European Association for the Study of the Liver (EASL) 2015
EASL 2015. Late-breaking Poster 12. Silymarin for the Treatment of Non-Alcoholic Steatohepatitis: Interim Analysis of a Randomized, Double-blind, Placebo-controlled Trial
W.K. Chan, et al.
CARE Faculty Perspective:
This is a randomized, double-blind, placebo-controlled trial examining the efficacy of silymarin (milk thistle) at a dose of 700mg PO TID in the Malaysian population, the interim results of which were presented after 48 weeks of treatment NASH was diagnosed with a baseline liver biopsy, a repeat of which was performed at the end of the study. A total of 30 patients were in the treatment arm, compared to 34 patients in the placebo group. The primary endpoint was defined as at least a 30% improvement in the NAFLD Activity Score (NAS), whereas histological endpoint was defined as an improvement in fibrosis stage, regardless of the change in NAS. Resolution of NASH was defined as a decrease in the NAS to less than 3. The mean age in both arms was approximately 50 years, with an equal distribution of men and women in both arms. The mean NAS was 5 in both arms, with 12 patients having a NAS of 3 or 4, and 18 patients with a NAS of 5 to 8 in the treatment arm, whereas in the control group 9 patients had a NAS of 3 or 4, and 25 patients had a NAS of 5 to 8. There were no cirrhotic patients in either arm. There was no statistical difference between the treatment and placebo groups with respect to the primary outcome of at least 30% improvement in NAS, or in histological outcome (See Table 1). However, the treatment arm did show evidence of benefit in NASH resolution.
The interim analysis shows that patients in both the silymarin and placebo groups demonstrated an improvement in their NAS, but although there was a trend towards a benefit from silymarin, it was not statistically significant. Despite this, there were a statistically significant proportion of patients in the treatment arm who demonstrated a resolution of their NASH (defined as a NAS<3), as well as an improvement in their fibrosis stages. However, the numbers in both arms for these outcomes, for which the study was not powered, are very small, and may be a result of a Type 1 error. Therefore, the final results will be of importance before recommending silymarin as a treatment for NASH. However, given that many patients start taking silymarin of their own volition, these interim results may indicate that there is no role in asking them to stop taking the herbal medication.
Table 1 - Summary of Pertinent Results
- CARE Liver Disease Faculty