- Category: Alternative & Complementary Therapy
- Published on Tuesday, 17 July 2012 00:00
- Written by Liz Highleyman
The milk thistle extract silymarin did not reduce elevated alanine aminotransferase (ALT) levels more than placebo in a controlled trial of chronic hepatitis C patients who did not achieve sustained response to prior treatment, researchers reported in the July 18, 2012, Journal of the American Medical Association.
Interferon-based therapy has been the mainstay of hepatitis C virus (HCV) therapy for 2 decades, but even with the addition of new direct-acting antiviral agents such as boceprevir (Victrelis) or telaprevir (Incivek), some patients do not achieve a cure, or sustained virological response. Over years or decades unsuppressed HCV infection can lead to serious liver disease including cirrhosis and hepatocellular carcinoma.
Patients and providers have tried a variety of alternative and complementary therapies for liver disease, with milk thistle (Silybum marianum) being one of the most common in Eastern and Western traditions. Silymarin is a mix of milk thistle flavonoids with anti-oxidant, anti-inflammatory, antiviral, and immunomodulatory properties in vitro.
Michael Fried from the University of North Carolina at Chapel Hill and fellow investigators with the Silymarin in NASH and C Hepatitis (SyNCH) Study Groupsought todetermine the effect of silymarin on liver disease activity in chronic hepatitis C patients who were not cured with interferon-based therapy. Results were also presented at the 2011 AASLD Liver Meeting in San Francisco.
This double-blind trial included 154 participants with chronic HCV infection at 4 U.S. centers. A majority were men, about 75% were white, and the median age was 54 years. Most had difficult-to-treat HCV genotype 1; people with decompensated cirrhosis, advanced steatosis (fatty liver), and HIV or hepatitis B virus coinfection were excluded. At baseline they had elevated ALT levels of 65 U/L or greater, a sign of liver inflammation.
Participants were randomly assigned to receive 420 mg or 700 mg of silymarin, at 3 to 5 times higher than usual doses, or matching placebo 3 times daily for 24 weeks.
Treatment was considered successful if ALT fell below 45 U/L (within the normal range) or below 65 U/L if the decrease was at least 50% from baseline. The researchers also looked at HCV RNA viral load levels and quality-of-life measures.
- After 24 weeks, only 2 participants (about 4%) in each study arm saw their ALT levels fall below the specified limits, indicating no significant treatment effect.
- Average declines in serum ALT were somewhat larger in the low- and high-dose silymarin groups compared with the placebo group (−14.4, −11.3, and −4.3), respectively, but the differences did not reach statistical significance.
- Changes in HCV RNA levels likewise did not differ significantly across the 3 study arms (-0.03, +0.04, and +0.07, respectively).
- Adherence was good and silymarin was well-tolerated, with mostly mild-to-moderate adverse events that were comparable across groups.
- Quality of life measures did not differ significantly in the treatment and placebo arms.
Based on these findings, the study investigators concluded, "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."
No significant changes in physical or mental health quality-of-life scores, chronic liver disease health-related quality-of-life scores, or in depression scores were observed in any treatment group, they elaborated.
MW Fried, VJ Navarro, N Afdhal, et al. (Silymarin in NASH and C Hepatitis Study Group.Effect of Silymarin (Milk Thistle) on Liver Disease in Patients With Chronic Hepatitis C Unsuccessfully Treated With Interferon Therapy: A Randomized Controlled Trial. JAMA 308(3):274-282. July 18, 2012.
JAMA. Treating Chronic Hepatitis C With Milk Thistle Extract Does Not Appear Beneficial. Media advisory for July 17, 2012.