Diagnostic performance of circulating biomarkers for non-alcoholic steatohepatitis

There 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.

Automated summary

There is currently no approved diagnostic biomarker for at-risk non-alcoholic steatohepatitis (NASH), which is associated with higher incidence of liver-related events and mortality. The FNIH-NIMBLE project evaluated the diagnostic performance of five blood-based panels in individuals with non-alcoholic fatty liver disease (NAFLD). Several biomarkers showed promising results in diagnosing at-risk NASH and assessing fibrosis severity.