Clinical trial NCT06344364: Digital Pathology and AI for Liver Outcomes in MASLD
Official title: Epidemiologic Liver Outcomes Retrospective Study to Confirm The Prognostic Value of the FibroNest Digital Pathology Fibrosis Biomarker (Ph-FCS) in Patients With MASLD (DPAILO-1)
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Metabolic Dysfunction-associated Steatotic Liver Disease
Keywords: NAFLD
MAFLD
digital pathology
artificial intelligence
fibrosis score
liver disease
hepatic decompensation
Lead sponsor: PharmaNest, Inc
Sponsor class: INDUSTRY
Collaborators: name: Chinese University of Hong Kong
name: University of Edinburgh
name: University of Seville
name: Imperial College London
name: Icahn School of Medicine at Mount Sinai
name: Fundacio Clinic Barcelona
name: Sorbonne University
name: Newcastle University
First posted: 2024-04-03
Enrollment: 1800
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult pts ( \>=18 years old) with MASLD defined histologically with \>1 year of clinical follow up and available recording liver-related outcomes either through hospitalization ICD-10 codes or through clinical observation.

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Performance of Hepatic Decompensation Event predictive value of the FibroNest Ph-FCS
timeFrame: Time-to-event analysis between 2 and 10 years
Secondary outcomes:
measure: Performance of Hepatic Decompensation Event predictive value of the NASH-CRN Fibrosis Stage, a biopsy-based score for fibrosis severity
timeFrame: Time-to-event analysis between 2 and 10 years
measure: Performance of Hepatic Decompensation Event predictive value of the FIB-4 biomarker, a non-invasive test
timeFrame: Time-to-event analysis between 2 and 10 years
measure: Performance of Hepatic Decompensation Event predictive value of the elastography (Fibroscan) biomarker, a non-invasive test
timeFrame: Time-to-event analysis between 2 and 10 years
Other outcomes:
Locations:
city: Sha Tin
country: Hong Kong
facility: The Chinese University of Hong Kong
city: Barcelona
country: Spain
facility: Fundació de Recerca Clinic Barcelona
city: Sevilla
country: Spain
facility: University of Seville
city: Edinburgh
country: United Kingdom
facility: University of Edinburgh
state: Scotland
city: London
country: United Kingdom
facility: Imperial College London
Study officials:
affiliation: Sorbonne University
name: Vlad Ratziu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kendall TJ, Jimenez-Ramos M, Turner F, Ramachandran P, Minnier J, McColgan MD, Alam M, Ellis H, Dunbar DR, Kohnen G, Konanahalli P, Oien KA, Bandiera L, Menolascina F, Juncker-Jensen A, Alexander D, Mayor C, Guha IN, Fallowfield JA. An integrated gene-to-outcome multimodal database for metabolic dysfunction-associated steatotic liver disease. Nat Med. 2023 Nov;29(11):2939-2953. doi: 10.1038/s41591-023-02602-2. Epub 2023 Oct 30.
citation: Ratziu V, Chen L, Petitjean L. et al. Novel Artificial Intelligence-Assisted Digital Pathology Quantitative Image Analysis Predicts the occurrence of Liver-related Clinical Events in the Multicentric, European, Hepatic Outcomes and Survival Fatty Liver Registry (HITSURFR) Study. Hepatology. 78(S1) S1-S2154 2084-A
citation: Sanyal AJ, Van Natta ML, Clark J, Neuschwander-Tetri BA, Diehl A, Dasarathy S, Loomba R, Chalasani N, Kowdley K, Hameed B, Wilson LA, Yates KP, Belt P, Lazo M, Kleiner DE, Behling C, Tonascia J; NASH Clinical Research Network (CRN). Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease. N Engl J Med. 2021 Oct 21;385(17):1559-1569. doi: 10.1056/NEJMoa2029349.