Liver injury is a primary factor in the pathogenesis of most liver diseases, which can lead to liver failure. Secondhand smoke (SHS) is a serious public problem. This research explored the correlation between SHS and the indicators of liver injury. This cross-sectional study was based on the National Health and Nutrition Examination Survey (NHANES) 2011-2016. The relationship between SHS and indicators of liver injury was explored by the weighted linear regression model and smooth curve fitting. The weighted threshold saturation effect model tested the relationship and inflection point between them. Mediation analyses were used to explore whether body mass index (BMI) mediates the correlation between SHS and liver injury indicators. Our cross-sectional study included 3811 non-smoking participants (aged 20-80 years). The full covariate adjustment model (β= -0.05; 95% CI: -0.08 - -0.02) showed a significant and negative correlation between log cotinine and albumin (ALB). Compared to the unexposed group, the ALB, and total protein (TP) were decreased by 0.16 g/dL, 0.26 g/dL in the heavy exposure group [ALB: -0.16 (-0.26 - -0.05), TP: -0.26 (-0.38 - -0.13)], respectively. Smoothed curve fitting revealed a nonlinear relationship between log cotinine and fibrosis-4 index (FIB-4 score), with the inflection point of log cotinine at -1.72. When log cotinine was < -1.72, the log cotinine significantly and positively correlated with the FIB-4 score (β=0.27; 95% CI: 0.06-0.49). BMI partially mediated the effect of SHS exposure on ALB or TP. SHS has harmful effects on the liver in never-smoking adults. BMI partially mediated the effect of SHS exposure on ALB or TP. More prospective and basic research in the future is necessary to focus on validating our results.
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