Correlation Between Impaired Sensitivity To Thyroid Hormone And Metabolism-related Fatty Liver Disease And Liver Fibrosis

Background:With the change of dietary structure as well as the development of society and economy,the incidence of obesity and metabolic syndrome is increasing year by year,and the incidence of metabolic dysfunction-associated fatty liver disease(MAFLD),which is closely related to it,is also increasing significantly.With a significant increase,MAFLD has become the most common liver disease affecting about 38.77%of population in both developed and developing countries.Several studies have confirmed that the thyroid dysfunction is closely related to the occurrence of metabolic syndrome,and 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 MAFLD and liver fibrosis remained unclear.We aimed to determine the associations of thyroid hormone sensitivity indices with MAFLD and liver fibrosis in Chinese euthyroid adults.Objective:To assess the relationships between the impaired central and peripheral sensitivity of thyroid hormone and MAFLD and liver fibrosis by calculating the indexes reflecting the central and peripheral sensitivity(TFQI),Free triiodothyronine/Free thyroxine ratio(FT3/FT4 ratio)of thyroid hormone in a large-sample euthyroid population.Methods:This community-based study included 8019 euthyroid adults living in Shunde,Foshan,Guangdong from November 2021 to September 2022.We collected basic data such as age,gender,hypertension,diabetes and other past medical history from the self-reported questionnaire,and measured basic parameters such as height,weight,BMI,waist circumference,and blood pressure.Thyroid hormones(free triiodothyronine,free thyroxine,thyrotropin),lipid levels(triglycerides,total cholesterol,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol)and blood glucose levels(fasting blood glucose,postprandial blood glucose)were measured.We also calculated the thyroid sensitivity indices,including free triiodothyronine to free thyroxine ratio(FT3/FT4 ratio),thyroid feedback quantilebased index by FT4(TFQIFT4),and thyroid feedback quantile-based index by FT3(TFQIFT3).FT3/FT4 ratio indicates peripheral thyroid hormone sensitivity while TFQIFT4 and TFQIFT3 indicate central thyroid hormone sensitivity.Liver steatosis and fibrosis were diagnosed by vibration-controlled transient elastography(VCTE).The multivariate logistic/linear regression and restricted cubic spline(RCS)analysis were conducted.All data were analyzed using IBM SPSS Statistics(version 24)and R(version 4.0.2).A two-tailed P value<0.05 was considered statistically significant.Results:Compared with participants in quartile 1st(Q1),the prevalence of MAFLD increased by 58%in quartile 4th(Q4)of FT3/FT4 ratio(OR 1.58,95%CI(1.35,1.86))and by 33%in Q4 of TFQIFT3(OR 1.33,95%CI(1.13,1.56))(both P<0.05).In addition,compared with participants in Q1,the prevalence of liver fibrosis increased by 44%in Q4 of TFQIFT3(OR 1.44,95%CI(1.02,2.03))(P<0.05).FT3/FT4 ratio was positively correlated with the prevalence of MAFLD,and TFQIFT3 was positively correlated with the prevalence of MAFLD and its progression to liver fibrosis.There was no associations between TFQIFT4 and the prevalence of MAFLD.in participants with MAFLD.However,FT3/FT4 ratio and TFQIFT4 were not associated with liver fibrosis in participants with MAFLD.Conclusions:Impaired sensitivity of thyroid hormone was associated with MAFLD and liver fibrosis in euthyroid population.More prospective and mechanism studies were warranted to confirm the conclusions.