Analysis of environmental chemical mixtures and nonalcoholic fatty liver disease: NHANES 1999–2014

We aimed to investigate the associations between chemical mixtures and the risk of nonalcoholic fatty liver disease (NAFLD) in this study. A total of 127 exposure analytes within 13 chemical mixture groups were included in the current analysis. Associations between chemical mixture exposure and prevalence of NAFLD were examined using weighted quantile sum (WQS) regressions. NAFLD was diagnosed by hepatic steatosis index (HSI) and US fatty liver index (USFLI). In USFLI-NAFLD cohort, chemical mixtures positively associated with NAFLD development included urinary metals (OR: 1.10, 95% CI: 1.04-1.16), urinary perchlorate, nitrate and thiocyanate (OR: 1.06, 95% CI: 1.02-1.11), urinary pesticides (OR: 1.24, 95% CI: 1.09-1.40), urinary phthalates (OR: 1.18, 95% CI: 1.09-1.28), urinary polyaromatic hydrocarbons (PAHs) (OR: 1.08, 95% CI: 1.03-1.14), and urinary pyrethroids, herbicides, and organophosphate pesticides metabolites (OR: 1.32, 95% CI: 1.15-1.51). All of the above mixtures were also statistically significant in WQS regressions in the HSI-NAFLD cohort. Besides, some chemical mixtures were only significant in HSI-NAFLD cohort including urinary arsenics (OR: 1.07, 95% CI: 1.02-1.12), urinary phenols (OR: 1.10, 95% CI: 1.02-1.19) and blood polychlorinated dibenzo-p-dioxins (OR: 1.10, 95% CI: 1.03-1.17). Three types of chemical mixtures only showed significant associations in the healthy lifestyle score (HLS) of 3-4 subgroup, including urinary perchlorate, nitrate and thiocyanate, urinary PAHs and blood polychlorinated dibenzo-p-dioxins. In conclusion, the exposure of specific types of chemical mixtures were associated with elevated NAFLD risk, and the effects of some chemical mixtures on NAFLD development exhibited differences in participants with different lifestyles.