Direct Measurement of Hepatic Extraction of Bile Acids in Subjects with and without Liver Disease

Abstract

1. The hepatic extraction ratio of 14C-labelled bile acids has been measured directly by hepatic vein catheterization in five patients without liver disease (glycocholic acid, three; cholic acid, two) and in 16 patients with histologically confirmed liver disease (glycocholic acid, seven; cholic acid, nine). 2. After intravenous administration of [14C]-glycocholic acid by bolus injection (two control subjects) or constant infusion (one control subject), directly measured hepatic extraction ratio was 0.91, 0.84 and 0.88, greater than that for indocyanine green. The extraction ratio of [14C]cholic acid in two subjects was 0.72 and 0.70, confirming a lower extraction of the unconjugated bile acid. 3. The hepatic extraction ratio of both bile acids was reduced in patients with chronic liver disease (range 0.07-0.69), although the extraction ratio of glycocholic acid remained normal in one patient with viral hepatitis. 4. Estimates of liver flow calculated from the extraction of [14C]glycocholic acid, but not cholic acid, correlated with those calculated from indocyanine green kinetics, although numbers were small. 5. Measurement of the hepatic extraction of individual bile acids, not previously reported in man, allows a more accurate description of the enterohepatic circulation.

Hepatic Uptake of Bile Acids in Man

“…Patient tion of unconjugated bile acids in the portal vein is probably small (cf. 19), the fractional uptake of these bile acids is less than that of conjugated bile acids (20). Unconjugated bile acids are always returning to the liver from the intestine, and the fraction of portal bile acids in unconjugated form might be greater in cholecystectomized patients.…”

Bile Acid Profile as Early Indicator of Allograft Function during Orthotopic Liver Transplantation

“…Less than 1 % of the total is present in pe ripheral blood [17,21], where the levels are maintained low by an efficient liver clear ance which eliminates 80-90% of the conju gated cholate, 70-80% of the conjugated CDCA and lesser percentages of nonconjugated bile acids [7,18], This clearance is car ried out in two steps -elimination from por tal blood and systemic clearance from pe ripheral blood -and depends upon hepato cellular function and hepatic blood flow [18].…”

Model‐based data analysis of individual human postprandial plasma bile acid responses indicates a major role for the gallbladder and intestine

“…However, in contrast to the use of total bile acid responses in (Guiastrennec et al, ), we included the major individual bile acids and their conjugates. In vivo , differences in bile acid hydrophobicity translate into differences in intestinal and hepatic uptake kinetics such as higher passive uptake of unconjugated bile acids from the intestinal lumen (Krag & Phillips, ) and the well‐characterized differences in hepatic extraction rates (Gilmore & Thompson, ; Marigold, Bull, Gilmore, Coltart, & Thompson, ). Therefore, postprandial dynamics and distribution differ between individual bile acids and this is relevant for bile acid receptor signaling.…”