First case description of a quadruple therapy with silibinin, telaprevir, ribavirin and pegIFNα2a in a liver transplanted patient with chronic Hepatitis C Virus infection

Aims: After liver transplantation antiviral therapy of chronic Hepatitis C Virus (HCV) reinfection of the graft remains challenging. Protease inhibitor based antiviral therapy seems to improve outcome of antiviral therapy but is still limited by dependency on previous treatment outcome with standard of care (SOC). Silibinin (SIL) has already proven potent antiviral efficacy in the pre-, peri- and post-transplantation period and has been shown lately to be a direct-acting antiviral drug.

Aims: To evaluate antiviral efficacy and safety of a quadruple therapy consisting of i.v. infusions of silibinin combined with a telaprevir based triple therapy in a liver transplanted patient suffering from chronic HCV genotype 1a infection with non-response to previous dual therapy and breakthrough during silibinin monotherapy.

Methods: We report 12 week data of a “quadruple” therapy of infusions of Legalon-SIL© (20 mg/kg body weight/day infused over 4 hours) for 26 consecutive days combined with telaprevir (1125 mg BID), RBV (1000 mg daily) and pegIFNα2a (135 µg/week) followed by a triple therapy (telaprevir/RBV/pegIFNα2a) scheduled for a total of 48 weeks.

Results: During the 26 days of quadruple therapy viral load declined from 9.14 × 10⁶ IU/ml to 7.4 × 10¹ IU/ml. Viral RNA was negative for the first time at treatment week 10 and remained negative thereafter (end of observation at treatment week 12). Total bilirubin concentration rose from 1.2 mg/dl to a maximum of 4.8 mg/dl, but declined to baseline 2 weeks after cessation of SIL infusion. Leukocyte and hemoglobin levels declined from 5.43/nl to 1.96/nl and 17 g/dl to 10.2 g/dl, respectively. Other side effects were not observed. Ciclosporine dose was reduced to one third of the pretherapeutic dose after initiation of telaprevir and required no change after the end of SIL therapy.

Conclusion: This is the first case description of above named antiviral quadruple therapy. We observed excellent antiviral efficacy and safety. Apart from completely reversible hyperbilirubinemia we observed no side effect attributable to silibinin. Hematological side effects were as expected with telaprevir based triple therapy. Controlled studies are needed to evaluate the antiviral potency of this drug combination.