Author(s): Fried MW, Navarro VJ, Afdhal N, Belle SH, Wahed AS,
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Abstract CONTEXT: 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. OBJECTIVE: To determine the effect of silymarin on liver disease activity in patients with chronic hepatitis C virus (HCV) infection unsuccessfully treated with interferon-based therapy. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blind, placebo-controlled trial conducted at 4 medical centers in the United States. Participants included 154 persons with chronic HCV infection and serum alanine aminotransferase (ALT) levels of 65 U/L or greater who were previously unsuccessfully treated with interferon-based therapy. Enrollment began in May 2008 and was completed in May 2010, with the last follow-up visit completed in March 2011. INTERVENTION: Participants were randomly assigned to receive 420-mg silymarin, 700-mg silymarin, or matching placebo administered 3 times per day for 24 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was serum ALT level of 45 U/L or less (considered within the normal range) or less than 65 U/L, provided this was at least a 50\% decline from baseline values. Secondary outcomes included changes in ALT levels, HCV RNA levels, and quality-of-life measures. RESULTS: After 24 weeks of treatment, only 2 participants in each treatment group (P ≥ .99) met the primary outcome measure (3.8\% [95\% CI, 0.5\% to 13.2\%] for placebo, 4.0\% [95\% CI, 0.5\% to 13.7\%] for 420-mg silymarin, and 3.8\% [95\% CI, 0.5\% to 13.2\%] for 700-mg silymarin). The mean decline in serum ALT activity at the end of treatment did not differ significantly (P = .75) across the 3 treatment groups (mean decline, -4.3 [95\% CI, -17.3 to 8.7] U/L for placebo, -14.4 [95\% CI, -41.6 to 12.7] U/L for 420-mg silymarin, -11.3 [95\% CI, -27.9 to 5.4] U/L for 700-mg silymarin); there likewise were no significant differences in HCV RNA levels (mean change, 0.07 [95\% CI, -0.05 to 0.18] log10 IU/mL for placebo, -0.03 [95\% CI, -0.18 to 0.12] log10 IU/mL for 420-mg silymarin, 0.04 [95\% CI, -0.08 to 0.16] log10 IU/mL for 700-mg silymarin; P = .54) or quality-of-life measures. The adverse event profile of silymarin was comparable with that of placebo. CONCLUSION: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00680342.
This article was published in JAMA
and referenced in Journal of Antivirals & Antiretrovirals