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标题：Exposure to per- and Polyfluoroalkyl Substances and Markers of Liver Injury: A Systematic Review and Meta-Analysis
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作者：Elizabeth Costello ; Sarah Rock ; Nikos Stratakis 等
期刊名称：Environmental Health Perspectives
印刷版ISSN：0091-6765
电子版ISSN：1552-9924
出版年度：2022
卷号：130
期号：4
DOI：10.1289/EHP10092
语种：English
出版社：OCR Subscription Services Inc
摘要：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