Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Preventive Medicine, School of Public Health, Sun Yat-sen University, 74 Zhongshan 2(nd) Road, Yuexiu District, Guangzhou 510080, China.
Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Preventive Medicine, School of Public Health, Sun Yat-sen University, 74 Zhongshan 2(nd) Road, Yuexiu District, Guangzhou 510080, China; Departments of Environmental Health Sciences and Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, NY 12144, USA.
Environ Res. 2019 May;172:81-88. doi: 10.1016/j.envres.2019.02.013. Epub 2019 Feb 11.
Exposure to chemicals may affect liver enzyme to increase the risk of liver diseases. Perfluoroalkyl acids (PFAAs) are one kind of persistent organic pollutants with hepatotoxic effect in organism. However, data is scarce to characterize the hepatotoxic effects of specific structural PFAA isomers in general population. To address this data gap, we evaluated the association between serum PFAAs concentration and liver function biomarkers in the Isomers of C8 Health Project in China. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to measure 18 serum PFAAs, except for linear and branched isomers of PFOA/PFOS, nine perfluorinated carboxylic acids (PFCAs) and two perfluorinated sulfonic acids (PFSAs) were also included, in 1605 adult residents of Shenyang, China. Values for nine serum liver function biomarkers were determined by full-automatic blood biochemical analyzer. Linear regression was used to evaluate associations between PFAAs and continuous liver function biomarkers and logistic regression to assess markers dichotomized per clinical reference intervals. Results indicated that serum PFAAs concentrations were associated with liver biomarker levels suggestive of hepatotoxicity, especially for liver cell injury. For example, a 1 ln-unit increase in total- perfluorooctanoic acid (PFOA) exposure was associated with a 7.4% [95% confidence interval (CI): 3.9%, 11.0%] higher alanine aminotransferase (ALT) level in serum. Interestingly, we observed association between branched PFAA isomers and liver biomarkers. For example, one ln-unit increase in branched perfluorooctane sulfonate (PFOS) isomers exposure was associated with a 4.3% increase in ALT level (95% CI: 1.2%, 7.4%) and a 33.0% increased odds of having abnormal ALT (95% CI: 5.0%, 67.0%). Also, we found that PFNA had positive association with ALT [(6.2%, 95% CI: 3.1%, 9.4%) and AST levels (2.5%, 95% CI: 0.5%, 4.5%)]. Logistic regression results showed that PFPeA, PFHxA, PFNA, PFDoDA, PFTrDA and PFTeDA had statistically association with abnormal prealbumin. Conclusively, our results support previous studies showing association between PFAAs exposure and liver function biomarkers. We found new evidence that branched PFAAs isomer exposure is associated with the risk of clinically relevant hepatocellular dysfunction.
暴露于化学物质可能会影响肝脏酶的活性，从而增加患肝病的风险。全氟烷基酸（PFAAs）是一类具有肝毒性的持久性有机污染物。然而，目前关于特定结构的 PFAAs 异构体在一般人群中的肝毒性效应的数据还很有限。为了解决这一数据空白，我们在中国的 C8 健康项目异构体研究中评估了血清 PFAAs 浓度与肝功能生物标志物之间的关系。采用高效液相色谱-串联质谱法（HPLC-MS/MS）检测了 18 种血清 PFAAs，除了线性和支链 PFOA/PFOS 异构体外，还包括 9 种全氟羧酸（PFCAs）和 2 种全氟磺酸（PFSAs）。该研究共纳入了中国沈阳的 1605 名成年居民，采用全自动生化分析仪测定了 9 种血清肝功能生物标志物的水平。线性回归用于评估 PFAAs 与连续肝功能生物标志物之间的关系，逻辑回归用于评估按临床参考区间划分的标志物。结果表明，血清 PFAAs 浓度与提示肝毒性的肝功能生物标志物水平相关，尤其是与肝损伤相关的标志物。例如，全氟辛酸（PFOA）暴露量增加 1ln 单位，血清丙氨酸氨基转移酶（ALT）水平升高 7.4%（95%置信区间：3.9%，11.0%）。有趣的是，我们观察到支链 PFAAs 异构体与肝功能生物标志物之间存在关联。例如，支链全氟辛烷磺酸（PFOS）异构体暴露量增加 1ln 单位，ALT 水平升高 4.3%（95%置信区间：1.2%，7.4%），ALT 异常的几率增加 33.0%（95%置信区间：5.0%，67.0%）。此外，我们发现 PFNA 与 ALT[（6.2%，95%置信区间：3.1%，9.4%）和 AST 水平（2.5%，95%置信区间：0.5%，4.5%）]呈正相关。逻辑回归结果显示，PFPeA、PFHxA、PFNA、PFDoDA、PFTrDA 和 PFTeDA 与前白蛋白异常呈统计学关联。综上所述，我们的研究结果支持了先前关于 PFAAs 暴露与肝功能生物标志物之间存在关联的研究。我们发现了新的证据，表明支链 PFAAs 异构体暴露与临床上相关的肝细胞功能障碍风险相关。
