A single blood protein, thrombospondin-2 (TSP2), has emerged as a promising noninvasive marker for assessing the more serious stages of metabolic dysfunction-associated steatotic liver disease, or MASLD. The finding comes from the LITMUS study, which compared 30 biomarkers and test combinations in people whose liver disease had been assessed through biopsy.
MASLD is a condition in which fat accumulates in the liver alongside metabolic dysfunction. For clinicians, the central challenge is not only identifying the condition but determining whether it has progressed to fibrosis, inflammation, or cirrhosis. Those distinctions shape treatment decisions and the need for closer monitoring.
A search for alternatives to biopsy
Liver biopsy has often been needed to establish the stage of disease. It can provide a direct look at liver tissue, but it is invasive because it requires taking a tissue sample. That makes it unsuitable as a simple, inexpensive tool for broad use or frequent follow-up.
Blood-based tests could offer a less burdensome route to liver assessment. The aim is not merely to find a laboratory value that changes with disease, but to identify tests that reliably distinguish people with progressive disease from those without significant scarring.
The LITMUS project was designed to supply a broad comparison of those options. Researchers analyzed data from 1,590 patients with MASLD who had been accurately diagnosed through tissue biopsy. Participants were enrolled from 2018 through 2023 at 37 liver centers in 13 countries across Europe and the United States.
How the tests performed
The study evaluated 30 individual biomarkers and combinations of tests for diagnosing MASLD and metabolic dysfunction-associated steatohepatitis, or MASH, its more progressive stage. MASH can involve inflammation and fibrosis, which is scarring of liver tissue.
None of the tested methods met the study’s predetermined threshold for diagnosing early fatty liver disease without significant fibrosis. That result is important: it suggests that a blood test cannot yet be treated as a complete substitute for established diagnostic approaches across every stage of disease.
Several approaches did perform well for identifying significant fibrosis and cirrhosis. More complex strategies that paired biomarkers with specialized ultrasound assessment, known as elastography, were among the stronger options. But the study also highlighted the potential value of a simpler standalone measure: TSP2.
TSP2 was described as one of the most promising blood-based markers for assessing progressive and advanced fibrosis as well as inflammation associated with MASH at risk. Its performance as a single marker is notable because simpler tests could be easier to incorporate into care than multi-part diagnostic combinations.
What TSP2 may indicate
Thrombospondin-2 is a connective-tissue protein. According to the researchers, its concentration in blood provides indications of fibrotic changes in liver tissue that are associated with a risk of cirrhosis.
That connection makes biological and clinical sense within the study’s purpose. Fibrosis is the accumulation of scar tissue, and the ability to identify it without repeatedly taking a liver sample could help clinicians focus attention on people with the greatest need for specialist evaluation and monitoring.
The Mainz team that developed and fully validated the TSP2 biomarker characterized it as a promising single marker, rather than a finished replacement for every existing assessment. The LITMUS comparison itself reinforces that distinction. Test performance varied according to the disease stage being evaluated, and no option cleared the prespecified bar for early disease without significant fibrosis.
Why the result matters
For people living with MASLD, staging is central to care. A test that can help establish whether advanced fibrosis or MASH-related inflammation is present could support decisions about treatment and follow-up while reducing reliance on invasive procedures.
The study also illustrates why validation across many sites matters. The participants came from dozens of liver centers in Europe and the United States, giving researchers a dataset that extends beyond a single hospital or narrowly defined patient group. Biopsy-based diagnoses provided a reference point against which the noninvasive tests could be judged.
Still, the results point to an incremental advance rather than a diagnostic endpoint. Blood tests may become a practical part of wider assessment, especially for progressive and advanced disease, but the study does not show that they can reliably diagnose every form or early stage of MASLD on their own.
The next question
The central opportunity is to turn promising markers into tools that are dependable in routine care. TSP2’s performance suggests it could help fill that role, particularly where clinicians need a noninvasive indication of fibrosis and inflammation. The strongest future pathways may also combine blood markers with imaging methods such as elastography.
For now, the LITMUS study offers a clearer view of where noninvasive testing is most useful. It finds meaningful promise in TSP2 for detecting the liver changes that carry the greatest risk, while also showing that early fatty liver disease remains harder to assess without more comprehensive evaluation.
This article is based on reporting by Medical Xpress. Read the original article.
Originally published on medicalxpress.com
