Associations of Heavy Metal Mixtures With Liver Function in Middle‐Aged and Elderly Adults: A Comparative Analysis of Blood and Urinary Biomarkers

Whether concurrent exposure to several heavy metals is related to liver function among generally healthy middle‐aged and older adults has rarely been examined. We therefore analyzed 2541 adults (≥ 40 years) from the 2017–2018 National Health and Nutrition Examination Survey (NHANES) cycle, in whom blood and urinary concentrations of multiple metals and a panel of nine liver function indices were determined. To disentangle mixture‐level and metal‐specific relationships, we combined conventional multiple linear regression with three complementary mixture approaches—Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression, and quantile g‐computation (qgcomp). Single‐metal analyses showed that several blood metals were significantly related to individual liver function indices. At the mixture level, BKMR linked the blood metal mixture to higher AST, TP, Alb, LDH, and TBil; WQS regression detected positive associations with all nine indices; and qgcomp confirmed positive associations for AST and Alb alongside inverse associations for TP and Glo. Across models, further analysis identified blood mercury (BHg) as the metals showing the most consistent contributions and showing the most consistent associations on liver function indices. In contrast, urinary heavy metal mixtures exhibited weak associations with most liver function indices, although the smaller urinary subsample may limit statistical power. Collectively, this study provides robust evidence of associations between combined heavy metal exposure, particularly in blood, and alterations in liver function indices in middle‐aged and elderly populations, which may inform exposure monitoring and clinical surveillance relevant to liver health.