Hepatitis

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

Masao Omata¹, Haruhiko Yoshida¹, Joji Toyota², Eiichi Tomita³, Shuhei Nishiguchi⁴, Norio Hayashi⁵, Shiro Iino⁶, Isao Makino⁷, Kiwamu Okita⁸, Gotaro Toda⁹, Kyuichi Tanikawa¹⁰, Hiromitsu Kumada¹¹ for the Japanese C-Viral Hepatitis Network

¹ Department of Gastroenterology, University of Tokyo Graduate School of Medicine, Tokyo, Japan
² Department of Gastroenterology, Sapporo Kosei General Hospital, Hokkaido, Japan
³ Department of Gastroenterology, Gifu Municipal Hospital, Gifu, Japan
⁴ Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
⁵ Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan
⁶ Seizankai Kiyokawa Hospital, Tokyo, Japan
⁷ Hokushinkai Megumino Hospitals, Hokkaido, Japan
⁸ Social Insurance Shimonoseki Kosei Hospital, Yamaguchi, Japan
⁹ Sempo Tokyo Takanawa Hospital, Tokyo, Japan
¹⁰ International Institute for Liver Research, Fukuoka, Japan
¹¹ Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan

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

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 [ClinicalTrials.gov] .

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.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

• Poupon, R., Serfaty, L. (2007). Ursodeoxycholic acid in chronic hepatitis C. Gut 56: 1652-1653 [Full Text]