Two international studies have evaluated the accuracy of different non-invasive tests for diagnosing and determining the severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and its most severe form, metabolic dysfunction-associated steatohepatitis (MASH). The results, published in the journals The Lancet and Nature Medicine, provide evidence to support progress towards more accurate and accessible diagnostic strategies that could reduce reliance on liver biopsy.

The studies are part of the international LITMUS programme (Liver Investigation: Testing Marker Utility in Steatohepatitis), an initiative bringing together 53 academic and industrial partners to develop, validate and evaluate biomarkers for diagnosing metabolic liver diseases and assessing their severity.

Non-invasive tests to assess liver fibrosis

The main study, published in The Lancet, analysed 26 biomarkers in 1,590 patients from 13 countries across Europe and the United States. The research compared different blood tests, biomarker panels and ultrasound-based elastography techniques with liver biopsy results, with the aim of identifying the most accurate tools for diagnosing these diseases and determining their severity.

The results indicate that the SOMAScan proteomic panel and several techniques for assessing liver stiffness, such as magnetic resonance elastography (MRE) and FibroScan-based tools, including the Agile 3+ score, showed high accuracy in detecting advanced liver fibrosis and cirrhosis. The ELF and ADAPT blood tests also exceeded the established performance thresholds for identifying cirrhosis.

By contrast, detecting cases of MASH at risk of progression (the group of patients targeted by most clinical trials) remains more complex. Among the tests evaluated in the main study, only the SOMAScan panel reached the pre-established diagnostic accuracy threshold for identifying these cases.

A stepwise diagnostic strategy

One of the most relevant findings of the main study concerns the performance of gamma-glutamyl transferase (gamma-GT), a simple, low-cost blood test. In the analyses conducted, this test outperformed the FIB-4 score, which is widely used for the initial assessment of liver fibrosis, as a first-line tool.

Based on these findings, the researchers propose a stepwise diagnostic strategy that, once validated in additional studies, could facilitate its incorporation into routine clinical practice. The strategy would begin with a gamma-GT test and, in cases requiring further assessment, continue with tests such as ELF or FibroScan. More advanced imaging techniques would be reserved mainly for specialist care.

This approach could help identify patients who need a more detailed assessment and better guide referrals to specialist services, while reducing the need for invasive procedures.

“One of the most relevant aspects of this study is that it points towards a more efficient diagnostic model, combining simple and accessible tests with more specific tools when needed. This could help better identify patients who require specialist assessment and optimise the use of healthcare resources,” explains Juan Manuel Pericàs, a researcher in the Liver Diseases Research Group at the Vall d’Hebron Research Institute (VHIR) and in the CIBER area for Liver and Digestive Diseases (CIBERehd CB06/04/0007), led by Dr Joan Genescà, a researcher on the project and an author of both studies. In addition, Dr Pericàs is Director of Commercial and Academic Clinical Research at VHIR.

Magnetic resonance elastography stands out in the imaging study

The second study, published in Nature Medicine, evaluated 24 diagnostic tests, mainly magnetic resonance imaging and ultrasound techniques, as well as elastography methods and some blood biomarkers. The study included 357 patients from nine countries across Europe and the United States with paired biopsy and imaging data.

The results also showed good performance by elastography techniques in detecting advanced fibrosis and cirrhosis. In particular, magnetic resonance elastography provided greater accuracy than liver stiffness measurements based on FibroScan.

A step forward in the diagnosis and monitoring of liver diseases

MASLD is one of the most common chronic liver diseases worldwide, affecting approximately 25–30% of the population. Its most severe form, MASH, can progress to cirrhosis and liver cancer. The development of specific treatments for this disease makes it even more important to have tests that can accurately identify patients who may benefit from them and monitor their progress.

Liver biopsy continues to play an important role in confirming certain diagnoses and selecting patients for clinical trials. However, it is an invasive procedure with limitations that can make both access to diagnosis and monitoring disease progression more difficult.

“This study reinforces the potential of non-invasive imaging techniques to determine the degree of liver fibrosis, particularly in advanced stages. However, it is necessary to distinguish between the ability to identify fibrosis and the ability to identify inflammation associated with MASH, as we still need more accurate diagnostic tools for the latter,” notes Juan Manuel Pericàs.