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The goal of this study was to characterize the effects of SPE on the BA liver transcriptome. We used messenger RNA sequencing to analyze global gene\u2010expression patterns in liver biopsies obtained at the time of portoenterostomy (n\u00a0=\u00a013) and 1\u00a0year after SPE (n\u00a0=\u00a08). Biopsies from pediatric (n\u00a0=\u00a02) and adult (n\u00a0=\u00a02) organ donors and other neonatal cholestatic conditions (n\u00a0=\u00a05) served as controls. SPE was accompanied by attenuation of inflammation and concomitant up\u2010regulation of key extracellular matrix (ECM) genes. Highly overexpressed genes promoting biliary fibrosis and bile duct integrity, such as integrin subunit beta 6 and previously unreported laminin subunit alpha 3, emerged as candidates to control liver fibrosis after SPE. At a cellular level, the relative abundance of activated hepatic stellate cells and liver macrophages decreased following SPE, whereas portal fibroblasts (PFs) and cholangiocytes persisted. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> The attenuation of inflammation following SPE coincides with emergence of an ECM molecular fingerprint, a set of profibrotic molecules mechanistically connected to biliary fibrosis. The persistence of activated PFs and cholangiocytes after SPE suggests a central role for these cell types in the progression of biliary fibrosis.<\/jats:p>","DOI":"10.1002\/hep4.1684","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T23:54:05Z","timestamp":1613001245000},"page":"1036-1050","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":14,"title":["Evolving Up\u2010regulation of Biliary Fibrosis\u2013Related Extracellular Matrix Molecules After Successful Portoenterostomy"],"prefix":"10.1097","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5271-2366","authenticated-orcid":false,"given":"Antti","family":"Kyr\u00f6nlahti","sequence":"first","affiliation":[{"name":"Pediatric Research Center,Children\u2019s Hospital,University of Helsinki and Helsinki University 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