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Their influence spans multiple cellular processes, including the activation of hepatic stellate cells, metabolic regulation, inflammation, and extracellular matrix remodelling.This review aims to provide a comprehensive overview of the molecular mechanisms by which THs modulate liver fibrosis, and to explore the therapeutic potential of targeting TH-related signaling in clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted an integrative narrative review of preclinical and clinical studies focusing on TH-mediated regulation of six key signaling pathways: TGF-\u03b2\/Smad, PI3K\/AKT\/mTOR, Wnt\/\u03b2-catenin, AMPK, NF-\u03baB, and MAPK\/ERK. Emphasis was particularly placed on their roles in HSC biology and fibrotic progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Although progress has been made in elucidating TH signaling in liver fibrosis, critical gaps remain\u2014especially regarding downstream signal integration, pathway crosstalk, and human translational evidence. Preclinical studies consistently demonstrate that thyroid hormones exert antifibrotic effects by modulating metabolic and inflammatory pathways; however, clinical data supporting these findings remain limited. Evidence suggests that THs may exert antifibrotic effects via modulation of metabolic and inflammatory networks, and early investigations into THR agonists offer encouraging therapeutic prospects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Targeting thyroid hormone signaling represents a promising frontier in antifibrotic therapy. Clarifying mechanistic interactions and conducting well-designed clinical trials will be essential to translate these insights into effective interventions for patients with chronic liver disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s40618-026-02820-8","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T07:05:39Z","timestamp":1772521539000},"page":"997-1010","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Navigating thyroid hormone signaling in liver fibrosis: mechanisms and clinical implications"],"prefix":"10.1007","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6900-7217","authenticated-orcid":false,"given":"Cunsi","family":"Ye","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopeng","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijian","family":"Quan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangquan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"2820_CR1","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/s41575-020-00390-6","volume":"18","author":"T Kisseleva","year":"2021","unstructured":"Kisseleva T, Brenner D (2021) Molecular and cellular mechanisms of liver fibrosis and its regression. 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