Central Sensitivity to Free Triiodothyronine With MAFLD and Its Progression to Liver Fibrosis in Euthyroid Adults

Abstract Context Impaired sensitivity to thyroid hormones has been demonstrated to be positively associated with the prevalence of metabolic disorders. However, the relationship between sensitivity to thyroid hormones and metabolic dysfunction–associated fatty liver disease (MAFLD) and liver fibrosis remained unclear. Objective We aimed to determine the associations of thyroid hormone sensitivity indices with MAFLD and its progression to liver fibrosis in Chinese euthyroid adults. Methods This community-based study included 7906 euthyroid adults. We calculated the thyroid sensitivity indices, including free triiodothyronine to free thyroxine (FT3/FT4) ratio, Thyroid Feedback Quantile-based Index by FT4 (TFQIFT4), and Thyroid Feedback Quantile-based Index by FT3 (TFQIFT3), indicating peripheral and central thyroid hormone sensitivity respectively. Liver steatosis and fibrosis were diagnosed by vibration-controlled transient elastography (VCTE). Multivariable logistic/linear regression and restricted cubic spline (RCS) analysis were conducted. Results Compared with participants in the first quartile (Q1), the prevalence of MAFLD was increased by 62% in the fourth quartile (Q4) of FT3/FT4 ratio (OR 1.62; 95% CI [1.38, 1.91]) and by 40% in Q4 of TFQIFT3 (OR 1.40; 95% CI [1.18, 1.65]) (both P < .05). No associations between TFQIFT4 and the prevalence of MAFLD were found. In addition, compared with participants in Q1, the prevalence of liver fibrosis was increased by 45% in Q4 of TFQIFT3 (OR 1.45; 95% CI [1.03, 2.06]) (P < .05) in participants with MAFLD. Conclusion Impaired central sensitivity to FT3 was associated with MAFLD and its progression to liver fibrosis. More prospective and mechanism studies are warranted to confirm these conclusions.