Combined exposure effects and potential mechanisms of volatile organic compounds on liver fibrosis in the US population: an integrative epidemiological and computational toxicology analysis

作者：Yinhang Cui, Xiaoyi Yan, Xiaocong Ma, Jiacheng Xie, Tingwei Quan, Lian Gu · 发表于：Toxicology Mechanisms and Methods · 年份：2026 · DOI：10.1080/15376516.2026.2648850 · 研究领域：Liver physiology and pathology、Carcinogens and Genotoxicity Assessment、Advanced Chemical Sensor Technologies

Background Volatile organic compounds (VOCs) are widespread environmental pollutants that can cause oxidative stress and hepatocellular damage. However, epidemiological evidence linking VOC exposure to liver fibrosis and the underlying molecular mechanisms remains limited.Methods Data were obtained from the 2017–2020 National Health and Nutrition Examination Survey (NHANES). Liver fibrosis was defined using the NAFLD fibrosis score (NFS > 0.676). Weighted logistic regression, restricted cubic spline (RCS), and weighted quantile sum (WQS) models were applied to evaluate individual and combined associations of nine blood VOCs with liver fibrosis after adjusting for demographic, lifestyle, and biochemical covariates. To explore potential mechanisms, network toxicology and molecular docking were conducted.Results VOCs were moderately correlated, indicating common co-exposure sources. The WQS model revealed a positive overall association between mixed VOC exposure and liver fibrosis, with 1,4-Dichlorobenzene contributing the greatest weight. In fully adjusted models, higher blood 1,4-Dichlorobenzene levels were significantly associated with increased odds of liver fibrosis (p-trend < 0.05). RCS analysis showed a nonlinear dose–response relationship between 1,4-Dichlorobenzene and liver fibrosis risk. Network toxicology identified 176 overlapping targets enriched in PI3K–AKT and MAPK signaling pathways, with SRC, AKT1, AKT3, PIK3CA, and PIK3CD as hub genes. Molecular docking confir...