Milk Thistle

Silibinin is the main flavonoid extracted from the milk thistle (Silibum marianum) plant. This compound has been used in several cultures for the treatment of a variety of liver diseases without a precise knowledge of its mode of action.

Because of its potential anti-oxidative action, pre-treatment with silibinin may improve response to interferon. Furthermore, silibinin inhibits viral replication in HCV laboratory replicon systems (Gastroenterology 132:1925. 2007).

In the current study, presented at the 43rd annual meeting of the European Association for the Study of the Liver (EASL) last week in Milan, researchers at the Medical University of Vienna in Austria discovered that silibinin is a potent antiviral agent active against the hepatitis C virus (HCV) in humans.

The study included16 non-responders to full dose pegylated interferon alfa-2a (Pegasys) plus ribavirin combination therapy. Most (12) were men, the mean age was 50 years, 14 had HCV genotype 1, 2 had genotype 4, and 13 had advanced (F3/F4) fibrosis.

Participants were pre-treated with 10 mg/kg/day intravenous (IV) silibinin (Legalon Sil) for 7 days before starting treatment with 180 mcg/week Pegasys plus 1000-1200 mg/day weight-based ribavirin, while also continuing on 140 mg thrice-daily silymarin (Legalon), an oral milk thistle product.

HCV RNA was quantified using the TaqMan assay at baseline, after 7 infusions of silibinin, and every 2 weeks while taking pegylated interferon/ribavirin.

Results

• Within 1 week, IV silibinin monotherapy lead to a decrease in HCV viral load in all patients (baseline: 6.2 MIU/mL; day 8: 0.96; P=0.00005).

• The mean log decline in viral load was 0.82.

• Mean ALT decreased from 162 to 118 (P=0.004).

• At the time of the abstract presentation, viral kinetics were available only for 3 patients.

• Viral load began to decrease started on day 3 of silibinin monotherapy and showed a linear decline over the next days.

• Treatment was well tolerated.

• While on antiviral treatment, HCV RNA tended to decline further (week 2: 0.81; week 4: 0.96; both P<0.001 vs baseline).

• However, viral load started to increase again at week 8 (log drop: 0.69).

• After 12 weeks, 5 patients had a log drop greater than 2.

Conclusion

These preliminary findings suggest that silibinin has marked antiviral activity against HCV, and this effect was unrelated to the action of interferon/ribavirin, according to the investigators.

They concluded that, "This drug may be a useful for treatment of chronic hepatitis C, especially in non-responders. The potential of silibinin for combination with new antivirals needs to be explored [further]."

Medical University of Vienna, Vienna, Austria.

5/02/08

Reference
P Ferenci, TM Scherzer, H Hofer, and others. Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to antiviral combination therapy. 43rd Annual Meeting of the European Association for the Study of the Liver (EASL 2008). Milan, Italy. April 23-27, 2008.