Successful prevention of hepatitis C virus (HCV) liver graft reinfection by silibinin mono-therapy (2010)

To the Editor:Therapeutic measurements to control hepatitis C reinfection afterorthotopic liver transplantation (OLT) still pose many problemsand remain unsatisfactory [1]. While hepatitis C viremiadecreases strongly during the anhepatic phase of OLT, initiationof viral replication does occur within hours or days [2,3]. At thisearly stage after OLT, i.e. once chronic HCV reinfection is estab-lished, the virologic response is often markedly reduced.Although speciﬁcally targeted antiviral therapeutic regimes forhepatitis C (STAT-C) are currently extensively studied, none ofthem have been tried in the post-OLT period treatment.However, as recently described by Ferenci et al. [4], high doseintravenous silibinin (Legalon SIL ) can express potent antiviralactivity. This effect was shown to be driven by direct inhibitionof the viral RNA polymerase NS5B [5,6].In this letter, we can report the ﬁrst successful prevention ofHCV reinfection after OLT by the administration of silibinin(1400 mg/d). This drug was applied immediately after OLT bydaily infusions for 14 days.At the time of OLT, the 57-year-old male patient exhibited aMELD Score of 23, Child-Pugh stage C liver cirrhosis, and a25 mm hepatocellular carcinoma in the left lobe. HCV infection(genotype 3a) was ﬁrst diagnosed in 1997 and three interferon-based treatment regimens – at last PegInterferon alpha and Riba-virin were given for 48 weeks 6 years before OLT – failed toinduce a sustained virologic response (SVR). The anhepatic phaseduring OLT surgical procedures lasted 61 min and postoperativecare transpired without complication after a short phase of renalinsufﬁciency and haemodialysis treatment on day 1 and 2.Immunosuppressive therapy included methyl-prednisolone,mycophenolatmofetil, and belatacept. Aminotransferase levelsreached normal values within 12 postoperative days. Bilirubinlevels rose to a maximum of 9.5 mg/dl 7 days after OLT andshowed a protracted mild elevation until 4 weeks later. Thepatient was discharged from the hospital 21 days after OLT.The levels of HCV RNA 3 months prior to OLT were rather low(17.800 IU/ml), and further declined signiﬁcantly during theanhepatic phase. Silibinin infusions were started 8 h after OLT.At this time HCV RNA levels measured 182 IU/ml, and droppedagain to 127 IU/ml after 48 h (RNA levels measured directly afterhaemodialysis are not available). Already from day 3 onwards,HCV RNA levels were below <15 IU/ml and became undetectableat day 9. During follow-up HCV RNA remained negative whenexamined at day 14, 21, 66, 84, and 168 (Fig. 1).This is the ﬁrst report of the successful suppression of earlyHCV reinfection after OLT with a 14 day course of silibininmono-therapy. This new treatment regimen thus induced anSVR, as after 6 months of follow-up, RNA for HCV was undetect-able. Accordingly, liver histology 6 months after OLT did notshow any cellular inﬂammation. Low pre-transplant HCV RNAlevels may be taken as a favourable prognostic factor for theunexpected therapeutic efﬁciency of silibinin. Applying silibininduring the anhepatic phase or even in the days before transplantmay expand the number of patients beneﬁting from thisapproach. This report may stimulate further trials and the con-cept of interferon-free HCV clearance induced by directantivirals.Conﬂicts of interestThe Authors have declared that they received funding from thedrug companies involved in order to carry out their research inthis manuscript.References