Silibinin: an old drug in the high tech era of liver transplantation.

HCV re-infection after liver transplantation is constant and accelerated in patients who are PCR-positive at the time of transplantation. Reinfection significantly impairs patient and graft survival [1]. At present, there are limited options available to prevent graft reinfection after transplantation or to successfully treat reinfected patients. Pretransplant antiviral combination therapy with (peg)interferon/ribavirin (PegIFN/RBV) is poorly tolerated and not very effective in patients infected with HCV genotype 1. In a prospective randomized controlled study, pretransplant treatment with PegIFN/RBV prevented post-transplant recurrence of HCV in 22% of a highly selected group of patients with HCV genotypes 1,4,6 [2]. Treatment after transplantation has also a limited efficacy and is associated with serious adverse effects. Currently, studies using triple therapy with PegIFN/RBV and a protease inhibitor (boceprevir or telaprevir) are ongoing, but again poor tolerance is a major issue. Thus there is urgent medical need to develop safe and effective treatments for this group of patients. Two case reports indicated that therapy with intravenous silibinin (iv-SIL; Legalon SIL , Rottapharm–Madaus) successfully eradicated the virus after transplantation [3,4]. Based on these encouraging observations, iv silibinin got EMA orphan drug designation for prevention of recurrent hepatitis C. Iv-SIL is a 1:1 mixture of silibinin A and silibinin B and is available as intravenous therapeutic agent for treatment of mushroom poisoning. However, acute liver failure related to mushroom (amanita or lepiota) poisoning is an uncommon condition and there is no definitive evidence that silibinin improves the outcome of these patients. In 2008, the potent antiviral activity of iv-SIL against HCV was described [5] and confirmed by in vitro studies [6]. Silibinin inhibits the HCV NS5B polymerase activity directly [7] or by interfering with the binding of the RNA to this enzyme [8]. Furthermore, the mechanisms of the antiviral action of silibinin appear also to