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INTRODUCTION
Glycyrrhizin for IFN-non responders 127
Chronic hepatitis C is a major cause of liver disease worldwide. Infection with the hepatitis
C virus may lead to a chronic infl ammation of the liver, which is manifested in elevated
liver enzymes such as alanine aminotransferase (ALT). This chronic infl ammation may
lead to fi brosis and subsequent cirrhosis. It has been estimated that the delay for developing
cirrhosis is about thirty years, but the individual prognosis may vary substantially
depending on factors such as age at infection, gender, alcohol abuse and co-infection
with hepatitis B or the human immunodefi ciency virus (HIV). 1
Over the past fi fteen years treatment regimens based on the administration of interferon
have proven to be increasingly effective against hepatitis C. Combination treatment with
pegylated interferon and ribavirin will lead to disappearance of the virus from the blood
in 50% to 80% of the patients. 2,3 If the virus remains undetectable in the blood at 6 months
after the end of treatment, we speak of a sustained virological response. Sustained
virological response is almost always associated with normalization of serum ALT and a
survival similar to the overall population. 4 There still remains a considerable proportion
of patients who do not achieve a sustained virological response. These patients are in
need of other therapeutic approaches. Various long-term interferon-based regimens are
under investigation. 5,6
In Japan, glycyrrhizin has been propagated as an anti-infl ammatory drug, capable of
minimizing disease activity in the chronically infected liver. Placebo controlled trials have
proven that the administration of glycyrrhizin leads to a signifi cant reduction of ALT levels
in chronic hepatitis C patients. 7 The question remains whether this reduction of ALT
levels leads to a reduced risk of liver-related morbidity and mortality. Ideally, one should
design a randomised controlled trial with a prolonged follow-up of at least several years
in order to investigate the effect of glycyrrhizin on these clinical endpoints. However,
even when such a study would be restricted to cirrhotics, based on the incidence of
HCC, decompensation and mortality, 8 it would take at least 5 years before we had an
answer whether glycyrrhizin is a benefi cial drug or not. Therefore we performed a large
retrospective multicenter study, analyzing independently data collected in Japan, the
only country so far where hepatologists have extensively used this compound. We were
especially careful to minimize the various biases associated with retrospective studies
and to apply the most sophisticated statistics designed for such studies.