The University of Southampton
University of Southampton Institutional Repository

AI-based digital pathology provides newer insights into lifestyle intervention-induced fibrosis regression in MASLD: an exploratory study

AI-based digital pathology provides newer insights into lifestyle intervention-induced fibrosis regression in MASLD: an exploratory study
AI-based digital pathology provides newer insights into lifestyle intervention-induced fibrosis regression in MASLD: an exploratory study
Background and aims: lifestyle intervention is the mainstay of therapy for metabolic dysfunction-associated steatohepatitis (MASH), and liver fibrosis is a key consequence of MASH that predicts adverse clinical outcomes. The placebo response plays a pivotal role in the outcome of MASH clinical trials. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence analyses can provide an automated quantitative assessment of fibrosis features on a continuous scale called qFibrosis. In this exploratory study, we used this approach to gain insight into the effect of lifestyle intervention-induced fibrosis changes in MASH.

Methods: we examined unstained sections from paired liver biopsies (baseline and end-of-intervention) from MASH individuals who had received either routine lifestyle intervention (RLI) (n = 35) or strengthened lifestyle intervention (SLI) (n = 17). We quantified liver fibrosis with qFibrosis in the portal tract, periportal, transitional, pericentral, and central vein regions.

Results: about 20% (7/35) and 65% (11/17) of patients had fibrosis regression in the RLI and SLI groups, respectively. Liver fibrosis tended towards no change or regression after each lifestyle intervention, and this phenomenon was more prominent in the SLI group. SLI-induced liver fibrosis regression was concentrated in the periportal region.

Conclusion: using digital pathology, we could detect a more pronounced fibrosis regression with SLI, mainly in the periportal region. With changes in fibrosis area in the periportal region, we could differentiate RLI and SLI patients in the placebo group in the MASH clinical trial. Digital pathology provides new insight into lifestyle-induced fibrosis regression and placebo responses, which is not captured by conventional histological staging.

fibrosis regression, lifestyle intervention, metabolic dysfunction-associated steatohepatitis, qFibrosis
1478-3223
Yuan, Hai-Yang
88c640c0-0279-4102-89de-14b99aaaeeba
Tong, Xiao-Fei
fc440372-1dc3-453f-b858-35f73db4efa2
Ren, Ya-Yun
86de4046-9cb1-4d21-9d99-5460216e1708
Li, Yang-Yang
afd37561-0c99-4cc9-b29c-50825c6ea841
Wang, Xin-Lei
fe6b98d5-9f60-450c-af5d-823d43ec9bf6
Chen, Li-Li
6113f6ca-94c6-4d3d-b849-19e093f2dbca
Chen, Sui-Dan
3bc79c7a-9d51-4aac-97fe-8e0829a59353
Jin, Xiao-Zhi
0eb2d537-7143-4036-85ce-de8eb444985b
Wang, Xiao-Dong
7be2b34b-1c57-4c89-b660-778b4ed88858
Targher, Giovanni
8a57cd78-c539-4b77-9ba8-1d7fff1c957f
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
Wei, Lai
9d5eeba6-fbf0-4292-a0cd-1dda04618ce7
Wong, Vincent Wai-Sun
7cddf4bb-4720-45f1-a052-7b87fb64c6d6
Tai, Dean
4a85af4a-829f-4329-b499-a8a39b900fc3
Sanyal, Arun J.
f961c7d5-5194-41e6-9b51-1ca705840443
You, Hong
09754004-cf42-43eb-9df4-ca9394be3922
Zheng, Ming-Hua
e4e24459-832c-465c-8f29-d1fbabb2dc3c
Yuan, Hai-Yang
88c640c0-0279-4102-89de-14b99aaaeeba
Tong, Xiao-Fei
fc440372-1dc3-453f-b858-35f73db4efa2
Ren, Ya-Yun
86de4046-9cb1-4d21-9d99-5460216e1708
Li, Yang-Yang
afd37561-0c99-4cc9-b29c-50825c6ea841
Wang, Xin-Lei
fe6b98d5-9f60-450c-af5d-823d43ec9bf6
Chen, Li-Li
6113f6ca-94c6-4d3d-b849-19e093f2dbca
Chen, Sui-Dan
3bc79c7a-9d51-4aac-97fe-8e0829a59353
Jin, Xiao-Zhi
0eb2d537-7143-4036-85ce-de8eb444985b
Wang, Xiao-Dong
7be2b34b-1c57-4c89-b660-778b4ed88858
Targher, Giovanni
8a57cd78-c539-4b77-9ba8-1d7fff1c957f
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
Wei, Lai
9d5eeba6-fbf0-4292-a0cd-1dda04618ce7
Wong, Vincent Wai-Sun
7cddf4bb-4720-45f1-a052-7b87fb64c6d6
Tai, Dean
4a85af4a-829f-4329-b499-a8a39b900fc3
Sanyal, Arun J.
f961c7d5-5194-41e6-9b51-1ca705840443
You, Hong
09754004-cf42-43eb-9df4-ca9394be3922
Zheng, Ming-Hua
e4e24459-832c-465c-8f29-d1fbabb2dc3c

Yuan, Hai-Yang, Tong, Xiao-Fei, Ren, Ya-Yun, Li, Yang-Yang, Wang, Xin-Lei, Chen, Li-Li, Chen, Sui-Dan, Jin, Xiao-Zhi, Wang, Xiao-Dong, Targher, Giovanni, Byrne, Christopher D., Wei, Lai, Wong, Vincent Wai-Sun, Tai, Dean, Sanyal, Arun J., You, Hong and Zheng, Ming-Hua (2024) AI-based digital pathology provides newer insights into lifestyle intervention-induced fibrosis regression in MASLD: an exploratory study. Liver International. (doi:10.1111/liv.16025).

Record type: Article

Abstract

Background and aims: lifestyle intervention is the mainstay of therapy for metabolic dysfunction-associated steatohepatitis (MASH), and liver fibrosis is a key consequence of MASH that predicts adverse clinical outcomes. The placebo response plays a pivotal role in the outcome of MASH clinical trials. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence analyses can provide an automated quantitative assessment of fibrosis features on a continuous scale called qFibrosis. In this exploratory study, we used this approach to gain insight into the effect of lifestyle intervention-induced fibrosis changes in MASH.

Methods: we examined unstained sections from paired liver biopsies (baseline and end-of-intervention) from MASH individuals who had received either routine lifestyle intervention (RLI) (n = 35) or strengthened lifestyle intervention (SLI) (n = 17). We quantified liver fibrosis with qFibrosis in the portal tract, periportal, transitional, pericentral, and central vein regions.

Results: about 20% (7/35) and 65% (11/17) of patients had fibrosis regression in the RLI and SLI groups, respectively. Liver fibrosis tended towards no change or regression after each lifestyle intervention, and this phenomenon was more prominent in the SLI group. SLI-induced liver fibrosis regression was concentrated in the periportal region.

Conclusion: using digital pathology, we could detect a more pronounced fibrosis regression with SLI, mainly in the periportal region. With changes in fibrosis area in the periportal region, we could differentiate RLI and SLI patients in the placebo group in the MASH clinical trial. Digital pathology provides new insight into lifestyle-induced fibrosis regression and placebo responses, which is not captured by conventional histological staging.

Text
draft 20240608 - Accepted Manuscript
Restricted to Repository staff only until 23 June 2025.
Request a copy
Text
Figure 1 - Accepted Manuscript
Restricted to Repository staff only until 23 June 2025.
Request a copy
Text
Figure 2 - Accepted Manuscript
Restricted to Repository staff only until 23 June 2025.
Request a copy
Text
Figure 3 - Accepted Manuscript
Restricted to Repository staff only
Request a copy
Text
Supplemental method - Accepted Manuscript
Restricted to Repository staff only
Request a copy
Text
Table 1 - Accepted Manuscript
Restricted to Repository staff only
Request a copy

Show all 6 downloads.

More information

Accepted/In Press date: 23 June 2024
e-pub ahead of print date: 4 July 2024
Published date: 1 October 2024
Additional Information: Publisher Copyright: © 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Keywords: fibrosis regression, lifestyle intervention, metabolic dysfunction-associated steatohepatitis, qFibrosis

Identifiers

Local EPrints ID: 491664
URI: http://eprints.soton.ac.uk/id/eprint/491664
ISSN: 1478-3223
PURE UUID: e604b48e-195a-47a9-8761-5173dd0b05d6
ORCID for Christopher D. Byrne: ORCID iD orcid.org/0000-0001-6322-7753

Catalogue record

Date deposited: 03 Jul 2024 09:49
Last modified: 16 Oct 2024 01:37

Export record

Altmetrics

Contributors

Author: Hai-Yang Yuan
Author: Xiao-Fei Tong
Author: Ya-Yun Ren
Author: Yang-Yang Li
Author: Xin-Lei Wang
Author: Li-Li Chen
Author: Sui-Dan Chen
Author: Xiao-Zhi Jin
Author: Xiao-Dong Wang
Author: Giovanni Targher
Author: Lai Wei
Author: Vincent Wai-Sun Wong
Author: Dean Tai
Author: Arun J. Sanyal
Author: Hong You
Author: Ming-Hua Zheng

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×