Agile scores in MASLD and ALD: External validation and their utility in clinical algorithms

Background Agile scores, including liver stiffness measurements (LSM) and routine clinical/laboratory biomarkers, have been developed for advanced fibrosis (F≥3) and cirrhosis, respectively, in patients with metabolic-associated steatotic liver disease (MASLD). We independently validated the diagnostic accuracy of these scores in MASLD, alcohol-related liver disease (ALD) and chronic hepatitis B or C (CHB/C) and assessed them in clinical algorithms with FIB-4 and LSM. Methods We included 4,243 patients (MASLD:912, ALD:386, CHB:597, CHC:2348) with LSM, liver biopsy and laboratory tests within 6 months. FIB-4, Agile 3+ and Agile 4 scores were calculated. Results For F≥3, diagnostic accuracy of Agile 3+ and LSM were similar in MASLD (AUC: 0.86 vs 0.86, P=0.831) and ALD (0.92 vs 0.94, P=0.123). For cirrhosis, Agile 4 was similar to LSM in MASLD (0.89 vs 0.90, P=0.412) and ALD (0.94 vs 0.95, P=0.513). Agile 3+/4 performed worse than LSM in CHB/C. Using predefined dual thresholds of 90% Se/Sp, correct classification rates in MASLD were 66% vs 61% using Agile 3+ vs LS dual cut-offs and 71% vs 67% in ALD. When using Agile 3+ or LSM as a second step after FIB-4>1.3, correct classification rates were higher with Agile 3+ than LSM, both for MASLD (75% vs 71%) and for ALD patients (76% vs 72%) with fewer indeterminate results. Positive agreement of LSM and Agile 3+/4 significantly increased the specificity of a diagnosis of advanced fibrosis/cirrhosis. Conclusion Agile 3+ and Agile 4 have equal diagnostic accuracy with LSM in both MASLD and ALD but result in fewer indeterminate results. Sequential use of FIB-4 and Agile 3+/4 or concurrent Agile 3+/4 and LSM can be used to further optimize F≥3 diagnosis.