Publication Date
4-1-2022
Journal
Environmental Health Perspectives
DOI
10.1289/EHP10092
PMID
35475652
PMCID
PMC9044977 DO
PubMedCentral® Posted Date
4-27-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Biomarkers, Environmental Pollutants, Fluorocarbons, Humans, Non-alcoholic Fatty Liver Disease, United States
Abstract
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
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 (��-score= 6.20, ��<0.001), PFOS (��-score= 3.55, ��<0.001), and PFNA (��-score= 2.27, ��=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
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