Blood-Based Biomarkers Can Reduce Use of Invasive Liver Biopsy as a Diagnostic Tool, Lower Clinical Trial Costs, and Increase Access to Care

The Foundation for the National Institutes of Health (FNIH) today announces study findings, published in Nature Medicine, demonstrating the effectiveness of noninvasive blood tests to diagnose nonalcoholic steatohepatitis (NASH).¹ The results are a significant milestone on the path to regulatory approval by the U.S. Food and Drug Administration (FDA). The findings came from the FNIH’s Biomarkers Consortium, which leads cross-sector efforts to validate and qualify biomarkers that accelerate the development of new therapeutics and health technologies.

The research is part of the Biomarkers Consortium’s Noninvasive Biomarkers of Metabolic Liver Disease (NIMBLE) project, a public-private partnership bringing together the FDA, academic researchers, and industry partners to rigorously evaluate blood and imaging tests to measure the presence of liver disease. Although several companies have developed such tests, none have met the burden of proof needed for FDA regulatory approval. This lack of approval limits the use of these tests for diagnosing NASH and recruiting patients into studies to develop therapies.

“This brings us a step closer toward the day when we can diagnose and treat patients with NASH without a potentially painful liver biopsy,” said Julie Gerberding, MD, MPH, President and CEO of the Foundation for the National Institutes of Health.

The study measured the performance of five biomarkers that could be scaled up for widespread deployment if proven effective: ELF, NIS4, PROC3, Fibrometer-VCTE, and OWLiver. Each biomarker was tested for use in diagnosing NASH and advanced liver disease. Four of the five biomarkers performed better than current blood-based lab tests, as determined by an AUROC of 0.7 or higher, a standard performance threshold for biomarkers. The 1,073 study participants, representing the full spectrum of disease severity, were selected from the NASH Clinical Research Network, which is supported by the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases.

NASH is a common cause of liver disease and a leading cause of liver-related morbidity and mortality. It affects up to 15 million people in the United States.² People with NASH do not display symptoms until later stages of the condition, leaving many undiagnosed until they develop cirrhosis, which may require a liver transplant. NASH also increases the risk of liver cancer, which can be fatal. Currently, the only method to diagnose NASH with certainty is a liver biopsy, a painful and expensive procedure that carries some risk of death for patients. By expanding the diagnostic options beyond liver biopsies, more healthcare facilities and healthcare professionals would be able to diagnose NASH with greater safety.

The need for a biopsy also hinders patient recruitment for clinical trials. These trials are necessary to approve new treatments for NASH, none of which are currently available to treat this growing population of patients. The use of noninvasive blood tests is anticipated to spark increased interest in new drug development, as these tests promise to facilitate enrollment in future studies and reduce the costs of running a trial.

“Currently, to qualify for enrollment in clinical trials of NASH, patients must undergo liver biopsy, and many patients do not qualify. The FNIH NIMBLE project is assessing diagnostic biomarker tests to identify which patients may not qualify for enrollment without subjecting them to an invasive procedure,” said Jeffrey Siegel, MD, Office Director of the Office of Drug Evaluation Sciences, FDA. “The FDA supports efforts to qualify non-invasive tests to meet this important goal.”

“These promising results advance the process of fully qualifying these biomarkers for use in clinical studies for new NASH therapies,” said Tania Kamphaus, PhD, Director of Translational Science, Metabolic Disorders, and Director of Patient Engagement at the FNIH, and a co-author of the Nature Medicine article. “With regulatory approval, these noninvasive tests could become a new diagnostic standard of care for patients with liver disease.”

Working alongside dedicated patient advocacy groups in the NASH space—including the Global Liver Institute, NASH Knowledge, and the Fatty Liver Foundation—the FNIH is contributing its expertise to enhance research and drive patient-centered initiatives to address this pressing health issue. For more information, visit Non-Invasive Biomarkers of Metabolic Liver Disease (NIMBLE) | FNIH.

About the Biomarkers Consortium: The Foundation for the National Institutes of Health’s Biomarkers Consortium (BC) leads cross-sector efforts to validate and qualify biomarkers that accelerate the development of new therapeutics and health technologies. The core operations of the BC are supported through its contributing membership program, which includes organizations representing private industry and not-for-profit organizations.

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.

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¹ In June 2023, numerous global liver associations introduced a revised terminology. The condition known as nonalcoholic steatohepatitis (NASH) is now known as metabolic dysfunction-associated steatohepatitis (MASH). FNIH acknowledges this advancement and actively collaborates with the patient and expert liver disease sectors to appropriately integrate the change.

² Fatty Liver Disease – American Liver Foundation

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“With regulatory approval, these noninvasive tests could become a new diagnostic standard of care for patients with liver disease.” - Dr. Tania Kamphaus