Association between serum per- and polyfluoroalkyl substances levels and metabolic dysfunction-associated steatotic liver disease

Experimental evidences have suggested that Per- and polyfluoroalkyl substances (PFASs) were hepatotoxicity, but epidemiologic inconsistencies. There were 1751 participants included in this study after excluding chronic hepatitis, cirrhosis, excessive alcohol drinkers, and those with missing key variables. Totally 30 PFASs were quantified using ultrahigh-pressure liquid chromatography tandem mass spectrometer (UPLC-MS). Metabolic dysfunction-associated steatotic liver disease (MASLD) defined as the presence of hepatic steatosis diagnosed on abdominal B-ultrasound in conjunction with at least one cardiometabolic risk factors (CMRF) and without other discernible cause. After multivariate adjustment, perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluoroalkyl carboxylates (Sigma PFCAs), and perfluoroheptanoic acid (PFHpA) were positively associated with the risk of MASLD. Specifically, for each natural log-transformed unit increase in PFOA, PFNA, and Sigma PFCAs, the risk of MASLD increased by 27% (95% confidence interval (CI): 1.09-1.48), 10% (95% CI: 0.99-1.23), and 29% (95% CI: 1.09-1.53), respectively. Compared with those in Tertile 1 of PFOA, PFNA, and Sigma PFCAs, the risk of MASLD was increased by 35% (95% CI: 1.06-1.71, P (trend) = 0.019), 46% (95% CI: 1.15-1.85, P (trend) = 0.0018), and 43% (95% CI: 1.13-1.82, P (trend) = 0.0032) in Tertile 3, respectively. For PFHpA (detection rate: 14.79%), individuals with PFHpA levels above the detection limit had increased risk of MASLD by 54% (95% CI: 1.17-2.01) compared with those with PFHpA levels below the detection limit. While 8:2 chlorinated polyfluoroethersulfonic acid (8:2 Cl-PFESA) was inversely associated with steatotic liver disease (SLD) combined with 4 or 5 CMRFs (odds ratio per ln-unit = 0.87, 95% CI: 0.77-0.99). Mixed exposure analysis showed PFNA manifested a significant positive effect, while PFUdA had a significant negative effect. No association was found between other PFASs and MASLD prevalence. More prospective studies are needed to validate our conclusions.