PubMed1975
Although chemistry and physiology of bile acids have been elucidated during the last two decades, tests concerning bile acid metabolism are still rarely used in clinical medicine. The aim of this study therefore was, to investigate bile acid metabolism in patients with liver diseases and to find prognostic valuable parameters which can be recommended for clinical use. Following an introducing review of biosynthesis and kinetics of bile acids, normal values are presented for pool size and synthesis of the two primary bile acids, for bile lipid composition, plasma bile acid concentration and for clearance and conjugation of intravenously injected 14C-cholic acid, which have been measured in healthy subjects. Bile acids were determined by thin-layer-chromatography, gas-liquid-chromatography and by an enzymatic and fluorimetric method. In all patients investigated with acute hepatic necrosis, plasma disappearance of radioactivity was greatly prolonged after intravenous injection of 14C-cholic acid. By estimating free 14C-cholic acid and 14C-cholic acid conjugates in plasma individually, two groups of patients could be distinguished: in patients who survived hepatic coma, the clearance of free 14C-cholic acid was significantly more rapid and the percentage of glycine and taurine conjugates of 14C-cholic acid in plasma was significantly higher than in patients who died in coma. This prognostic significant differentiation was possible by measuring the relationship of conjugated: unconjugated radioactivity in one single plasma sample taken three hours after injection. In patients with cirrhosis of the liver the plasma disappearance rate of radioactivity during 60 minutes following injection of 14C-cholic acid was significantly correlated with serum-bilirubin, SGOT, serum-albumin, prothrombine-time, plasma bile acids, and a clinical scoring. 14C-deoxycholic acid was found in plasma of only a few patients 24 hours after injection of the labelled cholic acid, and was related to the relatively good liver function in these patients. It is concluded that the following tests of bile acid metabolism are of clinical interest: 1. Measuring plasma bile acid concentration may serve as a sensitive liver function test. 2. Estimation of the conjugation of intravenously injected 14C-cholic acid is of prognostic value in patients with fulminant hepatic failure. 3. Determination of the initial plasma disappearance rate of 14C-cholic acid injected intravenously and its transformation to 14C-cholic acid injected intravenously and its transformation to 14C-deoxycholic acid may help to classify patients with cirrhosis of the liver.