Bile Acid Metabolism In Cirrhosis

Abstract

Several recent studies have demonstrated that patients with cirrhosis frequently lack deoxycholic acid in bile and plasma. In order to explain this observation, comparative experiments on the colonic absorption of deoxycholic acid and on the colonic conversion of cholic to deoxycholic acid were carried out in the cirrhotic patients with normal and very low percentages of deoxycholic acid. Deoxycholic or cholic acid (100 mg) plus 5 muc of each [14C] bile acid were administered by enema to 8 patients with and 5 without liver disease. Deoxycholic acid produced a significant increase in the percentage of biliary deoxycholic acid in patients with cirrhosis. However, the rate of appearance of 14C-deoxycholic acid in patients with cirrhosis was slower than in normal control subjects. Distribution of the 14C activity among the bile acids indicated that rehydroxylation of deoxycholic to cholic acid did not occur. The distribution of 14C activity in biliary bile acids after the rectal administration of [14C]cholic acid showed that patients with severe cirrhosis converted [14C]cholic to [14C]deoxycholic acid at a much slower rate than did cirrhotic patients with normal percentages of biliary deoxycholic acid. Feeding of cholic acid (450 mg per day) for 3 days to 4 cirrhotic patients resulted in a 2-fold increase in the percentage of biliary cholic acid, but only a small increase in the percentage of deoxycholic acid. In a separate group of 9 cirrhotic patients, fecal bile acid analysis indicated that cirrhotic patients had a significantly lower percentage of deoxycholic acid than 12 patients without liver disease; there was no significant difference in fecal lithocholic acid. The data suggest that alteration of bacterial flora and/or altered conditions for bacterial 7alpha-dehydroxylase enzyme activity in the colon could account for the virtual absence of biliary deoxycholic acid in severely cirrhotic patients.