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

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.

Abbreviations used in this paper: HCV, hepatitis C virus, Peg, pegylated, RBV, ribavirin