Effects of per- and polyfluoroalkyl substances on the liver: human-relevant mechanisms of toxicity

Per- and polyfluoroalkyl substances (PFAS) are abundantly used in a plethora of products with applications in daily life. As a result, PFAS are widely distributed in the environment, thus providing a source of exposure to humans. The majority of human exposure to PFAS is attributed to the human diet, which encompasses drinking water. Their chemical nature grants persistent, accumulative and toxic properties, which are currently raising concerns. Over the past few years, adverse effects of PFAS on different organs have been repeatedly documented. Numerous epidemiological studies established a clear link between PFAS exposure and liver toxicity. Likewise, effects of PFAS on liver homeostasis, lipid metabolism, bile acid metabolism and hepatocarcinogenesis have been reported in various in vitro and in vivo studies. This review discusses the role of PFAS in liver toxicity with special attention paid to human relevance as well as to the mechanisms underlying the hepatotoxic effects of PFAS. Future perspectives and remaining knowledge gaps were identified to enhance future PFAS risk assessment.