Metabolic Dysfunction-Associated Steatotic Liver Disease: Noninvasive fibrosis screening and novel therapies

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a broad spectrum of liver injury, but the probability of hepatic complications is concentrated among patients with advanced fibrosis. The emergence of disease-directed pharmacotherapy makes accurate, scalable risk stratification more consequential. This critical narrative review examines which adults warrant noninvasive fibrosis assessment, how sequential testing should guide referral and treatment selection, and what new therapies can reasonably be expected to achieve. A focused literature search conducted in 2026 consulted PubMed/MEDLINE, major hepatology and diabetes society guidelines, pivotal randomized trials, and official United States regulatory documents. Current guidance favors targeted case-finding in metabolic-risk populations using the fibrosis-4 index followed, when indicated, by transient elastography or serum biomarkers, with magnetic resonance elastography reserved for selected uncertainties. Resmetirom and semaglutide have received United States accelerated approval for noncirrhotic steatohepatitis with stage F2-F3 fibrosis; trial benefits are established for histological endpoints, whereas definitive reductions in clinical liver events remain unproven. Lifestyle and cardiometabolic risk management continue to underpin care. Noninvasive tests are best interpreted as complementary probabilistic tools, not direct substitutes for histological staging in every patient. A coherent pathway links detection of clinically meaningful fibrosis to individualized treatment while avoiding indiscriminate screening and premature therapeutic claims.