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 - Funding Information:
The results reported herein correspond to specific aims of grant R01ES030691 (L.C., R.M., D.V.C., S.P.E., D.I.W., D.V.) from the National Institutes of Health (NIH) National Institute of Environmental Health Science (NIEHS). Additional funding from the NIEHS included R21ES029681 (L.C., R.M., D.V.C., D.V.), R01ES029944 (L.C., D.V.C., D.I.W., D.V., S.R.), R01ES030364 (L.C., R.M., D.V.C., D.I.W., D.V., M.A.L., S.P.E., N.S., E.C.) R01ES032712 (V.V.), R21ES028903 (R.M., D.V., D.I.W., L.C.), P30ES007048 (R.M., L.C., D.V.C., S.P.E., S.R.), R21ES029328 (D.V.), P30ES023515 (D.V.), U2C ES030859 (D.I.W.), and T32ES013678 (E.C.). Additional funding from the NIH included P01CA196569, R01CA140561, R01ES016813, P30DK048522 (D.V.C.). Funding from the U.S. Department of Agriculture (USDA) National Institute of Food and Agriculture included the Hatch project [1002182 (M.A.L.)] and funding from USDA Agricultural Research Service agreement #58-3092-0-001 (S.S.).
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 -