Abstract
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.
Highlights
Phthalates are widely used in consumer goods and various personal care products
Statistical Office as the target population, the first stratification was performed in regional administrative districts and coastal floors, and the second stratification was carried out on a proportion of apartments closely related in socioeconomic level, as well as a proportion of people who engage in agriculture and fishing
According to the hepatic steatosis index (HSI) score, participants with HSI ≤ 30.0 were classified as non-Nonalcoholic fatty liver disease (NAFLD) (n = 1202), while those with HIS > 36.0 were placed in the NAFLD
Summary
Phthalates are widely used in consumer goods and various personal care products. High-molecular-weight phthalates, including di (2-ethylhexyl) phthalate (DEHP), di-isononyl phthalate, and di-n-octyl phthalate, are mainly used as plasticizers to increase the flexibility of consumer products. Low-molecular-weight phthalates, including diethyl phthalate and di-n-butyl phthalate (DBP), are used as plasticizers and solvents in cosmetics and pharmaceutical materials [1]. Following entry into the body, these compounds are rapidly metabolized in the liver and gut [2–4] and excreted via urine and feces [5,6].
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