Lu Yu, Zheng Li, Pei Jie Sun, Shu Yang Yan, Wan Ying Shi, Wen Qi Hao, Wan Ling Li, Ming Kun Yu, De Jin Yang, Ying Li Qu, Sai Sai Ji, Wen Li Zhang, Feng Zhao, Ya Wei Li, Hao Can Song, Jia Yi Cai, Ying Zhu, Song Tang, Feng Tan, Yue Bin Lyu, Xiao Ming Shi
Blood Co and Mn nonlinearly increased hepatic fibrosis risk, urinary Sn reduced it. T3 levels modulated these metal-specific risks, highlighting thyroid hormones as potential modifiers in HMMs-induced hepatotoxicity.
OBJECTIVE: To investigate associations between heavy metals and metalloids (HMMs) exposure and hepatic fibrosis risk, and to explore the modifying role of thyroid hormones.
METHODS: Using nationally representative data from 9,543 adults in the China National Human Biomonitoring (CNHBM) program, hepatic fibrosis risk was assessed with the Fibrosis-4 index (FIB-4). Weighted logistic and linear regression models were applied to evaluate links between 13 HMMs and fibrosis outcomes. Dose-response relationships were modeled with restricted cubic splines, and subgroup analyses were used to explore potential effect modification.
RESULTS: Blood cobalt (Co) ( OR = 1.613, 95% CI: 1.126-2.310) and blood manganese (Mn) ( OR = 1.699, 95% CI: 1.238-2.331) showed nonlinear positive associations with hepatic fibrosis risk, while urinary tin (Sn) ( OR = 0.888, 95% CI: 0.797-0.990) was inversely associated. Low triiodothyronine (T3) levels increased Co-induced fibrosis risk and may enhance the protective effect of Sn, while high T3 levels exacerbated Mn-related risk. Stratified analysis by thyroxine (T4) levels showed directionally consistent associations with the main findings.
CONCLUSION: Blood Co and Mn nonlinearly increased hepatic fibrosis risk, urinary Sn reduced it. T3 levels modulated these metal-specific risks, highlighting thyroid hormones as potential modifiers in HMMs-induced hepatotoxicity.