By Kristina Fiore, Staff Writer, MedPage Today
Published: July 17, 2012
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Silymarin, a milk thistle extract, probably will not be of much help to patients with chronic hepatitis C virus (HCV) who have already failed interferon therapy, researchers found.
In a randomized, controlled trial, there were no differences in improvements in alanine aminotransferase (ALT) levels between two doses of silymarin -- often used as an alternative therapy -- and placebo in these hard-to-treat patients, Michael Fried, MD, of the University of North Carolina at Chapel Hill, and colleagues reported in the July 18 issue of the Journal of the American Medical Association.
Currently, standard therapy for HCV involves a basic regimen of peginterferon and ribavirin, now buffered by two newer protease inhibitors. Still, a large proportion of patients don't respond to these therapies, and many others can't be treated with them because of medical comorbidities, the researchers said.
Patients often turn to alternative therapies such as silymarin in hopes of some added benefit. According to some estimates, about a third of HCV and cirrhosis patients report using the milk thistle extract for their disease -- but studies have yielded inconsistent results regarding its benefit.
So Fried and colleagues conducted a double-blind, placebo-controlled trial at four medical centers in the U.S., totaling 154 patients with chronic HCV who'd already failed interferon therapy. Just over half (56%) had never used milk thistle before.
Patients were enrolled between May 2008 and May 2010, with last follow-up in May 2011. The median age was 54, almost three-quarters (71%) of patients were male, and the median body mass index (BMI) was 29. Most patients (91%) had HCV genotype 1 infection.
They were randomly assigned to placebo or one of two doses of silymarin (420 mg or 700 mg) three times a day for 24 weeks. The primary outcome was a serum ALT of 45 U/L or less, or under 65 U/L provided that was at least a 50% drop from baseline values.
By study end, two participants from each treatment group met the primary outcome measure -- as did two patients in the placebo group.
The mean decline in serum ALT didn't differ significantly across the groups, either:
- -4.3 U/L for placebo
- -14.4 U/L for 420 mg silymarin
- -11.3 U/L for 700 mg silymarin
Nor were there any significant differences in HCV RNA levels or in quality-of-life measures, the researchers reported.
Adverse events were similar across all groups, with the most frequent being gastrointestinal symptoms, occurring in 12% of both silymarin groups compared with 5% of those on placebo.
The percentage of patients with serious adverse events was numerically higher in the silymarin groups, but Fried and colleagues noted that the power to detect differences was limited by the small number of patients in each group.
They concluded that 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 IFN-based regimens."
Recently, researchers reported that intravenous silibinin, another milk thistle extract, helped patients with liver toxicity resulting from mushroom poisoning. A trial of the compound in this indication is ongoing.
The study was supported by the National Center for Complementary and Alternative Medicine and the National Institute of Diabetes and Digestive and Kidney Diseases.
Rottapharm/Madaus donated the silymarin and placebo.
Abbott Molecular donated the HCV assays.
The researchers reported relationships with Genentech, Merck, Vertex, Gilead, Tibotec, Janssen, Bristol Myers Squibb, Abbott, Rottapharm/Madaus, Novartis, GlaxoSmithKline, Springbank, Medgenics, Boehringer Ingelheim, Ikaria, Anadys, and Gore.
Primary source: Journal of the American Medical Association
Fried MW, et al "Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy" JAMA 2012; 308(3): 274-282.