2016-11-Diagnosing-NASH-and-Severity-Poster-FINAL-AASLD

1 Diagnosing NASH and Assessing NASH Disease Severity by a ® Global Measure of Liver Function, the HepQuant SHUNT Test Steve Helmke1, John D Marr2, Michael Cookson1, Jennifer DeSanto1, Shannon Lauriski1, James F Trotter2, Gregory T Everson1 1.University of Colorado Anschutz Medical Campus, Aurora, CO; 2.Baylor University Medical Center, Dallas, TX Purpose HepQuant® SHUNT Test Function Map NASH is very difficult to diagnose and stage and the only accepted method is liver biopsy The patchy nature of NASH fibrosis causes biopsy sampling error and 40% variability in staging (Ratziu, et al, 2005) The HepQuant® SHUNT test generates a disease severity index (DSI) which is a global measure of liver function The goal of this pilot study was to determine if DSI could diagnose NASH and assess NASH disease severity Diagnosing NASH (31 Patients vs 50 Controls) Results AUROC optimum cutoff c-statistic HQ-SHUNT 0.94 DSI > 16.5 Sens Spec PPV NPV Youden Index (J) 84% 98% 96% 91% 0.82 The HepQuant SHUNT DSI could differentiate NASH patients from healthy control subjects, even overweight and obese controls, with high AUROC c-statistic, specificity, PPV, and Youden Index (J) Identifying NASH Patients with Med/Lg Varices AUROC optimum cutoff c-statistic HQ-SHUNT 0.92 Biopsy 0.80 DSI > 28 Identifying NASH Patients with Decompensation Sens Spec PPV NPV Youden Index (J) 89% 91% 80% 95% 0.80 HQ-SHUNT 0.99 0.59 Biopsy 0.80 Cirrhosis 100% 59% 50% 100% AUROC optimum cutoff c-statistic Sens Spec PPV NPV Youden Index (J) 100% 95% 90% 100% 0.95 Cirrhosis 100% 59% 50% 100% 0.59 DSI > 28 Methods There were 50 healthy controls, 30 of normal weight (BMI 18.5-25), 16 overweight (BMI 25-30), and obese (BMI>30) Patients were from centers, University of Colorado Denver (N=16) and Baylor University Medical Center Dallas (N=15), and 27 had biopsy-diagnosed NASH and had cryptogenic cirrhosis, concurrent obesity, and presumed late stage NASH There were patients with Brunt-Kleiner fibrosis stage F1, with F2, with F3, and 18 with F4 (cirrhosis) Clinical manifestations of NASH disease severity were captured from patient histories and included medium/large varices and any decompensation events (ascites, encephalopathy, variceal bleed, or jaundice) The HepQuant® SHUNT test involves serum sampling prior to, and at 5, 20, 45, 60, and 90 minutes after simultaneous administration of IV 13CCholate and oral d4-Cholate Clearances of 13C-Cholate and d4-Cholate were measured and DSI calculated from the clearances The ability of DSI to diagnose NASH and to assess NASH disease severity was evaluated by AUROC analyses (c-statistic) and by the diagnostic performance (sensitivity, specificity, PPV, NPV) at the optimum cutoffs which were defined by the maximum Youden Index (J) Clearances Define Hepatic Filtration Rates (HFRs) LCMS of serum 13C-Cholate X-axis is the Portal HFR, the ability to process the hepatic portal circulation (range - 50 mL/min/kg) LCMS of serum d4-Cholate Timed peripheral blood sampling Liver Bile Salt Transporters Clear Both Cholates Hepatic Artery Portal Vein Intestinal Bile Salt Transporters IV 13C-Cholate (20 mg) Oral d4-Cholate (40 mg) HepQuant® Y-axis is the Systemic HFR, the ability to process the systemic circulation (range – 10 mL/min/kg) Diagonals are the PortalSystemic SHUNT fraction (range 10% -120%) Hepatic Vein Shunt SHUNT Test Distance on the map from the upper right corner (upper limit of normal) is the Disease Severity Index (DSI) (range – 50) The optimum cutoff for differentiating NASH Patients from Controls was DSI 16.5 The HepQuant SHUNT DSI could identify NASH patients at risk of medium/large varices or those at risk of decompensation with a higher AUROC c-statistic, and much better specificity, PPV, and Youden Index (J) than a biopsy diagnosis of cirrhosis Conclusions  The HepQuant-SHUNT test could be a minimallyinvasive alternative to biopsy for the diagnosis of NASH  The HQ-SHUNT test DSI could outperform fibrosis stage in assessing NASH disease severity Financial disclosures: Gregory T Everson and Steve M Helmke have intellectual property rights related to US Patent 8,778,299, “Methods for Diagnosis and Intervention of Hepatic Disorders” Gregory T Everson has equity interest in HepQuant LLC Nothing to disclose: John D Marr, Michael Cookson, Jennifer DeSanto, Shannon Lauriski, and James F Trotter