Diagnostic performance of circulating biomarkers for non-alcoholic steatohepatitis.

Autor: Sanyal AJ; Virginia Commonwealth University School of Medicine, Richmond, VA, USA. arun.sanyal@vcuhealth.org., Shankar SS; Pfizer, Inc., Sacramento, CA, USA., Yates KP; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA., Bolognese J; Cytel, Inc., Waltham, MA, USA., Daly E; Cytel, Inc., Waltham, MA, USA., Dehn CA; P Value Communications, LLC, Cedar Knolls, NJ, USA., Neuschwander-Tetri B; Saint Louis University, St. Louis, MO, USA., Kowdley K; Liver Institute Northwest, Seattle, WA, USA., Vuppalanchi R; Indiana University School of Medicine, Indianapolis, IN, USA., Behling C; Department of Pathology, University of California San Diego School of Medicine, San Diego, CA, USA., Tonascia J; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA., Samir A; Center for Ultrasound Research & Translation, Department of Radiology, Massachusetts General Hospital,Harvard Medical School, Boston, MA, USA., Sirlin C; Deptartment of Radiology, University of California San Diego School of Medicine, San Diego, CA, USA., Sherlock SP; Pfizer, Inc., Boston, MA, USA., Fowler K; Deptartment of Radiology, University of California San Diego School of Medicine, San Diego, CA, USA., Heymann H; US Food and Drug Administration, Silver Springs, MD, USA., Kamphaus TN; US Food and Drug Administration, Silver Springs, MD, USA., Loomba R; NAFLD Research Center, Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA., Calle RA; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2023 Oct; Vol. 29 (10), pp. 2656-2664. Date of Electronic Publication: 2023 Sep 07.
DOI: 10.1038/s41591-023-02539-6
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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