Browsing by Author "Siddiqui, Mohammad S."

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    Performance Characteristics of Vibration-Controlled Transient Elastography for Evaluation of Non-Alcoholic Fatty Liver Disease
    (Wiley, 2017) Vuppalanchi, Raj; Siddiqui, Mohammad S.; Van Natta, Mark L.; Hallinan, Erin; Brandman, Danielle; Kowdley, Kris; Neuschwander-Tetri, Brent A.; Loomba, Rohit; Dasarathy, Srinivas; Abdelmalek, Manal; Doo, Edward; Tonascia, James A.; Kleiner, David E.; Sanyal, Arun J.; Chalasani, Naga; Department of Medicine, School of Medicine
    Background: Vibration-controlled transient elastography (VCTE) estimates liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) which are noninvasive assessments of hepatic fibrosis and steatosis respectively. However, prior VCTE studies reported high failure rate in patients with non-alcoholic fatty liver disease (NAFLD). Aim: To examine the performance characteristics of Fibroscan 502 Touch with two probes, medium (M+) and extra-large (XL+), in patients with NAFLD in a multicenter setting. Methods: A total of 1696 exams were attempted in 992 patients (BMI: 33.6 ± 6.5 kg/m2) with histologically confirmed NAFLD. Simultaneous assessment of LSM and CAP was performed using Fibroscan 502 Touch with an automatic probe selection tool. Testing was conducted twice in patients by either a single operator (88%) or two operators (12%). Failure was defined as the inability to obtain a valid examination. An examination was considered unreliable if LSM IQR/median was >30%. Significant disagreement between two readings was defined as greater than >95% limits of agreement between two readings. Results: A total of 1641 examinations yielded valid results with a failure rate of 3.2% (55/1696). The proportion of unreliable scans for LSM was 2.4%. The proportion of unreliable scans with operator experience in the top quartile (≥ 59 procedures) was significantly lower than lower three quarters combined (1.6% vs.4.7%, p=0.01 by Fisher's Exact test). The significant disagreement between first and second readings for LSM and CAP when obtained back to back was 18% and 11% respectively. Conclusion: VCTE for estimation of LSM and CAP can be successfully deployed in a multicenter setting with low failure (3.2%) and high reliability (>95%) rates and high reproducibility.
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    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
    (PLOS, 2022) Woreta, Tinsay A.; Van Natta, Mark L.; Lazo, Mariana; Krishnan, Arunkumar; Neuschwander-Tetri, Brent A.; Loomba, Rohit; Diehl, Anna Mae; 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.; NASH Clinical Research Network; Medicine, School of Medicine
    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.
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    Vibration-controlled Transient Elastography to Assess Fibrosis and Steatosis in Patients With Nonalcoholic Fatty Liver Disease
    (Elsevier, 2018) Siddiqui, Mohammad S.; Vuppalanchi, Raj; Van Natta, Mark L.; Hallinan, Erin; Kowdley, Kris V.; Abdelmalek, Manal; Neuschwander-Tetri, Brent A.; Loomba, Rohit; Dasarathy, Srinivasan; Brandman, Danielle; Doo, Edward; Tonascia, James A.; Kleiner, David E.; Chalasani, Naga; Sanyal, Arun J.; Medicine, School of Medicine
    Background & Aims Vibration-controlled transient elastography (VCTE), which measures liver stiffness, has become an important tool for evaluating patients with nonalcoholic fatty liver disease (NAFLD). We aimed to determine the diagnostic accuracy of VCTE in detection of NAFLD in a multicenter cohort of patients. Methods We performed a prospective study of 393 adults with NAFLD who underwent VCTE within 1 year of liver histology analysis (median time, 49 days; interquartile range, 25–78 days), from July 1, 2014 through July 31, 2017. Liver stiffness measurement (LSM) cutoffs for pairwise fibrosis stage and controlled attenuation parameter (CAP) cutoffs for pairwise steatosis grade were determined using cross-validated area under the receiver operating characteristics curve (AUROC) analyses. Diagnostic statistics were computed at sensitivity fixed at 90% and specificity fixed at 90%. Results LSM identified patients with advanced fibrosis with an AUROC of 0.83 (95% CI, 0.79– 0.87) and patients with cirrhosis with an AUROC of 0.93 (95% CI, 0.90–0.97). At fixed sensitivity, a cutoff LSM of 6.5 kPa excluded advanced fibrosis with a negative predictive value of 0.91; a cut-off LSM of 12.1 kPa excluded cirrhosis with a negative predictive value of 0.99. At fixed specificity, LSM identified patients with advanced fibrosis with a positive predictive 0.71 and patients with cirrhosis with a positive predictive value of 0.41. CAP analysis detected steatosis with an AUROC of 0.76 (95% CI, 0.64–0.87). In contrast, the VCTE was less accurate in distinguishing lower fibrosis stages, higher steatosis grades, or presence of NASH. Conclusion In a prospective study of adults with NAFLD, we found VCTE to accurately distinguish advanced vs earlier stages of fibrosis, using liver histology as the reference standard.