LITMUS Imaging Study for MASH and Fibrosis: Nature Medicine | July 2026

Introduction:

Reliable noninvasive biomarkers are essential to replace liver biopsy for diagnosing metabolic dysfunction-associated steatohepatitis (MASH) and staging fibrosis. The prospective multicenter LITMUS Imaging Study evaluated the diagnostic performance of leading imaging, serum, and composite biomarkers against centrally read liver histology.

Why was this study needed?

• Liver biopsy remains the gold standard but is invasive, costly, and unsuitable for routine monitoring.
• Accurate identification of at-risk MASH (F2–F3 fibrosis) is essential for selecting patients eligible for emerging therapies.
• Existing noninvasive tests have shown variable diagnostic performance.
• Prospective validation of multiple biomarkers using a common reference standard has been lacking.
• Better biomarkers are needed for both clinical practice and therapeutic trials.

Results:

• Magnetic resonance elastography (MRE) was the best imaging modality, demonstrating excellent performance for advanced fibrosis and cirrhosis, outperforming FibroScan-based liver stiffness measurements.
• NIS2 was the most accurate serum biomarker for identifying MASH and at-risk MASH, outperforming other blood-based tests, although no serum biomarker alone exceeded the predefined minimum acceptable performance threshold for treatment selection.
• Composite scores such as Agile3+ and Agile4+, together with MRE, provided the highest diagnostic accuracy for fibrosis staging, supporting their role in identifying patients with advanced fibrosis and cirrhosis.

Clinical Impact:

The LITMUS study provides one of the strongest prospective validations of noninvasive biomarkers in MASLD/MASH. It suggests that serum biomarkers are most useful for identifying inflammatory MASH, whereas elastography-based imaging and composite algorithms are superior for fibrosis staging. These tools are likely to become central to patient selection for newly approved therapies and future clinical trials.

Bottom Line:

No single noninvasive biomarker can accurately diagnose every stage of MASH. NIS2 is the leading serum biomarker for identifying at-risk MASH, while MRE and composite scores (Agile3+/Agile4+) provide the best assessment of advanced fibrosis and cirrhosis, supporting a multimodal diagnostic strategy rather than reliance on a single test.