Wang Ningning, Li Xuying, He Rui, Zheng Xiujuan, Li Mingqi, Nian Shijing, Wang Kewei
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China.
Department of Preventive Medicine, Qiqihar Medical University, Qiqihar, China.
Front Nutr. 2025 May 21;12:1566345. doi: 10.3389/fnut.2025.1566345. eCollection 2025.
Moderate heavy metals can lead to the occurrence of liver injury, but the specific mechanism remains unclear.
This study, based on data from the National Health and Nutrition Examination Survey (NHANES), analyzed associations between 10 heavy metals and hepatic injury in 5,613 adults, with a focus on the mediating role of the Systemic Immune-Inflammation Index (SII). Partial correlation analysis, weighted linear regression, weighted quantile sum (WQS) regression, and mediation effect models were used in the study.
SII showed significant negative correlations with hepatic fibrosis markers (FIB-4: = -0.290; NFS: = -0.382, both < 0.001) but no association with hepatic steatosis indices. Arsenic (As), cobalt (Co), and cesium (Cs) were identified as critical metals linking fibrosis indicators and SII. As mediated its pro-fibrotic effects by completely suppressing SII (OR = 0.0220-0.0581), while Co promoted NFS risk through complete mediation by SII (Q2 vs. Q1 OR = 1.26). Conversely, Cs exhibited anti-fibrotic protectionvia complete positive mediation through SII.
The findings demonstrate that Heavy metals differentially regulate immune-inflammatory pathways to influence hepatic fibrosis progression, providing new evidence for the mechanisms of environmental exposure-induced hepatic injury.
中等含量的重金属可导致肝损伤的发生，但其具体机制仍不清楚。
本研究基于美国国家健康与营养检查调查（NHANES）的数据，分析了5613名成年人中10种重金属与肝损伤之间的关联，重点关注全身免疫炎症指数（SII）的中介作用。研究中使用了偏相关分析、加权线性回归、加权分位数和（WQS）回归以及中介效应模型。
SII与肝纤维化标志物呈显著负相关（FIB-4：=-0.290；NFS：=-0.382，均P<0.001），但与肝脂肪变性指数无关联。砷（As）、钴（Co）和铯（Cs）被确定为连接纤维化指标和SII的关键金属。As通过完全抑制SII介导其促纤维化作用（OR=0.0220-0.0581），而Co通过SII的完全中介作用增加NFS风险（Q2与Q1相比，OR=1.26）。相反，Cs通过SII的完全正向中介作用表现出抗纤维化保护作用。
研究结果表明，重金属通过不同方式调节免疫炎症途径来影响肝纤维化进展，为环境暴露诱导肝损伤的机制提供了新证据。
