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Despite advances in etiological treatments, effective therapies for established fibrosis remain limited. Increasing evidence indicates that liver fibrosis is a dynamic and potentially reversible process. The Wnt\/\u03b2\u2010catenin pathway is central to both liver regeneration and fibrogenesis and has traditionally been interpreted in terms of quantitative activation. Recent studies demonstrate that \u03b2\u2010catenin\u2013dependent transcription is qualitatively regulated by its nuclear coactivators, CREB\u2010binding protein (CBP) and p300. CBP\u2010 and p300\u2010associated transcriptional programmes exert distinct biological effects, promoting fibrogenic or regenerative states, respectively. These findings support a broader conceptual framework in which liver fibrosis can be viewed as a transcriptionally regulated and potentially reversible pathological state. In this review, we first summarize the molecular basis of canonical Wnt\/\u03b2\u2010catenin signalling and its transcriptional regulation by CBP and p300. Then, we discuss the pathophysiological relevance of CBP\u2010 versus p300\u2010dependent \u03b2\u2010catenin transcription in liver fibrosis of various etiologies, including cholestatic injury, and review experimental and early clinical evidence suggesting that selective modulation of CBP\u2010associated transcription may promote early functional recovery, potentially preceding measurable regression of fibrotic burden. We close by considering implications for clinical trial design and the importance of function\u2010oriented endpoints in antifibrotic drug development.<\/jats:p>","DOI":"10.1111\/liv.70715","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T13:36:32Z","timestamp":1779802592000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reframing Wnt\/\u03b2\u2010Catenin Signalling in Liver Fibrosis: Transcriptional State Regulation by CBP and p300"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9352-4721","authenticated-orcid":false,"given":"Kiminori","family":"Kimura","sequence":"first","affiliation":[{"name":"Department of Hepatology Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital  Tokyo 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