Digital Pathology and AI for Liver Outcomes in MASLD (DPAILO-1)

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)

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, 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 1,200 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.

• Study Type: Observational
• Enrollment (Actual): 1241

Contacts and Locations

Study Locations

• Hong Kong
  • Shatin, Hong Kong
    • The Chinese University of Hong Kong
• Spain
  • Barcelona, Spain
    • Fundació de Recerca Clínic Barcelona
  • Seville, Spain, 41004
    • University of Seville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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)

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 score that aggregates quantitative histological features of fibrosis severity measured by high resolution quantitative image analysis.
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 score that aggregates quantitative histological features of fibrosis severity measured by high resolution quantitative image analysis.

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 FIB-4 biomarker, a non-invasive test	Area under Receiver Operating Characteristic Curve (AUROC) of FIB-4, as a prognostic/diagnostic biomarker for Hepatic Decompensation 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 elastography, as a prognostic/diagnostic biomarker for Hepatic Decompensation Events in patients with MASH.	Time-to-event analysis between 2 and 10 years
Performance of Hepatic Decompensation Event predictive value of the NASH-CRN Fibrosis Stage, a biopsy-based score for fibrosis severity	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.	Time-to-event analysis between 2 and 10 years

Collaborators and Investigators

• Sponsor: PharmaNest, Inc
• Collaborators: Chinese University of Hong Kong; University of Seville; Sorbonne University; Fundacio Clinic Barcelona
• Investigators: Principal Investigator: Vlad Ratziu, MD, PhD, Sorbonne University

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Other scientific references

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: March 27, 2024
• First Submitted That Met QC Criteria: March 27, 2024
• First Posted (Actual): April 3, 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: artificial intelligence; NAFLD; liver disease; digital pathology; hepatic decompensation; MAFLD; fibrosis score
• Additional Relevant MeSH Terms: Digestive System Diseases; Fatty Liver; Liver Diseases; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: PHN 1-080-23

Plan for Individual participant data (IPD)

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

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