Obeticholic acid improves hepatic bile acid excretion in patients with primary biliary cholangitis

Abstract

Hepatocytes Blood 11 C-CSar 11 C-CSar in bile ducts OCA-induced increase over placebo 0% 10% 70% PET of hepatic 11 C-CSar kinetics 11 C-CSar 11 C-CSar in biliary canaliculi Hepatocytes Highlights A randomised, placebo-controlled, crossover PET study of 8 patients with PBC.OCA enhances secretion of conjugated bile acids from hepatocytes into biliary canaliculi.OCA increases hepatic blood perfusion and uptake clearance of conjugated bile acids.OCA reduces the time hepatocytes are exposed to potentially toxic bile acids.

Reply to: “Obeticholic acid and hepatic bile acids: Excellent study faulty conclusion”

“…We appreciate the interest of Dr Javitt 1 in our recent study in patients with primary biliary cholangitis concerning the effect of obeticholic acid on the transport of the bile acid tracer [Nmethyl- 11 C]cholylsarcosine ( 11 C-CSar) from blood to bile, using positron emission tomography (PET). 2 Dr. Javitt questions the conclusion of our study that obeticholic acid enhances the secretion of endogenous conjugated bile acids. However, Dr. Javitt seems not to be familiar with the possibility of quantifying biological processes in vivo using up-to-date molecular tracer techniques based on dynamic PET.…”

Bile formation and secretion: An update

“…Using the conjugated bile acid tracer [N-methyl- 11 C]cholylsarcosine, Kjaergaard et al show that obeticholic acid, which is excreted into bile by BSEP, increased the hepatic transport of the tracer, and thus endogenous conjugated bile acids, from hepatocytes into the canaliculi in patients with PSC, thereby reducing the time hepatocytes are exposed to potentially cytotoxic bile acids. 96 In a separate study in patients awaiting cholecystectomy, obeticholic acid treatment, which increases the biliary cholesterol saturation index, also enriched the bile with FGF19; this possibly led to…”

Obeticholic acid and hepatic bile acids: Excellent study faulty conclusion

“…The excellent studies 1 that clearly demonstrate the enhanced clearance and excretion of [N-methyl-11 C]cholylsarcosine ( 11 S-CSar) following treatment with obeticholic acid do not fulfill criteria established by Gurpide and co-workers 2,3 for tracer studies that provide quantitative information with regard to endogenous pool sizes and their kinetics. Therefore, the conclusion that obeticholic acid improves endogenous bile acid excretion may not be correct.…”