Changes in markers of liver function in relation to changes in perfluoroalkyl substances - A longitudinal study

While it is known that perfluoroalkyl substances (PFASs) induce liver toxicity in experimental studies, the evidence of an association in humans is inconsistent.

The main aim of the present study was to examine the association of PFAS concentrations and markers of liver function using panel data.

We investigated 1002 individuals from Sweden (50% women) at ages 70, 75 and 80 in 2001-2014. Eight PFASs were measured in plasma using isotope dilution ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). Bilirubin and hepatic enzymes alanine aminotransferase (ALT), alkaline phosphatase (ALP), and γ-glutamyltransferase (GGT) were determined in serum using an immunoassay methodology. Mixed-effects linear regression models were used to examine the relationship between the changes in markers of liver function and changes in PFAS levels.

The changes in majority of PFAS concentrations were positively associated with the changes in activity of ALT, ALP, and GGT and inversely associated with the changes in circulating bilirubin after adjustment for gender and the time-updated covariates LDL- and HDL-cholesterol, serum triglycerides, BMI, statin use, smoking, fasting glucose levels and correction for multiple testing. For example, changes in perfluorononanoic acid (PFNA) were associated with the changes liver function markers β_BILIRUBIN = -1.56, 95% confidence interval (CI) -1.93 to -1.19, β_ALT = 0.04, 95% CI 0.03-0.06, and β_ALP = 0.11, 95% CI 0.06-0.15.

Our longitudinal assessment established associations between changes in markers of liver function and changes in plasma PFAS concentrations. These findings suggest a relationship between low-dose background PFAS exposure and altered liver function in the general population.