Co-exposure to PFAS, PFAS alternatives, and metals and liver function in Chinese adults.

Per- and polyfluoroalkyl substances (PFAS) and their alternatives are recognized environmental hepatotoxins, yet their combined effects with metals on liver health in human populations remain underexplored. This study measured serum levels of 13 PFAS (including legacy and emerging alternatives such as Cl-PFESAs) and plasma levels of 25 metals, and evaluated their individual and joint associations with five liver function biomarkers (ALT, AST, ALP, GGT, and DBIL) among 1263 adults in Guangzhou, China. Generalized additive models (GAMs) revealed that most individual pollutants were positively associated with liver function biomarkers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and direct bilirubin (DBIL). Advanced Bayesian kernel machine regression (A-BKMR) analyses, employed to assess the joint associations of these complex mixtures, further demonstrated significant positive associations between the overall mixture of PFAS, alternatives, and metals and these biomarkers. Crucially, PFOS and PFHpS among the PFAS, alongside Pb, Cd, Tl, Zn, and Fe among the metals, were identified as the primary contributors to the observed mixture effect. These findings provide additional epidemiological evidence that co-exposure to PFAS (including emerging alternatives) and metals is adversely associated with liver health, highlighting the importance of assessing complex environmental mixtures. Further population-based studies are warranted, including studies measuring metals in matrices other than plasma, to validate these associations and elucidate underlying biological pathways.