MASLD diagnosis and management guidelines emphasize risk stratification, lifestyle, and approved pharmacotherapies

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly NAFLD, is a rapidly increasing global cause of chronic liver disease. Characterized by fatty liver infiltration with at least one cardiometabolic risk factor, it progresses silently, often leading to severe outcomes like cirrhosis and hepatocellular carcinoma. Current standard-of-care often falls short in early detection and comprehensive management, particularly in primary care settings. This review addresses the critical need for improved diagnostic strategies and effective therapeutic interventions to mitigate long-term adverse outcomes in this high-risk population.

This comprehensive review synthesizes current understanding and provides updated recommendations for MASLD diagnosis and management. It outlines a sequential, two-step noninvasive testing approach for screening advanced fibrosis, emphasizing risk stratification using the Fibrosis-4 index. The review details secondary risk assessment methods, including vibration-controlled transient elastography or ultrasound-based methods, for individuals with indeterminate or high-risk scores. It also consolidates evidence for lifestyle interventions and discusses the role of newly approved pharmacotherapies in managing the disease spectrum.

The review underscores that effective MASLD management begins with robust risk stratification. Clinicians should initially use the Fibrosis-4 index to identify patients at risk for advanced fibrosis. For those with indeterminate or high-risk Fibrosis-4 scores, secondary assessment with vibration-controlled transient elastography or ultrasound-based methods is crucial. Monitoring and managing earlier stages of MASLD in primary care can significantly reduce adverse outcomes. Lifestyle interventions are paramount, with recommendations including at least 5% weight loss for individuals with overweight or obesity, adoption of a healthy diet, and at least 150 minutes of moderate aerobic physical activity per week.

Additional lifestyle advice includes smoking cessation and limited alcohol intake for those with no or mild fibrosis, with complete abstinence for more significant fibrosis. Significantly, Semaglutide and resmetirom are highlighted as the first FDA-approved pharmacotherapies for metabolic dysfunction-associated steatohepatitis (MASH) in patients with moderate or severe fibrosis, marking a pivotal advancement in treatment options.