{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:14:32Z","timestamp":1787004872321,"version":"build-2736575974"},"reference-count":42,"publisher":"Georg Thieme Verlag KG","issue":"09","funder":[{"DOI":"10.13039\/501100009102","name":"Education Department of Jiangxi\n                        Province,","doi-asserted-by":"crossref","award":["GJJ2400125"],"award-info":[{"award-number":["GJJ2400125"]}],"id":[{"id":"10.13039\/501100009102","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The interplay between liver fibrosis and thyroid function remains incompletely\n                    understood, particularly regarding thyroid hormone sensitivity. Thus, this study\n                    aims to explore the relationship between liver fibrosis and thyroid hormone\n                    sensitivity in euthyroid US individuals. This study involved 4,678 euthyroid\n                    participants from the National Health and Nutrition Examination Survey\n                    2007\u20132012. Key clinical parameters were extracted, including thyroid-stimulating\n                    hormone, free and total thyroxine, and liver function-related data. Thyroid\n                    hormone sensitivity was assessed by three indices: the Thyroid Function Quotient\n                    Index, Thyroid-Stimulating Hormone Index, and Thyrotrophic Thyroxine Resistance\n                    Index. Multiple regression analyses and machine learning models were performed\n                    to evaluate the relationships between liver fibrosis and thyroid sensitivity\n                    indices. Participants with advanced liver fibrosis indicated by fibrosis index 4\n                    (FIB-4) demonstrated significantly impaired thyroid hormone sensitivity\n                    indicated by Thyroid Function Quotient Index, Thyrotrophic Thyroxine Resistance\n                    Index, and Thyroid-Stimulating Hormone Index. Then, the logistic regression and\n                    restricted cubic spline analysis indicated that Thyroid Function Quotient Index,\n                    Thyrotrophic Thyroxine Resistance Index, and Thyroid-Stimulating Hormone Index\n                    were risk factors for liver fibrosis (odds ratio&gt;1, p&lt;0.05).\n                    Furthermore, we developed machine learning models using random forest and\n                    Boruta\u2019s algorithm identifying thyroid hormone sensitivity indices,\n                    Thyroid-Stimulating Hormone Index, Thyrotrophic Thyroxine Resistance Index, and\n                    Thyroid Function Quotient Index as key predictors for liver fibrosis. Mediation\n                    analysis indicates that uric acid is a weak mediator between thyroid hormone\n                    sensitivity and liver fibrosis. This study reveals that impaired thyroid hormone\n                    sensitivity is a risk factor for liver fibrosis progression in euthyroid\n                    individuals. These findings uncover a potential molecular link between thyroid\n                    hormone signaling and the development of liver fibrosis, warranting further\n                    investigation.<\/jats:p>","DOI":"10.1055\/a-2700-6797","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T23:06:44Z","timestamp":1757632004000},"page":"511-519","source":"Crossref","is-referenced-by-count":1,"title":["Impaired Thyroid Hormone Sensitivity is Associated with Increased\n                    Risk of Liver Fibrosis in Euthyroid Population: A Cross-Sectional Analysis of\n                    NHANES"],"prefix":"10.1055","volume":"57","author":[{"given":"Xingyu","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Nanchang\n                    University Second Affiliated Hospital, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiwen","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Urology, Nanchang University Second\n                    Affiliated Hospital, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hein Ko","family":"Oo","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Kanazawa\n                    University Graduate School of Medical Sciences, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/s41575-020-00381-6","article-title":"Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and\n                    prevention","volume":"18","author":"D Q Huang","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/hep.31173","article-title":"Changes in the global burden of chronic liver diseases from 2012 to 2017: the\n                    growing impact of NAFLD","volume":"72","author":"J M Paik","year":"2020","journal-title":"Hepatology"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment\n                    of prevalence, incidence, and outcomes","volume":"64","author":"Z M Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jhep.2023.03.017","article-title":"Global burden of liver disease: 2023 update","volume":"79","author":"H Devarbhavi","year":"2023","journal-title":"J Hepatol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.tem.2024.02.007","article-title":"Current status and future trends of the global burden of MASLD","volume":"35","author":"L Miao","year":"2024","journal-title":"Trends Endocrinol Metab"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.3350\/cmh.2024.1096","article-title":"Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver\n                    complications in adults with type 2 diabetes and metabolic\n                    dysfunction-associated steatotic liver disease: a target trial emulation\n                    study","volume":"31","author":"X Mao","year":"2025","journal-title":"Clin Mol Hepatol"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2025.0620","article-title":"Letter: Methodological concerns regarding GLP-1RA effects on MASLD outcomes","author":"X. 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Qin","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"303","DOI":"10.2337\/dc18-1410","article-title":"Impaired sensitivity to thyroid hormones is associated with diabetes and\n                    metabolic syndrome","volume":"42","author":"M Laclaustra","year":"2019","journal-title":"Diabetes Care"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.jhep.2022.10.035","article-title":"Longitudinal changes in fibrosis markers are associated with risk of cirrhosis\n                    and hepatocellular carcinoma in non-alcoholic fatty liver disease","volume":"78","author":"G Cholankeril","year":"2023","journal-title":"J Hepatol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.jhep.2020.06.007","article-title":"Repeated FIB-4 measurements can help identify individuals at risk of severe\n                    liver disease","volume":"73","author":"H Hagstr\u00f6m","year":"2020","journal-title":"J Hepatol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.jhep.2021.05.025","article-title":"EASL clinical practice guidelines on non-invasive tests for evaluation of liver\n                    disease severity and prognosis \u2013 2021 update","volume":"75","author":"A Berzigotti","year":"2021","journal-title":"J Hepatol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/j.cgh.2024.02.008","article-title":"Degree of discordance between FIB-4 and transient elastography: an application\n                    of current guidelines on general population cohort","volume":"22","author":"M Chang","year":"2024","journal-title":"Clin Gastroenterol Hepatol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"100780","DOI":"10.1016\/j.lanepe.2023.100780","article-title":"Prognostic utility of fibrosis-4 index for risk of subsequent liver and\n                    cardiovascular events, and all-cause mortality in individuals with obesity\n                    and\/or type 2 diabetes: a longitudinal cohort study","volume":"36","author":"Q M Anstee","year":"2023","journal-title":"Lancet Reg Health Eur"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.annemergmed.2022.05.011","article-title":"Machine learning in the prediction of trauma outcomes: a systematic review","volume":"80","author":"T Zhang","year":"2022","journal-title":"Ann Emerg Med"},{"key":"ref27","first-page":"1158541","article-title":"Machine learning for the prediction of cognitive impairment in older adults","volume":"17","author":"W Li","year":"2023","journal-title":"Front Neurosci"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1399517","DOI":"10.3389\/fendo.2024.1399517","article-title":"Association between thyroid function and nonalcoholic fatty liver disease: a\n                    dose-response meta-analysis","volume":"15","author":"L L Xiang","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"goad076","DOI":"10.1093\/gastro\/goad076","article-title":"Association between low-normal thyroid function and advanced liver fibrosis in\n                    metabolic dysfunction-associated fatty liver disease patients: a retrospective\n                    cohort study","volume":"12","author":"Z Li","year":"2024","journal-title":"Gastroenterol Rep (Oxf)"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.cgh.2017.08.014","article-title":"Subclinical hypothyroidism and low-normal thyroid function are associated with\n                    nonalcoholic steatohepatitis and fibrosis","volume":"16","author":"D Kim","year":"2018","journal-title":"Clin Gastroenterol Hepatol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"23714","DOI":"10.1038\/s41598-024-74792-9","article-title":"A screening study of high-risk groups for liver 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effects of thyroid hormones on hepatic lipid metabolism","volume":"14","author":"R A Sinha","year":"2018","journal-title":"Nat Rev Endocrinol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1016\/S0140-6736(19)32517-6","article-title":"Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a\n                    multicentre, randomised, double-blind, placebo-controlled, phase 2 trial","volume":"394","author":"S A Harrison","year":"2019","journal-title":"Lancet"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.1038\/s41591-023-02603-1","article-title":"Resmetirom for nonalcoholic fatty liver disease: a randomized, double-blind,\n                    placebo-controlled phase 3 trial","volume":"29","author":"S A Harrison","year":"2023","journal-title":"Nat Med"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1056\/NEJMoa2309000","article-title":"A phase 3, randomized, controlled trial of resmetirom in NASH with liver\n                    fibrosis","volume":"390","author":"S A Harrison","year":"2024","journal-title":"N Engl J Med"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"5923","DOI":"10.1038\/s41598-024-55845-5","article-title":"Serum uric acid levels and prognosis of patients with non-alcoholic fatty liver\n                    disease","volume":"14","author":"X Yang","year":"2024","journal-title":"Sci Rep"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"3587","DOI":"10.3390\/nu14173587","article-title":"The additive values of the classification of higher serum uric acid levels as a\n                    diagnostic criteria for metabolic-associated fatty liver disease","volume":"14","author":"J He","year":"2022","journal-title":"Nutrients"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s11739-019-02065-9","article-title":"Thyroid hormones modulate uric acid metabolism in patients with recent onset\n                    subclinical hypothyroidism by improving insulin sensitivity","volume":"15","author":"G Desideri","year":"2020","journal-title":"Intern Emerg Med"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.eprac.2024.03.003","article-title":"Correlation between impaired sensitivity to thyroid hormones and serum uric acid\n                    in female patients with obesity and after laparoscopic sleeve gastrectomy","volume":"30","author":"X Wen","year":"2024","journal-title":"Endocr Pract"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.jhep.2015.11.022","article-title":"Uric acid regulates hepatic steatosis and insulin resistance through the NLRP3\n                    inflammasome-dependent mechanism","volume":"64","author":"X Wan","year":"2016","journal-title":"J Hepatol"}],"container-title":["Hormone and Metabolic Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2700-6797.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T22:47:00Z","timestamp":1760741220000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2700-6797"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":42,"journal-issue":{"issue":"09","published-online":{"date-parts":[[2025,10,17]]},"published-print":{"date-parts":[[2025,9]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2700-6797","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0018-5043","1439-4286"],"issn-type":[{"value":"0018-5043","type":"print"},{"value":"1439-4286","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,9,11]]},"published":{"date-parts":[[2025,9]]}}}