How can we better identify patients with metabolic steatohepatitis (MASH) and assess liver fibrosis without resorting to a biopsy?
A large-scale, prospective, multicenter study conducted as part of the European LITMUS consortium provides new insights. Published in *Nature Medicine*, this study—in which Prof. Vlad Ratziu and Dr. Raluca Pais, hepatogastroenterologists at the IHU ICAN, participated—compares the performance of several blood biomarkers, imaging techniques, and diagnostic scores.
Metabolic steatosis: Better identifying patients at risk
Metabolic steatosis (MASLD) is closely associated with metabolic disorders and can progress in some patients to steatohepatitis (MASH), an inflammatory condition, and subsequently to advanced fibrosis and cirrhosis.
One of the major challenges, therefore, is to identify at an early stage the patients with the highest-risk forms of the disease.
Liver biopsy remains the gold standard for accurately characterizing liver lesions, but its invasive nature limits its widespread use.
The development and validation of noninvasive diagnostic tools are therefore essential to improving patient stratification and follow-up.
Compare the performance of different biomarkers
The LITMUS study, published in *Nature Medicine*, prospectively evaluated 357 participants with various stages of liver fibrosis.
The researchers compared several categories of noninvasive biomarkers:
- Blood biomarkers, including NIS2+
- Methods for assessing liver stiffness using imaging or elastography, including MRI and VCTE/FibroScan
- Composite scores such as Agile 3+ and Agile 4
The objective was to evaluate their ability to identify MASH—specifically “high-risk” MASH associated with fibrosis of at least stage F2—as well as to identify advanced stages of fibrosis and cirrhosis.
Different tools depending on the clinical objective
One of the key findings of the study is that no single tool is optimally suited to all diagnostic situations.
- Among the blood biomarkers evaluated, NIS2+ had the highest diagnostic accuracy for identifying MASH and MASH at risk.
- Performance was particularly high when assessing the most advanced stages of fibrosis. In particular, magnetic resonance elastography (MRE) proved highly effective in detecting advanced fibrosis and cirrhosis.
- For cirrhosis, several approaches—including MRE, measurement of liver stiffness using VCTE, and the Agile 3+ and Agile 4 scores—exceeded the minimum performance criterion defined by the study.
- The results thus suggest that noninvasive tools complement one another: blood biomarkers tend to be more effective at identifying patients at risk for HASH, while elastography and composite scores perform exceptionally well in characterizing advanced fibrosis and cirrhosis.
Toward Less Invasive and More Personalized Diagnostic Pathways
These findings represent an important step toward better defining the role of noninvasive biomarkers in the management of metabolic steatosis.
Having reliable tools to identify at-risk patients and assess the severity of their illness without increasing the number of invasive procedures could help improve their referral, follow-up, and access to treatment.
This publication also highlights the importance of large-scale international collaborations in validating these tools in well-characterized patient populations.
Professor Vlad Ratziu, an expert in metabolic liver diseases at IHU ICAN, Sorbonne University, Inserm, and AP-HP, contributed to this research conducted as part of the LITMUS consortium.
This approach is fully aligned with the IHU ICAN strategy: to develop a more preventive and personalized cardiometabolic medicine capable of better identifying individual trajectories and intervening earlier in the patient care pathway.
