Antiviral activity and safety profile of silibinin in HCV patients with advanced fibrosis after liver transplantation: a randomized clinical trial

Transpl Int. 2014 Jul;27(7):696-704. doi: 10.1111/tri.12324. Epub 2014 May 10.

Abstract

Response to interferon-based therapies in HCV recurrence after liver transplantation (LT) is unsatisfactory, and major safety issues aroused in preliminary experience with boceprevir and telaprevir. As transplant community identified HCV viral clearance as a critical matter, efficacious and safe anti-HCV therapies are awaited. The aim of this study was to assess efficacy and safety of intravenous silibinin monotherapy in patients with established HCV recurrence after LT, nonresponders to pegylated interferon and ribavirin. This is a single center, prospective, randomized, parallel-group, double-blind, placebo-controlled, phase 2 trial including 20 patients randomly assigned (3:1) to receive daily 20 mg/kg of intravenous silibinin or saline as placebo, for 14 consecutive days. On day 14 of treatment, viral load decreased by 2.30 ± 1.32 in silibinin group versus no change in the placebo group (P = 0.0002). Sixteen days after the end of the treatment, viral load mean values were similar to baseline. Treatment resulted well tolerated apart from a transient and reversible increase in bilirubin. Neither changes in immunosuppressant through levels nor dosage adjustments were necessary. Silibinin monotherapy has a significant antiviral activity in patients with established HCV recurrence on the graft not responding to standard therapy and confirms safety and tolerability without interaction with immunosuppressive drugs (ClinicalTrials.gov number: NCT01518933).

Keywords: HCV; antiviral therapy; drug interaction; liver transplantation; silibinin.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Double-Blind Method
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon-alpha / therapeutic use
  • Liver Transplantation*
  • Polyethylene Glycols / administration & dosage
  • Prospective Studies
  • Ribavirin / therapeutic use
  • Silybin
  • Silymarin / therapeutic use*

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Silymarin
  • Polyethylene Glycols
  • Ribavirin
  • Silybin

Associated data

  • ClinicalTrials.gov/NCT01518933