title: Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy.
abstract: OBJECTIVE
  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.
authors.affiliation: Internal Medicine 3, Department of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria. peter.ferenci@meduniwien.ac.at
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.forename: Thomas-Matthias
authors.initials: TM
authors.lastname: Scherzer
authors.forename: Heidrun
authors.initials: H
authors.lastname: Kerschner
authors.forename: Karoline
authors.initials: K
authors.lastname: Rutter
authors.forename: Sandra
authors.initials: S
authors.lastname: Beinhardt
authors.forename: Harald
authors.initials: H
authors.lastname: Hofer
authors.forename: Maximilian
authors.initials: M
authors.lastname: Schöniger-Hekele
authors.forename: Heidemarie
authors.initials: H
authors.lastname: Holzmann
authors.forename: Petra
authors.initials: P
authors.lastname: Steindl-Munda
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016166:Free Radical Scavengers / Q000097:blood; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007262:Infusions, Intravenous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020944:Silybum marianum; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000975:Antioxidants; D000998:Antiviral Agents; D004337:Drug Carriers; D016166:Free Radical Scavengers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012838:Silymarin; D011092:Polyethylene Glycols; D012254:Ribavirin; D000077385:Silybin; C100416:peginterferon alfa-2a