Hepatic bile acid transport increases in the postprandial state: A functional 11C-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-C-11]cholylsarcosine (C-11-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-11-CSar PET/CT (60 min) during fasting and from 15 min after ingestion of a standard liquid meal. Hepatobiliary secretion kinetics of C-11-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 C-11-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 C-11-CSar was not caused by changes in the basolateral clearance efficacy of C-11-CSar but rather by an upregulated apical transport, as shown by an increase in the rate constant for apical secretion of C-11-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 C-11-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. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).

Automated summary

This study investigated the changes in hepatic bile acid transport kinetics in healthy individuals postprandially using PET/CT with tracer C-11-CSar. The results showed an increase in hepatic blood perfusion and flow-independent hepatic intrinsic clearance of C-11-CSar after a standard liquid meal. The rate constant for bile acid transport from hepatocytes into biliary canaliculi and bile flow significantly increased in the postprandial state.