Risk of Nonalcoholic Fatty Liver Disease Is Associated with Urinary Phthalate Metabolites Levels in Adults with Subclinical Hypothyroidism: Korean National Environmental Health Survey (KoNEHS) 2012-2014

Nonalcoholic fatty liver disease (NAFLD) is a condition of excess accumulation of fats in the liver. Thyroid dysfunction is commonly observed in adult populations with NAFLD. In subjects with thyroid dysfunction, phthalates, which are chemical compounds widely used to increase the flexibility of various plastic products, may increase the risk of NAFLD prevalence. Therefore, our study aimed to evaluate the relationship between the levels of urinary phthalate metabolites and the risk of NAFLD stratified by the levels of thyroid-stimulating hormone (TSH). Data (n = 2308) were obtained from the Korean National Environmental Health Survey II (2012-2014). Using the hepatic steatosis index, participants were classified into non-NAFLD (<30) and NAFLD (>36) groups. Participants with euthyroidism were defined as 0.45-4.5 mIU/L for serum TSH and normal thyroxine (T4) levels (n = 2125). Subclinical hypothyroidism (SCH) was defined as a higher TSH level (4.5-10 mIU/L) with normal total T4 levels in the serum (n = 183). A multivariate analysis was performed to assess the association of the urinary phthalate concentration with the risk of NAFLD after stratification based on the thyroid hormone levels. The levels of phthalate metabolites in urine were not significantly associated with NAFLD in adults with euthyroidism. However, a significant increased risk of NAFLD in those with SCH was observed in the fourth quartile of mono (2-ethyl-5-hydroxyhexyl) phthalate (odds ratio (OR) 13.59, 95% confidence interval (CI) 12.13-86.44), mono (2-ethyl-5-oxohexyl) phthalate (OR 8.55, 95% CI 1.20-60.53), mono-(2-ethyl-5-carboxypentyl) phthalate (OR 9.06, 95% CI 1.78-45.96), and mono-benzyl phthalate (OR 6.05, 95% CI 1.62-22.54) compared to those of the lowest quartile after being adjusted with covariates. In conclusion, the levels of phthalate metabolites in urine are positively associated with NAFLD in adults with SCH. More experimental studies are needed to clarify the risk of NAFLD caused by phthalate exposure in cases with poor thyroid function.