Mózes, Ferenc EFerenc EMózesLee, Jenny AJenny ALeeVali, YasamanYasamanValiSelvaraj, Emmanuel AEmmanuel ASelvarajJayaswal, Arjun N AArjun N AJayaswalBoursier, JérômeJérômeBoursierde Lédinghen, VictorVictorde LédinghenLupșor-Platon, MonicaMonicaLupșor-PlatonYilmaz, YusufYusufYilmazChan, Wah-KheongWah-KheongChanMahadeva, SanjivSanjivMahadevaKarlas, ThomasThomasKarlasWiegand, JohannesJohannesWiegandShalimar, ShalimarShalimarShalimarTsochatzis, EmmanouilEmmanouilTsochatzisLiguori, AntonioAntonioLiguoriWong, Vincent Wai-SunVincent Wai-SunWongLee, Dae HoDae HoLeeHolleboom, Adriaan GAdriaan GHolleboomvan Dijk, Anne-MariekeAnne-Mariekevan DijkMak, Anne LindeAnne LindeMakHagström, HannesHannesHagströmAkbari, CamillaCamillaAkbariHirooka, MasashiMasashiHirookaLee, Dong HyeonDong HyeonLeeKim, WonWonKimOkanoue, TakeshiTakeshiOkanoueShima, ToshihideToshihideShimaNakajima, AtsushiAtsushiNakajimaYoneda, MasatoMasatoYonedaThuluvath, Paul JPaul JThuluvathLi, FengFengLiBerzigotti, AnnalisaAnnalisaBerzigotti0000-0003-4562-9016Mendoza Jaimes, Yuly PaulinYuly PaulinMendoza Jaimes0000-0003-4595-4724Noureddin, MazenMazenNoureddinTruong, EmilyEmilyTruongFournier-Poizat, CélineCélineFournier-PoizatGeier, AndreasAndreasGeierTuthill, TheresaTheresaTuthillYunis, CarlaCarlaYunisAnstee, Quentin MQuentin MAnsteeHarrison, Stephen AStephen AHarrisonBossuyt, Patrick MPatrick MBossuytPavlides, MichaelMichaelPavlides2024-10-262024-10-262024-08https://boris-portal.unibe.ch/handle/20.500.12422/176521BACKGROUND & AIMS There is a need to reduce the screen failure rate (SFR) in metabolic dysfunction-associated steatohepatitis (MASH) clinical trials (MASH+F2-3; MASH+F4) and identify people with high-risk MASH (MASH+F2-4) in clinical practice. We aimed to evaluate non-invasive tests (NITs) screening approaches for these target conditions. METHODS This was an individual participant data meta-analysis for the performance of NITs against liver biopsy for MASH+F2-4, MASH+F2-3 and MASH+F4. Index tests were the FibroScan-AST (FAST) score, liver stiffness measured using vibration-controlled transient elastography (LSM-VCTE), the fibrosis-4 score (FIB-4) and the NAFLD fibrosis score (NFS). Area under the receiver operating characteristics curve (AUROC) and thresholds including those that achieved 34% SFR were reported. RESULTS We included 2281 unique cases. The prevalence of MASH+F2-4, MASH+F2-3 and MASH+F4 was 31%, 24% and 7%, respectively. Area under the receiver operating characteristics curves for MASH+F2-4 were .78, .75, .68 and .57 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F2-3 were .73, .67, .60, .58 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F4 were .79, .84, .81, .76 for FAST, LSM-VCTE, FIB-4 and NFS. The sequential combination of FIB-4 and LSM-VCTE for the detection of MASH+F2-3 with threshold of .7 and 3.48, and 5.9 and 20 kPa achieved SFR of 67% and sensitivity of 60%, detecting 15 true positive cases from a theoretical group of 100 participants at the prevalence of 24%. CONCLUSIONS Sequential combinations of NITs do not compromise diagnostic performance and may reduce resource utilisation through the need of fewer LSM-VCTE examinations.enFAST FIB‐4 LSM‐VCTE MASH NFS at‐risk MASH non‐invasive tests600 - Technology::610 - Medicine & healtharticle10.48350/1956783857303410.1111/liv.15914