AGILE 3+ Score for the Diagnosis of Advanced Fibrosis and for Predicting Liver-related Events in NAFLD

Abstract

Background & aims: We aimed to assess the diagnostic accuracy of AGILE 3+, a recently developed score based on the combination of aspartate aminotransferase/alanine aminotransferase ratio, platelet count, diabetes status, sex, age, and liver stiffness measurement (LSM) by transient elastography, when compared with Fibrosis-4 (FIB-4) and LSM, for the diagnosis of advanced fibrosis and for the prediction of liver-related events (LREs) occurrence in patients with NAFLD.

Methods: A total of 614 consecutive patients with biopsy-proven NAFLD or clinical diagnosis of NAFLD-related compensated cirrhosis were enrolled. LREs were recorded during follow-up. FIB-4, LSM by transient elastography (FibroScan device), and AGILE 3+ were measured. The diagnostic performance of noninvasive criteria for advanced fibrosis and for the prediction of LREs was assessed using the area under the receiver operating characteristic curve (AUROC) and decision curve analysis.

Results: In patients with biopsy-proven NAFLD (n = 520), LSM and AGILE 3+ had higher AUROC than FIB-4 (0.88 for LSM and AGILE 3+ vs 0.78 for FIB-4; P < .001) for advanced fibrosis, and AGILE 3+ exhibited a smaller indeterminate area in the test (25.2% for FIB-4 vs 13.1% for LSM vs 8.3% for AGILE 3+). Within the entire cohort of patients, AGILE 3+ had significantly higher AUROC for predicting LREs with respect to LSM (AUROC 36 months 0.95 vs 0.93; P =.008; 60 months 0.95 vs 0.92; P = .006; 96 months 0.97 vs 0.95; P = .001). Decision curve analysis showed that all scores had modest net benefit for ruling-out advanced fibrosis at the risk threshold of 5% to 10% where advanced fibrosis was absent. At the risk threshold of 5% of false negatives or false positives in LRE at 36, 60, 96, and 120 months, AGILE 3+ outperformed both FIB-4 and LSM for ruling out LRE.

Conclusions: Depending on resource availability, clinical setting, and the risk scenarios, AGILE 3+ is an accurate and valid alternative to FIB-4 and LSM for the noninvasive assessment of disease severity and prognosis in patients with NAFLD.

Keywords: AGILE 3+; DCA; Fibrosis; NAFLD; NASH.