NIS2+™, an effective blood-based test for the diagnosis of at-risk nonalcoholic steatohepatitis in adults 65 years and older.

ABSTRACT

BACKGROUND: Older patients are at increased risk for at-risk NASH, defined as NASH with NAFLD activity scores (NAS) ≥4 and significant fibrosis (F ≥ 2). The aim of this study was to compare the performance of 2 new blood tests, NIS4® and NIS2+™, with FIB-4, NFS, ELF™, and alanine aminotransferase (ALT) for the diagnosis of at-risk NASH in a cohort of patients aged ≥65 years. METHODS: The clinical performance of multiple blood-based tests was assessed for their ability to detect at-risk NASH using the RESOLVE-IT diag cohort, a large population of patients with metabolic risk who were screened for potential inclusion in the RESOLVE-IT phase 3 trial. RESULTS: The study cohort (n = 2053) included patients with the full histological spectrum of NAFLD, with patients having liver fibrosis stages F0-4 and NAS scores 0-8. NIS4® and NIS2+™ showed similar assay performance in patients who were <65 versus ≥65 years of age (AUROC = 0.80 vs. 0.78, p = 0.47; 0.81 vs. 0.83 p = 0.45, respectively) for the identification of at-risk NASH. In patients ≥65 (n = 410), NIS2+™ exhibited the highest AUROC compared to NIS4®, FIB-4, NFS, ELF™, and ALT (AUROC = 0.83 vs. 0.78, 0.68, 0.58, 0.69, 0.74, respectively; all p ≤ 0.0009). For NIS2+™, the sensitivity and NPV for ruling-out at-risk NASH at the 0.46 cutoff were 90.2% and 86.0%, and the specificity and PPV for ruling-in at-risk NASH at the 0.68 cutoff were81.1% and 76.3%, respectively. CONCLUSIONS: The clinical performance of NIS2+™ was superior for the diagnosis of at-risk NASH in patients ≥65 years of age. These data support the clinical value of this blood-based test for the diagnosis of at-risk NASH in older adults.