Associations between per- and polyfluoroalkyl substances and liver fibrosis and steatosis in U.S. adolescents and adults

Background and Aims Per- and polyfluoroalkyl substances (PFAS) are associated with liver damage in experimental animals. This study aimed to examine associations between serum PFAS concentrations and liver fibrosis and steatosis in adolescents and adults from the general U.S. population. Methods We included 288 adolescents (12-19 years) and 1391 adults (at or above 20 years) from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 cycle. Serum concentrations of five prevalent PFAS compounds were examined, including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulphonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDeA). Liver fibrosis and hepatic steatosis were determined by ultrasound transient elastography. We used logistic regression and quantile g-computation to examine covariate-adjusted odds ratios (ORs) for cirrhosis and severe steatosis in relation to changes in individual PFAS concentrations and PFAS mixtures. Results The prevalence of cirrhosis and severe steatosis were 1.4% and 16% in adolescents, and 2.6% and 35% in adults. Serum PFOS (OR: 3.91, 95% CI: 1.59, 9.63) and PFNA (OR: 5.28, 95% CI: 2.88, 9.67) were positively associated with cirrhosis in adolescents, though confidence intervals were wide due to the limited number of cases. All examined PFAS compounds showed imprecise positive relationships with severe steatosis in adolescents. Per quartile increase in the total PFAS mixture was associated with a 2.17 (95% CI: 0.92, 5.11) fold increase in the odds for severe steatosis in adolescents. No associations for PFAS and cirrhosis or severe steatosis were found in adults. Conclusion In this U.S. representative study, we found positive associations between some PFAS compounds as well as PFAS mixtures with cirrhosis and severe steatosis in adolescents. Findings support the potential liver toxicity of PFAS, especially in younger age groups. Larger prospective studies are needed to confirm these results. Keywords: PFAS, liver toxicity, steatosis, liver cirrhosis, U.S., general population