In Japan, hepatitis C virus (HCV) is the single most frequent cause of
hepatocellular carcinoma (HCC), resulting in yearly deaths of over 30,000. Although the mechanism of how HCV induces HCC is not clear, persistent HCV
infection and necro-inflammatory changes in
chronic hepatitis C accelerate the development of
liver cirrhosis and can eventuate in HCC. Hence, means of eradicating HCV as well as suppressing
inflammation in the liver, even if patients stay infected with HCV, would decrease the incidence of HCC with
chronic hepatitis C. For more than 40 years, a preparation of
glycyrrhizin [
Stronger Neo-Minophagen C (SNMC)] has been used for the treatment of 'allergic'
hepatitis in Japan. In 1977,
intravenous injection with SNMC was started in patients with
chronic hepatitis or
liver cirrhosis, most of whom have turned out to be infected with hepatitis viruses. In a multicenter double-blind study,
alanine aminotransferase (ALT) levels decreased in the patients who received 40 ml/day of SNMC for 4 weeks at a rate significantly higher (p < 0.001) than controls receiving placebo. Furthermore, SNMC 100 ml/day for 8 weeks improved liver histology in 40 patients with
chronic hepatitis, in correlation with improved ALT levels in serum.
Liver cirrhosis occurred less frequently in 178 patients on long-term SNMC than in 100 controls (28 vs. 40% at year 13, p < 0.002). Finally, HCC developed less frequently in the 84 patients on long-term SNMC than in the 109 controls (13 vs. 25% at year 15, p < 0.002). Combined, these results indicate that a long-term treatment with SNMC prevents the development of HCC in the patients with
chronic hepatitis. SNMC is particularly helpful in the patients with
chronic hepatitis C who fail to respond to
interferon and in those who cannot be treated with it for various reasons.