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.

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