Silymarin Trial for Hepatitis C and NASH

The Silymarin Trial for Hepatitis C and NASH (SyNCH) is a randomized, double-masked, placebo-controlled phase II study that assessed the safety and efficacy of a standardized orally administered silymarin preparation (Legalon®) for the treatment of patients with chronic hepatitis C virus (HCV) who failed conventional antiviral therapy. The botanical product silymarin, an extract of milk thistle, is commonly used by patients to treat chronic liver disease, despite scant and conflicting evidence of its efficacy. In light of inconclusive past clinical trials, the SyNCH study aimed to determine the effect of silymarin on liver disease activity in patients with chronic hepatitis C virus (HCV). In the phase I trial, an initial dose-ranging study was performed to identify silymarin doses for further study. Two doses, 3 and 5 times higher than the customary dose, were selected for the phase II trial based on this early testing.

The study enrolled participants with chronic HCV infection and serum alanine aminotransferase (ALT) levels of at least 65 U/L who were previously unsuccessfully treated with interferon-based therapy were enrolled. Participants were randomly assigned to 1 of 3 groups: 420-mg silymarin, 700-mg silymarin, or matching placebo gelatin capsules administered 3 times daily for 24 weeks, a standard duration of treatment for which effective therapies for HCV have regularly demonstrated improvement in disease activity. The primary outcome measure for efficacy was serum ALT level of 45 U/L or less (approximate normal range) or attainment of at least 50% decline of ALT level to less than 65 U/L after the 24-week treatment period.
Results showed that after 24 weeks of treatment, only 2 participants in each treatment group met the primary outcome measure: 3.8% for placebo, 4.0% for 420-mg silymarin, and 3.8% for 700-mg silymarin. Higher than customary doses of silymarin did not significantly reduce serum ALT levels more than placebo in participants with chronic HCV infection unsuccessfully treated with interferon-based therapy.