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

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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-11C]cholylsarcosine (11C-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 11C-CSar PET/CT (60 min) during fasting and from 15 min after ingestion of a standard liquid meal. Hepatobiliary secretion kinetics of 11C-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 11C-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 11C-CSar was not caused by changes in the basolateral clearance efficacy of 11C-CSar but rather by an upregulated apical transport, as shown by an increase in the rate constant for apical secretion of 11C-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 11C-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.

Original languageEnglish
Article number100288
JournalJHEP Reports
Volume3
Issue3
Number of pages8
ISSN2589-5559
DOIs
Publication statusPublished - Jun 2021

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