Associations of per- and polyfluoroalkyl substances and nonalcoholic fatty liver disease in the United States adult population, 2003-2018

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide and a leading cause of liver-related mortality. Prior studies have linked per- and polyfluoroalkyl substances (PFAS) exposure to liver dysfunction and alterations in metabolic pathways, but the extent of a PFAS-NAFLD relationship is unclear. Thus, the aim of the current study was to examine whether there were associations between PFAS exposures and NAFLD in the US adult population over a 16-year period. Data from 10,234 persons who participated in the National Health and Nutrition Examination Survey between 2003 and 2018 were analyzed. Odds ratios and 95% confidence intervals were calculated using multivariable logistic regression for the associations between PFAS and NAFLD, defined by the Hepatic Steatosis Index (NAFLD-HSI), the Fatty Liver Index (NAFLD-FLI), and by Transient Elastography with Controlled Attenuation Parameter (NAFLD-TE-CAP). Overall, there was a significant inverse association between total PFAS and NAFLD-HSI ( -trend = 0.04). Significant inverse associations were also found between perfluorohexane sulfonic acid (PFHxS) and NAFLD-HSI ( -trend = 0.04), and NAFLD-FLI ( -trend = 0.03). Analysis by time period, 2003-2010 versus 2011-2018, found that while inverse associations were more apparent during the latter period when total PFAS ( -trend = 0.02), PFHxS ( -trend = 0.04), and perfluorooctanoic acid (PFOA) ( -trend = 0.03) were inversely associated with NAFLD-HSI and PFOA was inversely associated with NAFLD-FLI ( -trend = 0.05), there were no significant interaction effects. No significant associations between the PFAS and NAFLD-TE-CAP were found. The current study found no evidence of a positive association between the most common PFAS and NAFLD in the US population.