The Foundation for the National Institutes of Health (FNIH) has announced findings from a study published in Radiology that clarifies the variability in ultrasound elastography measurements of liver tissue. This research is expected to improve the interpretation of measurement changes in clinical trials focused on liver disease progression.
The study, conducted as part of the FNIH’s Noninvasive Biomarkers of Metabolic Liver Disease (NIMBLE) project, is a public-private partnership involving government agencies, academic researchers, and industry partners. NIMBLE aims to rigorously evaluate noninvasive blood and imaging tests for detecting and risk-stratifying liver disease. Prior NIMBLE studies have suggested that MRI and blood tests could serve as alternatives to invasive diagnostic biomarkers for liver disease.
Need for Non-Invasive Tools
Tania Kamphaus, PhD, Associate Vice President, Science Partnerships, and Director of Patient Engagement at the FNIH, emphasized the importance of non-invasive tools, stating, "Drug development for liver disease has been hindered by a lack of safe and noninvasive tools to measure treatment response in patients. With systematic evaluation and validation, current diagnostic imaging technologies, such as ultrasound, have potential to significantly advance research in this field."
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), affects approximately 25% of the global population and is a leading cause of liver-related morbidity and mortality. The disease progresses from fat deposits to inflammation, fibrosis, and cirrhosis. Currently, liver biopsy is the definitive diagnostic method, but it is invasive, costly, and carries risks. This necessitates the development of noninvasive tests for diagnosis, monitoring, and facilitating clinical trials.
Ultrasound Elastography Technologies
Ultrasound elastography is a noninvasive, relatively low-cost method that assesses liver tissue stiffness using low-frequency vibrations. Vibration-controlled transient elastography (VCTE) and shear wave elastography (SWE) are the most common ultrasound elastography technologies. However, their use in clinical trials has been limited due to an incomplete understanding of their sensitivity to biologic changes.
The study examined the consistency of liver stiffness measurements obtained via SWE and VCTE in 40 patients with varying degrees of MASLD-induced liver fibrosis. Each participant underwent 12 elastography exams using five different vendors over two days within a week, with different operators conducting each day’s exam.
Variability in Measurements
The study revealed substantial fluctuation in serial liver stiffness measurements obtained through ultrasound elastography. Investigators determined that a difference of less than 30.7% between serial SWE measurements might reflect technical variability rather than actual changes in liver stiffness. Similarly, a difference of less than 35.6% between serial VCTE measurements may be attributed to technical variability. The study also noted that measurement variability was significantly greater when using different ultrasound systems compared to repeated exams using the same system.
These findings offer critical insights for clinical practice, helping to prevent unnecessary changes in disease management due to measurement variability. Furthermore, they will inform future studies aimed at validating ultrasound technology for use in clinical trials focused on treating MASLD. The availability of non-invasive methods may encourage more patients to participate in clinical trials, thereby accelerating the development of new therapies.
The NIMBLE project is part of the FNIH Biomarkers Consortium, which promotes cross-sector collaborations to validate and qualify biomarkers for accelerating the development of new therapeutics and health technologies. Partners in the Biomarkers Consortium include the National Institutes of Health, the FDA, private industry, and nonprofit organizations.
