A paper out of Austria has some of us at NYBC VERY excited. Researchers looked at varying doses of a component of milk thistle known as silbinin, from 5 to 20 mg/kg/day over a period of 14 days. During the first 7 days, only the silbinin, which was injected, was administered. Subsequently, on day 8, pegylated interferon and ribavirin were given.
Most astonishingly, by the end of the 7 days, those receiving the 15 mg/kg dose saw a 2.11 log drop in their hepatitis C viral load. Those in the 20 mg/kg arm saw a whopping 3.02 log drop!! This in just 7 days? STUNNING!!
Unfortunately, adding the medication to these participants, who had already failed on IFN/riba therapy! resulted in the numbers deteriorating significantly. The silibinin treatment was very well tolerated.
Which raises a host of questions…would a higher dose work better? 25 or 30 mg/kg? What happens if the therapy is provided over a longer period?
This review wants to try it!
Ferenci P, Scherzer TM, Kerschner H, Rutter K, Beinhardt S, Hofer H, Schöniger-Hekele M, Holzmann H, Steindl-Munda P. 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. Epub 2008 Aug 3.
Comment in: Gastroenterology. 2009 Jul;137(1):390-1.
Internal Medicine 3, Department of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria. firstname.lastname@example.org
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.