Validation of the accuracy of the FAST™ score for detecting patients with at-risk nonalcoholic steatohepatitis (NASH) in a North American cohort and comparison to other non-invasive algorithms
Year: 2022
Type: article
Abstract: BACKGROUND AND AIMS: Management of patients with NASH who are at elevated risk of progressing to complications of cirrhosis (at-risk NASH) would be enhanced by an accurate, noninvasive diagnostic test. The new FAST™ score, a combination of FibroScan® parameters liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) and aspartate aminotransferase (AST), has shown good diagnostic accuracy for at-risk NASH (area-under-the-Receiver-Operating-Characteristic [AUROC] = 0.80) in European cohorts. We aimed to validate the FAST™ score in a North American cohort and show how its diagnostic accuracy might vary by patient mix. We also compared the diagnostic performance of FAST™ to other non-invasive algorithms for the diagnosis of at-risk NASH. METHODS: We studied adults with biopsy-proven non-alcoholic fatty liver disease (NAFLD) from the multicenter NASH Clinical Research Network (CRN) Adult Database 2 (DB2) cohort study. At-risk-NASH was histologically defined as definite NASH with a NAFLD Activity Score (NAS) ≥ 4 with at least 1 point in each category and a fibrosis stage ≥ 2. We used the Echosens® formula for FAST™ from LSM (kPa), CAP (dB/m), and AST (U/L), and the FAST™-based Rule-Out (FAST™ ≤ 0.35, sensitivity = 90%) and Rule-In (FAST™ ≥ 0.67, specificity = 90%) zones. We determined the following diagnostic performance measures: AUROC, sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV); these were calculated for the total sample and by subgroups of patients and by FibroScan® exam features. We also compared the at-risk NASH diagnostic performance of FAST™ to other non-invasive algorithms: NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) index, and AST to platelet ratio index (APRI). RESULTS: The NASH CRN population of 585 patients was 62% female, 79% white, 14% Hispanic, and 73% obese; the mean age was 51 years. The mean (SD) AST and ALT were 50 (37) U/L and 66 (45) U/L, respectively. 214 (37%) had at-risk NASH. The AUROC of FAST™ for at-risk NASH in the NASH CRN study population was 0.81 (95% CI: 0.77, 0.84. Using FAST™-based cut-offs, 35% of patients were ruled-out with corresponding NPV = 0.90 and 27% of patients were ruled-in with corresponding PPV = 0.69. The diagnostic accuracy of FAST™ was higher in non-whites vs. whites (AUROC: 0.91 vs 0.78; p = 0.001), and in patients with a normal BMI vs. BMI > 35 kg/m2 (AUROC: 0.94 vs 0.78, p = 0.008). No differences were observed by other patient characteristics or FibroScan® exam features. The FAST™ score had higher diagnostic accuracy than other non-invasive algorithms for the diagnosis of at-risk NASH (AUROC for NFS, FIB-4, and APRI 0.67, 0.73, 0.74, respectively). CONCLUSION: We validated the FAST™ score for the diagnosis of at-risk NASH in a large, multi-racial population in North America, with a prevalence of at-risk NASH of 37%. Diagnostic performance varies by subgroups of NASH patients defined by race and obesity. FAST™ performed better than other non-invasive algorithms for the diagnosis of at-risk NASH.
Source: PLoS ONE
Authors: Tinsay A. Woreta, Mark L. Van Natta, Mariana Lazo, Arunkumar Krishnan, Brent A. Neuschwander-Tetri, Rohit Loomba, Anna Mae Diehl, Manal F. Abdelmalek, Naga Chalasani, Samer Gawrieh, Srinivasan Dasarathy, Raj Vuppalanchi, Mohammad S. Siddiqui, Kris V. Kowdley, Arthur McCullough, Norah A. Terrault, Cynthia Behling, David E. Kleiner, Mark Fishbein, Paula Hertel, Laura A. Wilson, Emily P. Mitchell, Laura A. Miriel, Jeanne M. Clark, James Tonascia, Arun J. Sanyal
Institutions: Johns Hopkins University, Drexel University, Saint Louis University, University of California San Diego, Duke University, Indiana University School of Medicine, Cleveland Clinic, Virginia Commonwealth University, Liver Institute Northwest, University of Southern California, National Institutes of Health, National Cancer Institute, Northwestern University, Baylor College of Medicine, Texas Children's Hospital
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,805
Funders: U.S. Department of Defense, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Gilead Sciences, University of Southern California, Alnylam Pharmaceuticals, Celgene, Cleveland Clinic, Cleveland Clinic Foundation, University of Washington, Johns Hopkins University, Virginia Commonwealth University, Saint Louis University, NGM Biopharmaceuticals, Novo Nordisk, National Institutes of Health, Genentech, Allergan, University of California, San Diego, Johns Hopkins Bloomberg School of Public Health, School of Medicine, Indiana University, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Center for Advancing Translational Sciences, DOD Peer Reviewed Cancer Research Program
Awards: G1198267417, G1237558972, Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network, G2714352180, DETECTION AND MODELS OF TOXICANT EXPOSURE, Non-invasive screening of diabetics for advanced fibrosis due to NAFLD, G3273919290, San Diego Clinical and Translational Research Institute, Institute of Translational Health Sciences, G4512734604, Duke CTSA, Center for Clinical and Translational Research, G5430408733, Clinical and Translational Science Institute, G592323822, Ancillary Studies of NAFLD and NASH in HIV infected Adults, QUS Technology for Diagnosis and Grading of Hepatic Steatosis in NAFLD, G6662300753, G6827194995, G6864098839, Washington University Institute of Clinical and Translational Sciences, G7310623063, Indiana Clinical and Translational Science Institute (UL1), G8318409314, Clinical and Translational Science Collaborative of Cleveland, G8501164991, UC San Diego Clinical and Translational Research Institute, Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), Data Coordinating Center for the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Continuation, San Diego Digestive Diseases Research Center, Clinical Research Network in Nonalcoholic Steatohepatitis, Collaborative Clinical Research in Nonalcoholic Steatohepatitis, Washington University Institute of Clinical and Translational Sciences, Institute of Translational Health Sciences, Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Clinical Center-Cleveland site, Clinical Research on Nonalcoholic Fatty Liver Disease, The Saint Louis University Component of the NASH Clinical Research Network, Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)
OpenAlex ID: W4223909296