Exposure to perfluoroalkyl substances (PFAS) and liver injury: a systematic review and meta-analysis

Abstract

BACKGROUND AND AIM: Experimental evidence indicates that exposure to pollutants is associated with liver damage and “toxicant-associated fatty liver disease” (TAFLD). Perfluoroalkyl substances (PFAS) are synthetic chemicals widely used in industry and consumer products that persist in the environment and bioaccumulate in food webs and human tissues. Our objective was to systematically review the literature evaluating PFAS exposure and evidence of liver injury from epidemiology and rodent studies. METHODS: PubMed and Embase were searched through January 27, 2021 using keywords corresponding to PFAS exposure and liver injury. For data synthesis, results were limited to articles assessing two primary outcomes: serum alanine aminotransferase (ALT) and steatosis. Other measures of liver injury were included as secondary outcomes. For human studies, the evidence from at least three observational studies per PFAS were synthesized using a weighted z-score approach to determine the direction and significance of associations between PFAS and biomarkers of liver injury. For animal studies, data were synthesized to summarize direction and significance of effect of exposure and dose on hepatic enzyme abundance and activity. RESULTS:Our search identified 23 epidemiological and 75 rodent studies. Studies focused primarily on four PFAS congeners: perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulphonic acid (PFHxS). Positive associations with ALT were found for PFOA (Z-score: 6.20, p 0.001), PFOS (Z-score: 3.55, p 0.001), and PFNA (Z-score: 2.27, p = 0.023) in humans. PFOA exposure was also associated with higher aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) levels in humans. PFAS exposed rodents had increased ALT levels, steatosis, and liver weight compared to non-exposed rodents. CONCLUSIONS:There is consistent evidence for PFAS hepatotoxicity from both human and rodent studies. Future research should evaluate PFAS mixtures to elucidate potential synergistic effects. KEYWORDS: PFAS, Chemical exposures, Systematic review, Meta-analysis, Obesity and metabolic disorders