deoxycholic-acid and Hepatic-Encephalopathy

Topics: Ammonia; Animals; Blood-Brain Barrier; Capillary Permeability; Deoxycholic Acid; Hepatic Encephalopathy; Rats; Rats, Inbred Strains

The urinary and fecal bile acids of thirteen male patients with liver cirrhosis were analyzed by gas chromatography and gas chromatography-mass spectrometry to obtain information on their keto bile acid excretion. 3 alpha-Hydroxy-12-keto-5 beta-cholanoic, 3 alpha,12 alpha-dihydroxy-7-keto-5 beta-cholanoic, 3 alpha,7 alpha-dihydroxy-12-keto-5 beta-cholanoic and 3 alpha-hydroxy-7,12-diketo-5 beta-cholanoic acids were found in the urine of ten patients. In four of these patients, keto bile acids were the main bile acids excreted in the urine. However, the ratios of fecal keto bile acids to the total fecal bile acids in these four patients were similar to those in the other six patients whose urinary excretion of keto bile acids was low. Three of the four patients had clinical abnormalities, such as ascites, esophageal varices or a history of hepatic encephalopathy, that may indicate advanced liver dysfunction and/or presence of collateral circulation. These findings suggest that the occurrence of keto bile acids in the urine might be ascribed to the escape of these acids from reduction to hydroxy-forms in the liver, not to bacterial over-production in the intestine. However, the mechanism and significance of the presence of keto bile acids in the urine are still unknown.

Topics: Adult; Ascites; Bile Acids and Salts; Chenodeoxycholic Acid; Deoxycholic Acid; Esophageal and Gastric Varices; Feces; Hepatic Encephalopathy; Humans; Lithocholic Acid; Liver Cirrhosis; Male; Middle Aged

Bile acid pool size and kinetics were determined in 17 patients with cirrhosis and 11 patients without liver disease and correlated with the severity of liver disease as determined by the usual clinical and laboratory criteria. In order to assess the severity of liver disease, a grading system was devised which assigned numerical values to various clinical signs and laboratory results. The total clinical score and the patients were divided into two groups of advanced (7-18 points) or mild (1-6 points) cirrhosis. The clinical rating was then correlated with the various aspects of bile acid metabolism. Cholic acid synthesis was markedly reduced in the early stages of cirrhosis and continued to decrease with the advancement of the liver disease. There was an inverse correlation between synthesis of cholic acid and the severity of cirrhosis. Nine of the 10 patients with advanced cirrhosis and a very low cholic acid synthetic rate (average 68 mg per day) died within one to 13 months from the start of the study. Patients with mild cirrhosis also had significantly reduced cholic acid synthesis (average 152 mg per day) but they all were well and alive three to 23 months after the study. In contrast, chenodeoxycholic acid synthesis was not markedly affected in either patients with mild or advanced cirrhosis. There was also a high degree of correlation between the fractional daily turnover rate of cholic acid and the severity of liver disease. The fractional daily turnover rate of cholic acid was greatly reduced (50%) in patients with advanced cirrhosis. Deoxycholic acid was reduced in patients with mild cirrhosis and virtually absent from the bile of patients with advanced cirrhosis. The findings of the present report provide evidence that cholic acid synthesis is a sensitive indicator of the hepatocellular damage, whereas chenodeoxycholic acid synthesis is relatively unaffected by cirrhosis. The selective alteration in cholic acid synthesis probably resides in a deficiency of one or more enzymes regulating the formation of the 3-keto, 7 alpha, 12 alpha-dihydroxy precursor of cholic acid.

Topics: Adult; Aged; Ascites; Bile Acids and Salts; Chenodeoxycholic Acid; Cholic Acids; Deoxycholic Acid; Hepatic Encephalopathy; Humans; Kinetics; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Varicose Veins

Topics: Bile Acids and Salts; Chenodeoxycholic Acid; Cholic Acids; Chromatography, Gas; Deoxycholic Acid; Hepatic Encephalopathy; Humans; Lithocholic Acid; Liver; Liver Cirrhosis; Microscopy, Electron

Topics: Bile Acids and Salts; Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Chronic Disease; Deoxycholic Acid; Hepatic Encephalopathy; Hepatitis; Humans; Lithocholic Acid; Liver Cirrhosis; Liver Diseases