Background & Aims
Hepatobiliary secretion of bile acids is an important liver function. Here, we quantified
the hepatic transport kinetics of conjugated bile acids using the bile acid tracer
[N-methyl-11C]cholylsarcosine (11C-CSar) and positron emission tomography (PET).
Methods
Nine healthy participants and eight patients with varying degrees of cholestasis were
examined with 11C-CSar PET and measurement of arterial and hepatic venous blood concentrations of
11C-CSar.
Results
Results are presented as median (range). The hepatic intrinsic clearance was 1.50
(1.20–1.76) ml blood/min/ml liver tissue in healthy participants and 0.46 (0.13–0.91)
in patients. In healthy participants, the rate constant for secretion of 11C-CSar from hepatocytes to bile was 0.36 (0.30–0.62) min−1, 20 times higher than the rate constant for backflux from hepatocytes to blood (0.02,
0.005–0.07 min−1). In the patients, rate constant for transport from hepatocyte to bile was reduced
to 0.12 (0.006–0.27) min−1, 2.3 times higher than the rate constant for backflux to blood (0.05, 0.04–0.09). The increased
backflux did not fully normalize exposure of the hepatocyte to bile acids as mean
hepatocyte residence time of 11C-CSar was 2.5 (1.6–3.1) min in healthy participants and 6.4 (3.1–23.7) min in patients. The rate constant for transport of 11C-CSar from intrahepatic to extrahepatic bile was 0.057 (0.023–0.11) min−1 in healthy participants and only slightly reduced in patients 0.039 (0.017–0.066).
Conclusions
This first in vivo quantification of individual steps involved in the hepatobiliary secretion of a conjugated
bile acid in humans provided new insight into cholestatic disease.
Lay summary
Positron emission tomography (PET) using the radiolabelled bile acid (11C-CSar) enabled quantification of the individual steps of the hepatic transport of
bile acids from blood to bile in man. Cholestasis reduced uptake and secretion and
increased backflux to blood. These findings improve our understanding of cholestatic
liver diseases and may support therapeutic decisions.
Clinical trial registration number: The trial is registered at ClinicalTrials.gov
(NCT01879735).
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: February 26, 2017
Accepted:
February 17,
2017
Received in revised form:
January 23,
2017
Received:
August 9,
2016
Identification
Copyright
© 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
