Liver function biomarkers disorder is associated with exposure to perfluoroalkyl acids in adults: Isomers of C8 Health Project in China

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.