Patients who are not helped by the standard treatments for hepatitis C virus (HCV) infections often turn to unproven alternative therapies, including silymarin, an extract of milk thistle that is a popular supplement among patients with liver conditions. But a study published in JAMA today found that silymarin does not improve patient clinical outcomes or quality of life.
About one-third of patients with chronic hepatitis and cirrhosis take or have taken silymarin to improve their liver condition, according to the authors of the study, despite mixed results from previous studies about the supplement’s effectiveness. To provide more definitive data, Michael W. Fried, MD, and his colleagues conducted a multicenter placebo-controlled trial of 154 patients with chronic HCV infection who had been unsuccessfully treated with interferon-based therapy, the standard treatment for the infection. Patients were randomized to receive either 420-mg silymarin, 700-mg silymarin, or a placebo 3 times daily for 24 weeks. The treatment did not improve markers of liver function or reduce HCV RNA levels, and patients who took silymarin reported no better quality of life than those who took placebo.
Dr Fried, who directs the Liver Center at the University of North Carolina–Chapel Hill, discussed the findings with news@JAMA.
news@JAMA: Why was this study conducted?
Dr Fried: These complementary and alternative medicines are used extensively, but the evidence supporting their effectiveness are often slim. We wanted to do a rigorous placebo-controlled trial to come to a definitive conclusion about silymarin use among patients with chronic HCV who have failed standard therapies.
news@JAMA: What did you find?
Dr Fried: We did not find any signal of efficacy looking at markers of disease activity. We also looked at secondary measures such as quality of life and levels of virus and didn’t find any difference between patients who took silymarin and those who took placebo. We used much higher doses than usual silymarin supplements contain because we had looked at pharmacokinetics and knew higher doses would likely be necessary to have an effect.
news@JAMA: Some preclinical studies have suggested mechanisms by which silymarin might be useful for patients with liver conditions. Why do you think your study didn’t bear out the findings?
Dr Fried: Silymarin has several mechanisms: it’s an antioxidant, immune modulator, antifibrotic, and has antiviral properties. Based on this evidence we were kind of encouraged. But the fact that we didn’t see an effect might be due to patients not being able to achieve the level of the drug clinically needed to get that result. An intravenous formulation based on some of the components of silymarin did have effect in some early studies. But these oral formulations don’t appear to work.
news@JAMA: How would you like patients to use the findings?
Dr Fried: While people often look for alternatives to medication, silymarin doesn’t seem to have any beneficial effects. We didn’t find any safety signal associated with silymarin even at higher doses, but the study was not powered to look at adverse events. Patients should reconsider whether this is something they really want to use when we haven’t been able to prove clinical efficacy.
news@JAMA: Is there anything else patients with hepatitis C infection can do to improve their liver condition and quality of life?
Dr Fried: Patients should focus on maintaining liver health by maintaining an ideal weight and avoiding hepatotoxins, mainly alcohol. That can go a long way toward improving patient outcomes.
news@JAMA: The existing interferon-based treatments for hepatitis C infections fail many patients and have onerous adverse effects. Are there other drug treatments on the horizon?
Dr Fried: There is tremendous progress being made on direct-acting antivirals for patients with chronic HCV infections. There will be more effective and more tolerable treatments for HCV within the next few years.