Evaluation of Non-Invasive Tests for Metabolic Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), is a common liver problem which affects 30% of the United States population. Liver biopsy-based histopathology is accepted as the most accurate technique to detect patients at risk of developing serious liver conditions secondary to non-alcoholic steatohepatitis (MASH). However, the liver biopsy is an invasive test with risk for complications and even risk of mortality. Alternative non-invasive blood-based and imaging biomarkers are needed to replace liver biopsy for diagnosis and staging of MASH with fibrosis with the ultimate goal to guide timely decisions for clinical care including pharmacologic intervention for patients with MASH. The Non-Invasive Biomarkers for Metabolic Liver Disease (NIMBLE) project was commissioned by the FNIH to qualify non-invasive tests (NITs) for MASLD. It represents a collaborative effort involving the FNIH, Food and Drug Administration (FDA), academics and multiple industry partners to qualify biomarkers for diagnosis and staging of MASH with fibrosis. The NIMBLE project plan was designed to occur across two stages (Stage 1 and Stage 2) and with the ultimate goal to generate data on blood-based, Vibration Controlled Transient Elastography- (VCTE) based and imaging-based biomarkers to support seeking regulatory approval of one or more biomarker(s) or biomarker panel(s) for diagnosis and staging of MASH. Data generated within NIMBLE Stage 1 were able to successfully identify a set of candidate blood-based and imaging biomarkers that met prespecified criteria for further evaluation in Stage 2. The current study aims to deliver on that goal for NIMBLE Stage 2, namely, to confirm and extend the findings from NIMBLE Stage 1 in the setting of a prospective non-interventional trial in a population at risk for MASH with fibrosis. To that end, NIMBLE Study 2.0 is primarily designed to evaluate the performance characteristics of prespecified blood-based, VCTE-based and imaging-based biomarker(s) and biomarker panel(s) when calibrated against liver biopsy-based histology as well as currently available tools for diagnosis and staging of MASH in those at risk.