Global Consensus for MASLD Risk Stratification and Therapy : Clin Gastroenterol Hepatol | May 2026

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) have emerged as dominant causes of chronic liver disease worldwide, paralleling the epidemics of obesity and type 2 diabetes. Fibrosis stage remains the strongest determinant of liver-related and overall mortality, shifting modern management toward fibrosis-centered care. With recent approval of resmetirom and semaglutide for noncirrhotic MASH with F2–F3 fibrosis, there is a growing need for standardized, noninvasive, globally applicable treatment algorithms.

Problem Statement

Clinical practice remains heterogeneous regarding the use of noninvasive tests (NITs), thresholds for treatment initiation and definitions of therapeutic response. Existing guidance varies across regions, while advanced imaging modalities remain inaccessible in many routine practice settings. Furthermore, the expanding therapeutic landscape requires practical strategies integrating fibrosis risk stratification, cardiometabolic profiling and longitudinal treatment monitoring.

Summary

This updated international Delphi consensus involved 40 multidisciplinary global experts who reviewed emerging evidence from 2025 onward to establish standardized recommendations for MASLD management. The panel strongly endorsed a sequential fibrosis-based approach using Fibrosis-4 Index (FIB-4) as the preferred first-line screening test, followed by vibration-controlled transient elastography (VCTE) or Enhanced Liver Fibrosis (ELF) testing for secondary risk stratification.

For ELF testing, values below 9.2 were considered low risk for advanced fibrosis, whereas ELF ≥9.2 warranted hepatology referral and treatment consideration. Most experts favored higher treatment thresholds between 9.8 and 10.5 to improve specificity. ELF values >11.3 were considered suggestive of cirrhosis, making initiation of resmetirom or semaglutide inappropriate. For VCTE, liver stiffness <8 kPa indicated low risk, while values between 10–15 kPa represented the preferred therapeutic window for initiating pharmacologic therapy in noncirrhotic F2–F3 disease. Liver stiffness ≥20 kPa suggested cirrhosis and contraindicated treatment initiation with currently approved agents.

The consensus emphasized individualized pharmacologic selection through shared decision-making. Semaglutide was generally preferred in treatment-naïve patients with coexisting obesity or type 2 diabetes because of its cardiometabolic benefits, whereas resmetirom was favored in patients already receiving GLP-1 receptor agonists. Upfront combination therapy with semaglutide and resmetirom was not recommended because of insufficient evidence, although sequential addition of the alternate agent for suboptimal responders was considered reasonable.

Importantly, the document established objective response-monitoring criteria using NITs. A therapeutic response after approximately one year was defined as either a ≥30% reduction in liver stiffness on VCTE or a ≥0.5-point reduction in ELF score. Conversely, worsening fibrosis was defined as a >30% increase in liver stiffness or >0.5 increase in ELF, ideally confirmed using a second concordant NIT before treatment modification.

The consensus also reinforced that lifestyle optimization remains foundational even in the era of pharmacologic therapy. Mediterranean-style dietary patterns, minimization of ultra-processed foods, structured aerobic and resistance exercise, and sustained weight reduction remain critical components of management. The authors particularly highlighted the risk of lean muscle loss during GLP-1RA-induced weight reduction and emphasized the importance of adequate protein intake and resistance training to prevent sarcopenic obesity.

Overall, this consensus provides one of the first globally harmonized, fibrosis-centered, NIT-driven clinical algorithms integrating recently approved therapies into routine MASLD practice. The recommendations aim to standardize care pathways while maintaining flexibility for individualized cardiometabolic and hepatic risk assessment.