School of Public Health, Guilin Medical University, Guilin, Guangxi, 541199, China.
Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, 430000, China.
Environ Res. 2024 Dec 15;263(Pt 2):120092. doi: 10.1016/j.envres.2024.120092. Epub 2024 Sep 30.
Heavy metals and per- and polyfluoroalkyl substances (PFAS) are significantly associated with the risk of hepatic fibrosis. However, the potential mediating effect of kidney function in the relationship between heavy metals, PFAS, and hepatic fibrosis risk remains unexplored. This research gap limits the development of hepatic fibrosis prevention and treatment strategies. To address this, this study conducts a cross-sectional analysis based on data from 10,870 participants in NHANES 2005-2018 to explore the relationship between heavy metals, PFAS, and the risk of hepatic fibrosis, as well as the mediating effect of kidney function. Participants with a Fibrosis-4 index <1.45 are defined as not having hepatic fibrosis in this study. Results from generalized linear regression models and weighted quantile sum regression models indicate that both individual and combined exposures to heavy metals and PFAS are positively associated with the risk of hepatic fibrosis. Nonlinear exposure-response functions suggest that there may be a threshold for the relationship between heavy metals (except mercury) and PFAS with the risk of hepatic fibrosis. Furthermore, heavy metals and PFAS increase the risk of kidney function impairment. After stratification by kidney function stage, the relationship between heavy metals (except lead) and proteinuria is not significant, while PFAS show a significant negative association with proteinuria. The decline in kidney function has a significant mediating effect in the relationship between heavy metals and PFAS and the risk of hepatic fibrosis, with mediation effect proportions all above 20%. The findings suggest that individual or combined exposure to heavy metals and PFAS does not increase the risk of hepatic fibrosis until a certain threshold is reached, and the mediating role of declining kidney function is very important. These results highlight the need to consider kidney function in the context of hepatic fibrosis risk assessment and management.
重金属和全氟及多氟烷基物质（PFAS）与肝纤维化风险显著相关。然而，肾功能在重金属、PFAS 与肝纤维化风险之间关系中的潜在中介作用仍未得到探索。这一研究空白限制了肝纤维化预防和治疗策略的制定。为了解决这个问题，本研究基于 2005-2018 年 NHANES 数据中的 10870 名参与者进行了横断面分析，以探讨重金属、PFAS 与肝纤维化风险之间的关系，以及肾功能的中介作用。在本研究中，将 Fibrosis-4 指数<1.45 的参与者定义为没有肝纤维化。广义线性回归模型和加权分位数和回归模型的结果表明，个体和联合暴露于重金属和 PFAS 与肝纤维化风险呈正相关。非线性暴露-反应关系表明，重金属（汞除外）和 PFAS 与肝纤维化风险之间的关系可能存在一个阈值。此外，重金属和 PFAS 增加了肾功能损害的风险。按肾功能阶段分层后，重金属（铅除外）与蛋白尿之间的关系不显著，而 PFAS 与蛋白尿呈显著负相关。肾功能下降在重金属和 PFAS 与肝纤维化风险之间的关系中具有显著的中介作用，中介效应比例均高于 20%。研究结果表明，个体或联合暴露于重金属和 PFAS 不会增加肝纤维化的风险，直到达到一定的阈值，而肾功能下降的中介作用非常重要。这些结果强调了在评估和管理肝纤维化风险时需要考虑肾功能。
