deoxycholic-acid and Hepatitis

Different bile acids have different effects on liver cells, depending on the degree of hydroxylation of the bile acid and the orientation of hydroxy groups. In decreasing order of hydrophobicity, and therefore hepatotoxicity, the bile acids may be ranked as follows: lithocholic greater than deoxycholic greater than chenodeoxycholic greater than cholic greater than ursodeoxycholic acid. The rationale for the use of ursodeoxycholic acid in chronic liver disease is to increase the overall hydrophilicity of the bile acid pool, which, because of cholestasis, retains potentially hepatotoxic bile acids. Recent clinical studies have indicated that ursodeoxycholic acid improves liver function indices in patients with primary biliary cirrhosis and chronic hepatitis at doses ranging between 10 and 15 mg/kg/day. These doses would be considered in the high range in the use of ursodeoxycholic acid for gallstone dissolution. In a preliminary study we found that also lower doses were effective in primary biliary cirrhosis. Two studies to determine the optimal dose of ursodeoxycholic acid for chronic hepatitis and anicteric primary biliary cirrhosis were then carried out. Eighteen patients with primary biliary cirrhosis and 12 patients with chronic hepatitis were treated with 250, 500, and 750 mg of ursodeoxycholic acid per day for three consecutive 2-month periods. Highly significant decreases in serum enzyme levels were seen with the 250 mg/day dose, which were further improved by the higher doses. The improvement roughly paralleled the enrichment of conjugated bile acids with ursodeoxycholic acid. A separate study investigating the effect of shifting the bile acid pool composition toward less detergent moieties was also done.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Chronic Disease; Clinical Trials as Topic; Deoxycholic Acid; Hepatitis; Humans; Liver Cirrhosis, Biliary; Ursodeoxycholic Acid

Topics: Bile Acids and Salts; Bile Ducts; Cholestasis; Cholestyramine Resin; Deoxycholic Acid; Disease Models, Animal; Female; Glucuronates; Hepatitis; Humans; Ligation; Lithocholic Acid; Liver; Liver Cirrhosis; Male; Phenobarbital; Pregnancy; Pregnancy Complications; Sterols; Sulfates

Different bile acids have different effects on liver cells, depending on the degree of hydroxylation of the bile acid and the orientation of hydroxy groups. In decreasing order of hydrophobicity, and therefore hepatotoxicity, the bile acids may be ranked as follows: lithocholic greater than deoxycholic greater than chenodeoxycholic greater than cholic greater than ursodeoxycholic acid. The rationale for the use of ursodeoxycholic acid in chronic liver disease is to increase the overall hydrophilicity of the bile acid pool, which, because of cholestasis, retains potentially hepatotoxic bile acids. Recent clinical studies have indicated that ursodeoxycholic acid improves liver function indices in patients with primary biliary cirrhosis and chronic hepatitis at doses ranging between 10 and 15 mg/kg/day. These doses would be considered in the high range in the use of ursodeoxycholic acid for gallstone dissolution. In a preliminary study we found that also lower doses were effective in primary biliary cirrhosis. Two studies to determine the optimal dose of ursodeoxycholic acid for chronic hepatitis and anicteric primary biliary cirrhosis were then carried out. Eighteen patients with primary biliary cirrhosis and 12 patients with chronic hepatitis were treated with 250, 500, and 750 mg of ursodeoxycholic acid per day for three consecutive 2-month periods. Highly significant decreases in serum enzyme levels were seen with the 250 mg/day dose, which were further improved by the higher doses. The improvement roughly paralleled the enrichment of conjugated bile acids with ursodeoxycholic acid. A separate study investigating the effect of shifting the bile acid pool composition toward less detergent moieties was also done.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Chronic Disease; Clinical Trials as Topic; Deoxycholic Acid; Hepatitis; Humans; Liver Cirrhosis, Biliary; Ursodeoxycholic Acid

The perturbations in bile acids (BAs) in alcohol-associated hepatitis (AH) and its relationship to disease severity is not well defined. The aims of this study were to define (1) the effects of heavy alcohol consumption on BAs and related microbiome, (2) the additional changes with AH, and (3) the relationship of these changes to disease severity. In this multicenter study, plasma and fecal BAs and related microbiome were interrogated in healthy individuals, heavy drinking controls (HDCs) without overt liver disease, and AH. Compared to healthy controls, HDCs had increased glycine-conjugated 7α and 27α primary BAs and increased secondary BA glycocholenic sulfate (multiple-comparison adjusted P < 0.05 for all). Plasma-conjugated cholic and chenodeoxycholic acid increased in AH along with the secondary BAs ursodeoxycholic and lithocholic acid (P < 0.001 for all), whereas deoxycholic acid decreased; however fecal concentrations of both deoxycholic acid and lithocholic acid were decreased. Glycocholenic acid further increased significantly from HDCs to AH. HDCs and AH had distinct plasma and fecal BA profiles (area under the curve, 0.99 and 0.93, respectively). Plasma taurochenodeoxycholic acid and tauroursodeoxycholic acid were directly related to disease severity, whereas fecal ursodeoxycholic acid was inversely related. The fecal abundance of multiple taxa involved in formation of secondary BAs, especially deoxycholic acid (Clostridium cluster XIVa) was decreased in AH. Multiple genera containing taxa expressing 3α, 3β, 7α, and 7β epimerases were decreased with concordant changes in fecal BAs that required these functions for formation. Conclusion: There are distinct changes in BA-transforming microbiota and corresponding BAs in AH that are related to disease severity.

Topics: Bile Acids and Salts; Deoxycholic Acid; Feces; Hepatitis; Humans; Lithocholic Acid

Topics: Bile Acids and Salts; Biological Availability; Deoxycholic Acid; Diagnosis, Differential; Hepatitis; Humans; Liver Cirrhosis; Liver Diseases; Liver Function Tests; Ursodeoxycholic Acid

Serial measurement of serum bile acid levels was carried out in patients with digestive diseases before and after oral loading with 500 mg of ursodeoxycholic acid. In control cases, serum bile acid reached the maximum level 30 min after loading. Elevation also, of cholic, chenodeoxycholic and deoxycholic acid levels was noted in addition to marked enhancement of the ursodeoxycholic acid level. In patients with chronic aggressive hepatitis and cirrhosis, the serum bile acid level was higher than the controls in fasting state, and increased more significantly after loading. On the other hand, in patients with small intestinal disorders, the serum bile acid level in fasting state tended to be lower than the controls, and became significantly lower after loading. Thus, oral ursodeoxycholic acid tolerance test is found to be useful as a diagnostic test for digestive diseases.

Topics: Adult; Bile Acids and Salts; Deoxycholic Acid; Digestive System Diseases; Female; Hepatitis; Humans; Intestinal Diseases; Liver Cirrhosis; Male; Ursodeoxycholic Acid

We describe a method for radioimmunoassay of conjugated cholic acid, chenodeoxycholic acid, and deoxycholic acid in serum. In the method, 125I-labeled bile acid conjugates are used as the tracers along with antibodies raised against individual bile acid-bovine serum albumin conjugates. Antibody-bound and free bile acids were separated by polyethylene glycol precipitation (final concentration, 125 g/L). Before radioimmunoassay, 0.1-mL serum samples were precipitated with nine volumes of ethanol, and portions from the supernate were used in the assays. The lowest measurable amounts of the bile acids, expressed as pmol/tube, were: cholic acid conjugates, 2; chenodeoxycholic acid conjugates, 0.5; and deoxycholic acid conjugates. 2. Analytical recovery of bile acids added to bile acid-free serum ranged from 85 to 110%; intra-assay and inter-assay CVs ranged from 3.2 to 5.3% and from 5.3 to 12.2%, respectively. Concentrations (mean +/- SD) of the bile acid conjugates in serum from apparently healthy women and men (in mumol/L) were: cholic acid conjugates, 0.43 +/- 0.17 (n = 126); chenodeoxycholic acid conjugates, 0.47 +/- 0.23 (n = 111); and deoxycholic acid conjugates, 0.33 +/- 0.11 (n = 96). The values for primary bile acids were greatly increased in patients with various hepatobiliary diseases.

Topics: Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Deoxycholic Acid; Female; Hepatitis; Humans; Liver Cirrhosis; Male; Pregnancy; Pregnancy Complications; Radioimmunoassay

A sensitive radioimmunoassay for cholylglycine, chenodeoxycholylglycine, deoxycholylglycine, and sulfolithocholylglycine was established using antibodies obtained from rabbits injected with albumin conjugates of these bile acids. Glycine-conjugated bile acid levels were measured in sera from 25 control subjects and 110 patients who had hepatic disease (alcoholic cirrhosis, hepatitis, cholestasis, and hepatic malignancy). Sulfolithocholylglycine was elevated in the sera of all 110 patients with hepatic disease. Cholylglucine was within normal range in only three. Chenodeoxycholylglycine was elevated in most sera of patients who had hepatitis, cholestasis, or hepatic malignancy. It was normal in most sera of patients who had alcoholic cirrhosis, suggesting that chenodeoxycholic acid may be subject to further biotransformations in these patients. Deoxycholylglycine was elevated in a minority of patients, none of whom had cholestasis. The data suggest that serum bile acids, particularly sulfolithocholylglycine, are a highly sensitive index for hepatic dysfunction.

Topics: Alcoholism; Biliary Tract Diseases; Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Deoxycholic Acid; Glycocholic Acid; Hepatitis; Humans; Lithocholic Acid; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Radioimmunoassay

Large amounts of bile acid sulfate were found in the urine of patients with hepatobiliary diseases. In patients with acute hepatitis, daily excretion of bile acid into urine was 68.24 plus or minus 51.80 mumoles per day, and the percentage of sulfated bile acid was 83.4 plus or minus 16.7%. In patients with chronic hepatitis and cirrhosis, a slight increase of urinary bile acid was observed (2.89 plus or minus 2.69 and 5.27 plus or minus 4.28 mumoles per day, respectively), and the percentage of sulfated bile acid was 73.9 plus or minus 28.6 and 44.6 plus or minus 30.4%, respectively. In patients with obstructive jaundice, a moderate increase of urinary bile acid was found (32.62 plus or minus 18.35 mumoles per day), and the percentage of sulfated bile acid was 58.3 plus or minus 22.6%. In patients with hepatobiliary diseases, the elevation of both levels of sulfated and nonsulfated bile acids in serum was observed. The percentage of sulfated bile acid was 9% in normal serum, and varied from zero to 82.8% in pathological sera. A remarkable increase of sulfated bile acid was found in patients with obstructive juandice and acute hepatitis, while a slight elevation was found in patients with chronic hepatitis and cirrhosis. Sulfated bile acid in bile was nonexistent or below 0.5% of total bile acid. According to these findings, the increased bile acid in serum of patients with hepatobiliary diseases might be more easily excreted into the urine as sulfated bile acid.

Topics: Bile Acids and Salts; Biliary Tract Diseases; Carbon Radioisotopes; Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Chromatography, Gas; Deoxycholic Acid; Female; Hepatitis; Humans; Liver Cirrhosis; Liver Diseases; Male; Sulfates

Topics: Acute Disease; Adult; Ampulla of Vater; Bile Acids and Salts; Bile Duct Neoplasms; Carcinoma; Chenodeoxycholic Acid; Cholic Acids; Chromatography, Gel; Chromatography, Ion Exchange; Chromatography, Thin Layer; Deoxycholic Acid; Female; Glycocholic Acid; Hepatitis; Humans; Liver Function Tests; Male; Middle Aged; Sulfuric Acids; Taurocholic Acid

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