Hepatic Bile Acid Transport Increases in the Postprandial State: A functional 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 [-methyl-C]cholylsarcosine (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 C-CSar PET/CT (60 min) during fasting and from 15 min after ingestion of a standard liquid meal. Hepatobiliary secretion kinetics of 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% ( <0.01), and the flow-independent hepatic intrinsic clearance of 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 ( = 0.042). The increased intrinsic clearance of C-CSar was not caused by changes in the basolateral clearance efficacy of C-CSar but rather by an upregulated apical transport, as shown by an increase in the rate constant for apical secretion of C-CSar from hepatocyte to bile from 0.40 (0.25-0.54) min to 0.67 (0.36-0.98) min ( = 0.03). This resulted in a 33% increase in the intrahepatic bile flow ( = 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 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.