Digital Pathology and AI for Liver Outcomes in MASLD
- Conditions
- Metabolic Dysfunction-associated Steatotic Liver Disease
- Interventions
- Diagnostic Test: Digital Pathology FibroNest Phenotypic Fibrosis Composite Score (Ph-FCS)
- Registration Number
- NCT06344364
- Lead Sponsor
- PharmaNest, Inc
- Brief Summary
The aim of this multi-center, retrospective epidemiologic study is to confirm the prognostic performance of the Digital Pathology (DP) FibroNest Phenotypic Fibrosis Composite Score (Ph-FCS), derived from standard digital pathology liver biopsy images, in predicting clinical hepatic decompensation events in patients with metabolic dysfunction-associated steatohepatitis (MASH).
- Detailed Description
MASH, or metabolic dysfunction-associated steatohepatitis, presents histological liver changes resembling those caused by alcohol abuse, but in the absence of alcohol intake. Common among adults with conditions like obesity and type-2 diabetes, MASH, especially its severe form, is anticipated to become a leading cause of end-stage liver disease.
Currently lacking approved treatments, MASH poses a significant burden on liver health and transplantation. Diagnosis and assessment rely on subjective histological review, prone to variability and limitations in detecting subtle changes. Consequently, there's an urgent need for accurate, continuous histological biomarkers.
The FibroNest Ph-FCS offers a promising solution, utilizing high resolution digital pathology and sophisticated algorithmic methods for sensitive and reproducible fibrosis severity assessment and prediction of clinical events. In a 2003 proof of concept retrospective study on 400 patients, its prognostic performance was excellent.
In this proposed multi-center retrospective study, we aim to confirm the Ph-FCS's prognostic value on a large cohort of 1,700 MASLD patients. We will also compare the prognostic performance of the Ph-FCS with the prognostic performance of the NASH-CR Fibrosis stages, and with non-invasive biomarkers like Fib-4 and elastography/Fibroscan, also collected retrospectively from the point of initial diagnosis.
This study seeks to:
(i) Confirm Ph-FCS's prognostic utility on a large scale.
(ii) Compare biopsy-based Ph-FCS with NASH-CRN F Stages
(iii) Compare biopsy-based Ph-FCS with non-invasive biomarkers.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 1800
- Adult pts ( >=18 years old) with MASLD defined histologically.
- Liver biopsy with fibrosis stains available for digitization or already digitized.
- Clinical follow-up >1 year available recording liver-related outcomes either through hospitalization ICD-10 codes or through clinical observation
- Liver diseases other than MASLD Note: no exclusion based on bariatric surgery, significant weight loss or enrollment in NASH clinical studies, but data is collected for data analysis / competing effects (see data analysis plan)
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Non-Liver Related Event Digital Pathology FibroNest Phenotypic Fibrosis Composite Score (Ph-FCS) Absence of any of the liver events described in the second group in the patient clinical follow-up. Liver Related Event Digital Pathology FibroNest Phenotypic Fibrosis Composite Score (Ph-FCS) Liver-related events include liver-related death, hepatic decompensation events (variceal hemorrhage, ascites, hepatic encephalopathy), and hepatocellular carcinoma.
- Primary Outcome Measures
Name Time Method Performance of Hepatic Decompensation Event predictive value of the FibroNest Ph-FCS Time-to-event analysis between 2 and 10 years Area under Receiver Operating Characteristic Curve (AUROC) of the FibroNest Ph-FCS, as a prognostic/diagnostic biomarker for liver related events in patients with MASH.
- Secondary Outcome Measures
Name Time Method Performance of Hepatic Decompensation Event predictive value of the elastography (Fibroscan) biomarker, a non-invasive test Time-to-event analysis between 2 and 10 years Area under Receiver Operating Characteristic Curve (AUROC) of elastography, as a prognostic/diagnostic biomarker for Hepatic Decompensation Events in patients with MASH.
Performance of Hepatic Decompensation Event predictive value of the NASH-CRN Fibrosis Stage, a biopsy-based score for fibrosis severity Time-to-event analysis between 2 and 10 years Area under Receiver Operating Characteristic Curve (AUROC) of NASH-CRN F stage, as a biopsy-based prognostic/diagnostic biomarker for Hepatic Decompensation Events in patients with MASH.
Performance of Hepatic Decompensation Event predictive value of the FIB-4 biomarker, a non-invasive test Time-to-event analysis between 2 and 10 years Area under Receiver Operating Characteristic Curve (AUROC) of FIB-4, as a prognostic/diagnostic biomarker for Hepatic Decompensation Events in patients with MASH.
Trial Locations
- Locations (5)
The Chinese University of Hong Kong
🇭🇰Sha Tin, Hong Kong
Fundació de Recerca Clinic Barcelona
🇪🇸Barcelona, Spain
University of Seville
🇪🇸Sevilla, Spain
University of Edinburgh
🇬🇧Edinburgh, Scotland, United Kingdom
Imperial College London
🇬🇧London, United Kingdom