Low Thyroid Function is Associated with an Increased Risk of Advanced Fibrosis in Patients with Metabolic Dysfunction-associated Fatty Liver Disease

Overview

Journal BMC Gastroenterol

Publisher Biomed Central

Specialty Gastroenterology

Date 2023 Jan 5

PMID 36604612

Authors

Hong Fan

Lili Li

Zhenqiu Liu

Pengyan Zhang

Sheng Wu

Xinyu Han

Xingdong Chen

Chen Suo

Liou Cao

TieJun Zhang

Affiliations

Soon will be listed here.

Abstract

Aims: Observational studies showed that low thyroid function may perturb liver function. We aimed to evaluate the association of low thyroid function with both metabolic dysfunction-associated fatty liver disease (MAFLD) and advanced hepatic fibrosis.

Methods: Participants who underwent abdominal ultrasonography and thyroid function test in a Chinese hospital from 2015 to 2021were enrolled. Fibrosis-4 index (FIB-4) > 2.67 and/or non-alcoholic fatty liver disease fibrosis score (NFS) > 0.676 were used to define advanced fibrosis. Descriptive analyses were performed to characterize the epidemiology of MAFLD according to levels of thyroid-stimulating hormone (TSH). The logistic regression model was applied to estimate the association of low thyroid function with MAFLD and advanced fibrosis.

Results: A total of 19,946 participants (52.78% males, mean age: 47.31 years, 27.55% MAFLD) were included, among which 14,789 were strict-normal thyroid function, 4,328 were low-normal thyroid function, 829 were subclinical hypothyroidism. TSH levels were significantly higher in MAFLD patients with a FIB-4 > 2.67 and /or NFS > 0.676 than their counterparts. The logistic regression model adjusted for age and sex showed that low-normal thyroid function increased the risk of MAFLD (odds ratio [OR] = 1.09; 95% confidence interval [CI] 1.01-1.18). Multivariable regression model adjusted for age, sex, body mass index, type 2 diabetes, and hypertension showed low-normal thyroid function increased the risk of advanced fibrosis in patients with MAFLD (FIB-4 > 2.67: OR = 1.41, 95% CI 1.02-1.93; NFS > 0.676: OR = 1.72, 95% CI 1.08-2.72).

Conclusion: Elevated TSH concentrations are associated with advanced hepatic fibrosis, even in the euthyroid state.

Citing Articles

Hypothyroidism/subclinical hypothyroidism and metabolic dysfunction-associated steatotic liver disease: advances in mechanism and treatment.

Pu S, Zhao B, Jiang Y, Cui X Lipids Health Dis. 2025; 24(1):75.

PMID: 40016726 PMC: 11866868. DOI: 10.1186/s12944-025-02474-0.

Elevated thyroid autoantibodies as risk factors for metabolic dysfunction-associated fatty liver disease in type 2 diabetes mellitus.

Wu W, Yang Z, Li O, Gan L, Gao Y, Xiang C Front Endocrinol (Lausanne). 2024; 15:1478818.

PMID: 39703861 PMC: 11655225. DOI: 10.3389/fendo.2024.1478818.

Actions of thyroid hormones and thyromimetics on the liver.

Sinha R, Bruinstroop E, Yen P Nat Rev Gastroenterol Hepatol. 2024; 22(1):9-22.

PMID: 39420154 PMC: 7616774. DOI: 10.1038/s41575-024-00991-4.

Correlation Between Thyroid-Stimulating Hormone (TSH) and Liver Function Test Values in North Karnataka Patients Admitted to a Tertiary Care Hospital.

Murali Krishna S, Hegde S, Chellathurai M, Mohandas N, Guruswamy S, Pandit S Cureus. 2024; 16(4):e59004.

PMID: 38803746 PMC: 11128325. DOI: 10.7759/cureus.59004.

Low-Normal Thyroid Function Is Not Associated with Either Non-Alcoholic Fatty Liver Disease or with Metabolic Dysfunction-Associated Fatty Liver Disease.

Zuarth-Vazquez J, Moreno-Castaneda L, Soriano-Marquez J, Velazquez-Aleman A, Ramos-Ostos M, Uribe M Life (Basel). 2023; 13(4).

PMID: 37109577 PMC: 10144109. DOI: 10.3390/life13041048.

References

Eshraghian A, Hamidian Jahromi A . Non-alcoholic fatty liver disease and thyroid dysfunction: a systematic review. World J Gastroenterol. 2014; 20(25):8102-9. PMC: 4081681. DOI: 10.3748/wjg.v20.i25.8102. View

Xu C, Xu L, Yu C, Miao M, Li Y . Association between thyroid function and nonalcoholic fatty liver disease in euthyroid elderly Chinese. Clin Endocrinol (Oxf). 2011; 75(2):240-6. DOI: 10.1111/j.1365-2265.2011.04016.x. View

Le M, Yeo Y, Li X, Li J, Zou B, Wu Y . 2019 Global NAFLD Prevalence: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2021; 20(12):2809-2817.e28. DOI: 10.1016/j.cgh.2021.12.002. View

Qiu S, Cao P, Guo Y, Lu H, Hu Y . Exploring the Causality Between Hypothyroidism and Non-alcoholic Fatty Liver: A Mendelian Randomization Study. Front Cell Dev Biol. 2021; 9:643582. PMC: 8005565. DOI: 10.3389/fcell.2021.643582. View

Younossi Z, Anstee Q, Marietti M, Hardy T, Henry L, Eslam M . Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2017; 15(1):11-20. DOI: 10.1038/nrgastro.2017.109. View

Younossi Z . Long-Term Outcomes of Nonalcoholic Fatty Liver Disease: From Nonalcoholic Steatohepatitis to Nonalcoholic Steatofibrosis. Clin Gastroenterol Hepatol. 2017; 15(8):1144-1147. DOI: 10.1016/j.cgh.2017.05.029. View

van den Berg E, van Tienhoven-Wind L, Amini M, Schreuder T, Faber K, Blokzijl H . Higher free triiodothyronine is associated with non-alcoholic fatty liver disease in euthyroid subjects: the Lifelines Cohort Study. Metabolism. 2017; 67:62-71. DOI: 10.1016/j.metabol.2016.11.002. View

Jain R . Associations between the levels of thyroid hormones and lipid/lipoprotein levels: Data from National Health and Nutrition Examination Survey 2007-2012. Environ Toxicol Pharmacol. 2017; 53:133-144. DOI: 10.1016/j.etap.2017.05.002. View

Kim D, Kim W, Joo S, Bae J, Kim J, Ahmed A . Subclinical Hypothyroidism and Low-Normal Thyroid Function Are Associated With Nonalcoholic Steatohepatitis and Fibrosis. Clin Gastroenterol Hepatol. 2017; 16(1):123-131.e1. DOI: 10.1016/j.cgh.2017.08.014. View

10.

Angulo P, Hui J, Marchesini G, Bugianesi E, George J, Farrell G . The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007; 45(4):846-54. DOI: 10.1002/hep.21496. View

11.

Hollowell J, Staehling N, Flanders W, Hannon W, Gunter E, Spencer C . Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002; 87(2):489-99. DOI: 10.1210/jcem.87.2.8182. View

12.

Ludwig U, Holzner D, Denzer C, Greinert A, Haenle M, Oeztuerk S . Subclinical and clinical hypothyroidism and non-alcoholic fatty liver disease: a cross-sectional study of a random population sample aged 18 to 65 years. BMC Endocr Disord. 2015; 15:41. PMC: 4536732. DOI: 10.1186/s12902-015-0030-5. View

13.

Tan Y, Tang X, Mu P, Yang Y, Li M, Nie Y . High-Normal Serum Thyrotropin Levels Increased the Risk of Non-Alcoholic Fatty Liver Disease in Euthyroid Subjects with Type 2 Diabetes. Diabetes Metab Syndr Obes. 2021; 14:2841-2849. PMC: 8235944. DOI: 10.2147/DMSO.S313224. View

14.

Kim D, Yoo E, Li A, Fernandes C, Tighe S, Cholankeril G . Low-Normal Thyroid Function Is Associated With Advanced Fibrosis Among Adults in the United States. Clin Gastroenterol Hepatol. 2018; 17(11):2379-2381. PMC: 6525074. DOI: 10.1016/j.cgh.2018.11.024. View

15.

Mitchell F . Thyroid function: low T₄ levels a risk factor for fatty liver?. Nat Rev Endocrinol. 2012; 8(8):447. DOI: 10.1038/nrendo.2012.87. View

16.

Kim D, Kim W, Kim H, Therneau T . Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States. Hepatology. 2012; 57(4):1357-65. PMC: 3622816. DOI: 10.1002/hep.26156. View

17.

Cooper D, Biondi B . Subclinical thyroid disease. Lancet. 2012; 379(9821):1142-54. DOI: 10.1016/S0140-6736(11)60276-6. View

18.

Sinha R, Singh B, Yen P . Direct effects of thyroid hormones on hepatic lipid metabolism. Nat Rev Endocrinol. 2018; 14(5):259-269. PMC: 6013028. DOI: 10.1038/nrendo.2018.10. View

19.

Guo W, Qin P, Li X, Wu J, Lu J, Zhu W . Free Triiodothyronine Is Associated With Hepatic Steatosis and Liver Stiffness in Euthyroid Chinese Adults With Non-Alcoholic Fatty Liver Disease. Front Endocrinol (Lausanne). 2021; 12:711956. PMC: 8387962. DOI: 10.3389/fendo.2021.711956. View

20.

Pais R, Barritt 4th A, Calmus Y, Scatton O, Runge T, Lebray P . NAFLD and liver transplantation: Current burden and expected challenges. J Hepatol. 2016; 65(6):1245-1257. PMC: 5326676. DOI: 10.1016/j.jhep.2016.07.033. View