title: A large-scale, multicentre, double-blind trial of ursodeoxycholic acid in patients with chronic hepatitis C.
abstract: BACKGROUND
  Combined pegylated interferon and ribavirin has improved chronic hepatitis C (CH-C) therapy; however, sustained virological response is achieved in only about half of the patients with a 1b genotype infection. We assessed oral ursodeoxycholic acid (UDCA) on serum biomarkers as a possible treatment for interferon non-responders.
  
  
  METHODS
  CH-C patients with elevated alanine aminotransferase (ALT) were assigned randomly to 150 (n = 199), 600 (n = 200) or 900 mg/day (n = 197) UDCA intake for 24 weeks. Changes in ALT, aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) were assessed. This study is registered at ClinicalTrial.gov, identifier NCT00200343.
  
  
  RESULTS
  ALT, AST and GGT decreased at week 4 and then remained constant during drug administration. The median changes (150, 600 and 900 mg/day, respectively) were: ALT, -15.3, -29.2 and -36.2%; AST, -13.6, -25.0 and -29.8%; GGT, -22.4, -41.0 and -50.0%. These biomarkers decreased significantly less in the 150 mg/day than in the other two groups. Although changes in ALT and AST did not differ between the 600 and 900 mg/day groups, GGT was significantly lower in the 900 mg/day group. In subgroup analysis, ALT decreased significantly in the 900 mg/day group when the baseline GGT exceeded 80 IU/l. Serum HCV-RNA did not change in any group. Adverse effects were reported by 19.1% of the patients, with no differences between groups.
  
  
  CONCLUSIONS
  A 600 mg/day UDCA dose was optimal to decrease ALT and AST levels in CH-C patients. The 900 mg/day dose decreased GGT levels further, and may be preferable in patients with prevailing biliary injuries.
authors.affiliation: Department of Gastroenterology, University of Tokyo Graduate School of Medicine, Hongo 7-3-1, Bunkyo, Tokyo 113-8655, Japan. omata-2im@h.u-tokyo.ac.jp
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Yoshida
authors.forename: Joji
authors.initials: J
authors.lastname: Toyota
authors.forename: Eiichi
authors.initials: E
authors.lastname: Tomita
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiguchi
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
authors.forename: Shiro
authors.initials: S
authors.lastname: Iino
authors.forename: Isao
authors.initials: I
authors.lastname: Makino
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Okita
authors.forename: Gotaro
authors.initials: G
authors.lastname: Toda
authors.forename: Kyuichi
authors.initials: K
authors.lastname: Tanikawa
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001647:Bile Acids and Salts / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002756:Cholagogues and Choleretics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D001647:Bile Acids and Salts; D015415:Biomarkers; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase