Author information

¹From the Center for Ultrasound Research and Translation, Massachusetts General Hospital, 55 Fruit St, White Bldg, Rm 270, Boston, MA 02114 (T.T.P., A.O., X.W., Q.L., D.H., M.M., H.E., A.E.S.); Harvard Medical School, Boston, Mass (T.T.P., A.O., Q.L., A.E.S.); Pfizer, Cambridge, Mass (S.P.S.); Department of Radiology, University of Washington, Seattle, Wash (G.M.C.); Department of Ultrasound, Shenzhen University General Hospital, Shenzhen, China (Q.L.); Department of Radiology, Liver Imaging Group, University of California San Diego, La Jolla, Calif (M.S.M., Y.C., C.B.S., K.J.F.); MGH Fatty Liver Program, Gastrointestinal Unit, Massachusetts General Hospital, Boston, Mass (K.E.C.); BioAge Labs, Richmond, Calif (S.S.S.); Foundation for the National Institutes of Health, North Bethesda, Md (H.H., T.N.K.); Regeneron Pharmaceuticals, Tarrytown, NY (R.A.C.); Department of Medicine, Division of Gastroenterology, NAFLD Research Center, University of California at San Diego, La Jolla, Calif (R.L.); Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, Ohio (N.A.O.); and Department of Internal Medicine, Division of Internal Medicine, Division of Gastroenterology, Virginia Commonwealth University Medical Center, Richmond, Va (A.J.S.).

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Abstract

Background US shear-wave elastography (SWE) and vibration-controlled transient elastography (VCTE) enable assessment of liver stiffness, an indicator of fibrosis severity. However, limited reproducibility data restrict their use in clinical trials. Purpose To estimate SWE and VCTE measurement variability in nonalcoholic fatty liver disease (NAFLD) within and across systems to support clinical trial diagnostic enrichment and clinical interpretation of longitudinal liver stiffness. Materials and Methods This prospective, observational, cross-sectional study (March 2021 to November 2021) enrolled adults with NAFLD, stratified according to the Fibrosis-4 (FIB-4) index (≤1.3, >1.3 and <2.67, ≥2.67), at two sites to assess SWE with five US systems and VCTE with one system. Each participant underwent 12 elastography examinations over two separate days within 1 week, with each day's examinations conducted by a different operator. VCTE and SWE measurements were reported in units of meters per second. The primary end point was the different-day, different-operator reproducibility coefficient (RDC_DDDO) pooled across systems for SWE and individually for VCTE. Secondary end points included system-specific RDC_DDDO, same-day, same-operator repeatability coefficient (RC_SDSO), and between-system same-day, same-operator reproducibility coefficient. The planned sample provided 80% power to detect a pooled RDC_DDDO of less than 35%, the prespecified performance threshold. Results A total of 40 participants (mean age, 60 years ± 10 [SD]; 24 women) with low (n = 17), intermediate (n = 15), and high (n = 8) FIB-4 scores were enrolled. RDC_DDDO was 30.7% (95% upper bound, 34.4%) for SWE and 35.6% (95% upper bound, 43.9%) for VCTE. SWE system-specific RDC_DDDO varied from 24.2% to 34.3%. The RC_SDSO was 21.0% for SWE (range, 13.9%-35.0%) and 19.6% for VCTE. The SWE between-system same-day, same-operator reproducibility coefficient was 52.7%. Conclusion SWE met the prespecified threshold, RDC_DDDO less than 35%, with VCTE having a higher RDC_DDDO. SWE variability was higher between different systems. These estimates advance liver US-based noninvasive test qualification by (a) defining expected variability, (b) establishing that serial examination variability is lower when performed with the same system, and (c) informing clinical trial design. ClinicalTrials.gov Identifier NCT04828551 © RSNA, 2024 Supplemental material is available for this article.