BILE-ACID CONJUGATION IN EARLY-STAGE CHOLESTATIC LIVER-DISEASE BEFOREAND DURING TREATMENT WITH URSODEOXYCHOLIC ACID

The efficiency of bile acid conjugation before and during therapy with 600 mg/day of ursodeoxycholic acid was measured in seven adult patien ts with early chronic cholestatic liver disease (6 with primary biliar y cirrhosis; 1 with primary sclerosing cholangitis). Duodenal bile sam ples were obtained by aspiration and the proportion of unconjugated bi le acids was determined using lipophilic anion exchange chromatography to separate bile acid classes, followed by analysis of individual bil e acids by gas chromatography-mass spectrometry. The proportion of con jugated bile acids was determined by high-performance liquid chromatog raphy. Use of a Tc-99m-HIDA recovery marker permitted the absolute mas s of unconjugated bile acids in the gallbladder to be calculated. Unco njugated bile acids comprised 0.4% of total biliary bile acids before and 0.2% during ursodeoxycholic acid therapy, indicating highly effici ent conjugation of bile acids. During therapy, percentage unconjugated ursodeoxycholic acid significantly increased from (mean +/- S.D.) 13 +/- 13% to 54 +/- 12%; P < 0.002. When the unconjugated and conjugated fractions of bile acids were compared, there was an enrichment in unc onjugated fraction for cholic acid and ursodeoxycholic acid and a depl etion for chenodeoxycholic acid both in basal condition and during urs odeoxycholic acid therapy, suggesting that hydrophilic bile acids were conjugated less efficiently. During therapy, the conjugation efficien cy significantly increased for cholic acid and ursodeoxycholic acid. T he pretreatment mass of total unconjugated bile acids in the gallbladd er was (mean +/- S.D.) 4.4 +/- 3.2 mu mol, and was not significantly c hanged by ursodeoxycholic acid therapy (6.2 +/- 3.5 mu mol). However, ursodeoxycholic acid therapy caused a significant increase in the mass of unconjugated ursodeoxycholic acid. It is concluded that endogenous bile acids and exogenous ursodeoxycholic acid when given at the usual dose are efficiently conjugated in patients with early cholestatic li ver disease. Despite showing increased biliary unconjugated ursodeoxch olic acid during its oral administration, our data do not lend support to the occurrence of hypercholeresis due to cholehepatic shunting of bile acids.