Biochemical and histological effects of 26 weeks of glycyrrhizin treatment in chronic hepatitis C: a randomized phase II trial.
OBJECTIVE
Phase I/II studies of 4 weeks duration have confirmed the ALT lowering effect of glycyrrhizin in Western chronic hepatitis C patients. Our aim was to determine the dose frequency of glycyrrhizin required to maintain the ALT response beyond 4 weeks and evaluate its effect on liver histology and quality of life.


METHODS
HCV-RNA-positive patients with elevated ALT and marked fibrosis or necro-inflammation who were not eligible for interferon therapy were treated for 4 weeks with six infusions weekly of glycyrrhizin. Patients with an ALT response at week 4 were randomized to continue treatment for 22 weeks in three dose frequency groups: 6x, 3x or once weekly.


RESULTS
72/121 (60%) patients were randomized. At the end of treatment the ALT response was maintained in 60%, 24% and 9% of patients in the 6x, 3x, and once weekly groups, respectively (p<0.001). In ALT responders the necro-inflammation score improved non-significantly compared to ALT non-responders. Quality of life assessed by SF-36 increased in patients treated with the study drug, albeit unrelated to the occurrence of ALT response.


CONCLUSIONS
ALT responses induced by 4 weeks glycyrrhizin therapy can be maintained in a subset of chronic hepatitis C patients receiving at least three injections weekly. The observed ALT response did not translate in a significant histological improvement after 6 months treatment.
Orlent
Hans
H
Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands.
Hansen
Bettina E
BE
Willems
Marc
M
Brouwer
Johannes T
JT
Huber
Roman
R
Kullak-Ublick
Gerd A
GA
Gerken
Guido
G
Zeuzem
Stefan
S
Nevens
Frederik
F
Tielemans
Wanda C M
WC
Zondervan
Pieter E
PE
Lagging
Martin
M
Westin
Johan
J
Schalm
Solko W
SW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D019695:Glycyrrhizic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome
D000998:Antiviral Agents; D012367:RNA, Viral; D019695:Glycyrrhizic Acid; D000410:Alanine Transaminase