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Deuterium-labelled cholate (also known as d4-cholate or 2,2,4,4-d4-cholic acid) is a stable isotope-labeled diagnostic drug developed by HepQuant. It is used as a non-radioactive tracer in quantitative liver function tests, such as the HepQuant SHUNT and HepQuant DuO tests, to assess hepatocyte function, portal blood flow, and portal-systemic shunting. Following oral administration, d4-cholate is absorbed and transported to the liver via the portal vein, where it undergoes first-pass hepatic extraction mediated by basolateral transporters like NTCP and OATPs. In patients with chronic liver disease, impaired hepatocyte uptake and portal-systemic shunting lead to increased spillover of d4-cholate into the systemic circulation. The clearance of d4-cholate is measured in peripheral blood samples using LC-MS/MS to calculate the Disease Severity Index (DSI), which helps stratify liver disease severity, predict clinical decompensation, and rule out large esophageal varices.
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