Evidence Supporting Utility of the Oral Cholate Challenge Test of Liver Function and Physiology to Aid Clinical Management: A Review of Analytical and Clinical Validation Studies

Abstract

Current standard liver assessments rely on static laboratory values that reflect advanced disease or liver injury rather than overall hepatic health. This limitation highlights the need for dynamic measures of liver function to support accurate risk stratification, therapeutic monitoring, and clinical trial design. Quantitative liver function tests address this gap by providing physiologically based measures of hepatic clearance. Among these, cholate clearance is uniquely suited to assess hepatocellular function and portal-systemic shunting—key determinants of disease severity and prognosis. The oral cholate challenge test (OCCT), HepQuant DuO, is a simple, noninvasive method for quantifying cholate clearance using stable isotope-labeled cholate and liquid chromatography–tandem mass spectrometry analysis. This review highlights the test’s analytical and clinical validation across the spectrum of chronic liver disease. The test’s output parameters, Disease Severity Index, SHUNT%, and hepatic reserve, correlate with portal hypertension, varices, and risk for clinical outcomes. Applications for guiding endoscopic screening, predicting decompensation, and monitoring treatment response are highlighted. Comparative analyses show that the OCCT parameters outperform conventional laboratory tests of liver function and may complement anatomic or physical measurements, such as histology, magnetic resonance imaging, or elastography. Additional data supports its role as a sensitive biomarker and reasonably likely surrogate endpoint for drug trials of chronic liver disease. The OCCT addresses critical gaps in chronic liver disease and drug development and has the potential to transform the assessment of the patient with chronic liver disease.