Optimizing Noninvasive assessMent Of DysmEtabolic Compensated Advanced Liver Disease (MODELS)

Optimizing Noninvasive assessMent Of DysmEtabolic Compensated Advanced Liver Disease by Integration of Artificial Intelligence Model and omicS Data

Non-alcoholic fatty liver disease (NAFLD) is responsible for a significant proportion of liver-related deaths and healthcare costs in the United States, accounting for approximately 36% of liver-related deaths and over one billion dollars in annual healthcare expenses. [PMID: 34863359] A recent analysis of healthcare costs in Italy showed that out of the 9,729 NAFLD/NASH patients who were hospitalized and analyzed, the vast majority (97%) did not have advanced liver disease, while 1.3% had compensated advanced liver disease (cACLD), 3.1% had decompensated cirrhosis, 0.8% had hepatocellular carcinoma, and 0.1% underwent liver transplantation.

The burden of comorbidities was high across all patient cohorts, and patients with cACLD required a greater number of inpatient services, outpatient visits, and the pharmacy fills compared to those without advanced liver disease. As disease severity increased, mean total annual costs also increased primarily due to higher inpatient services costs. In Italy, as in other EU countries, most of the healthcare costs for patients were attributed to NAFLD/NASH-related liver complications. Thus, the optimization of the non-invasive diagnosis of cACLD represents an urgent need in dysmetabolic liver disease. These advancements will play a crucial role in early detection, risk stratification, and effective management of highly prevalent liver diseases such as NAFLD/NASH and their progression.

Study Overview

• Status: Recruiting
• Conditions: NAFLD; NASH
• Intervention / Treatment: Procedure: extra blood sampling

Detailed Description

The study aims to significantly enhance diagnostic innovation and contribute to the existing literature on the stratification of cACLD caused by metabolic-dysfunction liver disease, a major factor leading to cirrhosis, liver cancer, and liver transplant in individuals with non-communicable diseases. By integrating radiomics, digital pathology, non-invasive scores, and omics the results are expected to provide novel evidence for diagnostic advancements.

The incorporation of AI is anticipated to lead to more efficient diagnostic management, effectively addressing the impact of cACLD on healthcare systems. The outcomes of this research will yield a substantial database and intellectual content, both of which will be made available to the scientific community and multiple stakeholders, including patient associations, policymakers, healthcare providers, and industry players.

The primary goal is to foster innovation in diagnostics and mitigate the impact of cACLD on national health systems. By accurately predicting individuals at higher risk of liver or extra-hepatic complications, this study aims to revolutionize diagnostic methods, ultimately leading to improved patient outcomes and resource optimization in healthcare settings.

• Study Type: Interventional
• Enrollment (Estimated): 408
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Luca Miele; Phone Number: +390630157717; Email: luca.miele@policlinicogemelli.it

Study Locations

• Italy
  • Roma, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS, UOC Medicina Interna e Trapianto di Fegato
    • Principal Investigator: Luca Miele
    • Contact: Luca Miele; Phone Number: +390630157717; Email: luca.miele@policlinicogemelli.it
    • Sub-Investigator: Antonio Liguori

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• age>=18; sex (M,F);
• dysmetabolic liver disease according new nomenclature definition;
• suspicion of cACLD by LSM>=10 with VCTE;
• routine esogastroduodenoscopy report within 12 months of VCTE for identification of high-risk varices (HRV).

Exclusion Criteria:

• portal vein thrombosis,
• infiltrative liver neoplasms, and conditions are known for their potential influence on the LSM results (congestive liver disease, extrahepatic biliary obstruction, ALT > 5x upper normal limit).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: patients with MASLD and LSM>=10kPa; To set an interventional prospective, cohort study where individuals will have a liver health check to identify cACLD. We will exclude subjects with decompensation (ascites, encephalopathy, gastrointestinal bleeding, or in case of the presence of transjugular intrahepatic portosystemic shunt). We aim to recruit a prospective cohort and randomize after the end of the study to derivation (2/3) and validation cohort (1/3). The cohort will be stratified according to the presence of Type 2 diabetes (T2D) and obesity (BMI>= 30Kg/m2).

Procedure: extra blood sampling; search for biomarkers for the prevention of liver disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of patients identified with single diagnostic method	evaluate the efficacy of risk-stratification pathways for cACLD detection and outcome prediction in adults (age>18 years) with dysmetabolic liver disease in a tertiary care setting.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of patients identified with innovative diagnostic method omic-based	evaluate the possible integration of liquid biopsy for cACLD detection and outcome prediction	24 months

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Luca Miele, Fondazione Policlinico Universitario A. Gemelli, IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: July 11, 2024
• First Submitted That Met QC Criteria: March 14, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 14, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: 6843

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No