Advanced Search
View ORCID ProfileHanna Pulaski, Stephen A. Harrison, Shraddha S. Mehta, Arun J Sanyal, Marlena C. Vitali, Laryssa C. Manigat, Hypatia Hou, Susan P. Madasu Christudoss, Sara M. Hoffman, Adam Stanford-Moore, Robert Egger, Jonathan Glickman, Murray Resnick, Neel Patel, Cristin E. Taylor, Robert P. Myers, Chuhan Chung, Scott D. Patterson, Anne-Sophie Sejling, Anne Minnich, Vipul Baxi, G. Mani Subramaniam, Quentin M. Anstee, Rohit Loomba, Vlad Ratziu, Michael C Montalto, Andrew H Beck, Katy Wack
doi: https://doi.org/10.1101/2024.05.29.24308109
- Abstract
- Full Text
- Info/History
- Metrics
- Data/Code
- Preview PDF
Abstract
Metabolic-dysfunction associated steatohepatitis (MASH) is a major cause of liver-related morbidity and mortality, yet treatment options are limited. Manual scoring of liver biopsies, currently the gold standard for clinical trial enrollment and endpoint assessment, suffers from high reader variability. This study represents the most comprehensive multi-site analytical and clinical validation of an AI-based pathology system, Artificial Intelligence-based Measurement of Nonalcoholic Steatohepatitis (AIM-NASH), to assist pathologists in MASH trial histology scoring. AIM-NASH demonstrated high repeatability and reproducibility compared to manual scoring. AIM-NASH-assisted reads by expert MASH pathologists were superior to unassisted reads in accurately assessing inflammation, ballooning, NAS >= 4 with >=1 in each score category, and MASH resolution, while maintaining non-inferiority in steatosis and fibrosis assessment. These findings suggest AIM-NASH could mitigate reader variability, providing a more reliable assessment of therapeutics in MASH clinical trials.
Competing Interest Statement
HP, HH, ASM, RE, NP, AHP and KEW are full-time, salaried employees of PathAI, Inc. SAH is a paid consultant for Akero Therapeutics, Aligos Therppeutics, Altimmune Inc, Boehringer Ingelheim, Bluejay Therapeutics, Echosens North America Inc, Galecto Inc, Gilead Sciences Inc, Glaxo Smith Kline (GSK), Hepion Pharmaceuticals Inc, Hepta Bio Inc, Histoindex PTE LTD, Kriya Therapeutics, Madrigal Pharmaceuticals Inc, Medpace Inc, MGGM Therapeutics LLC, Neurobo Pharmaceuticals Inc, Northsea Therapeutics B.V., Novo Nordisk, Pfizer, Sagimet Biosciences, Terns Inc, and Viking Therapeutics and shareholder of Akero, Cirius Therapeutics, Galectin Therapeutics, Histoindex PTE. LTD, and Northsea Therapeutics. SSM, MCV, LCM, SPMC, SHM, CET and MCC were PathAI Inc. employees at the time of the study conduct. JG and MR are paid contractors of PathAI, Inc. RPM and GMS are full-time, salaried employees of OrsoBio Inc. CC is a full-time, salaried employee of Inipharm, Inc. SDP is a full-time salaried employee of Gilead Sciences Inc. ASS is a full-time, salaried employee of Novo Nordisk. AM was a paid consultant for Bristol Myers Squibb. VB is a full-time, salaried employee of Bristol Myers Squibb. ASJ has stock options in Genfit, Akarna, Tiziana, Indalo, Durect Inversago and Galmed; is a consultant to Astra Zeneca, Nimbus, Takeda, Jannsen, Gilead, Terns, Merck, Boehringer-Ingelheim, Bristol Myers Squibb, Lilly, Novartis, Novo Nordisk, Pfizer, and Genfit; has been an unpaid consultant to Intercept, Echosens, Immuron, Galectin, Affimune Prosciento. His institution has received grant support from Gilead, Bristol Myers Squibb, Intercept, Merck, Astra Zeneca and Novartis. He receives royalties from Elsevier and UptoDate. QMA is a coordinator of the EU IMI-2 LITMUS consortium, which is funded by the EU Horizon 2020 programme and EFPIA. This multi-stakeholder consortium includes industry partners. He has research grant funding from AstraZeneca, Boehringer Ingelheim and Intercept. He is a consultant on behalf of Newcastle University to Alimentiv, Akero, AstraZeneca, 89Bio, Boehringer Ingelheim, Bristol Myers Squibb, Galmed, Genfit, Genentech, Gilead, GlaxoSmithKline, HistoIndex, Intercept, Inventiva, QVIA, Janssen, Madrigal, Merck, NGMBio, Novartis, Novo Nordisk, PathAI, Pfizer, Pharmanest, Prosciento, Roche and Terns. He is a speaker for Novo Nordisk, Madrigal, Springer Healthcare and receives royalties from Elsevier Ltd. RL is a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bluejay Therapeutics, Bristol Myers Squibb, Eli Lilly, Galmed, Gilead, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Terns Pharmaceuticals and Viking Therapeutics. He is a co-founder of LipoNexus Inc. VR is a paid consultant for Novo-Nordisk, Northsea Madrigal, Enyo, Poxel, Bristol Myers-Squibb, Intercept, NGM Bio and Sagimet.
Funding Statement
This study was funded by PathAI
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Ethics committee/IRB of WCG gave ethical approval for this work
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.
Yes
Footnotes
↵* Co-first authors
↵# Employee of PathAI at the time of the study
Data Availability
The glass slides and WSIs used in these validation studies are from existing clinical trials and the authors had access to these during the study in accordance with the relevant license agreements. Due to the nature of the source data, it is not currently publicly available.
Copyright
The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
PostedMay 29, 2024.
Download PDF
Data/Code
Citation Tools
- Facebook Like
- Google Plus One
Subject Area
- Pathology
Subject Areas
All Articles
Addiction Medicine (325)
Allergy and Immunology (635)
Anesthesia (169)
Cardiovascular Medicine (2420)
Dentistry and Oral Medicine (292)
Dermatology (208)
Emergency Medicine (382)
Endocrinology (including Diabetes Mellitus and Metabolic Disease) (859)
Epidemiology (11845)
Forensic Medicine (10)
Gastroenterology (706)
Genetic and Genomic Medicine (3802)
Geriatric Medicine (353)
Health Economics (642)
Health Informatics (2436)
Health Policy (944)
Health Systems and Quality Improvement (913)
Hematology (344)
HIV/AIDS (799)
Infectious Diseases (except HIV/AIDS) (13383)
Intensive Care and Critical Care Medicine (771)
Medical Education (374)
Medical Ethics (105)
Nephrology (404)
Neurology (3554)
Nursing (201)
Nutrition (533)
Obstetrics and Gynecology (687)
Occupational and Environmental Health (672)
Oncology (1845)
Ophthalmology (542)
Orthopedics (224)
Otolaryngology (289)
Pain Medicine (234)
Palliative Medicine (68)
Pathology (452)
Pediatrics (1048)
Pharmacology and Therapeutics (431)
Primary Care Research (425)
Psychiatry and Clinical Psychology (3218)
Public and Global Health (6221)
Radiology and Imaging (1304)
Rehabilitation Medicine and Physical Therapy (758)
Respiratory Medicine (840)
Rheumatology (381)
Sexual and Reproductive Health (377)
Sports Medicine (328)
Surgery (409)
Toxicology (51)
Transplantation (174)
Urology (148)