Aligned ELF and VCTE cutoffs facilitate risk staging in patients with metabolic dysfunction-associated...

Clinical practice guidance for non-invasive test (NIT)-based management of metabolic dysfunction-associated steatohepatitis (MASH) includes the Enhanced Liver Fibrosis (ELF) Test and vibration-controlled transient elastography (VCTE). However, recommended thresholds were derived independently and not calibrated to yield equivalent liver-related event (LRE) risk across tests. We aimed to identify ELF and VCTE cutoffs that are aligned prognostically and to evaluate whether agreement-based combinations at aligned thresholds improve near-term risk stratification.

Individual-level data were pooled from patients across placebo-controlled trials of MASH and advanced fibrosis. Baseline ELF and VCTE were evaluated in relation to subsequent LREs and histological change at 1 year. Prognostic alignment was performed by identifying VCTE thresholds with observed LRE risks corresponding to pre-specified ELF cutoffs. Prognostic performance of single tests and ELF/VCTE combinations was assessed using event risk, likelihood ratios, Kaplan-Meier analysis, and discrimination metrics (C-index and ROC/AUC).

Risk-aligned pairings supported ELF 9.80/VCTE 12.0 kPa, ELF 10.50/VCTE 20.0 kPa and ELF 11.30/VCTE 30.0 kPa. Agreement-based ELF/VCTE stratification improved discrimination versus VCTE alone (AUROC 0.779 vs 0.705; p=0.0129). At ELF 11.30/VCTE 30.0 kPa, LRE risk increased across negative concordance, discordance, and positive concordance strata (1.3%, 5.4%, and 21.6%, respectively). For prediction of histological change using ELF 9.80/VCTE 12.0 kPa, F3-to-F4 progression rates were 2.2%, 14.4%, and 25.5%, and F4 regression rates were 56.9%, 27.3%, and 12.2% across negative concordance, discordance, and positive concordance strata, respectively.

ELF and VCTE thresholds can be aligned for comparable prognostic risk staging in advanced MASH. Agreement-based combinations of ELF and VCTE at aligned thresholds may help refine prediction of near-term liver-related events and histological change, supporting clinical risk assessment and informing MASH clinical trial enrichment strategies.

Current MASH care pathways increasingly rely on non-invasive tests, yet recommended ELF and VCTE thresholds have largely been established independently. We found that ELF and VCTE thresholds can be aligned according to comparable risk and that concordant and discordant test results provide clinically meaningful stratification of both liver-related outcomes and likelihood of histological progression and regression. These findings may help support more consistent risk assessment and patient stratification across clinical practice and research settings.