279-LB: NIS4, a Novel Blood Test, Can Identify "At-Risk" NASH (NAS>4 and Fibrosis>2) in T2D Patients

Background and Aim: T2D is an independent risk factor for the development of nonalcoholic steatohepatitis (NASH). Amongst NASH patients, those with elevated disease activity (NAS≥4) and fibrosis (F≥2) upon scoring of a liver biopsy are at higher risk of progressing to negative clinical outcomes. There is a lack of diagnostic tools to identify these “at-risk NASH patients that need clinical intervention. Here we compare the ability of NIS4, a novel blood test, to other available tests for detection of “at-risk” NASH in a T2D population. Methods: The blood and liver biopsy samples from 714 patients (446 non-T2D + 268 T2D) with metabolic risk factors for NASH were used. Disease activity (NAS) and fibrosis stage (F) were evaluated by a single expert pathologist. “At-risk” NASH was defined as NASH with NAS≥4 and F≥2. The diagnostic performance of NIS4 to identify patients with “at-risk” NASH in T2D subpopulation was assessed through ROC analysis and compared versus existing tests and statistical comparisons were done by DeLong testing. Results: In the total cohort (T2D prevalence = 38%), AUROC of NIS4 was 0.83 [95% CI: 0.80 - 0.86] for identifying “at-risk” NASH. The prevalence of “at-risk” NASH was higher in T2D (61%) vs. non-T2D (45%). AUROC was comparable in T2D and non-T2D: 0.80 [0.75 - 0.85] vs. 0.83 [0.80 - 0.87]. In T2D, a head to head comparison (AUROC; 95% CI) showed that NIS4 [0.80; 0.75-0.85] significantly outperformed all other tests for the identification of “at-risk” NASH: APRI [0.74; 0.68-0.80], FIB4 [0.70; 0.64-0.77], ELF [0.70; 0.64-0.77], FibroTest [0.68; 0.61-0.74], and NFS [0.60; 0.52-0.67]. Conclusion: Amongst T2D patients with suspected NASH, the prevalence of “at-risk” NASH is high. This highlights the need for active surveillance amongst T2D patients. For that purpose, NIS4 outperforms other tests and is a promising non-invasive tool to identify and potentially track T2D patients who need clinical intervention to manage their disease.