deoxycholic-acid and Cystic-Fibrosis

Topics: Anti-Infective Agents; Bacterial Adhesion; Biofilms; Cystic Fibrosis; Deoxycholic Acid; Drug Delivery Systems; Escherichia coli; Humans; Methicillin-Resistant Staphylococcus aureus; Nanomedicine; Pseudomonas aeruginosa; Pulmonary Disease, Chronic Obstructive; Staphylococcus aureus; Ursodeoxycholic Acid

To evaluate the fasting and postprandial serum bile acid composition in patients with cystic fibrosis-associated liver disease (CFLD) after chronic administration of ursodeoxycholic acid (UDCA) (20 mg/kg/day). The aim was to specifically focus on the extent of biotransformation of UDCA to its hepatotoxic metabolite, lithocholic acid, because of recent concerns regarding the safety of long-term, high-dose UDCA treatment for CFLD.. Twenty patients with CFLD (median age 16 years, range: 2.4-35.0) prescribed UDCA therapy for at least 2 years were studied. Total and individual serum bile acids were measured by stable-isotope dilution mass spectrometry, in fasting and 2-hour postprandial samples taken during chronic UDCA (20 mg/kg/day) administration.. During chronic UDCA administration (median duration 8 years, IQR: 6-16), UDCA became the predominant serum bile acid in all patients (median, IQR: 3.17, 1.25-5.56 μmol/L) and chenodeoxycholic acid concentrations were greater than cholic acid (1.86, 1.00-4.70 μmol/L vs 0.40, 0.24-2.71 μmol/L). The secondary bile acids, deoxycholate and lithocholate, were present in very low concentrations in fasted serum (<0.05 μmol/L). After UDCA administration, 2-hour postprandial concentrations of both UDCA and chenodeoxycholic acid significantly increased (P < .01), but no significant changes in serum lithocholic acid concentrations were observed.. These data do not support recent suggestions that enhanced biotransformation of UDCA to the hepatotoxic secondary bile acid lithocholic occurs when patients with CFLD are treated with relatively high doses of UDCA.

Topics: Adolescent; Adult; Bile Acids and Salts; Biotransformation; Child; Child, Preschool; Cystic Fibrosis; Deoxycholic Acid; Female; Humans; Lithocholic Acid; Liver Diseases; Male; Tandem Mass Spectrometry; Ursodeoxycholic Acid; Young Adult

The prevalence of biliary and hepatic diseases is increasing in patients with cystic fibrosis as more of them reach adult life. There is no effective treatment or method of preventing cholestasis in cystic fibrosis, although beneficial effects have been ascribed to the tertiary bile acid, ursodeoxycholate, in other forms of chronic cholestasis. We evaluated prospectively the effects of a six month course of ursodeoxycholate (15-20 mg/kg per day) in eight, mostly adult, patients with cystic fibrosis and chronic cholestasis. Bile acid treatment improved inflammatory activity (average decrease in alanine aminotransferase, 60%, p less than 0.005) and cholestasis (alkaline phosphatase, 47%; p less than 0.01) in all patients. Quantitative liver function, measured by 45 minute sulphobromophthalein retention and by the 14C-aminopyrine breath test, improved in all patients while galactose elimination capacity showed a slight decrease. Patients' nutritional state improved as evidenced by a 1.8 kg weight gain and an increase in muscle mass suggested by a 26% increase in 24 hour urinary creatinine excretion. Steatorrhea was not affected by bile acid treatment. Ursodeoxycholic acid may be beneficial in the treatment of chronic cholestasis in cystic fibrosis by improving liver function and also the patient's nutritional state.

Topics: Adolescent; Adult; Child; Cholestasis; Chronic Disease; Cystic Fibrosis; Deoxycholic Acid; Female; Humans; Liver; Liver Function Tests; Male; Nutritional Status; Prospective Studies; Ursodeoxycholic Acid

The biliary bile acid composition was determined for patients with cystic fibrosis and associated liver disease before and after the administration of ursodeoxycholic acid (10 to 15 mg/kg body wt/day). Bile acids were analyzed by fast atom bombardment ionization-mass spectrometry, high performance liquid chromatography and gas chromatography-mass spectrometry after individual bile acids were separated according to their mode of conjugation using the lipophilic anion exchanger, diethylaminohydroxypropyl Sephadex LH-20. More than 50 individual bile acids were identified in the bile of cystic fibrosis patients and these acids were predominantly secreted as glycine and taurine conjugates. Small proportions (less than 8% of the total) of unconjugated and sulfate conjugates were present. Of interest was the identification of two side-chain-elongated (C25) bile acids, homocholic and homochenodeoxycholic acids. After ursodeoxycholic acid was administered, duodenal bile became enriched with the conjugated species of ursodeoxycholic acid (accounting for 11.9% to 32.5% of the total biliary bile acids), but to a lesser extent than reported previously for patients with other liver diseases or gallstones who received comparable doses of ursodeoxycholic acid, and this presumably occurs because of bile acid malabsorption that is a feature of cystic fibrosis. The mean glycine/taurine ratio increased from 2.4 before ursodeoxycholic acid administration to 5 after ursodeoxycholic acid administration even though these patients also received taurine. Despite the relatively low enrichment of the bile by ursodeoxycholic acid, biochemical indices of liver function all improved in these patients after ursodeoxycholic acid administration.

Topics: Adolescent; Bile Acids and Salts; Child; Chromatography, High Pressure Liquid; Cystic Fibrosis; Deoxycholic Acid; Female; Gas Chromatography-Mass Spectrometry; Humans; Liver Diseases; Male; Mass Spectrometry; Ursodeoxycholic Acid

The hydrophilic bile acid ursodeoxycholic acid (UDCA) has recently been shown to improve indexes of liver function in adult patients with various liver diseases. The clinical and biochemical responses to UDCA administration (10 to 15 mg/kg body weight per day) were therefore investigated in nine patients with cystic fibrosis and evidence of liver disease. All patients were receiving pancreatic enzymes and taurine supplementation. Liver function tests were done and serum bile acid concentrations and biliary bile acid composition were determined before and during UDCA therapy; fat balance studies and fecal bile acid excretion were carried out before and 6 months after UDCA treatment. After 2 months of bile acid therapy, biliary bile acid composition was enriched in UDCA from approximately 5% before treatment to 25%, at the expense of cholic and chenodeoxycholic acids, thus making the pool more hydrophilic. This enrichment is lower than that reported for adults with chronic liver diseases. Serum concentrations of UDCA increased significantly but variably. UDCA became the predominant fecal bile acid excreted (12% to 67%), indicating a variable absorption of the administered bile acid. Liver function improved in all patients after 2 to 6 months of therapy, although the degree of improvement (aspartate aminotransferase, -34%; alanine aminotransferase, -41%; gamma-glutamyltranspeptidase, -41% alkaline phosphatase, -19%) was lower than that observed in adults with chronic liver diseases. Mean coefficient of fat absorption and growth rate were, on average, unaffected by UDCA therapy, although an improvement was noted for three patients with greater severity of steatorrhea. The study indicates that UDCA can be used safely in this patient population but that higher doses of UDCA may be of greater benefit in the treatment of the liver disease associated with cystic fibrosis.

Topics: Adolescent; Bile Acids and Salts; Child; Cystic Fibrosis; Deoxycholic Acid; Female; Humans; Liver Diseases; Liver Function Tests; Male; Taurine; Ursodeoxycholic Acid

Topics: Cholecystitis; Cystic Fibrosis; Deoxycholic Acid; Humans; Ursodeoxycholic Acid

Topics: Adult; Cholecystography; Cholelithiasis; Cystic Fibrosis; Deoxycholic Acid; Female; Humans; Male; Ursodeoxycholic Acid

Serum levels of ursodeoxycholic acid (UDCA) were measured by radioimmunoassay in 20 children with cystic fibrosis (CF) and in eight controls, who had received 300 mg of this bile acid orally. Area under the curve (AUC) after UDCA load was significantly reduced (25.24 +/- 9.54) in CF patients, as compared to controls (52.98 +/- 5.87 mean values +/- SD percent dose/liter X hr X kg body weight, P less than 0.001). AUC values were compared with daily fecal bile acids (BA) and fat excretion, and with serum fasting conjugated cholic (CCA) and chenodeoxycholic (CCDCA) acid levels. Total fecal BA were increased in CF patients (7.84 +/- 5.57 mg/kg/day) as compared to control values (2.7 +/- 1.1 mean +/- SD, P less than 00.5); they were inversely correlated with AUC values (r = 0.48) but not with steatorrhea (r = 0.32). UDCA load seems to be useful in detecting BA malabsorption in CF. Fasting CCA levels did not significantly differ in CF patients (0.87 +/- 0.61 mumol/liter) and in controls (0.60 +/- 0.26 mumol/liter) and did not correlate with fecal BA excretion. Fasting CCDCA mean levels were significantly increased (mainly in CF patients with liver damage), suggesting a lowered first-pass extraction in the liver: their determination may be useful in the follow-up of liver involvement in CF.

Topics: Adolescent; Bile Acids and Salts; Chenodeoxycholic Acid; Child; Child, Preschool; Cholic Acids; Cystic Fibrosis; Deoxycholic Acid; Feces; Female; Humans; Intestinal Absorption; Intestinal Mucosa; Lipid Metabolism; Lipids; Male; Ursodeoxycholic Acid

Urinary bile acid excretion and liver morphology were compared in 25 patients with cystic fibrosis (CF). None showed clinical signs of liver disease. Most of the patients had normal liver function tests. Bile acids were determined in 24-h samples by a modification of the method of Almé. All patients had increased urinary excretion of trihydroxy bile acids, mainly cholic, 3 beta, 7 beta, 12 alpha- and 3 alpha, 7 beta, 12 alpha-trihydroxy-5 beta-cholanoic acids. Lithocholic acid excretion was lower in CF than in normal children. The urinary excretion of 3 beta-hydroxy-5-cholenoic acid was not increased in CF. In three patients with cirrhosis the urinary excretion of chenodeoxycholic acid was increased. The ratio of cholic to 3 beta-hydroxy-5-cholenoic acids was increased in all but three patients, and the ratio of chenodeoxycholic to 3 beta-hydroxy-5-cholenoic acids was increased in those with cirrhosis. These ratios differed more between cirrhotic and non-cirrhotic CF patients in this series than the ratio of cholic to chenodeoxycholic acids.

Topics: Adolescent; Adult; Bile Acids and Salts; Child; Child, Preschool; Cholic Acids; Cystic Fibrosis; Deoxycholic Acid; Fatty Liver; Humans; Infant; Lithocholic Acid; Liver; Liver Cirrhosis; Liver Function Tests; Taurolithocholic Acid

Mucoid strains of Pseudomonas aeruginosa isolated from the respiratory tract of patients with cystic fibrosis (CF), those obtained from non-CF patients, and those obtained in vitro by the action of phage, were found to be stable in their mucoid colonial form when serially subcultured on deoxycholate-citrate agar. The ability of anionic, cationic and neutral surfactants to stabilise mucus production is described. The possible importance of dipalmitoyl lecithin as a stabilising agent for mucus production in vivo is considered, with particular reference to the role of mucoid P. aeruginosa in CF disease.

Topics: Acetylcysteine; Cetrimonium Compounds; Citrates; Culture Media; Cystic Fibrosis; Deoxycholic Acid; Ferric Compounds; Humans; Lactose; Mucus; Neutral Red; Phosphatidylcholines; Polysorbates; Pseudomonas aeruginosa; Sodium Dodecyl Sulfate; Species Specificity; Surface-Active Agents; Thiosulfates