TY - JOUR
T1 - Exposure to per-and Polyfluoroalkyl Substances and Markers of Liver Injury
T2 - A Systematic Review and Meta-Analysis
AU - Costello, Elizabeth
AU - Rock, Sarah
AU - Stratakis, Nikos
AU - Eckel, Sandrah P.
AU - Walker, Douglas I.
AU - Valvi, Damaskini
AU - Cserbik, Dora
AU - Jenkins, Todd
AU - Xanthakos, Stavra A.
AU - Kohli, Rohit
AU - Sisley, Stephanie
AU - Vasiliou, Vasilis
AU - La Merrill, Michele A.
AU - Rosen, Hugo
AU - Conti, David V.
AU - McConnell, Rob
AU - Chatzi, Leda
N1 - Publisher Copyright:
© 2022, Public Health Services, US Dept of Health and Human Services. All rights reserved.
PY - 2022/4
Y1 - 2022/4
N2 - BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. https://doi.org/10.1289/EHP10092.
AB - BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. https://doi.org/10.1289/EHP10092.
UR - http://www.scopus.com/inward/record.url?scp=85129780093&partnerID=8YFLogxK
U2 - 10.1289/EHP10092
DO - 10.1289/EHP10092
M3 - Review article
C2 - 35475652
AN - SCOPUS:85129780093
SN - 0091-6765
VL - 130
JO - Environmental Health Perspectives
JF - Environmental Health Perspectives
IS - 4
M1 - 046001
ER -