Factors Affecting Plasma Clearance of [14C]Cholic Acid in Patients with Cirrhosis

Abstract

1. Clearance of [14C]cholic acid from the systemic circulation was studied in six normal subjects and eight patients with biopsy-proven hepatic cirrhosis. In both groups, during fasting, the curve for disappearance of radioactivity from the serum during the first 100 min after [14C]cholic acid injection was double-exponential in form. During the early phase, clearance was significantly more rapid, and concentrations of conjugated and free bile acid were significantly lower, in normals than in cirrhotics. 2. Radioactivity disappeared from the systemic circulation of normals within 3 h, and neither intravenous cholecystokinin nor the ingestion of food influenced serum radioactivity. Almost all cirrhotic patients had ‘spontaneous’ rises in serum radioactivity, which began approximately 2 h after [14C]cholic acid injection. Cholecystokinin or food given 4–8 h after [14C]cholic acid administration, produced rises. Continuous aspiration of duodenal juice markedly reduced these rises. Reinfusion of duodenal juice into the upper intestine was followed by a rise in serum radioactivity. 3. All rises were due, almost exclusively, to conjugated bile acids. 4. Impaired bile acid clearance in cirrhotics may result from inefficient hepatic extraction of bile acids, increased leakage of conjugated bile acids from hepatic cells and shunting from portal to systemic circulations. The latter factor is probably responsible for elevated, fluctuating, plasma bile acid concentrations in cirrhotic patients.

Kinetics of 14C-glycocholic acid clearance in normal man and in patients with liver disease.

“…The biexponential shape of the bile acid plasma disappearance curve has been previously noted, but not adequately explained (Kaye et al, 1973;Cowen et al, 1975;Horak et al, 1976). All subjects were fasted, and so enterohepatic recirculation of bile acid during the 90 minute test period is unlikely, and the shape of thecurve is unaffected by duodenal intubation and aspiration of bile (Cowen et al, 1975).…”

Assessment of the plasma disappearance of cholyl'l14C-glycine as a test of hepatocellular disease.

“…In addition, consideration has to be given to the fact that hepatic blood flow is an important factor in the rapid elimination of cholyl-114C-glycine from plasma (Gillette, 1971) and may be reduced in liver disease (Leevy and Kiernan, 1973). Indeed, it has been shown by Kaye et al (1973) that portosystemic shunting of blood leads to delayed plasma elimination of 2414C-cholic acid. A possible explanation for the slight increases in the plasma elimination of cholyl-1l4C-glycine after a fatty meal compared with fasting state could be increases in portal flow.…”

Diagnositic value of serum bile acid estimations in liver disease.

“…Postprandial elevations of serum bile acids in these patients probably result from the passage of bile acids down the intestine to the absorption site in the terminal ileum. In liver disease the elevation of postprandial bile acids results from the inability of the liver cell to remove bile acids from portal blood or from portosystemic shunting by which the bile acids bypass the hepatocyte (Kaye et al, 1973).…”