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, doubleblind, 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 placebotreated 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 F .05). Administered UDCA was also conjugated predominantly with glycine (87%). (HEPATOLOGY 1999;29:1649-1654.)
Despite extensive use of ursodeoxycholic acid (UDCA) in the therapy of primary biliary cirrhosis (PBC), relatively little information is available on the effect of UDCA on the composition of bile acids excreted in bile. Mazzella et al. 1 presented data for 9 patients with histological stages I to III after 4 weeks of 600 mg/d. Van de Meeberg et al. 2 in their report on cholestatic liver disease included data from 8 patients with PBC receiving 10 mg/kg/d for 3 months. Crosignani et al. 3 provided their findings at 6 months for 10 patients (7 with stage IV histology, 1 each in stages I, II, and III) receiving 8 mg/kg/d (500 mg/d). Batta et al. 4 reported their findings on 3 patients receiving 10 to 12 mg/kg/d (900 mg/d) for 6 months.
In the present report, data on bile acid composition in bile are provided for a much larger number of patients who were enrolled in a 2-year, randomized, double-blind, placebocontrolled trial of UDCA in PBC. 5 Bile was analyzed in 98 patients obtained at the time of entry into the trial, and 2 years later from 51 patients who had been randomized to receive placebo medication and 55 patients receiving UDCA at bedtime at a dose of 10 to 12 mg/kg/d.