Agile 3+ and 4 Scores Accurately Predict Major Adverse Liver Outcomes, Liver Transplant, Progression of MELD Score, the Development of Hepatocellular Carcinoma, and Death in NAFLD

Background and Aims: Based on liver stiffness measurement by vibration controlled transient elastography (LSM by VCTE), the Agile 3+ and 4 are novel noninvasive scores that accurately identify advanced fibrosis (≥ F3) and cirrhosis (F4), respectively. We investigated and compared the Agile 3+ and 4 scores’ performances in predicting adverse events to LSM alone, FIB-4 and Fibroscan-AST (FAST) score. Method: This retrospective analysis included NAFLD patients with LSM by VCTE and laboratory testing from a tertiary care center from 2013 to 2022. Adverse events were defined as major adverse liver outcomes (MALO), hepatocellular carcinoma, liver transplant, and death. MALO was defined as ascites, hepatic encephalopathy, or esophageal variceal bleeding. We used the Cox proportional hazard rate model and the Harrell’s concordance (C) statistic to compare predictive performances. Results: 733 total subjects with median follow-up of 27.0 months were included. Average age was 58.1 years and 32.8% had type 2 diabetes. Average alanine aminotransferase was 46.6 IU/L, aspartate aminotransferase: 34.5 IU/L, albumin: 4.4 g/dL, and platelets: 241.1 × 10⁹/L. Fourteen subjects had 21 adverse outcomes, including 10 MALO, 5 HCC, 4 liver transplants, 3 progression of MELD score, and 6 deaths. Agile 3+ and 4 respectively had the highest C stats of 0.911 (C stat SE 0.028) and 0.909 (C stat SE 0.029) compared to LSM (C stat 0.857, C stat SE 0.045), FIB-4 (C stat 0.843, C stat SE 0.037) or FAST (C stat 0.703, C stat SE 0.085). Conclusion: The Agile 3+ and 4 scores had the highest likelihood of accurately predicting adverse outcomes including MALO and death compared to LSM alone, FIB-4 or FAST score.