Digital Pathology and AI for Liver Outcomes in MASLD (DPAILO-2)

NCT ID: NCT06493253

Last Updated: 2025-08-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 1700 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-09-01
• Study Completion Date: 2026-03-01

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.

Conditions

Metabolic Dysfunction-associated Steatotic Liver Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Non-Liver Related Event

Absence of any of the liver events described in the second group in the patient clinical follow-up.

Digital Pathology FibroNest Phenotypic Fibrosis Composite Score (Ph-FCS)

Intervention Type: DIAGNOSTIC_TEST

Biomarker name: FibroNest Phenotypic Fibrosis Composite Score Acronym: FibroNest Ph- FCS Type of Biomarker: Histologic based, Digital, Quantitative Image Analysis, Imaging modality Definition: A quantitative, normalized (no unit) and continuous composite

Liver Related Event

Liver-related events include liver-related death, hepatic decompensation events (variceal hemorrhage, ascites, hepatic encephalopathy), and hepatocellular carcinoma.

Digital Pathology FibroNest Phenotypic Fibrosis Composite Score (Ph-FCS)

Intervention Type: DIAGNOSTIC_TEST

Biomarker name: FibroNest Phenotypic Fibrosis Composite Score Acronym: FibroNest Ph- FCS Type of Biomarker: Histologic based, Digital, Quantitative Image Analysis, Imaging modality Definition: A quantitative, normalized (no unit) and continuous composite

Interventions

Digital Pathology FibroNest Phenotypic Fibrosis Composite Score (Ph-FCS)

Biomarker name: FibroNest Phenotypic Fibrosis Composite Score Acronym: FibroNest Ph- FCS Type of Biomarker: Histologic based, Digital, Quantitative Image Analysis, Imaging modality Definition: A quantitative, normalized (no unit) and continuous composite

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nonalcoholic Steatohepatitis Clinical Research Network (NASH)

UNKNOWN

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: collaborator

PharmaNest, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arun J Sanyal, MD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Cynthia Belhling, MD

Role: STUDY_DIRECTOR

University California San Diego

David E Kleiner, MD. PhD

Role: STUDY_DIRECTOR

Nonalcoholic Steatohepatitis Clinical Research Network

Locations

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

Central Contacts

Li C Chen, PhD.

Role: CONTACT

li.chen@pharmanest.com

+1 609 375 2003

Louis Petitjean

Role: CONTACT

louis.petitjean@pharmanest.com

+1 609 375 2003

Facility Contacts

Arun J Sanyal, MD

Role: primary

arun.sanyal@vcuhealth.org

+1 804 828-1981

References

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.

Reference Type: BACKGROUND

PMID: 34670043 (View on PubMed)

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

Reference Type: BACKGROUND

Study Documents

Document Type: Clinical Study Report

The NAFLD Adult Database 2 continued the longitudinal follow-up of participants enrolled in earlier NASH CRN studies and recruited new participants with recent liver biopsies. Comprehensive data, including demographics, medical history, symptoms, medication use, alcohol use and routine laboratory studies were collected on all participants at entry and at annual visits for up to 10 years after enrollment. A liver biopsy was collected at baseline if not collected in a prior NASH CRN study.

View Document

Other Identifiers

PHN 1-020-24

Identifier Type: -

Identifier Source: org_study_id