Effect of a medium dose of ursodeoxycholic acid with or without taurine supplementation on the nutritional status of patients with cystic fibrosis: a randomized, placebo-controlled, crossover trial. Ursodeoxycholic acid for liver disease associated with cystic fibrosis: a double-blind multicenter trial. The Italian Group for the Study of Ursodeoxycholic Acid in Cystic Fibrosis. Effect of ursodeoxycholic acid on liver and bile duct disease in primary sclerosing cholangitis. A 3-year pilot study with a placebo-controlled study period. Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial. A randomized clinical trial of oral ursodeoxycholic acid in obstructive jaundice. A randomised controlled trial of ursodeoxycholic acid and S-adenosyl-l-methionine in the treatment of gestational cholestasis. Ursodeoxycholic acid therapy in pregnant women with cholestasis. Ursodeoxycholic acid does not improve the clinical course of primary sclerosing cholangitis over a 2-year period. High-dose ursodeoxycholic acid in primary sclerosing cholangitis: a 5-year multicenter, randomized, controlled study.
Ursodeoxycholic acid administration has been reported to improve cholestasis and inflammatory activity in primary biliary cirrhosis and, in an uncontrolled study, also in young adults with cystic fibrosis (CF) and chronic cholestasis. As an improvement in nutritional status was also observed in these young adult patients, we investigated whether the administration of a medium dose of ursodeoxycholic acid ameliorates the nutritional status of malnourished young adult CF patients with chronic liver disease. The study included 51 patients (27 male patients and 24 female patients; age range, 8-32 years; median, 14) with body mass percentiles < 90%. Patients were randomly assigned to receive either ursodeoxycholic acid (10-12 mg/kg/day) alone or with taurine (18-22 mg/kg/day). Patients were followed in a crossover fashion within each group; 6 months of treatment was randomly alternated with 6 months of placebo. Nine patients dropped out before concluding the study. Liver function tests, nutritional status, and coefficients of fat absorption were determined at entry and after each 6 months of placebo or treatment. Nutritional status and fat absorption were not significantly modified by either treatment. Liver function tests improved after ursodeoxycholic acid administration only in patients with concomitant chronic liver disease. Our findings indicate that 6 months of therapy with a medium dose of ursodeoxycholic acid, either alone or with taurine, does not improve the nutritional status of young malnourished CF patients. Higher doses given for longer periods might be worth investigating. Liver disease is increasingly recognized as a major cause of morbidity in cystic fibrosis (CF). Preliminary data suggest that ursodeoxycholic acid (UDCA) may be beneficial for treatment of this manifestation. We performed a double-blind, multicenter trial in these patients to establish efficacy and safety of UDCA in terms of the improvement of clinical and nutritional indicators besides standard liver function tests. We also intended to establish whether taurine supplementation has a beneficial effect in patients receiving UDCA. From June to December 1990, we enrolled in 12 centers 55 CF patients with liver disease (39 male subjects; median age, 13.8 years). They were randomly assigned to receive for 1 year one of the following treatments: UDCA (15 mg/kg body weight daily) plus taurine (30 mg/kg body weight daily), UDCA plus placebo, placebo plus taurine, or double placebo. Clinical and laboratory evaluations were performed every 3 months. After 1 year, deterioration of overall clinical conditions, as indicated by the Shwachman-Kulczycki score (SKS), occurred in patients who received placebo but not in those who received UDCA (P = .025). Patients treated with UDCA also showed an improvement in gamma-glutamyl transpeptidase (GGT) (P = .004) and 5'-nucleotidase (P = .006) levels. Treatment with taurine was followed by a significant increase in serum prealbumin levels (P = .053), a trend toward a reduction in fat malabsorption, and no effect on the biochemical profile. No severe side effects occurred with any treatment. Thus, we concluded that UDCA administration improves clinical and biochemical parameters in CF patients with liver disease. Taurine supplementation may be indicated in patients with severe pancreatic insufficiency and poor nutritional status. Primary sclerosing cholangitis is a cholestatic disease of the liver characterized by progressive fibrotic inflammation and obliteration of the extra- and/or intrahepatic bile ducts. There is no effective therapy. We, therefore, studied the safety and efficacy of ursodeoxycholic acid in patients with primary sclerosing cholangitis with or without additional ulcerative colitis. In a 1-year ursodeoxycholic acid treatment period, which preceded the controlled study period, ursodeoxycholic acid was well tolerated in 22 of 24 patients with ulcerative colitis and in all three patients without ulcerative colitis. In two patients with ulcerative colitis the dose of 750 mg ursodeoxycholic acid/day led to diarrhea, but following reduction of the dose to 500 and 250 mg/day ursodeoxycholic acid was well tolerated. After 1 year of ursodeoxycholic acid treatment, 20 patients were randomly assigned to receive either ursodeoxycholic acid 750 mg/day or placebo. All of them finished a double-blind, placebo-controlled study period. During ursodeoxycholic acid treatment, the liver enzymes improved markedly. The difference in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyltransferase between the placebo and ursodeoxycholic acid group was significant (p < 0.05). Following ursodeoxycholic acid treatment, pruritus and fatigue improved in half of the patients but the difference between the placebo and ursodeoxycholic acid group was not significant. According to the ethical guidelines, after 3 months of placebo treatment, the controlled study had to be discontinued because of a more than twofold increase of serum transaminases in 8/10 patients on placebo. After the end of the controlled study, all patients were continuously treated with ursodeoxycholic acid for up to 4 years.(ABSTRACT TRUNCATED AT 250 WORDS) 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. Forty patients with obstructive jaundice (bilirubin greater than 100 mumol/l) were entered into a randomized trial of oral ursodeoxycholic acid for 48 h before surgery versus no additional therapy. Pre-operative venous and operative portal total bile salt concentrations were higher in the bile salt treated patients (P less than 0.001). Portal endotoxaemia during operation was reduced in ursodeoxycholic acid treated patients (P less than 0.05). There was no significant difference in systemic venous endotoxaemia, renal function or postoperative morbidity or mortality. This study suggests pre-operative oral bile salt therapy may be of no clinical benefit in patients with obstructive jaundice. To compare the efficacy of S-adenosyl-l-methionine and ursodeoxycholic acid in improving serum biochemical abnormalities in gestational cholestasis.
                Randomised clinical trial.
                University hospital.
                All women at <36 weeks of gestation with severe gestational cholestasis during June 1996 to December 2001.
                Enrolled women were randomly assigned oral S-adenosyl-l-methionine 500 mg twice daily or oral ursodeoxycholic acid 300 mg twice daily until delivery.
                Reduction in the concentration of serum bile acids. Other variables considered included obstetric and neonatal outcome, clinical symptoms and other laboratory measurements (serum levels of transaminases and bilirubin). The two groups were compared using Student's t test, Wilcoxon's signed rank sum test and Fisher's exact test, with a two-tailed P < 0.05 being considered significant.
                Of the 46 women enrolled, 24 received ursodeoxycholic acid and 22 S-adenosyl-l-methionine. At enrolment, gestational age, duration of therapy, rate of nulliparity, pruritus score and biochemical characteristics were similar between the groups. Both therapies significantly and equally improved pruritus. Women receiving ursodeoxycholic acid had a significantly greater improvement in the concentration of serum bile acids (P= 0.001), aspartate aminotransferase (P= 0.01), alanine aminotransferase (<0.001) and bilirubin (P= 0.002) compared with those receiving S-adenosyl-l-methionine. Duration of therapy was significantly greater in women receiving ursodeoxycholic acid compared with S-adenosyl-l-methionine (P= 0.04), whereas gestational age at delivery and rate of prematurity were similar in the two groups.
                In women with intrahepatic cholestasis of pregnancy, ursodeoxycholic acid is more effective than S-adenosyl-l-methionine at improving the concentration of serum bile acids and other tests of liver function, whereas both therapies are equally effective at improving pruritus. To test the efficacy and safety of ursodeoxycholic acid (UDCA) in the treatment of intrahepatic cholestasis of pregnancy (ICP) by a randomized, double-blind, placebo-controlled trial.
                Eight patients with pruritus and abnormal liver function tests received 600 mg/day of UDCA in two doses for 20 days, compared with a control group of eight patients who received placebo for 20 days.
                No adverse reactions were detected in any patient. During UDCA therapy a statistically significant improvement in pruritus, serum bile salt levels, serum glutamic pyruvic transaminase, alkaline phosphatase, gamma-glutamyl transpeptidase and total and direct bilirubin was observed. Only two patients treated with UDCA underwent cesarean sections due to reasons unrelated to the therapeutic trial. All newborns had an Apgar score >7 and normal postnatal growth.
                Although the number of patients in this study was very small, we suggest that UDCA treatment has a role in improving clinical and biochemical results in ICP. Ursodeoxycholic acid has been shown to be a useful agent in the clinical management of patients with primary biliary cirrhosis and autoimmune chronic active hepatitis. Its efficacy is presumed to be based upon its ability to act as a detergent and to incite a choleresis. Recent additional data suggest it also reduces HLA antigen expression on liver and biliary epithelial cells and impairs T cell reactivity.
                A randomized controlled study of 59 patients with primary sclerosing cholangitis was performed over a 24 months period with 3 groups being studied. Group I consisted of 20 patients who were given ursodeoxycholic acid 300 mg orally twice a day; group II consisted of 19 patients who were given colchicine 0.6 mg orally BID; and group III was an untreated medical control group. All three groups were seen at regular 3-month intervals and had quarterly, annual and terminal studies performed to assess their disease status.
                No difference between groups was evident after two full years of therapy when parameters of liver injury, liver function, liver size and hepatic copper content were compared between groups. Similarly, no difference in ERCP findings was evident between groups either at entry or after two years of therapy.
                These data suggest that ursodeoxycholic acid is no better than colchicine or simple medical follow-up. Thus, neither ursodeoxycholic acid or colchicine can be considered to be effective therapies for primary sclerosing cholangitis. There is no medical treatment of proven benefit for primary sclerosing cholangitis. This study aimed at studying the effect of a higher dose of ursodeoxycholic acid than previously used on survival, symptoms, biochemistry, and quality of life in this disease.
                A randomized placebo-controlled study was performed in tertiary and secondary gastroenterology units. A total of 219 patients were randomized to 17 to 23 mg/kg body weight per day of ursodeoxycholic acid (n = 110) or placebo (n = 109) for 5 years. Follow-up data are available from 97 patients randomized to ursodeoxycholic acid and for 101 randomized to placebo. Quality of life was assessed by using the Medical Outcomes Study 36-item Short-Form Health Survey.
                The combined end point "death or liver transplantation" occurred in 7 of 97 (7.2%) patients in the ursodeoxycholic acid group vs 11 of 101 (10.9%) patients in the placebo group (P = .368; 95% confidence interval, -12.2% to 4.7%). The occurrence of liver transplantation as a single end point showed a similar positive trend for ursodeoxycholic acid treatment (5/97 [5.2%] vs 8/101 [7.9%]; 95% confidence interval, -10.4% to 4.6%). Three ursodeoxycholic acid and 4 placebo patients died from cholangiocarcinoma, and 1 placebo patient died from liver failure. Alkaline phosphatase and alanine aminotransferase tended to decrease during the first 6 months. There were no differences between the 2 groups in symptoms or quality of life. Analyses of serum ursodeoxycholic acid concentration gave no evidence that noncompliance may have influenced the results.
                This study found no statistically significant beneficial effect of a higher dose of ursodeoxycholic acid than previously used on survival or prevention of cholangiocarcinoma in primary sclerosing cholangitis.
There are few trials assessing the effectiveness of ursodeoxycholic acid. There is insufficient evidence to justify its routine use in cystic fibrosis.