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Gut 56:1747-1753 doi:10.1136/gut.2007.120956
  • Hepatitis

A large-scale, multicentre, double-blind trial of ursodeoxycholic acid in patients with chronic hepatitis C

Open Access
  1. Masao Omata1,
  2. Haruhiko Yoshida1,
  3. Joji Toyota2,
  4. Eiichi Tomita3,
  5. Shuhei Nishiguchi4,
  6. Norio Hayashi5,
  7. Shiro Iino6,
  8. Isao Makino7,
  9. Kiwamu Okita8,
  10. Gotaro Toda9,
  11. Kyuichi Tanikawa10,
  12. Hiromitsu Kumada11
  1. 1
    Department of Gastroenterology, University of Tokyo Graduate School of Medicine, Tokyo, Japan
  2. 2
    Department of Gastroenterology, Sapporo Kosei General Hospital, Hokkaido, Japan
  3. 3
    Department of Gastroenterology, Gifu Municipal Hospital, Gifu, Japan
  4. 4
    Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
  5. 5
    Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan
  6. 6
    Seizankai Kiyokawa Hospital, Tokyo, Japan
  7. 7
    Hokushinkai Megumino Hospitals, Hokkaido, Japan
  8. 8
    Social Insurance Shimonoseki Kosei Hospital, Yamaguchi, Japan
  9. 9
    Sempo Tokyo Takanawa Hospital, Tokyo, Japan
  10. 10
    International Institute for Liver Research, Fukuoka, Japan
  11. 11
    Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
  1. Professor Masao Omata, Department of Gastroenterology, University of Tokyo Graduate School of Medicine, Hongo 7-3-1, Bunkyo, Tokyo 113-8655, Japan; omata-2im{at}h.u-tokyo.ac.jp
  • Revised 23 May 2007
  • Accepted 5 June 2007
  • Published Online First 15 June 2007

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.

Footnotes

  • Abbreviations:
    ALT
    alanine aminotransferase
    AST
    aspartate aminotransferase
    CH-C
    chronic hepatitis C
    GGT
    gamma-glutamyl transpeptidase
    HCV
    hepatitis C virus
    UDCA
    ursodeoxycholic acid