Silibinin Is a Potent Antiviral Agent in Patients With Chronic Hepatitis C Not Responding to Pegylated interferon/ribavirin Therapy

Gastroenterology. 2008 Nov;135(5):1561-7. doi: 10.1053/j.gastro.2008.07.072. Epub 2008 Aug 3.

Abstract

Background & aims: Oral Silibinin (SIL) is widely used for treatment of hepatitis C, but its efficacy is unclear. Substantially higher doses can be administered intravenously (IV).

Methods: Pedigreed nonresponders to full-dose pegylated (Peg)-interferon/ribavirin (PegIFN/RBV) were studied. First, 16 patients received 10 mg/kg/day SIL IV (Legalon Sil; Madaus, Köln, Germany) for 7 days. In a subsequent dose-finding study, 20 patients received 5, 10, 15, or 20 mg/kg/day SIL for 14 days. In both protocols, PegIFN alpha-2a/RBV were started on day 8. Viral load was determined daily.

Results: Unexpectedly, in the first study, HCV-RNA declined on IV SIL by 1.32 +/- 0.55 log (mean +/- SD), P < .001 but increased again in spite of PegIFN/RBV after the infusion period. The viral load decrease was dose dependent (log drop after 7 days SIL: 0.55 +/- 0.5 [5 mg/kg, n = 3], 1.41 +/- 0.59 [10 mg/kg, n = 19], 2.11 +/- 1.34 [15 mg/kg, n = 5], and 3.02 +/- 1.01 [20 mg/kg, n = 9]; P < .001), decreased further after 7 days combined SIL/PegIFN/RBV (1.63 +/- 0.78 [5 mg/kg, n = 3], 4.16 +/- 1.28 [10 mg/kg, n = 3], 3.69 +/- 1.29 [15 mg/kg, n = 5], and 4.85 +/- 0.89 [20 mg/kg, n = 9]; P < .001), and became undetectable in 7 patients on 15 or 20 mg/kg SIL, at week 12. Beside mild gastrointestinal symptoms, IV SIL monotherapy was well tolerated.

Conclusions: IV SIL is well tolerated and shows a substantial antiviral effect against HCV in nonresponders.

Trial registration: ClinicalTrials.gov NCT00684268.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Antioxidants / administration & dosage
  • Antioxidants / therapeutic use*
  • Antiviral Agents / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Carriers
  • Drug Resistance, Viral*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Free Radical Scavengers / blood
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification*
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Infusions, Intravenous
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Milk Thistle
  • Polyethylene Glycols / therapeutic use*
  • Polymerase Chain Reaction
  • RNA, Viral / genetics
  • Recombinant Proteins
  • Ribavirin / therapeutic use*
  • Silybin
  • Silymarin / administration & dosage
  • Silymarin / therapeutic use
  • Time Factors
  • Treatment Outcome
  • Viral Load

Substances

  • Antioxidants
  • Antiviral Agents
  • Drug Carriers
  • Free Radical Scavengers
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Silymarin
  • Polyethylene Glycols
  • Ribavirin
  • Silybin
  • peginterferon alfa-2a

Associated data

  • ClinicalTrials.gov/NCT00684268