New findings show how blood-based biomarkers could improve detection of advanced liver disease and guide decisions about further testing.
Two major international studies from the Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) program have established diagnostic benchmarks for non-invasive tests used to detect and evaluate metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe form, metabolic dysfunction-associated steatohepatitis (MASH), reducing reliance on invasive liver biopsy.
The main LITMUS study, published in The Lancet, evaluated 26 predominantly blood-based biomarkers as well as ultrasound-based liver stiffness measurements in 1,590 patients across 13 countries in Europe and the US. The companion LITMUS Imaging study, published in Nature Medicine, assessed 24 diagnostic tests, focusing on MRI and elastography techniques compared against blood biomarkers, in 357 patients with paired biopsy and imaging data across nine countries in Europe and the US.
“Together, these two studies give us the most complete picture yet of which diagnostic tests work for liver disease, and how to combine them into a pathway health systems can easily implement,” says Quentin Anstee, professor, Ruth & Lionel Jacobson chair in personalised medicine at Newcastle University, UK, honorary consultant hepatologist at Newcastle Hospitals NHS Foundation Trust, and LITMUS consortium coordinator, in a release. “For advanced liver scarring and cirrhosis, we now have tools good enough to use with real confidence. Detecting active liver inflammation remains more challenging, but promising non-invasive tests are becoming available.”
Diagnostic Performance Across Blood and Imaging Biomarkers
The prospective investigations compared routine and advanced diagnostic assays against liver biopsy histology evaluated by expert pathologists.
For detecting advanced liver fibrosis and cirrhosis, the SOMAScan proteomic panel, MR elastography (MRE), and FibroScan-based elastography tools, including the Agile 3+ score, demonstrated the highest levels of diagnostic accuracy. In addition, the Enhanced Liver Fibrosis (ELF) and ADAPT blood tests both exceeded predefined performance thresholds for detecting cirrhosis.
In first-line triage, a simple, inexpensive gamma-glutamyl transferase (gamma-GT) blood test outperformed the widely used FIB-4 score. For identifying “at-risk MASH”—the patient population typically targeted in therapeutic clinical trials—only the SOMAScan proteomic panel met the study’s predefined accuracy threshold.
In the imaging arm, elastography modalities performed effectively for detecting advanced fibrosis and cirrhosis, with MRE demonstrating superior accuracy over FibroScan-based liver stiffness measurements.
Clinical Pathways and Trial Implications
MASLD affects up to one in three adults globally and up to seven in 10 individuals living with type 2 diabetes or obesity. With the emergence of licensed therapies for MASH entering clinical practice, the need for scalable, non-invasive diagnostic strategies has grown.
Based on the study results, researchers proposed a tiered diagnostic pathway that, pending further validation, could be adopted by health systems: gamma-GT testing as an initial screen, followed by ELF or FibroScan for patients requiring further assessment, with specialized imaging reserved for specialist care.
The findings also affect clinical trial enrollment protocols. Because regulatory agencies require histological confirmation of “at-risk MASH” for inclusion in late-phase trials, liver biopsy remains necessary for now; however, the strong performance of the SOMAScan panel highlights its potential for future adoption.
The LITMUS program is an international consortium comprising 53 academic and industry partners, funded by the European Innovative Medicines Initiative 2 Joint Undertaking.
Photo caption: Professor Quentin Anstee, Ruth & Lionel Jacobson Chair in Personalized Medicine at Newcastle University, UK, and joint senior author of both studies and the LITMUS consortium coordinator.
Photo credit: Newcastle University, UK
