The Foundation for the National Institutes of Health Announces Study Results Published in Radiology Guiding Use of Ultrasound Elastography in Clinical Trials for Liver Disease
NORTH BETHESDA, Md., September 11, 2024—The Foundation for the National Institutes of Health (FNIH) highlights study findings identifying variations in ultrasound measurements of liver tissue that may allow clinicians and researchers to better interpret whether changes in measurements indicate disease progression.
The research, published in Radiology, is part of the FNIH’s Noninvasive Biomarkers of Metabolic Liver Disease (NIMBLE) project, a public-private partnership bringing together government agencies, academic researchers, and industry partners to rigorously evaluate noninvasive blood and imaging tests to detect and risk stratify liver disease. The publication of this study’s findings follows the publication of related studies from NIMBLE that found MRI and blood tests could offer potential alternatives to invasive diagnostic biomarkers for liver disease.
“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,” said Tania Kamphaus, PhD, Associate Vice President, Science Partnerships, and Director of Patient Engagement at the FNIH. Dr. Kamphaus is a co-author of the Radiology article.
Metabolic dysfunction-associated steatotic liver disease (MASLD), also referred to as nonalcoholic fatty liver disease (NAFLD), is the most common chronic liver disease, typically progressing from excess fat deposits to inflammation, fibrosis, and, ultimately, cirrhosis. It affects about 25% of the worldwide population and is a leading cause of liver-related morbidity and mortality. Currently, the only method to diagnose and stage liver disease with certainty is a liver biopsy, a potentially painful and expensive procedure with risk of complications and even death. Because of the limitations associated with liver biopsy, a strong need exists for noninvasive tests to diagnose and monitor liver disease and to facilitate clinical trials for new treatments.
Ultrasound elastography is a safe, relatively low-cost, noninvasive method that uses low-frequency vibrations to create an image of the liver that shows tissue stiffness, an aid in determining liver fibrosis. The most common ultrasound elastography technologies presently in clinical use include vibration-controlled transient elastography (VCTE) and shear wave elastography (SWE). To date, these technologies have had limited use in clinical trials owing to insufficient understanding of their sensitivity to biologic change.
The study examined the consistency of liver stiffness measured by SWE and VCTE ultrasound technologies in patients with MASLD. Researchers enrolled a total of 40 patients across a spectrum of MASLD-induced liver fibrosis. Each participant underwent 12 elastography exams, using five different vendors, over two separate days within a week. A different operator conducted each day’s exam.
The study found that there can be substantial fluctuation in serial measurements of liver stiffness by ultrasound elastography techniques. The investigators concluded that a difference of less than 30.7% between serial SWE measurements may reflect variations caused by the technology—known as technical variability—rather than a true change in liver stiffness. Similarly, a difference of less than 35.6% between serial VCTE measurements may reflect technical variability. The study also determined that variability in measurements was significantly greater when using different ultrasound systems than when repeating exams using the same system.
These findings provide key information for everyday clinical practice. Defining the expected variability will help prevent clinicians from implementing unnecessary changes in disease management following liver stiffness fluctuations that may stem from measurement variability. In addition, the findings will guide future studies designed to robustly determine the accuracy of ultrasound technology and eventually validate these imaging biomarkers for use in clinical trials focused on treating MASLD. Without the need for a liver biopsy, patients may be more likely to enroll in clinical trials, thus accelerating the development of new therapies.
NIMBLE is a project of the FNIH Biomarkers Consortium, which leads cross-sector efforts to validate and qualify biomarkers that accelerate the development of new therapeutics and health technologies. Biomarkers Consortium partners include the National Institutes of Health, the FDA, private industry, and nonprofit organizations. For more information about NIMBLE, visit Non-Invasive Biomarkers of Metabolic Liver Disease (NIMBLE) | FNIH.
About the Foundation for the National Institutes of Health:
The Foundation for the National Institutes of Health (FNIH) builds public-private partnerships that connect leading biomedical scientists at the National Institutes of Health (NIH), life sciences companies, foundations, academia, and regulatory agencies, including the Food and Drug Administration and European Medicines Agency. Through team science, we solve complex health challenges and accelerate breakthroughs for patients, regardless of who they are or what health challenges they face. The FNIH accelerates new therapies, diagnostics, and potential cures; advances global health and equity in care; and celebrates and helps train the next generations of scientists. Established by Congress in 1990 to support the mission of the NIH, the FNIH is a not-for-profit 501(c)(3) charitable organization. For more information about the FNIH, please visit fnih.org.