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

• Published in: PloS one 2022-01, Vol.17 (4), p.e0266859
• Main Authors: Woreta, Tinsay A, Van Natta, Mark L, Lazo, Mariana, Krishnan, Arunkumar, Neuschwander-Tetri, Brent A, Loomba, Rohit, Mae Diehl, Anna, Abdelmalek, Manal F, Chalasani, Naga, Gawrieh, Samer, Dasarathy, Srinivasan, Vuppalanchi, Raj, Siddiqui, Mohammad S, Kowdley, Kris V, McCullough, Arthur, Terrault, Norah A, Behling, Cynthia, Kleiner, David E, Fishbein, Mark, Hertel, Paula, Wilson, Laura A, Mitchell, Emily P, Miriel, Laura A, Clark, Jeanne M, Tonascia, James, Sanyal, Arun J
• Format: Article
• Language: English
• Subjects: Accuracy; Adult; Algorithms; Aspartate aminotransferase; Biology and Life Sciences; Biopsy; Cirrhosis; Cohort Studies; Complications; Diagnosis; Diagnostic systems; Fatty liver; Female; Fibrosis; Humans; Laboratories; Liver; Liver - diagnostic imaging; Liver - pathology; Liver cirrhosis; Liver Cirrhosis - diagnostic imaging; Liver Cirrhosis - etiology; Liver diseases; Male; Medical diagnosis; Medicine; Medicine and Health Sciences; Middle Aged; Mortality; Non-alcoholic Fatty Liver Disease - complications; Non-alcoholic Fatty Liver Disease - diagnosis; Obesity; Obesity - complications; Parameters; Patients; Population studies; Public health; Risk; Sensitivity; Severity of Illness Index; Stiffness; Subgroups
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0266859

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. 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). 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 f