Clinical trial NCT06493253: Digital Pathology and AI for Liver Outcomes in MASLD (DPAILO-2)
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-2)
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Metabolic Dysfunction-associated Steatotic Liver Disease
Keywords: MASH
Lead sponsor: PharmaNest, Inc
Sponsor class: INDUSTRY
Collaborators: name: Nonalcoholic Steatohepatitis Clinical Research Network (NASH)
name: Virginia Commonwealth University
First posted: 2024-07-09
Enrollment: 1700
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patient from the NAFLD Adult Database 2 Registry including Adult pts ( \>=18 years old) with MASLD defined histologically with \>1 year of clinical follow up and available recording liver-related outcomes 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 (Metabolic Dysfunction-Associated Steatohepatitis):

MASH presents histological liver changes similar to those caused by alcohol abuse, but occurs in the absence of alcohol intake. It is common among adults with conditions such as obesity and type-2 diabetes. Severe MASH is expected to become a leading cause of end-stage liver disease.

Current Challenges:

There are currently no fully approved treatments for MASH which places a significant burden on liver health and transplantation. Diagnosis and assessment rely on subjective histological reviews, which are prone to variability and limitations in detecting subtle changes. Therefore, there is an urgent need for accurate and continuous histological biomarkers.

FibroNest Ph-FCS Solution:

The FibroNest Ph-FCS offers a promising solution by 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, the Ph-FCS demonstrated excellent prognostic performance.

Proposed Study:

This multi-center retrospective study aims to confirm the Ph-FCS's prognostic value using patient liver biopsies and clinical outcome data from the NAFLD Adult Database 2 registry (NCT01030484). The prognostic performance of the Ph-FCS will be compared to:

1. The NASH-CRN Histological Fibrosis Stages established from the same biopsies.
2. Non-invasive biomarkers like Fib-4 and elastography/Fibroscan, also collected retrospectively from the point of initial diagnosis.

Study Objectives:

(i) Confirm the Ph-FCS's prognostic utility on a large scale. (ii) Compare the Ph-FCS's prognostic performance with that of the NASH-CRN Fibrosis Stages established from the same biopsies.

(iii) Compare biopsy-based Ph-FCS with non-invasive biomarkers.

Eligibility criteria: From NCT01030484:

* Age at least 18 years during the consent process
* Willingness to be in the study for 1 or more years
* Ability and willingness to give written, informed consent to be screened for and, if eligible, to be enrolled into the Database 2 study
* Minimal or no alcohol use history consistent with NAFLD (see exclusion criteria)
* Collection of a liver biopsy that is obtained within 120 days of enrollment as part of standard of care or for evaluation in FLINT trial
* Collection of biosamples (serum, plasma, DNA, and, if available, liver tissue) within 90 days prior to enrollment and 0-90 days before or 4-90 days after the standard of care liver biopsy

Exclusion Criteria:

From NCT01030484

* Clinical or histological evidence of alcoholic liver disease or alcohol consumption during the two years before entry (\> 20g/day for men, \>10g/day women)
* History of total parenteral nutrition
* History of gastric or jejunoileal bypass preceding the diagnosis of NAFLD
* Biliopancreatic diversion or bariatric surgery
* Evidence of advanced liver disease with Child-Pugh-Turcotte score equal to or greater than 10
* Short bowel syndrome
* Suspected or confirmed hepatocellular carcinoma
* Positive for HIV
* Evidence of HBV or HCV infection
* Low alpha-1-antitrypsin level and ZZ phenotype
* Wilson's disease
* Known glycogen storage disease, dysbetalipoproteinemia, phenotypic hemochromatosis
* Vascular lesions
* Iron overload greater than 3+
* Zones of confluent necrosis, infarction, massive or sub-massive, pan-acinar necrosis
* Multiple epithelioid granulomas
* Congenital hepatic fibrosis
* Polycystic liver disease
* Other metabolic or congenital liver disease

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
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: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Arun J Sanyal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University California San Diego
name: Cynthia Belhling, MD
role: STUDY_DIRECTOR
affiliation: Nonalcoholic Steatohepatitis Clinical Research Network
name: David E Kleiner, MD. PhD
role: STUDY_DIRECTOR
References:
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.
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