Silibinin Is a Potent Antiviral Agent in Patients With Chronic Hepatitis C Not Responding to Pegylated Interferon/Ribavirin Therapy
Received 28 May 2008; accepted 24 July 2008. published online 04 August 2008.
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, PegIFNα-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.
⁎Internal Medicine 3, Department of Gastroenterology and Hepatology, Medical University of Vienna, Austria
‡Clinical Institute of Virology, Medical University of Vienna, Austria
Address requests for reprints to: Peter Ferenci, MD, Prof, Universitätsklinik für Innere Medizin III, Medical University of Vienna, AKH, Waehringer Guertel 18-20, A 1090 Wien, Austria. fax: (43) 1 0 40400 4735
The authors disclose the following: Conflicts of interest: P. Ferenci: Roche, Basel, CH; member of the Global Advisory Board and of the speakers bureau and receives financial support for clinical studies. All other authors have no conflicts of interest.
Supported by an unrestricted research grant by Roche Austria, and silibinin (Legalon Sil) and silimaryin (Legalon) were provided by Rottapharm-Madaus, Köln, Germany. None of the companies was involved in the design, conduct, and evaluation of this protocol.
ABSTRACT