Metabolic dysfunction‑associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease worldwide and ranges from isolated steatosis to metabolic dysfunction‑associated steatohepatitis (MASH) with progressive fibrosis up to cirrhosis. There is a clear need for validated noninvasive tests to identify MASH and to stage fibrosis because disease progression and greater fibrosis are associated with higher risk of adverse clinical outcomes.
The LITMUS Imaging Study is a prospective, multicenter effort to validate diagnostic biomarkers — imaging, serum, and composite scores — against centrally read histology for steatohepatitis and fibrosis in MASLD.
This study enrolled 357 participants prospectively across multiple centers with centrally read liver biopsies used as the reference standard. The provided text reports the overall fibrosis distribution but does not include the full enrollment criteria, demographic breakdown, or other selection details; those specifics were not reported in the excerpt supplied.
The study compared several noninvasive tests. Imaging approaches included magnetic resonance elastography (MRE) and FibroScan vibration‑controlled transient elastography (VCTE‑LSM). Serum biomarkers and composite scores evaluated included NIS2+, Agile 3+ and Agile 4 among others referenced.
Primary diagnostic targets were centrally read MASH, at‑risk MASH (defined as MASH with at least stage 2 fibrosis), advanced fibrosis, and cirrhosis. The investigators used a predefined minimum acceptable performance criterion (MAC) to judge whether a biomarker’s diagnostic accuracy met acceptable standards.
Among the 357 participants, fibrosis stages by histology were distributed as follows: F0 12%, F1 16%, F2 25%, F3 32% and F4 15%.
Serum and imaging biomarkers demonstrated variable accuracy for diagnosing steatohepatitis. Among serum tests, NIS2+ showed the highest diagnostic accuracy for MASH (AUC 0.83) and for at‑risk MASH (AUC 0.82). However, neither AUC statistically exceeded the study’s MAC (P = 0.15 for MASH; P = 0.19 for at‑risk MASH).
For imaging biomarkers, MRE achieved the highest imaging performance for MASH (AUC 0.71) and for at‑risk MASH (AUC 0.75), but these values remained below the MAC set by the study.
Overall, the study reports that serum biomarkers tended to outperform imaging approaches specifically for identifying at‑risk MASH.
Noninvasive tests performed better for fibrosis staging than for diagnosing steatohepatitis. MRE met the MAC for advanced fibrosis with an AUC of 0.91 (P < 0.01). Composite scores also performed well: Agile 3+ met the MAC for advanced fibrosis (AUC 0.84; P = 0.03).
For cirrhosis (F4), multiple biomarkers exceeded the MAC. Notably, MRE had an AUC of 0.91 (P < 0.01), VCTE‑LSM had an AUC of 0.87 (P < 0.01), Agile 3+ had an AUC of 0.89 (P < 0.01) and Agile 4 had an AUC of 0.88 (P < 0.01).
These results show excellent accuracy of elastography and composite scores for identifying advanced fibrosis and cirrhosis.
The LITMUS Imaging Study found a relative divergence in strengths depending on the diagnostic target. Serum biomarkers — exemplified by NIS2+ — tended to provide higher accuracy for identifying at‑risk MASH, although not reaching the MAC in this report. Conversely, imaging elastography (MRE, VCTE‑LSM) and composite scores (Agile 3+, Agile 4) demonstrated superior performance for staging fibrosis, particularly advanced fibrosis and cirrhosis, where several tests met or exceeded the MAC.
In this prospectively collected, centrally read cohort, noninvasive tests showed greater reliability for fibrosis staging than for diagnosing steatohepatitis. MRE and elastography‑based approaches together with composite scores reached clinically acceptable accuracy for advanced fibrosis and cirrhosis. Serum markers such as NIS2+ showed promising accuracy for MASH and at‑risk MASH but did not exceed the predefined MAC in this dataset.
The provided article excerpt does not include full methodological details (for example, participant inclusion/exclusion criteria, complete list of biomarkers tested, or study limitations and follow‑up). Those elements would be necessary for clinicians and guideline panels to fully assess the generalizability and applicability of the findings.
Overall, these results support use of elastography and validated composite scores for noninvasive staging of advanced fibrosis and cirrhosis in MASLD, while indicating that continued development or refinement of tests is needed for robust noninvasive diagnosis of steatohepatitis.