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Emerging research focuses on the critical role of hepatic macrophages in mediating liver repair and regeneration following injury, where they closely interact with hepatocytes as well as hepatic stellate cells (HSCs) to regulate inflammation, fibrosis, tissue remodeling, and regeneration. The latest single-cell and spatial omics technologies have profoundly deepened our understanding of the hepatic immune response, revealing the remarkable phenotypic and spatial heterogeneity of macrophages, including distinct subsets such as lipid-associated macrophages (LAMs) within steatotic and fibrotic regions. Macrophage subsets sense systemic (e.g. gut\u2013liver axis, adipose tissue) and local stress signals and orchestrate disease-defining cellular responses in hepatocytes, HSC, and other immune cells. Dynamic tools such as intravital microscopy have further unveiled functional properties in the spatial context hitherto unknown. Herein, we review the multifaceted roles of hepatic macrophages in liver injury and repair, with an emphasis on their role in steatosis, inflammation, fibrosis, and regeneration. We also discuss how these insights may inform the development of novel macrophage-targeted therapeutic interventions.<\/jats:p>","DOI":"10.1093\/stmcls\/sxaf072","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:57:35Z","timestamp":1762865855000},"source":"Crossref","is-referenced-by-count":14,"title":["Macrophage heterogeneity and plasticity in liver injury and repair mechanisms"],"prefix":"10.1093","volume":"44","author":[{"given":"Tianjiao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Hepatology & Gastroenterology, Charit\u00e9 - Universit\u00e4tsmedizin Berlin , Berlin D-13353,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Horn","sequence":"additional","affiliation":[{"name":"Department of Hepatology & Gastroenterology, Charit\u00e9 - Universit\u00e4tsmedizin Berlin , Berlin D-13353,","place":["Germany"]},{"name":"BIH Biomedical Innovation Academy, BIH Charit\u00e9 Digital Clinician Scientist Program, Berlin Institute of Health at Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Berlin 10178,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6195-3866","authenticated-orcid":false,"given":"Moritz","family":"Peiseler","sequence":"additional","affiliation":[{"name":"Department of Hepatology & Gastroenterology, Charit\u00e9 - Universit\u00e4tsmedizin Berlin , Berlin D-13353,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6206-0226","authenticated-orcid":false,"given":"Frank","family":"Tacke","sequence":"additional","affiliation":[{"name":"Department of Hepatology & Gastroenterology, Charit\u00e9 - Universit\u00e4tsmedizin Berlin , Berlin 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