Purpose NASH is very difficult to diagnose and stage and the only accepted method is liver biopsy.. The HepQuant ® SHUNT test generates a disease severity index DSI which is a global
Trang 1Purpose
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
Results
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)
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
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
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
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Conclusions
The HepQuant-SHUNT test could be a
minimally-invasive alternative to biopsy for the diagnosis of NASH
The HQ-SHUNT test DSI could outperform fibrosis stage
in assessing NASH disease severity
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Methods
There were 50 healthy controls, 30 of
normal weight (BMI 18.5-25), 16 overweight
(BMI 25-30), and 4 obese (BMI>30) Patients
were from 2 centers, University of Colorado
Denver (N=16) and Baylor University
Medical Center Dallas (N=15), and 27 had
biopsy-diagnosed NASH and 4 had
cryptogenic cirrhosis, concurrent obesity,
and presumed late stage NASH There were
4 patients with Brunt-Kleiner fibrosis stage
F1, 4 with F2, 5 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 13
C-Cholate and oral d4-C-Cholate Clearances of
13 C-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)
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HepQuant ® SHUNT Test Function Map
Portal Vein
Hepatic Artery
Oral d4-Cholate
(40 mg)
IV 13 C-Cholate (20 mg)
LCMS of serum
13 C-Cholate
LCMS of serum d4-Cholate
Intestinal Bile Salt Transporters
Liver Bile Salt Transporters Clear Both Cholates
Hepatic Vein
Timed peripheral blood sampling
X-axis is the Portal HFR, the ability to process the hepatic portal circulation
(range 1 - 50 mL/min/kg)
Y-axis is the Systemic HFR, the ability to process the systemic circulation
(range 1 – 10 mL/min/kg)
Diagonals are the Portal-Systemic SHUNT fraction
(range 10% -120%) Distance on the map from the upper right corner (upper limit of normal) is the Disease Severity Index (DSI) (range 0 – 50)
The optimum cutoff for differentiating NASH Patients from Controls was DSI 16.5
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HepQuant® SHUNT Test
AUROC c-statistic optimum cutoff Sens Spec PPV NPV Youden
Index (J)
HQ-SHUNT 0.92 DSI > 28 89% 91% 80% 95% 0.80
Biopsy 0.80 Cirrhosis 100% 59% 50% 100% 0.59
Identifying NASH Patients with Med/Lg Varices
AUROC c-statistic optimum cutoff Sens Spec PPV NPV Youden
Index (J)
HQ-SHUNT 0.99 DSI > 28 100% 95% 90% 100% 0.95
Biopsy 0.80 Cirrhosis 100% 59% 50% 100% 0.59
Identifying NASH Patients with Decompensation
AUROC c-statistic optimum cutoff Sens Spec PPV NPV Youden
Index (J)
HQ-SHUNT 0.94 DSI > 16.5 84% 98% 96% 91% 0.82
Clearances Define Hepatic Filtration Rates
(HFRs)