Expert Delphi Consensus on Surrogate Endpoints for Treatment Assessment in Metabolic Dysfunction-associated Steatohepatitis

Background & Aims The growing burden of metabolic dysfunction-associated steatohepatitis (MASH) and the urgency for effective therapies have driven the adoption of surrogate endpoints for treatment evaluation. Consensus on the most appropriate measures for regulatory approval, clinical practice, or reimbursement remains limited. This study aimed to establish expert consensus on appropriate surrogate endpoints and potential surrogate outcome measures in MASH. Methods A modified Delphi process was conducted with 23 international experts across hepatology, gastroenterology, and others. A targeted literature review informed 2 structured survey rounds. Round 1 addressed measures relevant to establishing efficacy/effectiveness for reimbursement; Round 2 explored their application for monitoring treatment effectiveness in clinical practice. Consensus was defined as ≥75% agreement, and strong consensus as ≥95%. The process was conducted and reported in accordance with established frameworks, including Conducting and REporting DElphi Studies (CREDES). Results Histological endpoints—specifically, ≥1-stage fibrosis improvement without MASH worsening, and MASH resolution without fibrosis worsening—were considered appropriate for regulatory/reimbursement settings, mostly owing to current regulatory guidelines. In clinical practice, noninvasive tests (NITs) were preferred. There was consensus that a ≥30% reduction in liver stiffness measurement (LSM) assessed via vibration-controlled transient elastography (VCTE) or magnetic resonance elastography (MRE) is a meaningful indicator of treatment response and reasonably likely translates to improved long-term outcome benefit. Consensus also supported replacing liver biopsy with NITs in practice. Conclusions This international Delphi study highlights histological and NIT-based measures as key for MASH treatment evaluation. It also supports a shift toward NITs—particularly LSM by VCTE or MRE—for disease monitoring in routine practice, with implications for trial design, reimbursement, and clinical guidelines.