Within‐individual reproducibility of a dual sample oral cholate challenge test (DuO) and simplified versions of the HepQuant SHUNT test

Abstract

Current noninvasive liver tests measure fibrosis, inflammation, or steatosis and do not measure function. The HepQuant platform of noninvasive tests uniquely assesses both liver function and physiology through the hepatic uptake of stable isotopes of cholate. However, the prototypical HepQuant SHUNT test (SHUNT V1.0) is cumbersome to administer, requiring intravenous and oral administration of cholate and six peripheral venous blood samples over 90 min. To alleviate the burden of test administration, we explored whether an oral only (DuO) version, and other simplified versions, of the test could provide reproducible measurements of liver function. DuO requires only oral dosing and two blood samples over 60 min. The simplified SHUNT test versions were SHUNT V1.1 (oral and IV dosing but four blood samples) and SHUNT V2.0 (oral and IV dosing but only two blood samples over 60 min). In this paper, we describe the reproducibility of DuO and the simplified SHUNT tests relative to that of SHUNT V1.0; equivalency is described in a separate paper. Data from two studies comprising 236 SHUNT tests in 94 subjects were analyzed retrospectively by each method. All simplified methods were highly reproducible across test parameters with intraclass correlation coefficients >0.93 for test parameters Disease Severity Index (DSI) and Hepatic Reserve. DuO and SHUNT V2.0 improved reproducibility in measuring portal‐systemic shunting (SHUNT%). These simplified tests, particularly DuO and SHUNT V2.0, are easier to administer and less invasive, thus, having the potential to be more widely accepted by care providers administering the test and by patients receiving the test.

Liver function and portal‐systemic shunting quantified by the oral cholate challenge test and risk for large oesophageal varices

“…The methods for calculating the parameters of the HepQuant SHUNT test and their within-individual reproducibility are described in detail in separate publications. 17,18 The following test parameters were calculated:…”

“…Various HepQuant test versions were computed from measurements of labelled cholate concentrations in blood samples collected using the HepQuant SHUNT test. These test versions have been previously described 12,18 and are summarised below.…”

“…• SHUNT V2.0 further simplifies by shortening the testing window and requiring only two blood draws at 20 and 60 min. SHUNT V2.0 uses a compartmental model 18,20 to measure portal cholate clearance and noncompartmental exponential fits to measure systemic cholate clearance.…”