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In advanced fibrosis, we found that an autocrine HSC signaling circuit emerged that was composed of 68 receptor-ligand interactions conserved between murine and human NASH. These predicted interactions were supported by the parallel appearance of markedly increased direct stellate cell-cell contacts in murine NASH. As proof of principle, pharmacological inhibition of one such autocrine interaction, neurotrophic receptor tyrosine kinase 3\u2013neurotrophin 3, inhibited human HSC activation in culture and reversed advanced murine NASH fibrosis. In summary, we uncovered a repertoire of antifibrotic drug targets underlying advanced fibrosis in vivo. The findings suggest a therapeutic paradigm in which stage-specific therapies could yield enhanced antifibrotic efficacy in patients with advanced hepatic fibrosis.<\/jats:p>","DOI":"10.1126\/scitranslmed.add3949","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T13:58:14Z","timestamp":1672840694000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":182,"title":["An autocrine signaling circuit in hepatic stellate cells underlies advanced fibrosis in nonalcoholic steatohepatitis"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5037-4316","authenticated-orcid":true,"given":"Shuang","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New\u00a0York, NY 10029, 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