Emerging Indices Outperform Traditional Fibrosis Scores in Young Metabolic Dysfunction-Associated Steatotic Liver Disease Across Divergent Screening Goals.

BACKGROUND: Although numerous noninvasive indices have been proposed to assess significant fibrosis (SF), none have been validated specifically in young adults with metabolic dysfunction-associated steatotic liver disease (MASLD). This study evaluated their performance in younger patients across two cohorts with distinct screening goals. METHODS: We retrospectively analyzed two MASLD cohorts: a primary care (PC) cohort (n = 972) and a tertiary care (TC) cohort (n = 342). SF was defined as liver stiffness ≥ 7.0 kPa on vibration-controlled transient elastography. The diagnostic performance of emerging indices-fibrosis-8 index, steatosis-associated fibrosis estimator, metabolic-associated fibrosis score-5-was compared with traditional scores-fibrosis-4 index, aspartate aminotransferase-to-platelet ratio index, and nonalcoholic fatty liver disease fibrosis score. RESULTS: Across both settings, emerging indices consistently outperformed traditional scores for SF discrimination. The areas under the receiver operating characteristic curves were higher for the emerging indices than for the traditional indices in both cohorts. Decision curve analyses demonstrated that emerging indices provided greater net clinical benefit and larger reductions in unnecessary procedures, with thresholds differing by setting such that lower thresholds favored referral in the PC cohort, whereas higher thresholds were more appropriate for biopsy decisions in the TC cohort. Conventional cutoffs widely used in practice demonstrated limited sensitivity in this population, suggesting that refinement may be required. CONCLUSIONS: Traditional noninvasive fibrosis indices showed limited performance in young adults with MASLD, whereas emerging indices appeared more suitable for achieving the screening goals of referral in PC and biopsy decision-making in TC.