Validation of AGILE-4 Score for Assessing Cirrhosis 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 cirrhosis 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-4 score is a novel NIT which includes liver stiffness measurement (LSM) on transient elastography and commonly measured clinical parameters (gender, AST, ALT, platelet count and presence or absence of diabetes mellitus). 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-4 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. Cirrhosis (F4) on biopsy was present in 38 (9.97%) patients. AGILE-4 score showed good calibration (p=0.147 on Hosmer-Lemeshow test, 95 % CI of slope: 0.79 to 1.166, 95% CI of x-intercept: -0.041 to 0.028) in our cohort of patients. The AUROC of AGILE-4 for discriminating cirrhosis on histology was 0.81 which was significantly higher than that of APRI [0.66, p<0.001] and NFS [0.67, p=0.017] but similar to that of FIB-4 [0.76, p=0.154] and LSM [0.79, p=0.50]. The rule-in AGILE-4 cut-off (0.565) had a PPV of 52.6% with a sensitivity and specificity of 39.2% and 65.6%, respectively. The rule-out cut-off (<0.251) had a negative predictive value of 95.8% (sensitivity:93.4% and specificity:97.3%). Only 54(14.1%) patients had an AGILE-4 score in the grey-zone (0.251-0.565). Proportion of patients in the grey-zone with AGILE-4 (14.1%) was significantly lower than with FIB-4 (32.8%, p<0.001), NFS (27.5%, p<0.001) and APRI (56.4%, p<0.001) but similar to LSM (12.8%, p=0.67). Conclusion: AGILE-4 score has similar AUROC compared to LSM and FIB-4 for detecting cirrhosis on histology and does not help to reduce the grey-zone in comparison to LSM.