Main
NAFLD, obesity, NASH, metabolic dysregulation
NONALCOHOLIC FATTY LIVER DISEASE, OBESITY, SECONDARY, TYPE 2 DIABETES
Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic dysregulation and is commonly identified in individuals with obesity, type 2 diabetes and dyslipidemiaAt present, a liver biopsy is needed to definitively diagnose NASH; however, liver biopsy is an invasive procedure with associated morbidity. As such, noninvasive tests (biomarkers and/or imaging techniques) that can replace serial liver biopsies in (1) identifying patients with NASH and (2) monitoring treatment response (in the setting of an approved therapy) are urgently needed. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) is an accurate imaging technique that quantifies hepatic fat content. A systematic review and meta-analysis performed by Stine et al. showed that adults with NASH who achieved a ≥30% reduction from baseline in hepatic fat (measured by MRI-PDFF) had greater odds of achieving NASH reduction and resolution, suggesting this threshold could be used as a marker for improvement in NASHThyroid hormone receptor (THR)-β is responsible for regulating metabolic pathways in the liver and is frequently impaired in NASHTo increase the overall size of the safety database, MAESTRO-NAFLD-1 was a randomized, DB, placebo-controlled phase 3 trial to evaluate the safety and tolerability of 80 and 100 mg resmetirom versus placebo over 52 weeks of treatment in adults with NAFLD (presumed NASH) diagnosed utilizing noninvasive biomarkers and imaging (as opposed to an invasive diagnostic liver biopsy). Primary, key secondary and secondary end points from MAESTRO-NAFLD-1 are reported here.