Exposure to serum perfluoroalkyl substances and biomarkers of liver function: The Korean national environmental health survey 2015-2017.

BACKGROUND: Exposure to perfluoroalkyl substances (PFAS) may increase the risk of liver disease by disrupting cholesterol and lipid synthesis/metabolism, leading to higher liver-enzyme concentrations. However, most studies assessing association between PFAS and liver enzymes focused on individual PFAS. Moreover, PFAS concentrations differ based on sex and obesity status, and it remains unclear whether these factors affect associations with liver function. Therefore, we examined the association between exposure to both individual and combined PFAS and liver-function biomarkers and assessed sex and obesity as effect modifiers in Korean adults. METHODS: We measured serum concentrations of the five most abundant PFAS (PFOA, PFOS, PFHxS, PFDA, PFNA) and three liver enzymes (alanine transaminase [ALT], aspartate aminotransferase [AST], γ-glutamyl transferase [GGT]) in 1404 adults from the Korean National Environmental Health Survey Cycle 3, 2015-2017. We used linear regression to evaluate associations between individual PFAS and liver-function biomarkers, assessing sex and obesity as possible effect modifiers, and performed Bayesian kernel machine regression and quantile g-computation to evaluate the overall effect of PFAS mixture on biomarkers of liver function. RESULTS: Among 1404 Korean adults, all five PFAS were detected. Geometric mean concentration was highest for PFOS (16.11 µg/L), followed by PFOA (5.83 µg/L), PFHxS (2.21 µg/L), PFNA (2.03 µg/L), and PFDA (1.06 µg/L). In multivariable linear regression, all PFAS were positively associated with ALT, AST, and GGT; 2-fold increase in each PFAS was associated with 3.4-8.6% higher ALT, 2.4-4.6% higher AST, and 4.6-11.1% higher GGT (all p < 0.05). Positive associations for PFOA, PFDA, and PFNA with AST were stronger in men, and positive associations for PFOS with ALT and GGT were stronger in women. Compared to obese participants, nonobese participants had higher average percent changes in each enzyme, particularly GGT, when individual PFAS concentration doubled. Additionally, increased exposure to PFAS mixtures was associated with higher ALT, AST, and GGT. In quantile g-computations, simultaneous quartile increase in all PFAS was significantly associated with 6.9% (95%CI: 3.7, 10.2) higher ALT, 4.5% (95%CI: 2.4, 6.6) higher AST, and 8.3% (95%CI: 3.7, 13.1) higher GGT levels, on average. CONCLUSIONS: Exposure to individual and combined PFAS is associated with higher liver enzymes in Korean adults, providing additional evidence for the association between PFAS exposure and risk of liver disease.