Agile scores are a good predictor of liver-related events in patients with NAFLD.

Agile scores are a good predictor of liver-related events in patients with NAFLDJournal of HepatologyPreviewWe have read with great interest the recent paper by Sanyal et al., wherein they developed new FibroScan-based scores, Agile 4 and Agile 3+, to identify cirrhosis and advanced fibrosis (AF) (F≥3) in patients with non-alcoholic fatty liver disease (NAFLD), using several large international cohorts.1 Importantly, this new approach is primarily focused on reducing the proportion of patients with indeterminate results and improving the positive predictive value to rule-in cirrhosis or AF. Full-Text PDF Enhanced diagnosis of advanced fibrosis and cirrhosis in individuals with NAFLD using FibroScan-based Agile scoresJournal of HepatologyVol. 78Issue 2PreviewCurrently available non-invasive tests, including fibrosis-4 index (FIB-4) and liver stiffness measurement (LSM by VCTE), are highly effective at excluding advanced fibrosis (AF) (F ≥3) or cirrhosis in people with non-alcoholic fatty liver disease (NAFLD), but only have moderate ability to rule-in these conditions. Our objective was to develop and validate two new scores (Agile 4 and Agile 3+) to identify cirrhosis or AF, respectively, with optimized positive predictive value and fewer indeterminate results, in individuals with NAFLD attending liver clinics. Full-Text PDF Open Access We thank Nakastuka and colleagues for their results that provide independent validation of the diagnostic accuracy of the new Agile scores.[1]Nakatsuka T. Tateishi R. Sato M. Fujishiro M. Koike K. Agile scores are a good predictor of liver-related events in patients with NAFLD.J Hepatol. 2023; S0168-8278: 00161-00167Google Scholar We were also very interested by their results showing a good prognostic accuracy for Agile 3+ and Agile 4 in their cohort of patients with non-alcoholic fatty liver disease (NAFLD). We evaluated whether these results can be reproduced in 341 patients with NAFLD retrospectively included at Angers University Hospital (France). The outcome evaluated was liver-related events (LREs), a composite endpoint combining cirrhosis complications (ascites, variceal bleeding, occurrence of at-risk bleeding varices, jaundice, encephalopathy) or hepatocellular carcinoma. None of the patients had previous history of LREs before inclusion, and LREs during the follow-up period were ascertained by chart review. Fibrosis-4 (FIB-4), vibration-controlled transient elastography (VCTE) with the FibroScan device, Agile 3+ and Agile 4 were available for all patients at baseline. Each non-invasive test stratified patients into three risk groups (low-risk, intermediate risk, high-risk) according to their published thresholds: <1.30 and >2.67 for FIB-4[2]Shah A.G. Lydecker A. Murray K. Tetri B.N. Contos M.J. Sanyal A.J. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease.Clin Gastroenterol Hepatol. 2009; 7: 1104-1112Abstract Full Text Full Text PDF PubMed Scopus (907) Google Scholar; <10 kPa and >15 kPa for VCTE (Baveno thresholds)[3]de Franchis R. Bosch J. Garcia-Tsao G. Reiberger T. Ripoll C. Baveno V.I.I.F. Baveno VII - renewing consensus in portal hypertension.J Hepatol. 2022; 76: 959-974Abstract Full Text Full Text PDF PubMed Scopus (436) Google Scholar; <0.451 and ≥0.679 for Agile 3+[4]Sanyal A.J. Foucquier J. Younossi Z.M. Harrison S.A. Newsome P.N. Chan W.K. et al.Enhanced diagnosis of advanced fibrosis and cirrhosis in individuals with NAFLD using FibroScan-based Agile scores.J Hepatol. 2023; 78: 247-259Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar; <0.251 and ≥0.565 for Agile 44. Median age at baseline was 58 years (IQR 51-63), median BMI was 30.8 kg/m2 (IQR 27.8-34.4), median FIB-4 was 1.36 (IQR 1.00-1.98), and median VCTE was 8.8 kPa (6.3-13.3). 65% of the patients were male and 36% had diabetes. The proportion of patients included in the low-/intermediate-/high-risk groups with FIB-4, VCTE, Agile 3+ and Agile 4 were, respectively: 43%/46%/11%, 57%/23%/20%, 56%/15%/29%, and 83%/9%/8%. LREs occurred in 27 (8%) patients after a median follow-up of 5.2 years (IQR 2.9-7.2). Agile 3+ and Agile 4 provided higher time-dependent ROC curves than VCTE or FIB-4 for LRE prediction (Fig. 1A). Kaplan-Meier curves for FIB-4 and VCTE show significant differences for all paired comparisons between low-, intermediate-, and high-risk groups (Fig. 1B,C). On the contrary, the difference was significant only for high-risk vs. other groups with Agile 3+ and Agile 4, demonstrating these two tests differentiated a single subset of patients with impaired prognosis (Fig. 1D,E). Interestingly, most of the patients who experienced LREs during the follow-up were included in the high-risk group with Agile 3+ (23 of 27 patients, 85%), vs. only 10 (37%) in the high-risk FIB-4 group, 15 (56%) in the high-risk VCTE group, and 12 (44%) in the high-risk Agile 4 group. Because Agile 3+ and Agile 4 both include the same biomarkers and can be calculated at the same time, we evaluated a patient stratification based on the combination of these two tests: low-risk group (Agile 3+ <0.679), high-risk group (Agile 3+ ≥0.679 and Agile 4 <0.565), and very high-risk group (Agile 3+ ≥0.679 and Agile 4 ≥0.565). The proportion of patients included in these three groups were respectively 71%, 21% and 8%. LREs occurred in four patients (1.7%) from the low-risk group, 11 patients (15%) from the high-risk group, and 12 patients (44%) from the very high-risk group (Fig. 1F). As in the cohort from Japan, Agile 3+ and Agile 4 showed good prognostic accuracy in our NAFLD cohort from Europe. The association of Agile 3+ and Agile 4 improves the prognosis assessment. Further studies with large sample sizes and long-term follow-up are needed to develop a fine-tuned liver risk stratification using non-invasive tests in NAFLD. The authors received no financial support to produce this manuscript. Jerome Boursier: Board advisory and research grants to his institution from EchoSens. Marine Roux: none. Arun Sanyal: Grant to his institution from EchoSens. Please refer to the accompanying ICMJE disclosure forms for further details. JB: manuscript writing; MR: data curation and analysis; AS: critical revision. The following are the supplementary data to this article: Download .pdf (.26 MB) Help with pdf files Multimedia component 1