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Glycyrrhizin for IFN-non responders 131
Four hundred and sixty-fi ve patients received intravenous glycyrrhizin therapy, given as
Stronger Neo Minophagen C (SNMC), which was started at various follow-up times. One
hundred and sixty-four of these patients had advanced fi brosis. The mean treatment
duration with glycyrrhizin was 4.1 years (SD 2.6), 79% of the patients received treatment
for 3 years or longer. The patients received a mean dose of 506 mg glycyrrhizin (191 ml
SNMC) per week (range 106-1855 mg). Six patients stopped treatment because of side
effects. Other treatments given to the interferon non-responders were interferon plus
ribavirin (n=23), ursodeoxycholic acid (n=657) and herbal medicines (n=93). The patients
receiving interferon plus ribavirin were censored at the start of this treatment.
Events
One hundred and seven patients developed HCC. We performed a Kaplan Meier analysis
in order to investigate the infl uence of raised ALT levels on the risk of developing
HCC (fi gure 2). In patients with normal ALT levels during the fi rst year of follow-up, the
5-year incidence of HCC was 3.1% (95% CI 0.8-5.5). The incidence of HCC increased to
4.9 (95%CI 2.0-7.8) for ALT levels between 1 and 1.5 xULN, 8.3% (95%CI 4.1-12.5) for ALT
levels between 1.5 and 2 xULN and 8.3% (95%CI 4.2-12.3) for ALT levels between 2 and 3
xULN. The highest occurrence of HCC was seen in patiënts with ALT levels above thrice
the ULN during the fi rst year of follow-up: 16.6% (95% CI 9.3-24.0).
Time dependent Cox regression analysis showed that older age, male sex, higher fi brosis
stage and non-response to glycyrrhizin were signifi cantly associated with a higher risk
for developing HCC (table 2).
Subgroup analysis of patients with fi brosis stage 3 and 4 showed a trend towards less
development of HCC among patients with a response to glycyrrhizin (hazard ratio=0.50
(95% CI 0.22-1.12, p=0.09).
Seventy-four percent (343/465) of the patients treated with glycyrrhizin had ALT levels above
1.5 xULN at the start of therapy and 66% (228/343) of these responded by decreased ALTlevels.
In comparison, the rate of spontaneous ALT normalisation in patients with elevated
ALT levels at start of follow-up who were not treated with glycyrrhizin was 33% (114/344) at 3
months after inclusion into the study. In an analysis of all 465 treated patients, patients with
an ALT-response had a signifi cant lower chance of developing HCC than non-responders;
hazard ratio 0.39 (95% CI 0.21-0.72, p