Tetrachloroethylene Is Associated With Presence of Significant Liver Fibrosis: A National Cross-Sectional Study in US Adults

Abstract

Background & Aims: Tetrachloroethylene (PCE) is a volatile organic compound (VOC) used in industrial settings. Pre-clinical studies have linked PCE to hepatotoxicity, but clinical data beyond selected occupational cohorts represent a critical knowledge gap. Methods: We utilised data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020, a nationally representative survey of the US population. Significant liver fibrosis was defined as liver stiffness measurement > 8.2 kPa by vibration-controlled transient elastography. We used multivariate logistic regression to assess the association of PCE with significant liver fibrosis, controlling for potential demographic and clinical confounders. A negative control analysis was performed using N-Acetyl-S-(2-hydroxyethyl)-l-cysteine, a biomarker representing exposure to a mixture of VOCs. Results: Among 1614 adults, 116 had detectable PCE, representing a weighted percentage of 7.4% (95% CI 5.1%–10.7%). Values ranged from 0.034 to 57.5 ng/mL, with a median concentration of 0.09 ng/mL (IQR 0.07–0.22 ng/mL). Detectable PCE (aOR 3.17 [95% CI 1.23–8.20]) was associated with significant liver fibrosis, an independent association supported by the negative control analysis. Additionally, the association between PCE and significant liver fibrosis was dose-dependent (aOR per 1 ng/mL increase 5.13 [1.09–24.26]). The absolute risk difference between the predicted probability of significant liver fibrosis for detectable vs. undetectable PCE was 27.7% (95% CI 4.3%–51.0%). Conclusion: In this nationally representative US study, PCE was associated with significant liver fibrosis with a dose-dependent effect, and a negative control analysis suggesting that this association is distinct to PCE. Our results should encourage prospective studies to confirm PCE as a contributor to liver disease to inform environmental policies.