Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy.
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.
Ferenci
Peter
P
Internal Medicine 3, Department of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria. peter.ferenci@meduniwien.ac.at
Scherzer
Thomas-Matthias
TM
Kerschner
Heidrun
H
Rutter
Karoline
K
Beinhardt
Sandra
S
Hofer
Harald
H
Schöniger-Hekele
Maximilian
M
Holzmann
Heidemarie
H
Steindl-Munda
Petra
P
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
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