Nonalcoholic steatohepatitis, or NASH, is a serious liver condition associated with obesity and type 2 diabetes. It impacts between 9 and 15 million people in the United States. The condition, which is a progressed version of nonalcoholic fatty liver disease, is caused by a buildup of fat in the liver, leading to inflammation and scarring. Individuals with NASH often show very few early symptoms. As a result, this elusive disease frequently remains undiagnosed. Many patients only discover they have the condition after it has progressed to cirrhosis, a late-stage, irreversible form of liver scarring, or deadly liver cancer.

Currently, an invasive and painful liver biopsy is the only method available to diagnose NASH. Unfortunately, patients tend to balk at undergoing repeated biopsies or enrolling in drug development trials that employ biopsies. With these concerns in mind, FNIH’s Noninvasive Biomarkers of Metabolic Liver Disease (NIMBLE) initiative is working to standardize and compare the best tools for diagnosing NASH, including noninvasive and more accurate blood-based and imaging biomarkers. The completed first stage of the NIMBLE project has successfully made advancements towards noninvasive liver testing, including:

• The FDA has accepted letters of intent (LOIs) for 10 noninvasive biomarkers being tested in NIMBLE – both blood-based and imaging-based – to serve as enrichment tools for diagnosing “at risk” NASH.
• NIMBLE Stage 1 findings demonstrate that noninvasive biomarkers can diagnose “at risk” populations that are likely to progress to cirrhosis. This will reduce the number of patients who need to be confirmed through biopsy procedures, which then reduces the risk of morbidity resulting from biopsies, enhances patient safety, and boosts the efficiency of clinical trials.
• This identification of patients who are likely in the “at risk” category also increases the potential for them to be recruited to clinical trials for developing disease-altering therapies. This reduces the use of clinical trial resources significantly, resulting in substantial cost savings for clinical trial sponsors.

NIMBLE’s innovative approach has already shown incredible potential for revolutionizing medical research and patient care. As a result of the initiative’s achievements, numerous abstracts were presented at the annual American Association for the Study of Liver Diseases (AASLD) conference and the European Association for the Study of the Liver (EASL) conference. Moreover, correspondence was published in the high-impact journal Nature Medicine highlighting the program’s findings to date.

FNIH’s NIMBLE initiative is focused on building bridges to breakthroughs and accelerating the diagnosis and treatment of liver disease. As Roberto Calle, co-chair of NIMBLE and Executive Medical Director at Regeneron, shared: “What we are doing with NIMBLE is precisely setting up the stage, so that when we finally have that sought-after therapy, we can bring it to patients and identify those who really need it.”