Updated Global Consensus Recommendations for Risk Stratification, Treatment Initiation, and Response Monitoring in Metabolic Dysfunction-Associated Steatotic Liver Disease.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) have increased in prevalence alongside the global epidemics of obesity and type 2 diabetes and now represent one of the leading causes of chronic liver disease. Patients with MASLD and significant fibrosis (≥F2) are at increased risk for adverse outcomes. With advances in noninvasive tests (NITs) and the recent approval of resmetirom and semaglutide for noncirrhotic MASH with F2-F3 fibrosis, we provide updated consensus guidance on standardized risk stratification, treatment initiation, and response monitoring.

METHODS: A structured Delphi process was conducted following a systematic updated literature review (January 2025-November 2025), covering the period since publication of the initial consensus recommendations, and included iterative anonymous voting among 40 international experts representing hepatology, gastroenterology, endocrinology, internal medicine, and primary care. Consensus was predefined as ≥70% agreement.

RESULTS: Forty-two statements were developed; 86% achieved consensus in the first round, and all remaining statements reached consensus after refinement and the second round. The panel endorsed a sequential risk-stratification strategy beginning with Fibrosis-4 Index (FIB-4) as the first-line assessment, followed by vibration-controlled transient elastography or Enhanced Liver Fibrosis (ELF) testing for secondary stratification. Treatment consideration with resmetirom or semaglutide was supported for noncirrhotic MASLD with liver stiffness measurement values of 10 to 20 kPa or ELF values of 9.2 to 11.3, after exclusion of cirrhosis. Upfront combination therapy with both drugs was not recommended. Selection of pharmacologic therapy was to be determined through shared decision-making between patient and provider and individualized according to the patient's cardiometabolic profile. Treatment response at 1 year was defined as a ≥30% reduction in liver stiffness or a ≥0.5-point reduction in ELF.

CONCLUSIONS: This updated international consensus provides practical algorithms that integrate most commonly used noninvasive testing with recently approved pharmacologic therapies for MASLD, addressing current variability in clinical practice and supporting standardized implementation of risk-based care.