[Exposures to volatile organic compounds are positively correlated with risks of metabolic dysfunction-associated steatotic liver disease].

OBJECTIVES: To assess the association between urinary levels of volatile organic compound metabolites (mVOCs) and risks of metabolic dysfunction-associated steatotic liver disease (MASLD) in the general adult population. METHODS: Based on 4 cycles of cross-sectional surveys from the 2011-2018 National Health and Nutrition Examination Survey (NHANES), generalized linear models were employed to evaluate the associations between individual mVOC exposures and the risk of MASLD. A two-stage Least Absolute Shrinkage and Selection Operator-Weighted Quantile Sum (LASSO-WQS) regression model was constructed to investigate the relationship between mixed mVOCs exposures and MASLD risk, and the relative contributions of the individual compounds were quantitatively analyzed. RESULTS: The single-exposure analysis revealed significant positive associations of 2-aminothiazoline-4-carboxylic acid (ATCA), N-acetyl-S‑(2-carboxyethyl)‑L-cysteine (CEMA), and N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA) with MASLD risk after adjusting for confounders. In the two-stage mixed-exposure analysis, the first-stage LASSO regression identified 6 mVOCs with stronger association with MASLD risk. The second-stage WQS regression demonstrated a statistically significant positive association between mixed mVOCs exposures and MASLD risk (OR=1.306, 95% CI: 1.132-1.507; P<0.001), with CEMA contributing the highest weight (36%). CONCLUSIONS: The study reveals a significant positive association between urinary levels of mVOCs mixtures and MASLD risk, suggesting potential hepatotoxic effects of VOC (especially CEMA) exposures, which urges future mechanistic studies of VOC mixture-related health impacts and listing of CEMA for health risk control.