deoxycholic-acid and Cholangitis--Sclerosing

Topics: Cholangitis, Sclerosing; Clinical Trials as Topic; Deoxycholic Acid; Humans; Liver Cirrhosis, Biliary; Pilot Projects; Prospective Studies; Ursodeoxycholic Acid

Ursodeoxycholic acid (UDCA) improves liver biochemistry in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Since UDCA acts partly by reducing the intestinal absorption of hydrophobic endogenous bile salts and is poorly absorbed from the intestine, a multiple dose regimen has been advocated. Single dose treatment, on the other hand, may improve compliance.. The effects of a single or multiple dose regimen on liver enzymes and serum and biliary bile salts composition were evaluated.. Twenty-seven patients (19 PSC, 8 PBC), most with early stage disease, received UDCA (10 mg kg-1 day-1) in a single dose at bed time (n = 13) or in three divided gifts with meals (n = 14) over 3 months. Five patients had both treatment regimens in random order with a 1-month wash-out period in between.. Liver biochemistry equally improved in both groups. Biliary enrichment (% UDCA of total bile salts, mean +/- SEM) was 40.1 +/- 2.4 in the single dose group vs 40.8 +/- 2.8 in the multiple dose group (p = NS) and was positively correlated with biochemical improvement (AP: r = 0.47, p = 0.02; GGT: r = 0.58, p = 0.002; ASAT: r = 0.67, p = 0.002; ALAT: r = 0.52, p = 0.01). Biochemical improvement was not correlated with the concentration or %UDCA in serum. Patients participating in the cross-over design had comparable biochemical response and biliary %UDCA during both regimens.. Single and multiple dose UDCA have similar effects on liver biochemistry and biliary enrichment in cholestatic liver disease. Biochemical improvement appears to be related to biliary (but not serum) enrichment with UDCA.

Topics: Adult; Alkaline Phosphatase; Bile Acids and Salts; Chenodeoxycholic Acid; Cholagogues and Choleretics; Cholangitis, Sclerosing; Chromatography, Gas; Cross-Over Studies; Deoxycholic Acid; Dose-Response Relationship, Drug; Female; Follow-Up Studies; gamma-Glutamyltransferase; Humans; Liver Cirrhosis, Biliary; Male; Middle Aged; Regression Analysis; Transaminases; Treatment Outcome; Ursodeoxycholic Acid

The efficacy and safety of ursodeoxycholic acid for the treatment of primary sclerosing cholangitis were evaluated in a prospective, randomized, double-blind, placebo-controlled trial. Fourteen patients with primary sclerosing cholangitis documented by cholestatic serum enzyme pattern, liver histological appearance and endoscopic retrograde cholangiography were included in the trial. Six patients received ursodeoxycholic acid (13 to 15 mg/kg body wt/day), and eight patients received placebo. Two patients had to be withdrawn from the study, one because of UDCA-related diarrhea and the other because of worsening of the disease during placebo treatment. Patients in the ursodeoxycholic acid group improved significantly during 1 yr of treatment with respect to serum levels of bilirubin (median = -50%), alkaline phosphatase (median = -67%), gamma-glutamyltransferase (median = -53%), AST (median = -54%) and ALT (median = -36%) compared with the placebo group, but not with respect to serum levels of hydrophobic bile acids. During ursodeoxycholic acid treatment, histopathological features also improved significantly, as evaluated by multiparametric score. Expression of human leukocyte antigen class I molecules appeared to be markedly reduced on liver cells after ursodeoxycholic acid treatment. We conclude that ursodeoxycholic acid is beneficial in reducing disease activity in patients with primary sclerosing cholangitis.

Topics: Adolescent; Adult; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Chenodeoxycholic Acid; Cholangitis, Sclerosing; Cholic Acid; Cholic Acids; Deoxycholic Acid; Diarrhea; Double-Blind Method; Female; Humans; Liver; Male; Middle Aged; Prospective Studies; Ursodeoxycholic Acid

Topics: Cholangitis, Sclerosing; Clinical Trials as Topic; Colitis, Ulcerative; Deoxycholic Acid; Humans; Liver Function Tests; Pilot Projects; Ursodeoxycholic Acid

Recent clinical studies have indicated that ursodeoxycholic acid (ursodiol), administered at dosages ranging between 10 and 15 mg/kg/day, improves liver function indices in both cholestatic and inflammatory chronic liver diseases. These dosages would be considered high for the use of ursodiol in gallstone dissolution therapy. To investigate the dose-response relationship to ursodiol administration, we planned a few studies in patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and chronic hepatitis (CH). Patients with PBC were subdivided into two groups on the basis of their serum bilirubin values, with 2 mg/dl as the dividing line. Ursodiol was given at dosages of 250, 500, and 750 mg/day for consecutive periods of two months, the order of treatment being randomly assigned to each patient. The enrichment with ursodiol of biliary bile acids was similar in both PBC and CH and, within the PBC group, in both anicteric and icteric patients. Highly significant decreases in serum enzyme levels were observed in all groups with the 250 mg/day dose, corresponding to about 4-5 mg/kg/day. The two higher doses induced further improvements in serum enzyme levels, especially in patients with PBC, but no significant differences were found between the 500 and the 750 mg/day doses. The improvements were roughly proportional to the enrichment of conjugated biliary bile acids with ursodiol. Serum bilirubin levels, an important prognostic factor in PBC, were also significantly reduced by ursodiol administration in patients with initial serum levels higher than 2 mg/dl. The present study indicated that ursodiol is a potentially useful drug for chronic liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bile; Bilirubin; Cholangitis, Sclerosing; Deoxycholic Acid; Dose-Response Relationship, Drug; Female; Hepatitis, Chronic; Humans; Lipid Metabolism; Liver Cirrhosis, Biliary; Liver Function Tests; Male; Middle Aged; Random Allocation; Time Factors; Ursodeoxycholic Acid

Topics: Cholangitis, Sclerosing; Clinical Trials as Topic; Deoxycholic Acid; Humans; Liver Cirrhosis, Biliary; Pilot Projects; Prospective Studies; Ursodeoxycholic Acid

The effects of ursodeoxycholic acid (UDCA, 750-1250 mg/day) were evaluated prospectively in 15 patients with primary sclerosing cholangitis (PSC). Five patients had associated inflammatory bowel disease. After 6 months of treatment, the proportion of patients suffering from fatigue or pruritus decreased from 60% to 20% and from 33% to 20%, respectively. No exacerbation of associated disorders was observed. Serum alkaline phosphatase levels (normal less than 100 IU/l) decreased from 401 +/- 53 to 222 +/- 42 (mean +/- S.E.; p less than 0.001), those of gamma-glutamyl transpeptidase, (normal less than 40 IU/l) from 520 +/- 89 to 185 +/- 32 (p less than 0.001) and those of alanine aminotransferases, (normal less than 30 IU/l) from 79 +/- 12 to 42 +/- 6 (p less than 0.02). In three patients, the discontinuation of UDCA was associated with an aggravation of the liver test results. In conclusion, this study shows that 6 months of treatment with UDCA leads to clinical and biochemical improvements in patients with PSC. These results suggest that UDCA could be an effective treatment for PSC, and may justify a controlled therapeutic trial.

Topics: Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Cholangitis, Sclerosing; Deoxycholic Acid; Female; gamma-Glutamyltransferase; Humans; Liver; Male; Middle Aged; Time Factors; Transaminases; Ursodeoxycholic Acid

Ursodeoxycholic acid treatment (600 mg/day) was evaluated in a patient with asymptomatic primary sclerosing cholangitis. Serum levels of biliary enzymes decreased to normal ranges within 1 month's treatment and remained normal for 26 months. Serum chenodeoxycholic acid had been replaced by ursodeoxycholic acid, and hepatic copper metabolism, assessed by x-ray probe analysis, improved during the treatment. However, neither biliary tract sclerosis nor portal tract pathology changed with the treatment. These observations suggest that ursodeoxycholic acid protects the liver in primary sclerosing cholangitis by improving the metabolism of bile acid and copper.

Topics: Adult; Bile Acids and Salts; Cholangitis, Sclerosing; Copper; Deoxycholic Acid; Humans; Liver; Male; Ursodeoxycholic Acid

Topics: Adult; Cholangitis, Sclerosing; Deoxycholic Acid; Humans; Male; Ursodeoxycholic Acid