Background Nonalcoholic Fatty Liver Disease (NAFLD) is a common co-morbidity of obesity. Elevated TSH levels (eTSH), also associated with obesity, may contribute to the dysmetabolic state that predisposes to NAFLD.

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Background: Nonalcoholic Fatty Liver Disease (NAFLD) is a common co-morbidity of obesity. Subclinical hypothyroidism (SH), also associated with obesity, may contribute to the dysmetabolic state that predisposes to NAFLD. Objective: To assess the relationship between SH and NAFLD in children with biopsy-proven NAFLD compared to controls. Design and Methods: In this retrospective study of children with biopsy-proven NAFLD and age-matched controls, the association of SH with NAFLD was assessed followed by causal mediation analyses under the counter-factual framework. Results: Sixty-six cases and 4067 age-matched controls were included in the study. Children with NAFLD were more likely to be male (74.6 vs 39.4%, p < 0.001), have higher modified BMI-z scores (2.3 ±1.6 vs 1±1.6, p < 0.001), and abnormal metabolic parameters (TSH, ALT, HDL-C, non-HDL-C, LDL-C, and TG). Multivariate analyses controlling for age, sex and severity of obesity showed significant association between the 4th quartile of TSH and NAFLD. Causal mediation analysis demonstrates that TSH mediates 44% of the effect of modified BMI-z score on NAFLD. This comprises of 16.2% (OR = 1.1, p < 0.001) caused by the indirect effect of TSH and its interaction with modified BMI-z, and 26.5% (OR = 1.1, p = 0.01) as an autonomous effect of TSH on NAFLD regardless of the obesity. Conclusions: The association of SH and biopsy-proven NAFLD is demonstrated in children from predominantly Latino population. Further, a causal mediation analysis implicates an effect of TSH on NAFLD, independent of obesity.