Naoumov, NV;
Brees, D;
Loeffler, J;
Chng, E;
Ren, Y;
Lopez, P;
Tai, D;
... Sanyal, AJ; + view all
(2022)
Digital pathology with artificial intelligence analyses provides greater insights into treatment-induced fibrosis regression in NASH.
Journal of Hepatology
, 77
(5)
pp. 1399-1409.
10.1016/j.jhep.2022.06.018.
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Naoumov et al Digital Pathology AI_Liver Fibrosis JHEP2022.pdf - Published Version Download (1MB) | Preview |
Abstract
BACKGROUND & AIMS: Liver fibrosis is a key prognostic determinant for clinical outcomes in non-alcoholic steatohepatitis (NASH). Current scoring systems have limitations, especially in assessing fibrosis regression. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence analyses provides standardized evaluation of NASH features, especially liver fibrosis and collagen fiber quantitation on a continuous scale. This approach was applied to gain in-depth understanding of fibrosis dynamics after treatment with tropifexor (TXR), a non-bile acid farnesoid X receptor agonist in patients participating in the FLIGHT-FXR study (NCT02855164). METHOD: Unstained sections from 198 liver biopsies (paired: baseline and end-of-treatment) from 99 patients with NASH (fibrosis stage F2 or F3) who received placebo (n = 34), TXR 140 μg (n = 37), or TXR 200 μg (n = 28) for 48 weeks were examined. Liver fibrosis (qFibrosis®), hepatic fat (qSteatosis®), and ballooned hepatocytes (qBallooning®) were quantitated using SHG/TPEF microscopy. Changes in septa morphology, collagen fiber parameters, and zonal distribution within liver lobules were also quantitatively assessed. RESULTS: Digital analyses revealed treatment-associated reductions in overall liver fibrosis (qFibrosis®), unlike conventional microscopy, as well as marked regression in perisinusoidal fibrosis in patients who had either F2 or F3 fibrosis at baseline. Concomitant zonal quantitation of fibrosis and steatosis revealed that patients with greater qSteatosis reduction also have the greatest reduction in perisinusoidal fibrosis. Regressive changes in septa morphology and reduction in septa parameters were observed almost exclusively in F3 patients, who were adjudged as ‘unchanged’ with conventional scoring. CONCLUSION: Fibrosis regression following hepatic fat reduction occurs initially in the perisinusoidal regions, around areas of steatosis reduction. Digital pathology provides new insights into treatment-induced fibrosis regression in NASH, which are not captured by current staging systems.
| Type: | Article |
|---|---|
| Title: | Digital pathology with artificial intelligence analyses provides greater insights into treatment-induced fibrosis regression in NASH |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jhep.2022.06.018 |
| Publisher version: | https://doi.org/10.1016/j.jhep.2022.06.018 |
| Language: | English |
| Additional information: | © 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver under a Creative Commons license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | Non-alcoholic Steatohepatitis, Digital Pathology with Artificial Intelligence, Second Harmonic Generation Microscopy, Fibrosis Regression Perisinusoidal Fibrosis, Farnesoid X Receptor Agonists and NASH Treatment |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10202911 |
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