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

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)

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).

Study Overview

• Status: Completed
• Conditions: Metabolic Dysfunction-associated Steatotic Liver Disease
• Intervention / Treatment: Diagnostic test: Digital Pathology FibroNest Phenotypic Fibrosis Composite Score (Ph-FCS)

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.

• Study Type: Observational
• Enrollment (Actual): 1578

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23284
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Non-Liver Related Event; Absence of any of the liver events described in the second group in the patient clinical follow-up.	Diagnostic test: 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
Liver Related Event; Liver-related events include liver-related death, hepatic decompensation events (variceal hemorrhage, ascites, hepatic encephalopathy), and hepatocellular carcinoma.	Diagnostic test: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance of Hepatic Decompensation Event predictive value of the FibroNest Ph-FCS	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.	Time-to-event analysis between 2 and 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance of Hepatic Decompensation Event predictive value of the NASH-CRN Fibrosis Stage	Area under Receiver Operating Characteristic Curve (AUROC) of the NASH-CRN Fibrosis Stage, as a prognostic/diagnostic biomarker for liver related events in patients with MASH.	Time-to-event analysis between 2 and 10 years
Performance of Hepatic Decompensation Event predictive value of the elastography (Fibroscan) biomarker, a non-invasive test	Area under Receiver Operating Characteristic Curve (AUROC) of the elastography (Fibroscan) biomarker, as a prognostic/diagnostic biomarker for liver related events in patients with MASH.	Time-to-event analysis between 2 and 10 years

Collaborators and Investigators

• Sponsor: PharmaNest, Inc
• Collaborators: Virginia Commonwealth University; Nonalcoholic Steatohepatitis Clinical Research Network (NASH)
• Investigators: Principal Investigator: Arun J Sanyal, MD, Virginia Commonwealth University; Study Director: Cynthia Belhling, MD, University California San Diego; Study Director: David E Kleiner, MD. PhD, Nonalcoholic Steatohepatitis Clinical Research Network

Publications and helpful links

General Publications

• 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
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2025
• Primary Completion (Actual): March 15, 2026
• Study Completion (Actual): March 15, 2026

Study Registration Dates

• First Submitted: July 2, 2024
• First Submitted That Met QC Criteria: July 2, 2024
• First Posted (Actual): July 9, 2024

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: MASH
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: PHN 1-020-24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Study Data/Documents

1. Clinical Study Report
   Information identifier: NCT01030484
   Information comments: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No