Hepatic bile acid transport increases in the postprandial state: A functional (11)C-CSar PET/CT study in healthy humans

BACKGROUND & AIMS: It is not known how hepatic bile acids transport kinetics changes postprandially in the intact liver. We used positron emission tomography (PET)/computed tomography (CT) with the tracer [N-methyl-(11)C]cholylsarcosine ((11)C-CSar), a synthetic sarcosine conjugate of cholic acid, to quantify fasting and postprandial hepatic bile acid transport kinetics in healthy human participants. METHODS: Six healthy human participants underwent dynamic liver (11)C-CSar PET/CT (60 min) during fasting and from 15 min after ingestion of a standard liquid meal. Hepatobiliary secretion kinetics of (11)C-CSar was calculated from PET data, blood samples (arterial and hepatic venous) and hepatic blood flow measured using indocyanine green infusion. RESULTS: In the postprandial state, hepatic blood perfusion increased on average by 30% (p <0.01), and the flow-independent hepatic intrinsic clearance of (11)C-CSar from blood into bile increased by 17% from 1.82 (range, 1.59–2.05) to 2.13 (range, 1.75–2.50) ml blood/min/ml liver tissue (p = 0.042). The increased intrinsic clearance of (11)C-CSar was not caused by changes in the basolateral clearance efficacy of (11)C-CSar but rather by an upregulated apical transport, as shown by an increase in the rate constant for apical secretion of (11)C-CSar from hepatocyte to bile from 0.40 (0.25–0.54) min(−1) to 0.67 (0.36–0.98) min(−1) (p = 0.03). This resulted in a 33% increase in the intrahepatic bile flow (p = 0.03). CONCLUSIONS: The rate constant for the transport of bile acids from hepatocytes into biliary canaliculi and the bile flow increased significantly in the postprandial state. This reduced the mean (11)C-CSar residence time in the hepatocytes. LAY SUMMARY: Bile acids are important for digestion of dietary lipids including vitamins. We examined how the secretion of bile acids by the liver into the intestines changes after a standard liquid meal. The transport of bile acids from liver cells into bile and bile flow was increased after the meal.