Analysis of Plasma Bile Acid Profiles in Patients with Liver Diseases Associated with Cholestasis

Abstract

Bile acids in plasma of patients with intra- or extra-hepatic cholestasis have been analyzed by gas chromatography-mass spectrometry after fractionation into groups by mode of conjugation. During cholestasis plasma concentrations ranged from 14 to 252 nmol/l. The predominant bile acid was cholic acid, comprising 44% to 89% of total bile acids. Tetrahydroxy- and trihydroxy-cholanoates with a tentative 6-hydroxy structure were identified, whereas 1-hydroxylated bile acids were not found. 3β-Hydroxy-5-cholenoic acid was the most important monohydroxycholanoate, comprising up to 13% of total bile acids in serum. The ratio of cholic to chenodeoxycholic acid in patients with primary biliary cirrhosis was in all cases more than 1. With the exception of 1-hydroxylated bile acids the main bile acids in urine and plasma were the same. Renal clearance of individual conjugated and sulfated bile acids could be calculated for some of the patients, assuming insignificant metabolism of bile acids in the kidney. The renal clearance of cholic acid conjugates tended to be higher than that of chenodeoxycholic acid conjugates, and sulfates of cholic acid conjugates tended to have a higher renal clearance than sulfates of chenodeoxycholic acid conjugates. The clearance of sulfated 3bT-hydroxy-5-cholenoic acid was still smaller. Chenodeoxycholic acid predominated in two healthy persons. Unconjugated bile acids accounted for 30% and 53%, respectively, of total bile acids. Sulfates of lithocholic, allolithocholic, and 3bt-hydroxy-5-cholenoic acids were found after stimulation with a test meal.