Sanyal, Arun J.Shankar, Sudha S.Yates, Katherine P.Bolognese, JamesDaly, EricaDehn, Clayton A.Neuschwander-Tetri, BrentKowdley, KrisVuppalanchi, RajBehling, Cynthia A.Tonascia, JamesSamir, AnthonySirlin, ClaudeSherlock, Sarah P.Fowler, KathrynHeymann, HelenKamphaus, Tania N.Loomba, RohitCalle, Roberto A.2023-10-202023-10-202023Sanyal AJ, Shankar SS, Yates KP, et al. Diagnostic performance of circulating biomarkers for non-alcoholic steatohepatitis. Nat Med. 2023;29(10):2656-2664. doi:10.1038/s41591-023-02539-6https://hdl.handle.net/1805/36523There are no approved diagnostic biomarkers for at-risk non-alcoholic steatohepatitis (NASH), defined by the presence of NASH, high histological activity and fibrosis stage ≥2, which is associated with higher incidence of liver-related events and mortality. FNIH-NIMBLE is a multi-stakeholder project to support regulatory approval of NASH-related biomarkers. The diagnostic performance of five blood-based panels was evaluated in an observational (NASH CRN DB2) cohort (n = 1,073) with full spectrum of non-alcoholic fatty liver disease (NAFLD). The panels were intended to diagnose at-risk NASH (NIS4), presence of NASH (OWLiver) or fibrosis stages >2, >3 or 4 (enhanced liver fibrosis (ELF) test, PROC3 and FibroMeter VCTE). The prespecified performance metric was an area under the receiver operating characteristic curve (AUROC) ≥0.7 and superiority over alanine aminotransferase for disease activity and the FIB-4 test for fibrosis severity. Multiple biomarkers met these metrics. NIS4 had an AUROC of 0.81 (95% confidence interval: 0.78–0.84) for at-risk NASH. The AUROCs of the ELF test, PROC3 and FibroMeterVCTE for clinically significant fibrosis (≥stage 2), advanced fibrosis (≥stage 3) or cirrhosis (stage 4), respectively, were all ≥0.8. ELF and FibroMeter VCTE outperformed FIB-4 for all fibrosis endpoints. These data represent a milestone toward qualification of several biomarker panels for at-risk NASH and also fibrosis severity in individuals with NAFLD.en-USAttribution 4.0 InternationalNonalcoholic fatty liver disease (NAFLD)Nonalcoholic steatohepatitis (NASH)NAFLD activity score (NAS)Fibrosis stageCirrhosisSteatohepatitisFibrosisBiomarkersDiagnostic panelContext of useValidationDiagnostic markersArticle