deoxycholic-acid and Hepatitis--Chronic

Hydrophobic bile acids have been shown to be hepatotoxic, whereas treatment with ursodeoxycholic acid, a hydrophilic bile acid, has improved liver function indices in patients with chronic liver disease. Taurine administration has also been suggested to be useful for chronic hepatitis, taurine-conjugated bile acids being more hydrophilic than glycine-conjugated bile acids. To determine if taurine and ursodeoxycholic acid are beneficial and if their effects are additive, a double-blind, randomized trial was designed comparing the effects of ursodeoxycholic acid, taurine, and a combination of the two on indices of liver injury in 24 patients with chronic hepatitis. They were assigned at random to two of the four following treatments: ursodeoxycholic acid (600 mg/day), taurine (1.5 g/day), ursodeoxycholic acid plus taurine (600 mg + 1.5 g/day) or placebo, given in two successive cycles of 2 mo each, according to a balanced incomplete-block design. Ursodeoxycholic acid became the predominant biliary bile acid when administered alone or in combination with taurine, and taurine conjugate levels increased during taurine administration. Ursodeoxycholic acid reduced aspartate aminotransferase (35%), alanine aminotransferase (33%), and gamma-glutamyl transpeptidase (41%), whereas taurine alone did not. The addition of taurine to ursodeoxycholic acid produced only minor changes in the effects of ursodeoxycholic acid alone. Results were confirmed by the administration of ursodeoxycholic acid, in a successive open phase of the study, to the entire patient population, which was large enough for different subsets of patients to be compared. Serum bile acids were measured at entry and during the open phase: primary bile acids did not change, whereas ursodeoxycholic acid levels increased from trace amounts to very high levels, especially in patients with more severe histological disease. It is concluded that ursodeoxycholic acid, but not taurine, improves enzymatic indices of liver injury in chronic hepatitis.

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Bile Acids and Salts; Clinical Enzyme Tests; Deoxycholic Acid; Double-Blind Method; Female; gamma-Glutamyltransferase; Hepatitis, Chronic; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Taurine; 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

Clinical and experimental investigations have suggested that ursodeoxycholic acid (ursodiol) may have cytoprotective or choleretic action and therefore be beneficial in patients with intrahepatic cholestasis or chronic liver disease. In an open-label study, we treated 45 patients with chronic hepatitis with 300 mg of ursodiol three times daily for six months. At four months, gamma-glutamyl transpeptidase (gamma-GTP) and leucine aminopeptidase levels had decreased. SGOT and SGPT levels also decreased significantly. Evaluation of histologic changes has not yet been completed. No significant differences in improvement of liver function tests were found in a comparison with 19 historical controls. We also studied eight patients with primary biliary cirrhosis, treated for more than one and a half years with 600 mg of ursodiol per day. At one month, itching diminished in five patients who had pruritus. ALPase and gamma-GTP levels decreased significantly, and GOT and GPT levels were also reduced. IgM levels did not change, but the titer of antimitochondrial body decreased by half in two patients. Levels of glycoursodeoxycholic acid increased, and in three patients follow-up liver biopsy showed marked improvement. These preliminary results suggest that ursodiol is safe and effective for the treatment of chronic hepatitis and primary biliary cirrhosis, but a large-scale, controlled trial is needed.

Topics: Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Deoxycholic Acid; gamma-Glutamyltransferase; Hepatitis, Chronic; Humans; Leucyl Aminopeptidase; Liver Cirrhosis, Biliary; Liver Function Tests; Ursodeoxycholic Acid

Topics: Alanine Transaminase; Aspartate Aminotransferases; Deoxycholic Acid; Hepatitis, Chronic; Humans; Liver Cirrhosis, Biliary; Ursodeoxycholic Acid

Chemical dissolution of cholesterol gallstones using ursodeoxycholic acid (UDCA) in six patients with histologically confirmed HBsAg-negative chronic active hepatitis was started after a minimum of one year of therapy with steroids, azathioprine, or chloroquine and a treatment-free period of 8-15 months. The treatment with UDCA lasted 3-20 months with a daily dose of 8-11 mg/kg. Four patients served as controls. A decrease in transaminases (P less than 0.05) occurred in all patients during the UDCA therapy. After completion of the treatment, the figures rose again, but did not return to the initial value. The stones dissolved in five patients. A second liver biopsy was carried out in two patients after UDCA therapy, and this showed no detectable deterioration. Four patients refused biopsy because the laboratory parameters had improved under UDCA. A stone recurred in one patient six months after the end of therapy; the others have remained free of stones for up to 24 months.

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Cholelithiasis; Cholesterol; Deoxycholic Acid; Female; Follow-Up Studies; Glycocholic Acid; Hepatitis, Chronic; Humans; Male; Middle Aged; Time Factors; Ursodeoxycholic Acid