Exposure to per- and Polyfluoroalkyl Substances and Markers of Liver Injury: A Systematic Review and Meta-Analysis,Environmental Health Perspectives

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Exposure to per- and Polyfluoroalkyl Substances and Markers of Liver Injury: A Systematic Review and Meta-Analysis
Environmental Health Perspectives ( IF 10.1 ) Pub Date : 2022-4-27 , DOI: 10.1289/ehp10092
Elizabeth Costello ₁ , Sarah Rock ₁ , Nikos Stratakis ₁ , Sandrah P Eckel ₁ , Douglas I Walker ₂ , Damaskini Valvi ₂ , Dora Cserbik ₃ , Todd Jenkins ₄ , Stavra A Xanthakos ₅ , Rohit Kohli ₆ , Stephanie Sisley ₇ , Vasilis Vasiliou ₈ , Michele A La Merrill ₉ , Hugo Rosen ₁₀ , David V Conti ₁ , Rob McConnell ₁ , Leda Chatzi ₁

Affiliation

Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Barcelona Institute for Global Health, Barcelona, Spain.
Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital Los Angeles, Los Angeles, California, USA.
Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA.
Department of Environmental Toxicology, University of California, Davis, Davis, California, USA.
Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.

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 $z$ -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 ( $lowercase italic z-score equals$ 6.20, $lowercase italic p less than 0.001$ ), PFOS ( $lowercase italic z-score equals$ 3.55, $lowercase italic p less than 0.001$ ), and PFNA ( $lowercase italic z-score equals$ 2.27, $lowercase italic p less than 0.023$ ). 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

中文翻译：

暴露于全氟和多氟烷基物质和肝损伤标志物：系统评价和荟萃分析

摘要

背景：

实验证据表明，暴露于某些污染物与肝损伤有关。全氟烷基物质和多氟烷基物质 (PFAS) 是一种持久性合成化学品，广泛用于工业和消费品中，并在食物网和人体组织（如肝脏）中生物积累。

客观的：

本研究的目的是对文献和荟萃分析进行系统评价，以评估啮齿动物和流行病学研究中的 PFAS 暴露和肝损伤证据。

方法：

PubMed 和 Embase 使用与 PFAS 暴露和肝损伤相对应的关键字搜索了从最早可用索引年到 2021 年 12 月 1 日的所有研究。对于数据综合，结果仅限于人类和啮齿动物研究，评估以下肝损伤指标：血清丙氨酸氨基转移酶 (ALT)、非酒精性脂肪肝病、非酒精性脂肪性肝炎或脂肪变性。对于人体研究，每个 PFAS 至少使用三项观察性研究来进行加权 $z$ - 评分荟萃分析以确定关联的方向和意义。对于啮齿动物研究，综合数据以定性总结效果的方向和意义。

结果：

我们的搜索产生了 85 项啮齿动物研究和 24 项流行病学研究，主要针对来自美国的人。研究主要集中在传统 PFAS：全氟辛酸 (PFOA)、全氟辛烷磺酸 (PFOS)、全氟壬酸 (PFNA) 和全氟己烷磺酸。人类研究的荟萃分析显示，较高的 ALT 水平与暴露于 PFOA 相关（ $lowercase italic z-score equals$ 6.20, $lowercase italic p less than 0.001$ ), 全氟辛烷磺酸 ( $lowercase italic z-score equals$ 3.55, $lowercase italic p less than 0.001$ ) 和 PFNA ( $lowercase italic z-score equals$ 2.27, $lowercase italic p less than 0.023$ ）。PFOA 暴露还与人类体内较高的天冬氨酸氨基转移酶和 γ-谷氨酰转移酶水平有关。在啮齿动物中，PFAS 暴露始终导致更高的 ALT 水平和脂肪变性。