PharmaNest, in collaboration with Virginia Commonwealth University (VCU) and the National Institutes of Health (NIH), has launched the Digital Pathology and AI for Liver Outcomes Study-2 (DPAILO-2), a confirmatory retrospective analysis involving 1,765 patients with metabolic dysfunction-associated steatohepatitis (MASH), part of the NASH Clinical Research Network’s (NASH CRN) DB2 cohort. The study aims to validate the prognostic accuracy of PharmaNest’s AI-powered FibroNest Ph-FCS biomarker—a continuous, high-resolution fibrosis score derived from single-fiber analysis of digital liver biopsy images. The research leverages ultra-high-resolution, Masson’s Trichrome-stained slides processed using PharmaNest’s proprietary AI platform, enabling precise quantification of fibrosis progression at the microscopic level. The primary objective is to assess whether Ph-FCS can predict hepatic decompensation more effectively than traditional fibrosis staging or non-invasive tests. Secondary goals include comparative evaluations against current clinical benchmarks and exploratory use of FibroMAP, a spatial clustering tool, to identify novel fibrosis risk phenotypes from paired biopsies. VCU will manage study governance, compliance, and statistical analysis, while PharmaNest will deliver AI-derived biomarkers within the 2025 timeline. The NIH’s NASH CRN provides clinical oversight and ensures adherence to network-wide research standards. The project builds on prior validation of Ph-FCS in over 400 patients with more than a decade of follow-up, reinforcing its potential as a regulatory-grade digital biomarker. The findings could significantly enhance precision in liver disease monitoring, support clinical decision-making, and accelerate therapeutic development in MASLD. Industry experts highlight the study’s transformative potential. Dr. Arun Sanyal, lead investigator at VCU, emphasizes the importance of robust, objective histological biomarkers in guiding patient care and drug trials. Dr. David Kleiner of NIH underscores the synergy between NASH CRN’s clinical depth and PharmaNest’s AI innovation, calling it a pivotal step toward quantitative, reproducible liver assessment. Dr. Mathieu Petitjean, CEO of PharmaNest, views the study as a milestone in validating continuous biomarkers and advancing spatial pathology tools. PharmaNest, a leader in AI-driven digital pathology, specializes in single-fiber analysis for fibrosis and inflammation, with applications in both preclinical and clinical research. VCU’s Stravitz-Sanyal Institute is a key hub for liver and metabolic disease innovation, while the NIH-funded NASH CRN remains a central force in advancing NAFLD/MASLD research. This collaboration exemplifies the growing integration of AI and digital pathology into mainstream clinical research, promising more accurate, scalable, and personalized approaches to liver disease management.