Browsing by Author "Neuschwander-Tetri, Brent"

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    Comparison of clinical prediction rules for ruling out cirrhosis in nonalcoholic fatty liver disease (NAFLD)
    (Wiley, 2022) Brandman, Danielle; Boyle, Marie; McPherson, Stuart; Van Natta, Mark L.; Sanyal, Arun J.; Kowdley, Kris; Neuschwander-Tetri, Brent; Chalasani, Naga; Abdelmalek, Manal F.; Terrault, Norah A.; McCullough, Art; Bettencourt, Ricki; Caussy, Cyrielle; Kleiner, David E.; Behling, Cynthia; Tonascia, James; Anstee, Quentin M.; Loomba, Rohit; Members of the Nonalcoholic Steatohepatitis Clinical Research Network; Medicine, School of Medicine
    Background and aims: Patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis benefit from referral to subspecialty care. While several clinical prediction rules exist to identify advanced fibrosis, the cutoff for excluding cirrhosis due to NAFLD is unclear. This analysis compared clinical prediction rules for excluding biopsy-proven cirrhosis in NAFLD. Methods: Adult patients were enrolled in the NASH Clinical Research Network (US) and the Newcastle Cohort (UK). Clinical and laboratory data were collected at enrolment, and a liver biopsy was taken within 1 year of enrolment. Optimal cutoffs for each score (eg, FIB-4) to exclude cirrhosis were derived from the US cohort, and sensitivity, specificity, positive predictive value, negative predictive value and AUROC were calculated. The cutoffs were evaluated in the UK cohort. Results: 147/1483 (10%) patients in the US cohort had cirrhosis. All prediction rules had similarly high NPV (0.95-0.97). FIB-4 and NAFLD fibrosis scores were the most accurate in characterising patients as having cirrhosis (AUROC 0.84-0.86). 59/494 (12%) patients in the UK cohort had cirrhosis. Prediction rules had high NPV (0.92-0.96), and FIB-4 and NAFLD fibrosis score the most accurate in the prediction of cirrhosis in the UK cohort (AUROC 0.87-0.89). Conclusions: This cross-sectional analysis of large, multicentre international datasets shows that current clinical prediction rules perform well in excluding cirrhosis with appropriately chosen cutoffs. These clinical prediction rules can be used in primary care to identify patients, particularly those who are white, female, and <65, unlikely to have cirrhosis so higher-risk patients maintain access to specialty care.
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    The Nimble Stage 1 Study Validates Diagnostic Circulating Biomarkers for Nonalcoholic Steatohepatitis
    (Springer Nature, 2023) Sanyal, Arun J.; Shankar, Sudha S.; Yates, Katherine P.; Bolognese, James; Daly, Erica; Dehn, Clayton A.; Neuschwander-Tetri, Brent; Kowdley, Kris; Vuppalanchi, Raj; Behling, Cynthia A.; Tonascia, James; Samir, Anthony; Sirlin, Claude; Sherlock, Sarah P.; Fowler, Kathryn; Heymann, Helen; Kamphaus, Tania N.; Loomba, Rohit; Calle, Roberto A.; Medicine, School of Medicine
    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.