Associations of exposure to perchlorate, thiocyanate, and nitrate with metabolic dysfunction-associated steatotic liver disease: Evidence from a population-based cross-sectional study in the United States

Perchlorate, thiocyanate, and nitrate (PTN) are prevalent environmental endocrine disruptors in humanaccessible environments. However, the available evidence regarding the relationship between PTN and liver impairment, especially metabolic dysfunction-associated fatty liver disease (MASLD), remains limited. Therefore, the present study aimed to investigate the associations between PTN and MASLD. Participant data from the National Health and Nutrition Examination Surveys 2017-2020, a cross-sectional survey of the US population, were included in the present study. Ion chromatography-electrospray tandem mass spectrometry was employed to measure PTN levels. Vibration-controlled transient elastography and metabolic indicators were used to diagnose MASLD. Logistic regression models and multiple exposure methods (including weighted quantile sum, quantile G-computation, and Bayesian kernel machine regression) were used to evaluate the associations of individual and combined PTN exposure with MASLD. Causal mediation analyses were used to explore potential mediators. Among the 1393 participants (mean [SD] age, 50.41 [16.78] years; 52.26% female) included, 472 (33.9%) had MASLD. A unit increase in natural log-transformed perchlorate (OR = 1.180, 95% CI: 1.041-1.374) and nitrate (0.797, 0.657-0.967) was significantly associated with MASLD, while thiocyanate (1.024, 0.906-1.157) did not exhibit a significant association with MASLD. Moreover, combined PTN exposure was not significantly associated with MASLD, and perchlorate and nitrate were identified as the most crucial exposures for increasing and decreasing MASLD risk, respectively. Furthermore, biological age (proportion mediated = 15.2%, P = 0.035) and its acceleration (15.0%, 0.037) may mediate the perchlorate-MASLD association. In conclusion, these findings suggested that exposure to perchlorate increases the risk of MASLD, whereas nitrate mitigates this risk. Additionally, combined PTN exposure is not significantly associated with MASLD, and biological age mediates the perchlorate-MASLD association.