A large-scale, multicentre, double-blind trial of ursodeoxycholic acid in patients with chronic hepatitis C.
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.
Omata
Masao
M
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
Yoshida
Haruhiko
H
Toyota
Joji
J
Tomita
Eiichi
E
Nishiguchi
Shuhei
S
Hayashi
Norio
N
Iino
Shiro
S
Makino
Isao
I
Okita
Kiwamu
K
Toda
Gotaro
G
Tanikawa
Kyuichi
K
Kumada
Hiromitsu
H
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
D001647:Bile Acids and Salts; D015415:Biomarkers; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase