Intravenous glycyrrhizin for the treatment of chronic hepatitis C: a double-blind, randomized, placebo-controlled phase I/II trial.
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.
van Rossum
T G
TG
Department of Hepatogastroenterology, Erasmus Medical Center, Rotterdam, The Netherlands.
Vulto
A G
AG
Hop
W C
WC
Brouwer
J T
JT
Niesters
H G
HG
Schalm
S W
SW
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D019695:Glycyrrhizic Acid / Q000008:administration & dosage*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019695:Glycyrrhizic Acid