The typically silent progression of metabolic dysfunction-associated steatohepatitis (MASH) makes early diagnosis of this increasingly prevalent disease challenging, but critical, as symptoms often do not manifest before patients develop irreversible cirrhosis. While the gold standard for diagnosis remains liver biopsy, several non-invasive tests in development could soon make quicker and less painful diagnosis a reality.
Despite its prevalence and association with severe liver disease, routine screening is not recommended, even in high-risk individuals. Currently, the gold standard for diagnosis is liver biopsy, though promising non-invasive diagnostic methods are on the horizon.
Certain risk factors, however, may raise clinical suspicion. Patients with obesity, diabetes, hypertension, or hypercholesterolemia—alongside elevated liver enzymes (ALT and AST) or incidental findings of hepatic steatosis on imaging—warrant further evaluation. Before proceeding to liver biopsy, clinicians may want to consider less invasive strategies once viral and genetic causes are ruled out.[1],[2]
Biomarkers advance the quest for non-invasive diagnosis
Although no FDA-approved non-invasive biomarkers currently differentiate MASH from MASLD, the Biomarkers Consortium’s Noninvasive Biomarkers of Metabolic Liver Disease (NIMBLE) project is making strides. Among the most promising candidates are five biomarkers that demonstrate superior performance to liquid biopsies: Enhanced Liver Fibrosis (ELF), NIS4, PROC3, Fibrometer-VCTE, and OWLiver.[3]
These markers hold potential not only for diagnosis but also for monitoring treatment response in noncirrhotic MASH, a growing area of focus for the FDA, which has convened multiple conferences in recent years to accelerate biomarker development.[3],[4]
Identifying fibrosis facilitates risk assessment
Identifying patients with advanced fibrosis is crucial, as those with stage 2 fibrosis or higher face the greatest risk of progressing to cirrhosis and hepatocellular carcinoma. While imaging generally struggles to distinguish between MASLD and MASH, both transient elastography and magnetic resonance elastography have proven effective in identifying liver fibrosis by providing a visual representation of liver stiffness.[5] The Fibrosis-4 (Fib-4) score and AST-to-platelet ratio also indicate the degree of fibrosis.
With advancing research and a growing commitment from regulatory agencies, the landscape of MASH diagnosis and management is rapidly evolving. These developments promise to improve diagnostic accuracy, reduce reliance on invasive procedures and ultimately provide earlier interventions for high-risk patients.
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