Validation of AGILE-3+ Score for Assessing Advanced Fibrosis in Indian Patients with Nonalcoholic Fatty Liver Disease (NAFLD): An Interim Analysis of the Multicentric Indian Consortium on NAFLD (ICON D) Study

Background and Aim: Non-invasive tests (NITs) are important tools for ruling-out advanced fibrosis in NAFLD. However, many patients still require liver-biopsy due to the comparatively poor positive predictive value (PPV) and substantial grey-zone associated with NITs. AGILE-3+ score is a novel NIT which includes liver stiffness measurement (LSM) on transient elastography and commonly measured clinical parameters (age, gender, AST, ALT, platelet count and presence or absence of DM). Methods: In an on-going real-life study of ICON-D, interim data across 42 centers over 4 years (n=8043) was analysed to explore the diagnostic accuracy of AGILE-3+ in comparison to APRI, NFS, FIB-4 and LSM among biopsy proven patients with NAFLD. Results: Data on liver-biopsy was available in 381 [males:63.2%, age:42(32-52)] patients. Advanced fibrosis (F3) on biopsy was present in 70 (18.3%) patients. AGILE-3+ score showed good calibration (p=0. 474 on Hosmer-Lemeshow test, 95 % CI of slope: 0.82 to 1.218, 95% CI of x-intercept: -0.05 to 0.04) in our cohort of patients. The AUROC of AGILE-3+ score for discriminating on histology was 0.78 which was significantly higher than that of FIB-4 (0.72, p=0.001) and NFS (0.69, p=0.028) but similar to that of LSM (0.78, p=0.78). The rule in cut-off (0.68) had a PPV of 52.6% with a sensitivity and specificity of 43.4% and 61.6%, respectively. The rule out cut-off (0.45) had a NPV of 91.9% (sensitivity:88.7% and specificity:94.2%). Only 46(12%) patients had an AGILE-3+ score in the grey-zone (0.45-0.68). The proportion of patients in the grey-zone was significantly lower with AGILE-3+ (12%) compared to LSM (29.9%, p<0.001), FIB-4 (37.5%, p<0.001), NFS (27.5%, p<0.001) and APRI (56.4%, p<0.001). Conclusion: The AGILE-3+ score showed good calibration and AUROC for detecting advanced fibrosis (F3) on histology. The impressive PPV and substantial reduction in grey-zone may help in reducing the number of patients requiring confirmatory liver biopsy.