Biliary bile acids in primary biliary cirrhosis: effect of ursodeoxycholic acid

Abstract

Bile acid composition in fasting duodenal bile was assessed at entry and at 2 years in patients with primary biliary cirrhosis (PBC) enrolled in a randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) (10-12 mg/kg/d) taken as a single bedtime dose. Specimens were analyzed by a high-pressure liquid chromatography method that had been validated against gas chromatography. Percent composition in bile (mean +/- SD) for 98 patients at entry for cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA), lithocholic (LCA), and ursodeoxycholic (UDCA) acids, respectively, were 57.4 +/- 18.6, 31.5 +/- 15.5, 8.0 +/- 9.3, 0.3 +/- 1.0, and 0.6 +/- 0.9. Values for CA were increased, whereas those for CDCA, DCA, LCA, and UDCA were decreased when compared with values in normal persons. Bile acid composition of the major bile acids did not change after 2 years on placebo medication. By contrast, in patients receiving UDCA for 2 years, bile became enriched with UDCA on average to 40.1%, and significant decreases were noted for CA (to 32.2%) and CDCA (to 19.5%). No change in percent composition was observed for DCA and LCA. Percent composition at entry and changes in composition after 2 years on UDCA were similar in patients with varying severity of PBC. In patients whose bile was not enriched in UDCA (entry and placebo-treated specimens), CA, CDCA, DCA, and the small amount of UDCA found in some of these specimens were conjugated to a greater extent with glycine (52%-64%) than with taurine (36%-48%). Treatment with UDCA caused the proportion of all endogenous bile acids conjugated with glycine to increase to 69% to 78%, while the proportion conjugated with taurine (22%-31%) fell (P <.05). Administered UDCA was also conjugated predominantly with glycine (87%).

Fig. 1

Changes in bile acid composition for the major bile acids in bile according to stratum (1, 2, 3–4) after 2 years of treatment with placebo or UDCA.

Fig. 2

Comparison of percent CA (A), and percent CDCA (B) with percent UDCA in bile after 2 years of treatment with UDCA. The numbers indicate the stratum from which each bile specimen was obtained.

Fig. 3

Mode of conjugation, expressed as percent conjugation with glycine (mean ± SE), for endogenous bile acids (CA, CDCA, DCA), and UDCA in biliary bile acids of PBC patients on entry or after treatment with placebo (light stippling) or after treatment with UDCA (dark stippling). Patients who were pretreatment or who had been treated with placebo had < 5% UDCA in biliary bile acids; those treated with UDCA had > 30% UDCA in biliary bile acids. Treatment with UDCA caused the proportion of bile acids conjugated with glycine to increase (P < .05). ( ), UDCA < 5%; ( ), UDCA > 30%.