Associations of PFOA and PFOS exposure with liver injury: Evidence from Two Population Studies and integrative adverse outcome pathway analysis

作者：You Y, Guan X, Zhao H, Wu T, Wang C, Xiao Y, Zhou Y, Hong S, Fu Y, He M, Guo H · 发表于：Environmental pollution (Barking, Essex : 1987) · 年份：2025 · DOI：10.1016/j.envpol.2025.127059 · 研究领域：Fluorocarbons、Alkanesulfonic Acids、Caprylates、Environmental Pollutants、Environmental Exposure、Female、Humans、Adult、Middle Aged、Adverse Outcome Pathways、Liver、China

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are representatives of perfluoroalkyl substances (PFAS) that could persist in the environment and concentrated in animal livers. However, epidemiological studies on the associations of PFOA/PFOS exposure with liver injury in women are limited, with mechanisms not fully understood. This study aimed to clarify these associations and explore possible mechanisms. Plasma or serum levels of PFOA, PFOS, liver enzymes (alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT)), and liver fibrosis scores (aspartate aminotransferase to platelet ratio index (APRI), gamma-glutamyl transpeptidase to platelet ratio index (GPRI), and fibrosis-4 (FIB-4)) were measured in 883 females from the Dongfeng-Tongji (DFTJ) cohort and 5,845 females from the National Health and Nutrition Examination Survey (NHANES) 2003-2018. We observed that increased level of PFOA exposure was associated with elevated ALT[β (95 %CI) = 0.06 (0.001,0.12) and 0.03 (0.01,0.05)], GGT[β (95 %CI) = 0.06 (-0.01,0.12) and 0.07 (0.03,0.11)], and GPRI[β (95 %CI) = 0.08 (0.01,0.16) and 0.08 (0.04,0.12)], while the increased level of PFOS was associated with higher FIB-4 index[β (95 %CI) = 0.04 (0.0002,0.08) and 0.08(0.06,0.10)] in both DFTJ cohort and NHANES. The integrative analysis of adverse outcome pathway (AOP) suggested that PFOA/PFOS exposure could activate ADIPOQ, INS, TNF-α, and NDUFS3,...