Presence of Legacy and Emerging PFAS in Human Liver Specimens Banked in the United States from 2000 to 2024

Per- and polyfluoroalkyl substances (PFAS) are persistent, bioaccumulative chemicals linked to liver toxicity and metabolic disease. 54 PFAS were measured in 211 adult human livers collected between 2000 and 2024 to reveal temporal trends, relative PFAS abundance, and demographic predictors of hepatic burden. PFAS were detected in 210 individuals, with 15 compounds found in ≥30 livers. Total summed PFAS concentrations decreased by 94% over the 24-year period in weighted linear regression, and by 68% after adjusting for age, sex, and liver health in multivariate models. Since 2019, a ∼950-fold variability in concentration was observed, and the PFAS profile in the liver shifted from sulfonates and carboxylates to proportionally more sulfonamides and fluorotelomers. Sampling year was the strongest predictor of hepatic PFAS concentration in multivariate models. Age was positively associated with several long-chain PFAS, which is consistent with years-long elimination half-lives. Males had higher perfluoroundecanoic acid, perfluorododecanoic acid, and 9-chlorohexadecafluoro-3-oxanonane-1-sulfonic acid concentrations, whereas females had higher 8:2 fluorotelomer sulfonic acid concentrations. Nonalcoholic fatty liver disease was associated with lower concentrations of seven PFAS. While legacy PFAS declined following phaseouts, other PFAS increasingly drive liver burdens, with our data showing targeted PFAS comprise <10% of extractable organofluorine, highlighting the inadequacy of substance-by-substance regulatory approaches.