Global performance of non-invasive tests in MASLD: Insights from the G-MASLD study

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent worldwide. Performance of non-invasive tests (NITs) in patients with MASLD recruited from different regions of the world was evaluated. METHODS: MASLD patients with liver biopsies and NIT data [fibrosis-4 index (FIB-4), enhanced liver fibrosis (ELF), and liver stiffness measurement (LSM)] were enrolled through the Global NASH Council collaboration (G-MASLD). FibroScan-AST (FAST) and Agile-3+/Agile-4 were calculated. NITs' performance for predicting ≥F2 (significant fibrosis), ≥F3 (advanced fibrosis), or cirrhosis (F4) was determined in patients from different regions. RESULTS: A total of 17,792 MASLD patients from 41 countries were included: 14% had F0, 32% F1, 18% F2, 22% F3, 13% F4 (cirrhosis); 48% NAS ≥5. Advanced fibrosis prediction by NITs was variable across regions for FIB-4 [pooled AUC (95% CI)=0.80 (0.79-0.81)], the lowest in Latin America [0.75 (0.71-0.79)], the highest in MENA [0.84 (0.82-0.87)], and ELF [pooled AUC=0.77 (0.76-0.79)], the lowest in Europe [0.72 (0.69-0.76)], the highest in North America [0.80 (0.78-0.82)]. Prediction of advanced fibrosis by LSM [pooled AUC=0.84 (0.83-0.85)] was similar across regions except North America [0.78 (0.76-0.81)]. In addition, FAST [AUC=0.75 (0.74-0.76)] and Agile-3+ [AUC=0.87 (0.86-0.88)] performed similarly across regions. Similar trends were observed for the NITs predicting significant fibrosis. Finally, the accuracy of Agile-4 for predicting cirrhosis [AUC=0.90 (0.89-0.91)] was the lowest in North America [0.85 (0.83-0.87)], the highest in MENA [0.96 (0.94-0.98)]. CONCLUSIONS: The diagnostic performance of common NITs for fibrosis in MASLD varies across the world. In the large multinational G-MASLD sample, the most accurate NITs were Agile-3+ and Agile-4 composite scores.