Exposure to per-and polyfluoroalkyl substances and markers of liver injury: A systematic review and meta-analysis

Authors: COSTELLO, ELIZABETH - University Of Southern California; ROCK, SARA - University Of Southern California; STRATAKIS, NIKOS - University Of Southern California; ECKEL, SANDRAH - University Of Southern California; WALKER, DOUGLAS - The Icahn School Of Medicine At Mount Sinai; VALVI, DAMASKINI - The Icahn School Of Medicine At Mount Sinai; CSERBIK, DORA - University Of Barcelona; JENKINS, TODD - Children'S Hospital - Cincinnati, Ohio; XANTHAKOS, STAVRA - Children'S Hospital - Cincinnati, Ohio; KOHLI, ROHIT - Children'S Hospital Los Angeles; SISLEY, STEPHANIE - Children'S Nutrition Research Center (CNRC); VASILIOU, VASILIS - Yale University; LA MERRILL, MICHELE - University Of California, Davis; ROSEN, HUGO - University Of Southern California; CONTI, DAVID - University Of Southern California; MC CONNELL, ROB - University Of Southern California; CHATZI, LEDA - University Of Southern California

Submitted to: Environmental Health Perspectives
Publication Type: Review Article
Publication Acceptance Date: 3/21/2022
Publication Date: 4/27/2022
Citation: Costello, E., Rock, S., Stratakis, N., Eckel, S.P., Walker, D.I., Valvi, D., Cserbik, D., Jenkins, T., Xanthakos, S.A., Kohli, R., Sisley, S., Vasiliou, V., LaMerrill, M.A., Rosen, H., Conti, D.V., McConnell, R., Chatzi, L. 2022. Exposure to per-and polyfluoroalkyl substances and markers of liver injury: A systematic review and meta-analysis. Environmental Health Perspectives. 130(4). Article 46001. https://doi.org/10.1289/EHP10092.
DOI: https://doi.org/10.1289/EHP10092

Interpretive Summary:

Technical Abstract: Experimental evidence indicates that exposure to certain pollutants is associated with liver damage. Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals widely used in industry and consumer products and bioaccumulate in food webs and human tissues, such as the liver. The objective of this study was to conduct a systematic review of the literature and meta-analysis evaluating PFAS exposure and evidence of liver injury from rodent and epidemiological studies. PubMed and Embase were searched for all studies from earliest available indexing year through 1 December 2021 using keywords corresponding to PFAS exposure and liver injury. For data synthesis, results were limited to studies in humans and rodents assessing the following indicators of liver injury: serum alanine aminotransferase (ALT), nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, or steatosis. For human studies, at least three observational studies per PFAS were used to conduct a weighted z-score meta-analysis to determine the direction and significance of associations. For rodent studies, data were synthesized to qualitatively summarize the direction and significance of effect. Our search yielded 85 rodent studies and 24 epidemiological studies, primarily of people from the United States. Studies focused primarily on legacy PFAS: perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid. Meta-analyses of human studies revealed that higher ALT levels were associated with exposure to 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). PFOA exposure was also associated with higher aspartate aminotransferase and gamma-glutamyl transferase levels in humans. In rodents, PFAS exposures consistently resulted in higher ALT levels and steatosis. There is consistent evidence for PFAS hepatotoxicity from rodent studies, supported by associations of PFAS and markers of liver function in observational human studies. This review identifies a need for additional research evaluating next-generation PFAS, mixtures, and early life exposures.