Objective: To review the clinical utility and diagnostic accuracy of non-invasive liver fibrosis assessment using the PRO-C3 biomarker and the ADAPT algorithm in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).
Methods: Literature and clinical studies from major international guidelines (EASL 2024, APASL 2025) and multicenter clinical validation trials were synthesized to evaluate the diagnostic accuracy of PRO-C3 and the ADAPT algorithm compared to liver biopsy and other non-invasive tests.
Results: PRO-C3 directly measures active fibrogenesis by quantifying the N-terminal propeptide of type III collagen cleaved by disease-specific N-protease. The ADAPT algorithm integrates four accessible inputs: PRO-C3, patient age, diabetes status, and platelet count. In a European multicenter validation cohort (n = 683), the ADAPT algorithm achieved superior area under the curve (AUC) compared to PRO-C3 alone: 74.3% for significant fibrosis (F2-F4), 80.3% for advanced fibrosis (F3-F4), and 85.4% for cirrhosis (F4). Leveraging a high specificity strategy (ranging from 80.4% to 90.0% at corresponding cut-offs of 9.0, 10.0, and 11.0), ADAPT effectively minimizes false positive rates associated with initial screening markers such as FIB-4.
Conclusion: The PRO-C3 biomarker integrated into the ADAPT algorithm represents an advanced and highly specific non-invasive tool for staging liver fibrosis in MASLD. It provides a reliable second-step screening solution that optimizes clinical resources and prevents unnecessary transient elastography (VCTE) referrals.