{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:13:06Z","timestamp":1791245586732,"version":"4.1.0"},"reference-count":267,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300526"],"award-info":[{"award-number":["82300526"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health commission of Hubei Province Scientific Research Project","award":["WJ2025M003"],"award-info":[{"award-number":["WJ2025M003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a progressive spectrum of metabolic liver injury in which immune activation, metabolic stress, and stromal remodeling evolve in a tightly interdependent manner. Although early disease stages are dominated by metabolic overload, accumulating evidence indicates that immunometabolic rewiring and fibro-inflammatory amplification critically shape the transition toward metabolic dysfunction-associated steatohepatitis (MASH) and advanced fibrosis. This review synthesizes emerging insights into how hepatocyte stress responses, innate and adaptive immune circuits, and extracellular matrix-producing stromal populations interact to form a dynamic, feed-forward network driving disease progression. Particular emphasis is placed on the deterministic role of immune\u2013fibrotic coupling in shaping clinical phenotypes, disease trajectory, and therapeutic responsiveness. Rather than focusing on individual molecular layers, we highlight how integrated clinical, imaging, and biomarker-informed frameworks can capture immune\u2013fibrotic signatures relevant to risk stratification and precision intervention. Building on this systems-level perspective, we outline next-generation therapeutic strategies targeting immunometabolic circuits, cross-organ communication, and multi-system dysfunction. Finally, we discuss how future precision medicine\u2014supported by integrative biomarker profiling and dynamic physiological assessment\u2014may reshape MASLD management and improve long-term hepatic and cardiometabolic outcomes.<\/jats:p>","DOI":"10.3390\/biology15020148","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T15:12:04Z","timestamp":1768403524000},"page":"148","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Immune Determinants of MASLD Progression: From Immunometabolic Reprogramming to Fibrotic Transformation"],"prefix":"10.3390","volume":"15","author":[{"given":"Senping","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Yangtze University, Jingzhou 434000, China"},{"name":"Department of Pharmacology, School of Medicine, Yangtze University, Jingzhou 434023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoshan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Yangtze University, Jingzhou 434000, China"},{"name":"Department of Pharmacology, School of Medicine, Yangtze University, Jingzhou 434023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongquan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Yangtze University, Jingzhou 434000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9471-2508","authenticated-orcid":false,"given":"Jiawei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Yangtze University, Jingzhou 434000, China"},{"name":"Department of Pharmacology, School of Medicine, Yangtze University, Jingzhou 434023, China"},{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1007\/s13679-024-00574-z","article-title":"Non-invasive Scores and Serum Biomarkers for Fatty Liver in the Era of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD): A Comprehensive Review from NAFLD to MAFLD and MASLD","volume":"13","author":"Abdelhameed","year":"2024","journal-title":"Curr. 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