The botanical product silymarin, an extract of milk thistle commonly used by some patients with chronic liver disease, did not provide greater benefit than a placebo for patients with treatment-resistant chronic hepatitis C virus infection, according to a study by UNC scientists published in the July 18 issue of the Journal of the American Medical Association.
Chronic hepatitis C virus infection, or HCV, affects almost 3 percent of the global population and may lead to cirrhosis, liver failure, and liver cancer. A large proportion of patients do not respond to certain treatments for this infection, and many others cannot be treated because of co-existing illnesses. “Thus, alternative medications with disease-modifying activity may be of benefit,” according to background information in the article. Thirty-three percent of patients with chronic HCV infection and cirrhosis reported current or past use of silymarin for the treatment of their disease. Clinical studies that have evaluated milk thistle for a variety of liver diseases have yielded inconsistent results.
“This was the largest and most robust randomized placebo-controlled clinical trial ever conducted with silymarin in patients with chronic HCV infection,” says Roy Hawke, PharmD, PhD, a clinical assistant professor at the UNC Eshelman School of Pharmacy and one of the study’s coauthors. “Therefore, patients should re-evaluate their use of silymarin in light of the overwhelming evidence for its lack of clinical benefits in this study, and the recent availability of new direct-acting antivirals that have been shown to be highly effective.”
Michael W. Fried, MD, a professor in the UNC School of Medicine conducted the study along with Hawke and other colleagues in order to assess the use of silymarin for treating chronic HCV infection. The multicenter, placebo-controlled trial was conducted at four medical centers in the United States over three years. Participants included 154 persons with chronic HCV infection and serum alanine aminotransferase (an enzyme that reflects liver function known as ALT) levels of 65 U/L or greater who were previously unsuccessfully treated with interferon-based therapy. Participants were randomly assigned to receive 420-mg silymarin, 700-mg silymarin, or matching placebo administered three times per day for twenty-four weeks. The primary outcome measure for the study was a 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 percent decline from baseline values. Secondary outcomes included changes in ALT levels, HCV RNA levels, and quality-of-life measures.
At the end of treatment, only two participants in each treatment group achieved the prespecified primary end point. The percentages of participants who achieved the primary end point were 3.8 percent in the placebo group, 4.0 percent in the 420-mg silymarin group, and 3.8 percent in the 700-mg silymarin group. The researchers also found that there was no statistically significant difference across treatment groups when changes in serum ALT levels from the beginning of the study to end of treatment were analyzed. Also, average serum HCV RNA levels did not change significantly during the twenty-four weeks of therapy.
There were no significant changes in physical or mental health components of quality-of-life scores, in chronic liver disease health-related quality-of-life assessments, or in depression scores in any group. Frequency of adverse events reported by individual patients also did not differ significantly among the treatment groups.
“In summary, oral silymarin, used at higher than customary doses, did not significantly alter biochemical or virological markers of disease activity in patients with chronic HCV infection who had prior treatment with interferon-based regimens,” the authors conclude.