Abstract
The HepQuant SHUNT test quantifies hepatic functional impairment from the simultaneous
clearance of cholate from the systemic and portal circulations for the purpose of
monitoring treatment effects or for predicting risk for clinical outcome. Compartmental
models are defined by distribution volumes and transfer rates between volumes to estimate
parameters not defined by noncompartmental analyses. Previously, a noncompartmental
analysis method, called the minimal model (MM), demonstrated reproducible and reliable
measures of liver function (Translational Research 2021). The aim of this study was
to compare the reproducibility and reliability of a new physiologically based compartmental
model (CM) vs the MM. Data were analyzed from 16 control, 16 nonalcoholic steatohepatitis
(NASH), and 16 hepatitis C virus (HCV) subjects, each with 3 replicate tests conducted
on 3 separate days. The CM describes transfer of cholates between systemic, portal,
and liver compartments with assumptions from measured or literature-derived values
and unknown parameters estimated by nonlinear least-squares regression. The CM was
compared to the MM for 6 key indices of hepatic disease in terms of intraclass correlation
coefficient (ICC) with a lower acceptable limit of 0.7. The CM correlated well with
the MM for disease severity index (DSI) with R2 (95% confidence interval) of 0.96 (0.94–0.98, P < 0.001). Acceptable reproducibility (ICC > 0.7) was observed for 6/6 and 5/6 hepatic
disease indices for CM and MM, respectively. SHUNT, a measure of the absolute bioavailability,
had ICC of 0.73 (0.60–0.83, P = 0.3095) for MM and 0.84 (0.76–0.90, P = 0.0012) for CM. The CM, but not the MM, allowed determination of anatomic shunt
and hepatic extraction and improved the within individual reproducibility.
Abbreviations:
13C-CA (carbon-13-labeled cholate), AIC (Akaike Information Criterion), BMI (body mass index), CI (confidence interval), CLD (chronic liver disease), CM (compartmental model), d4-CA (deuterium-labeled cholate), DSI (disease severity index), ER (extraction ratio), HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial), HCV (hepatitis C virus), HFR (hepatic filtration rate), HR (hepatic reserve), ICC (intraclass correlation coefficient), IV (intravenous), LC/MS (liquid chromatography/mass spectrometry), MM (minimal model), MSE (mean squared error), NAFLD (nonalcoholic fatty liver disease), NASH (nonalcoholic steatohepatitis), PK (pharmacokinetics), TBV (total blood volume)To read this article in full you will need to make a payment
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Article Info
Publication History
Published online: August 06, 2022
Accepted:
August 3,
2022
Received in revised form:
July 22,
2022
Received:
June 20,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Inc. All rights reserved.
