eprintid: 10202906 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/20/29/06 datestamp: 2025-01-07 09:55:09 lastmod: 2025-01-07 09:55:09 status_changed: 2025-01-07 09:55:09 type: article metadata_visibility: show sword_depositor: 699 creators_name: Naoumov, NV creators_name: Kleiner, DE creators_name: Chng, E creators_name: Brees, D creators_name: Saravanan, C creators_name: Ren, Y creators_name: Tai, D creators_name: Sanyal, AJ title: Digital quantitation of bridging fibrosis and septa reveals changes in natural history and treatment not seen with conventional histology ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D17 keywords: digital pathology with artificial intelligence, liver fibrosis, metabolic dysfunction-associated steatohepatitis, quantitative assessment fibrosis regression, second harmonic generation microscopy note: © 2024 The Author(s). Liver International published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). abstract: BACKGROUND AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) with bridging fibrosis is a critical stage in the evolution of fatty liver disease. Second harmonic generation/two-photon 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-depth understanding of intra-stage fibrosis changes and septa analyses in a homogenous, well-characterised group with MASH F3 fibrosis. METHODS: Paired liver biopsies (baseline [BL] and end of treatment [EOT]) of 57 patients (placebo, n = 17 and tropifexor n = 40), 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. RESULTS: qFibrosis demonstrated fibrosis progression or regression in 14/17 (82%) patients receiving placebo, while the CRN scoring categorised 11/17 (65%) as ‘no change’. Radar maps with qFibrosis readouts visualised quantitative fibrosis dynamics in different areas of liver lobules even in cases categorised as ‘No Change’. Measurement of septa parameters objectively differentiated regressive and progressive septa (p < .001). Quantitative changes in individual septa parameters (BL to EOT) were observed both in the ‘no change’ and the ‘regression’ subgroups, as defined by the CRN scoring. CONCLUSION: 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. date: 2024-12 date_type: published publisher: Wiley official_url: https://doi.org/10.1111/liv.16092 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2325299 doi: 10.1111/liv.16092 medium: Print-Electronic lyricists_name: Naoumov, Nikolai lyricists_id: NNAOU69 actors_name: Naoumov, Nikolai actors_id: NNAOU69 actors_role: owner funding_acknowledgements: Z01 BC010685 [Intramural NIH HHS]; [Novartis Pharma AG]; [HistoIndex Pte. Ltd]; [National Institutes of Health, National Cancer Institute] full_text_status: public publication: Liver International volume: 44 number: 12 pagerange: 3214-3228 event_location: United States citation: Naoumov, NV; Kleiner, DE; Chng, E; Brees, D; Saravanan, C; Ren, Y; Tai, D; Naoumov, NV; Kleiner, DE; Chng, E; Brees, D; Saravanan, C; Ren, Y; Tai, D; Sanyal, AJ; - view fewer <#> (2024) Digital quantitation of bridging fibrosis and septa reveals changes in natural history and treatment not seen with conventional histology. Liver International , 44 (12) pp. 3214-3228. 10.1111/liv.16092 <https://doi.org/10.1111/liv.16092>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10202906/1/Liver%20International%20-%202024%20-%20Naoumov%20-%20Digital%20quantitation%20of%20bridging%20fibrosis%20and%20septa%20reveals%20changes%20in%20natural%20%284%29.pdf