A new generation of non-invasive tests of liver fibrosis with improved accuracy in MASLD

Background & Aims The accuracy of non-invasive tests (NITs) should be >= 80% (EASL recommendation). We aimed to compare the accuracies of the recommended NITs for advanced fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD) and to develop NITs with improved accuracy. Methods A total of 1,051 patients with MASLD were allocated to derivation (n = 637) and validation (n = 414) sets. The main outcome (Kleiner F3+F4) was primarily evaluated by accuracy. Recommended NITs included: FIB-4, Fibrotest, FibroMeter, liver stiffness measurement (LSM by Fibroscan), Elasto-FibroMeter (FibroMeter-LSM combination), and ELF (enhanced liver fibrosis) in 396 patients. We used machine learning-optimized multitargeting to develop new NITs: FIB-9 (including nine common biomarkers), FIB-11 (adding two specialized blood markers) and FIB-12 (adding LSM). Results In the whole population, the accuracies of recommended NITs were insufficient: Fibrotest, 68.0%; FIB-4, 71.2%; FibroMeter, 75.1%; LSM, 75.9%; Elasto-FibroMeter, 78.6%. Therefore, new NITs (FIB-9, FIB-11, FIB-12) were developed in the derivation set. In the validation set, AUROCs were: FIB-4, 0.757; Fibrotest, 0.766; FibroMeter, 0.850; LSM, 0.852; FIB-9, 0.863; FIB-11, 0.880; Elasto-FibroMeter, 0.894; FIB-12, 0.912 (p <0.001). The FIB-12 AUROC was superior to the ELF AUROC (0.906 vs. 0.865, p = 0.039). Accuracies were: FIB-4, 68.8%; Fibrotest, 68.6%; LSM, 75.4%; FibroMeter, 76.3%; FIB-9, 78.7%; Elasto-FibroMeter, 79.7%; FIB-11, 80.2%; FIB-12, 83.3% (p <0.001 between all NITs). Scores were segmented by >= 90% sensitivity and specificity cut-offs or NIT match, which individualized subgroups with NIT accuracies >= 80%, e.g. for FIB-9: 85.8% in 68.1% of patients using two cut-offs and 83.2% in 71.7% of patients where FIB-9 agreed with FIB-4. Conclusions Recommended NITs had accuracies <80% for advanced fibrosis in MASLD. Several NIT segmentations individualized subgroups with accuracies >= 80%. New NITs further improved accuracy. The simple FIB-9 (available via a free calculator) provided accuracy equaling or surpassing recommended NITs. FIB-12 outperformed other NITs. (c) 2024 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).