Liyuan Zhou,1,* Lanxuan Jiang,1,* Yu An,1 Jia Liu,1 Guang Wang,1 Ying Wang,2 Ning Yang1 

1Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2Medical Examination Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Ying Wang; Ning Yang, Email hdwangying0517@163.com; yangningcy@mail.ccmu.edu.cn

Purpose: The relationship between non-alcoholic fatty liver disease (NAFLD) and thyroid function is controversial. A mild acquired thyroid hormone resistance may exist and explain these contradictions. This study aims to investigate the associations of thyroid hormone sensitivity with NAFLD and the severity of liver fibrosis in euthyroid populations.
Patients and Methods: Twenty-nine thousand three hundred and eighty-six adult subjects were recruited from the medical examination center of the Beijing Chao-Yang Hospital. Free triiodothyronine (FT3)/free thyroxine (FT4), thyroid feedback quartile-based index for FT4 (TFQIFT4) and for FT3 (TFQIFT3), thyroid stimulating hormone index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and thyrotropin triiodothyronine resistance index (TT3RI) were calculated. Logistic regression analysis was used to analyze the associations of thyroid hormone sensitivity indices with the risks of NAFLD and related metabolic disorders. The correlation between thyroid hormone sensitivity and the severity of liver fibrosis evaluated by noninvasive fibrosis indices was analyzed through ordinal logistic regression.
Results: Euthyroid adults with NAFLD had elevated levels of serum FT3 and FT4, reduced TSH, and impaired sensitivity to thyroid hormones. Compared with participants in the first quartile group, the risk of NAFLD was higher in the fourth quartile of TFQIFT3 (OR 1.25, 95% CI 1.13– 1.39, P < 0.001) and FT3/FT4 (OR 1.45, 95% CI 1.32– 1.60, P < 0.001) after adjusting for metabolic confounders. Among NAFLD patients, higher FT3/FT4 positively correlated with increased severity of liver fibrosis, with ORs per SD of 10.80 (95% CI 4.12– 28.53, P < 0.001) for aminotransferase-to-platelet ratio index, 4.74 (95% CI 1.56– 14.38, P = 0.006) for NAFLD fibrosis score and 3.21 (95% CI 1.02– 10.08, P = 0.046) for fibrosis-4 index.
Conclusion: Impaired central sensitivity to FT3 and higher FT3/FT4 were associated with increased risks of NAFLD and related metabolic disorders. In patients with NAFLD, higher FT3/FT4 correlated with its progression to liver fibrosis. These findings might provide novel insight into the monitoring and evaluation of the risk of NAFLD and the severity of liver fibrosis.

Keywords: sensitivity to thyroid hormones, NAFLD, liver fibrosis, metabolic disorders, euthyroid adults