{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:13:36Z","timestamp":1788779616655,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T00:00:00Z","timestamp":1725840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Metabolic dysfunction\u2010associated steatohepatitis (MASH) with bridging fibrosis is a critical stage in the evolution of fatty liver disease. Second harmonic generation\/two\u2010photon excitation fluorescence (SHG\/TPEF) microscopy with artificial intelligence (AI) provides sensitive and reproducible quantitation of liver fibrosis. This methodology was applied to gain an in\u2010depth understanding of intra\u2010stage fibrosis changes and septa analyses in a homogenous, well\u2010characterised group with MASH F3 fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Paired liver biopsies (baseline [BL] and end of treatment [EOT]) of 57 patients (placebo, <jats:italic>n<\/jats:italic>\u2009=\u200917 and tropifexor <jats:italic>n<\/jats:italic>\u2009=\u200940), with F3 fibrosis stage at BL according to the clinical research network (CRN) scoring, were included. Unstained sections were examined using SHG\/TPEF microscopy with AI. Changes in liver fibrosis overall and in five areas of liver lobules were quantitatively assessed by qFibrosis. Progressive, regressive septa, and 12 septa parameters were quantitatively analysed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>qFibrosis demonstrated fibrosis progression or regression in 14\/17 (82%) patients receiving placebo, while the CRN scoring categorised 11\/17 (65%) as \u2018no change\u2019. Radar maps with qFibrosis readouts visualised quantitative fibrosis dynamics in different areas of liver lobules even in cases categorised as \u2018No Change\u2019. Measurement of septa parameters objectively differentiated regressive and progressive septa (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001). Quantitative changes in individual septa parameters (BL to EOT) were observed both in the \u2018no change\u2019 and the \u2018regression\u2019 subgroups, as defined by the CRN scoring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>SHG\/TPEF microscopy with AI provides greater granularity and precision in assessing fibrosis dynamics in patients with bridging fibrosis, thus advancing knowledge development of fibrosis evolution in natural history and in clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.16092","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T09:37:47Z","timestamp":1725874667000},"page":"3214-3228","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Digital quantitation of bridging fibrosis and septa reveals changes in natural history and treatment not seen with conventional histology"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3091-4990","authenticated-orcid":false,"given":"Nikolai V.","family":"Naoumov","sequence":"first","affiliation":[{"name":"Division of Medicine University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3442-4453","authenticated-orcid":false,"given":"David E.","family":"Kleiner","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, Post\u2010Mortem Section National Cancer Institute  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Chng","sequence":"additional","affiliation":[{"name":"Histoindex Pte. Ltd.  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Brees","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3214-5696","authenticated-orcid":false,"given":"Chandra","family":"Saravanan","sequence":"additional","affiliation":[{"name":"Novartis Institute of Biomedical Research  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayun","family":"Ren","sequence":"additional","affiliation":[{"name":"Histoindex Pte. Ltd.  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Tai","sequence":"additional","affiliation":[{"name":"Histoindex Pte. Ltd.  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8682-5748","authenticated-orcid":false,"given":"Arun J.","family":"Sanyal","sequence":"additional","affiliation":[{"name":"Stravitz\u2010Sanyal Institute of Liver Disease and Metabolic Health Virginia Commonwealth University School of Medicine  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,9]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0144-8"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30251"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.015"},{"key":"e_1_2_12_5_1","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1097\/HEP.0000000000000520","article-title":"A multi\u2010society Delphi consensus statement on new fatty liver disease 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