Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: a randomized controlled trial.
BACKGROUND
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.


METHODS
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.


METHODS
Participants were randomly assigned to receive 420-mg silymarin, 700-mg silymarin, or matching placebo administered 3 times per day for 24 weeks.


METHODS
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.


CONCLUSIONS
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.


BACKGROUND
clinicaltrials.gov Identifier: NCT00680342.
UNC Liver Center, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC 27599, USA. mfried@med.unc.edu
Michael W
MW
Fried
Victor J
VJ
Navarro
Nezam
N
Afdhal
Steven H
SH
Belle
Abdus S
AS
Wahed
Roy L
RL
Hawke
Edward
E
Doo
Catherine M
CM
Meyers
K Rajender
KR
Reddy
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects*; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects; D004279:DNA, Viral / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012838:Silymarin / Q000008:administration & dosage* / Q000009:adverse effects; D017211:Treatment Failure; D016896:Treatment Outcome
D000975:Antioxidants; D004279:DNA, Viral; D012838:Silymarin; D007372:Interferons; D000410:Alanine Transaminase