Abstract
BACKGROUND: The correlation between serum cotinine and fatty liver index (FLI) needs further investigation for the early identification, prevention, and treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: Data from the NHANES database spanning from March 2017 to 2018 was used to perform the population-based study to assess the relationship between serum cotinine and FLI. A variance estimation strategy was applied to address the data volatility. To examine the correlation between serum cotinine and FLI, a weighted multivariate logistic regression model was used. Initial normality assessment through the Kolmogorov-Smirnov test indicated non-normal distribution. Median and interquartile range were employed for description of non-normally distributed measurement data, and group comparisons were made using the Kruskal-Wallis H test. Proportions were used for ordinal data description and comparisons, with the chi-square test used for categorical data. Smooth curve fittings and generalized additive models were used to explore the non-linear relationship between serum cotinine and FLI. RESULTS: Finally, 2350 subjects (mean age: 49.83 ± 18.30, 1135 males and 1215 females) were selected for analysis. After adjusting for confounders, serum cotinine showed positive correlation with FLI in adults (β = 0.009, 95% CI: 0.003 to 0.014, P = 0.001). Additionally, individuals in the unexposed and passively exposed groups had lower FLI compared to those in the actively exposed group (β = -3.041, 95% CI: -4.728 to -1.353, P < 0.001; β = -2.159, 95% CI: -4.231 to -0.087, P = 0.041; respectively). Subgroup analyses by gender revealed positive associations between serum cotinine and FLI in both males (β = 0.007, 95% CI: 0.000 to 0.014, P = 0.048) and females (β = 0.012, 95% CI: 0.003 to 0.021, P = 0.007). Additionally, a positive correlation was found in "other races" subgroup (β = 0.017, 95% CI: 0.004 to 0.029, P = 0.008) rather than the subgroups of "Mexican American, Other Hispanic, Non-Hispanic White, and Non-Hispanic Black". The relationship between serum cotinine and FLI exhibited an inverted U-shaped curve with the turning point occurring at 521 ng/mL. CONCLUSION: This study of a nationally representative sample demonstrates a positive association between serum cotinine and FLI, characterized by an inverted U-shaped curve. Both active and passive smoking emerge as a risk factor for the development and progression of MASLD. Smoking cessation is recommended to manage MASLD and support liver and cardiovascular health.