Scientists Improve Non-Invasive Liver Disease Diagnosis

The main LITMUS study, published in The Lancet, analysed blood test results and ultrasound-based measurements of liver stiffness in 1,500 patients. It is the largest international study of its kind.

The accompanying LITMUS Imaging Study, published in Nature Medicine, examined advanced MRI and elastography techniques in more than 350 patients.

Professor Quentin Anstee, co-author of the studies, said: “Taken together, these studies provide us with the most comprehensive picture yet of which diagnostic tests are effective for liver disease and how they can be combined into a system that can be readily implemented in healthcare. For detecting advanced liver scarring and cirrhosis, we now have sufficiently effective tools that can be used with confidence. Identifying active liver inflammation remains challenging, but promising non-invasive tests are emerging,” Nauchnaya Rossiya reports.

Metabolic dysfunction-associated liver disease affects one in three adults worldwide and seven out of ten people living with obesity or type 2 diabetes.

As the first licensed medications for metabolic dysfunction-associated liver disease enter clinical practice, demand is growing for accurate non-invasive methods of diagnosing and monitoring the condition.

The studies evaluated dozens of biomarkers based on blood tests, imaging and elastography, including both cutting-edge techniques and routine diagnostic tests already used by clinicians. Their accuracy was compared with liver biopsy results assessed by experienced pathologists.

The findings provide robust, promising and independent evidence based on large, multinational patient cohorts. According to the researchers, they offer the most realistic assessment to date of the potential of non-invasive approaches to diagnosing liver disease.

Key findings of the studies:

- For advanced liver fibrosis (scarring) and cirrhosis, the SOMAScan proteomic panel, magnetic resonance elastography (MRE) and FibroScan-based elastography, including the Agile 3+ score, demonstrated the highest levels of diagnostic accuracy.

- The ELF and ADAPT blood tests exceeded the predefined thresholds for detecting cirrhosis.

- For identifying patients at risk — the population targeted by most clinical trials — only the SOMAScan panel met the predefined accuracy threshold.

- A simple, inexpensive gamma-glutamyl transferase (GGT) blood test outperformed the widely used FIB-4 index as a first-line assessment tool. It could be followed by FibroScan or ELF testing to confirm disease severity in routine clinical practice.

The findings support a simplified diagnostic pathway that, following further validation, could be implemented across healthcare systems: use GGT as the initial screening test, followed by ELF or FibroScan for patients requiring further assessment, with advanced imaging reserved for specialist care.

This approach could help more patients receive an accurate diagnosis without undergoing an invasive liver biopsy, while ensuring that specialist resources are directed where they are needed most.

The findings also have important implications for MASH clinical trials. Since regulatory authorities require confirmation that patients with MASH are at risk of disease progression to qualify for late-stage clinical trials, liver biopsy is likely to remain necessary. However, the strong performance of SOMAScan suggests that the method could become widely adopted.

The LITMUS Imaging Study also found that elastography techniques are well suited to detecting advanced liver fibrosis and cirrhosis, with magnetic resonance elastography outperforming FibroScan-based liver stiffness measurements.