Original Research Article| Volume 233, P5-15, July 2021

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The within-individual reproducibility of the disease severity index from the HepQuant SHUNT test of liver function and physiology

Published:January 02, 2021DOI:
      The HepQuant SHUNT test quantifies liver function and blood flow using systemic and portal clearances of cholate. The test can identify the risk of well-compensated patients to develop complications of cirrhosis. To confirm the reliability of a single HepQuant SHUNT test we defined its within-individual reproducibility. Healthy subjects (n = 16), 16 with nonalcoholic steatohepatitis (NASH), and 16 with chronic hepatitis C virus (HCV) underwent 3 HepQuant SHUNT tests on 3 separate days within 30 days. The test involves simultaneous administration of 20 mg 13C-cholate IV and 40 mg d4-cholate PO, and subsequent collection of 3 mL blood samples at 5, 20, 45, 60, and 90 minutes. Clearances are expressed as systemic and portal hepatic filtration rate. Portal-systemic shunting (SHUNT), a disease severity index (DSI), and an estimate of DSI (STAT) are calculated from the clearances. Reproducibility was determined by the intraclass correlation coefficient (ICC > 0.70) and Bland-Altman analysis. Equal numbers of NASH and HCV patients had either early (F0-F2) or advanced (F3/F4) stages of fibrosis. All F3/F4 subjects were clinically compensated. The intraclass correlation coefficient (ICC) for DSI was 0.94 (0.90–0.96 95% confidence interval) indicating excellent reproducibility. The other test parameters had ICCs ranging from 0.74 (SHUNT) to 0.90 (STAT). In Bland-Altman analysis, the mean of differences between measurements of DSI was 0.13 with standard deviation 2.12. The excellent reproducibility of the HepQuant SHUNT test, particularly DSI, supports the use this minimally invasive, blood-based test as a reliable test of liver function and physiology.


      13C-CA ([24-13C] cholic acid), CI (confidence interval), CTP (Child-Turcotte-Pugh), d4-CA ([2,2,4,4-2H(d)] cholic acid), DSI (disease severity index), HALT-C (hepatitis C antiviral long-term treatment against cirrhosis), HCV (chronic hepatitis C), HFR (hepatic filtration rate), HVPG (hepatic venous pressure gradient), ICC (intraclass correlation coefficient), INR (international normalized ratio), LC/MS (liquid chromatography/mass spectrometry), MELD (model for end-stage liver disease), NASH (nonalcoholic steatohepatitis)
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