The Cholate Challange Test: Clinical Applications for Hepatology by Dr. Gregory Everson

Overview

This lecture by Dr. Gregory T. Everson presents the Cholate Challenge Test (Hepquant DUO), a non-invasive quantitative liver function test, detailing its physiological basis, clinical parameters, and practical applications in advanced chronic liver disease management.

Key Clinical Topics

• Mechanism and administration of the Hepquant DUO test using deuterium-labeled cholate
• Derivation of key test parameters: Disease Severity Index (DSI), shunt fraction, and hepatic reserve
• Clinical applications in advanced fibrosis and compensated cirrhosis
• Risk stratification for portal hypertension and large esophageal varices
• Guiding decisions around esophagogastroduodenoscopy (EGD) and antifibrotic therapy eligibility
• Performance of the test in obese and MASLD patient populations

Key Learning Points

• Hepquant DUO test: Administered orally using D4-cholate (deuterium-labeled); blood samples drawn at 20 and 60 minutes; clearance curves generate liver function parameters
• Hepatic extraction in health: Approximately 80% of orally administered cholate is extracted in a single hepatic pass; only 20% reaches systemic circulation
• Disease Severity Index (DSI): Proprietary composite score reflecting hepatic function impairment; correlates with histologic staging and variceal risk
• Shunt fraction: Quantifies the proportion of portal flow bypassing hepatic extraction into systemic circulation; increases with progressive liver disease
• Hepatic reserve: Patient-facing metric scored 0–100%, representing remaining functional liver capacity relative to healthy lean individuals
• Standard LFTs in advanced disease: Bilirubin, albumin, INR, and platelet count may remain essentially normal even in compensated cirrhosis with large esophageal varices, underscoring the limitations of conventional testing
• Target population: Adults with advanced fibrosis, suspected portal hypertension, compensated cirrhosis, or apparent recompensated decompensated cirrhosis
• Obesity and MASLD: The test maintains diagnostic accuracy in obese populations using the same cutoffs, unlike some established algorithms
• Hepquant tests are not yet FDA approved; analyzed exclusively in Hepquant's CLIA-certified laboratory in Denver, Colorado

Clinical Data & Study Results

• Burton et al. (455 subjects): DSI demonstrated stepwise worsening across healthy lean controls, obese controls, advanced fibrosis, cirrhosis without varices, cirrhosis with small varices, and cirrhosis with large varices; standard LFTs showed no significant differentiation across these groups
• DSI < 18.3: Associated with low risk for portal hypertension and large esophageal varices; application of this threshold could reduce unnecessary EGDs by 41%
• DSI > 24: Associated with high risk for large esophageal varices; EGD recommended with close clinical follow-up
• Platelet count ≥ 135,000 in intermediate DSI zone (18.3–24): Associated with low variceal risk; combined with DSI < 18.3 cutoff, reduces unnecessary EGDs by up to 60%
• Platelet count < 135,000 in intermediate DSI zone: Reclassifies patient to higher risk; EGD and intensive follow-up recommended
• ShuntV pivotal study (23 U.S. centers): Population was 87% overweight, >66% obese, >50% diabetic, >50% with MASLD; DSI maintained same sensitivity and miss rate for large varices as in normal-weight cohorts
• Case example: 51-year-old woman, BMI 39, MASLD, biopsy-proven F3–F4 fibrosis, HVPG 7 mmHg; DSI 33, shunt 60%, hepatic reserve 45%; EGD confirmed large varices requiring banding; deemed ineligible for resmetirom

Practical Takeaways

• Consider Hepquant DUO testing in