Intravenous glycyrrhizin for the treatment of chronic hepatitis C: a double-blind, randomized, placebo-controlled phase I/II trial.

Abstract

BACKGROUND:

In Japan, glycyrrhizin therapy is widely used for chronic hepatitis C and reportedly reduces the progression of liver disease to hepatocellular carcinoma. The aims of this study were to evaluate the effect of glycyrrhizin on serum alanine aminotransferase (ALT), hepatitis C virus (HCV)-RNA and its safety in European patients.

METHODS:

Fifty-seven patients with chronic hepatitis C, non-responders or unlikely to respond (genotype 1/cirrhosis) to interferon therapy, were randomized to one of the four dose groups: 240, 160 or 80 mg glycyrrhizin or placebo (0 mg glycyrrhizin). Medication was administered intravenously thrice weekly for 4 weeks; follow up also lasted for 4 weeks.

RESULTS:

Within 2 days of start of therapy, serum ALT had dropped 15% below baseline in the three dosage groups (P < 0.02). The mean ALT decrease at the end of active treatment was 26%, significantly higher than the placebo group (6%). A clear dose-response effect was not observed (29, 26, 23% ALT decrease for 240, 160 and 80 mg, respectively). Normalization of ALT at the end of treatment occurred in 10% (four of 41). The effect on ALT disappeared after cessation of therapy. During treatment, viral clearance was not observed: the mean decrease in plasma HCV-RNA after active treatment was 4.1 x 10(6) genome equivalents/mL (95% confidence interval, 0-8.2 x 10(6); P > 0.1). No major side-effects were noted. None of the patients withdrew from the study because of intolerance.

CONCLUSIONS:

Glycyrrhizin up to 240 mg, thrice weekly, lowers serum ALT during treatment, but has no effect on HCV-RNA levels. The drug appears to be safe and is well tolerated. In view of the reported long-term effect of glycyrrhizin, further controlled investigation of the Japanese mode of administration (six times weekly) for induction appears of interest.

• Authors: T G van Rossum, A G Vulto, W C Hop, J T Brouwer, H G Niesters, S W Schalm
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 14 Issue 11 Pg. 1093-9 (Nov 1999) ISSN: 0815-9319 [Print] Australia
• PMID: 10574137 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Glycyrrhizic Acid

Topics

• Adult
• Aged
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage)
• Disease Progression
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Female
• Glycyrrhizic Acid (administration & dosage)
• Hepatitis C, Chronic (drug therapy)
• Humans
• Infusions, Intravenous
• Liver Function Tests
• Male
• Middle Aged