Ursocholic acid, a hydrophilic bile acid, fails to improve liver function parameters in primary biliary cirrhosis: comparison with ursodeoxycholic acid.

OBJECTIVE: To compare the effect of short term feeding of ursocholic acid, a hydrophilic bile acid, as the unconjugated acid and the taurine conjugate, on clinical and biochemical features and bile acid metabolism with that of ursodeoxycholic acid in four patients with primary biliary cirrhosis. METHODS: Four patients with stage II primary biliary cirrhosis were studied. Two were fed ursocholic acid (900 mg/day), and two were given tauroursocholate (900 mg/day) in three divided doses. After 1 month, all patients were given 900 mg/day of ursodeoxycholic acid. Fasting serum, bile, and 24-hour urine levels were measured before and at the end of ursocholic acid and tauroursocholate feeding and after 1 month of ursodeoxycholic acid feeding. Clinical and biochemical symptoms were measured by routine hospital methods, and bile acids were measured by gas-liquid chromatography. RESULTS: One month of ursocholic acid or tauroursocholate feeding did not improve clinical or biochemical findings in any patient. Approximately 21-25% ursocholic acid was present in the serum and bile, with substantial metabolism to deoxycholic acid. Increased ursocholic acid was excreted in the urine. In comparison, ursodeoxycholic acid improved biochemical parameters and was 45-65% enriched in the serum and bile. CONCLUSION: Ursocholic acid as the free bile acid or as taurine conjugate, although more hydrophilic, is poorly enriched in serum and bile and is ineffective in patients with primary biliary cirrhosis.

Effect of long-term treatment with ursodiol on clinical and biochemical features and biliary bile acid metabolism in patients with primary biliary cirrhosis.

The effect of ursodiol on the clinical and biochemical features, serum, urinary, and biliary bile acids was investigated over a 2-yr treatment period in 14 patients with primary biliary cirrhosis (stages II-IV). Pruritus and fatigue improved, and alkaline phosphatase and liver transferases declined significantly in all patients during therapy. In four patients, less inflammation was noted by liver biopsy after 2 yr, but histology of disease did not change. Serum and urinary bile acids were increased several-fold before treatment, with cholic acid predominating. Ursodiol accounted for 30% of biliary bile acids after administration (gallstone subjects approximately 50%), and was conjugated with glycine and taurine in a ratio of 7.3:1. However, in the endogenous bile acids, the ratio increased from 1.2:1 to only 2.1:1. About 6% unconjugated bile acids were secreted into the bile (healthy controls < 1%). Thus, in patients with primary biliary cirrhosis, a larger fraction of free bile acids and a higher proportion of taurine-conjugated bile acids are secreted into the bile, compared with healthy controls. Ursodiol improves symptoms and histology with lower biliary enrichment with this bile acid.

Effect of ursodeoxycholic acid on bile acid metabolism in primary biliary cirrhosis.

We have compared the effect of ursodeoxycholic acid with placebo on the clinical state, blood liver chemistries and serum and urinary bile acids in four patients with primary biliary cirrhosis. All parameters were evaluated monthly, and bile acid composition was measured by capillary gas-liquid chromatography. At the time of admission, all patients showed intense pruritus, and their serum alkaline phosphatase, AST and ALT levels were elevated 4.3, 2.7 and 2.3 times over control values. Serum bile acids were elevated almost 38-fold with 2.5 times more cholic acid than chenodeoxycholic acid. Urinary bile acid output was elevated 28 times the control values, and 36% were 1 beta-hydroxycholic acid, 1 beta-hydroxydeoxycholic acid and hyocholic acid (3 alpha,6 alpha, 7 alpha-trihydroxy-5 beta-cholanoic acid). Three months of placebo administration did not significantly affect the clinical or biochemical presentations, and the serum and urinary bile acid composition did not change. In contrast, ursodeoxycholic acid feeding (12 to 15 mg per kg per day) for 6 months abolished pruritus in two and lessened itching in two subjects and reduced serum alkaline phosphatase, AST and ALT levels by 21, 35 and 47%, respectively. The mean values for the total serum bile acid concentrations in these patients declined 26% from the pretreatment value, but the proportion of ursodeoxycholic acid increased from 3 to 40% of the total bile acids; thus, total fasting serum endogenous bile acid levels decreased almost 50%. Similar changes were noted in the urinary bile acids, in which ursodeoxycholic acid became the major bile acid, and approximately 18% were hydroxylated at C-1, C-6 and C-21.(ABSTRACT TRUNCATED AT 250 WORDS)