AGILE 3+ and AGILE 4 Accurately Identify Advanced Fibrosis and Cirrhosis in Indian MASLD: JCEH | August 2026

Introduction:

Accurate fibrosis assessment is central to risk stratification in MASLD, but commonly used non-invasive tests (NITs) often leave many patients in an indeterminate “grey zone.” This multicenter ICON-D study validated AGILE 3+ and AGILE 4 for detecting advanced fibrosis and cirrhosis in Indian patients using liver biopsy as the reference standard.

Why was this study needed?

Fibrosis is the strongest predictor of liver-related outcomes in MASLD.

Common NITs such as FIB-4, NFS and APRI are better at ruling out than confidently ruling in advanced disease.

Large grey zones frequently lead to additional testing or liver biopsy.

AGILE scores required validation in the large and diverse Indian MASLD population.

Results:

Among 381 biopsy-confirmed patients from 35 centers, AGILE 3+ performed well for advanced fibrosis (≥F3), while AGILE 4 showed high specificity for cirrhosis (F4).

Both AGILE scores had substantially smaller grey zones than APRI, FIB-4, NFS and liver stiffness measurement (LSM).

A sequential strategy of LSM followed by AGILE 3+/4 further improved diagnostic performance while keeping the indeterminate group small.

Overall, AGILE scores performed comparably to LSM while providing better patient classification.

Clinical Impact:

This large Indian validation supports AGILE 3+ and AGILE 4 as practical tools for confidently identifying advanced fibrosis and cirrhosis in MASLD. Their greatest advantage is the smaller grey zone, potentially reducing unnecessary liver biopsies and helping identify patients requiring specialist care, surveillance, or pharmacotherapy.

Bottom Line:

AGILE 3+ and AGILE 4 are validated, clinically useful fibrosis tools in Indian MASLD. Combining liver stiffness measurement with AGILE scoring provides an effective sequential strategy for identifying advanced fibrosis and cirrhosis while minimizing diagnostic uncertainty.