Drug & Device Development

Silibinin infusion has antiviral effect against HCV in nonresponders

Last Updated: 2008-12-25 8:00:37 -0400 (Reuters Health)

By Megan Rauscher

NEW YORK (Reuters Health) - Intravenous silibinin, a flavanone derived from milk thistle, provides a "substantial" antiviral effect in patients with chronic hepatitis C (HCV) who have not responded to standard full-dose pegylated interferon plus ribavirin (PegIFN/RBV), clinicians from Austria report.

In comments to Reuters Health, lead investigator Dr. Peter Ferenci said: "Milk thistle preparations (have been) used for treatment of liver diseases for centuries. A final proof of efficacy is missing. This study shows for the first time in humans that silibinin given intravenously is a potent antiviral in patients with chronic hepatitis C, thus linking 'folk medicine' to evidence-based medicine."

Dr. Ferenci and colleagues from Medical University of Vienna treated 16 HCV patients who failed to respond to full-dose PegIFN/RBV combination therapy with IV silibinin 10 mg/kg/day for 7 days. On day 8, PegIFN/RBV was started.

They report in the November issue of Gastroenterology that serum HCV RNA declined in all patients on IV silibinin monotherapy, with a mean log decline of 1.32 within 1 week (p < 0.001). "Unexpectedly," however, HCV RNA levels increased again after the infusion period in spite of PegIFN/RBV therapy.

IV silibinin "failed to improve the outcome of nonresponders by augmenting the response to interferon, which was the primary hypothesis of the study," the investigators note. This clinical trial was then discontinued.

However, in a subsequent dose-finding study, 6 of 14 patients achieved HCV RNA levels of less than 15 IU/mL after a 14-day infusion of 15 or 20 mg/kg/day silibinin, Dr. Ferenci and colleagues report. As in the first study, PegIFN/RBV combination therapy was started on day 8. "These patients are still on treatment," the authors note.

At week 12, HCV RNA became undetectable in 7 patients who received the 14-day infusion of IV silibinin at the 15- or 20-mg dose.

Intravenous silibinin was well tolerated with no serious adverse effects. The most common side effect was a transient sensation of heat.

Summing up, Dr. Ferenci noted that there currently is no available treatment for nonresponders to PegIFN/RBV therapy. "There is unmet medical need for new treatment strategies like the one described in my paper," he said.

While further study is needed, the current observations suggest that silibinin "may be a very useful drug treatment of PegIFN/RBV nonresponders or in future combinations with HCV protease or polymerase inhibitors," Dr. Ferenci and colleagues conclude.

Gastroenterology 2008;135:1561-1567.