Silymarin in non-cirrhotics with non-alcoholic steatohepatitis: A randomized, double-blind, placebo controlled trial

Autoři: Victor J. Navarro aff001;  Steven H. Belle aff002;  Massimo D’Amato aff003;  Nezam Adfhal aff004;  Elizabeth M. Brunt aff005;  Michael W. Fried aff006;  K. Rajender Reddy aff007;  Abdus S. Wahed aff002;  Stephen Harrison aff008
Působiště autorů: Department of Digestive Disease and Transplantation, Einstein Medical Center and Sidney Kimmel Medical College, Philadlephia, Pennsylvania, United States of America aff001;  Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, United States of America aff002;  Clinical Research, Rottapharm Biotech, Monza MB, Italy aff003;  Division of Hepatology, Department of Medicine, Beth-Israel Deaconess Medical Center, Boston, Massachusetts, United States of America aff004;  Department of Pathology and Immunology, Washington University School of Medicine, CB 8118, St. Louis, Missouri, United States of America aff005;  Department of Medicine, Division of Gastroenterology and Hepatology, Liver Center, University of North Carolina, Chapel Hill, North Carolina, United States of America aff006;  Department of Medicine, Division of Gastroenterology University of Pennsylvania, Philadelphia, Pennsylvania, United States of America aff007;  Department of Medicine, Division of Gastroenterology, Brooke Army Medical Center, Fort Sam Houston, Texas, United States of America aff008
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0221683


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:, Identifier: NCT00680407.

Klíčová slova:

Medicine and health sciences – Surgical and invasive medical procedures – Biopsy – Health care – Health care providers – Medical doctors – Pathologists – Gastroenterology and hepatology – Liver diseases – Fatty liver – Cirrhosis – Pathology and laboratory medicine – Anatomical pathology – Cytopathology – Steatosis – Biology and life sciences – Anatomy – Histology – Developmental biology – Fibrosis – People and places – Population groupings – Professions – Medical personnel – Research and analysis methods – Research design – Clinical research design – Adverse events


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