51. Silymarin in non-cirrhotics with non-alcoholic steatohepatitis: A randomized, double-blind, placebo controlled trial
- Author
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Victor J Navarro, Steven H Belle, Massimo D'Amato, Nezam Adfhal, Elizabeth M Brunt, Michael W Fried, K Rajender Reddy, Abdus S Wahed, Stephen Harrison, and Silymarin in NASH and C Hepatitis (SyNCH) Study Group
- Subjects
Steatosis ,Medical Doctors ,Biopsy ,Health Care Providers ,Placebo-controlled study ,Chronic liver disease ,Pathology and Laboratory Medicine ,law.invention ,Cytopathology ,0302 clinical medicine ,Randomized controlled trial ,law ,Clinical endpoint ,Medicine and Health Sciences ,Medical Personnel ,Multidisciplinary ,Liver Diseases ,3. Good health ,Professions ,Cirrhosis ,Research Design ,030220 oncology & carcinogenesis ,Medicine ,030211 gastroenterology & hepatology ,Anatomy ,Research Article ,medicine.medical_specialty ,Histology ,Clinical Research Design ,Science ,Surgical and Invasive Medical Procedures ,Gastroenterology and Hepatology ,Placebo ,Research and Analysis Methods ,03 medical and health sciences ,Internal medicine ,medicine ,Adverse effect ,Intention-to-treat analysis ,business.industry ,Biology and Life Sciences ,medicine.disease ,Fibrosis ,Clinical trial ,Pathologists ,Health Care ,Fatty Liver ,Anatomical Pathology ,People and Places ,Population Groupings ,Adverse Events ,business ,Developmental Biology - Abstract
The botanical product silymarin, an extract of milk thistle, is commonly used by patients to treat chronic liver disease and may be a treatment for NASH due to its antioxidant properties. We aimed to assess the safety and efficacy of higher than customary doses of silymarin in non-cirrhotic patients with NASH. This exploratory randomized double-blind placebo controlled multicenter Phase II trial tested a proprietary standardized silymarin preparation (Legalon®, Rottapharm|Madaus, Mylan) and was conducted at 5 medical centers in the United States. Eligible adult patients had liver biopsy within 12 months showing NASH without cirrhosis with NAFLD Activity Score (NAS) ≥4 per site pathologist's assessment. Participants were randomized to Legalon® 420 mg, 700 mg, or placebo t.i.d. for 48 weeks. The primary endpoint was histological improvement ≥2 points in NAS. Of 116 patients screened, 78 were randomized. There were no significant differences in adverse events among the treatment groups. After 48-50 weeks, 4/27 (15%) in the 700 mg dose, 5/26 (19%) participants randomized to 420 mg, and 3/25 (12%) of placebo recipients reached the primary endpoint (p = 0.79) among all randomized participants, indicating no benefit from silymarin in the intention to treat analysis Review by a central pathologist demonstrated that a substantial number of participants (49, 63%) did not meet histological entry criteria and that fibrosis stage improved most in the placebo treated group, although not significantly different from other groups. Silymarin (Legalon®) at the higher than customary doses tested in this study is safe and well tolerated. The effect of silymarin in patients with NASH remains inconclusive due to the substantial number of patients who entered the study but did not meet entry histological criteria, the lack of a statistically significant improvement in NAS of silymarin treated patients, and the unanticipated effect of placebo on fibrosis indicate the need for additional clinical trials. Trial Registration: clinicaltrials.gov, Identifier: NCT00680407.
- Published
- 2019