, and lead with an increased risk of liver function abnormalities. Furthermore, plasma lead showed a positive linear association with the risk of direct bilirubin abnormalities.