The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Silymarin in non-cirrhotics with non-alcoholic steatohepatitis: A randomized, double-blind, placebo controlled trial
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Figures
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Silymarin (an extract of milk thistle) may improve liver enzymes but the few, small, RCTs available 395,396 did not document histological improvement.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [396]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Design and validation of a histological scoring system for nonalcoholic fatty liver disease†
Kleiner, D. E., Brunt, E. M., Van Natta, M., Behling, C., Contos, M. J., Cummings, O. W., Ferrell, L. D., Liu, Y., Torbenson, M. S., Unalp‐Arida, A., et al. (2005) · Hepatology · doi:10.1002/hep.20701 · Cited by 10,791
Self-citationNonalcoholic Steatohepatitis: A Proposal for Grading and Staging The Histological Lesions
Brunt, E. M., Janney, C. G., Di Bisceglie, A. M., Neuschwander-Tetri, B. A., & Bacon, B. R. (1999) · American Journal of Gastroenterology · doi:10.1111/j.1572-0241.1999.01377.x · Cited by 3,907
Self-citationNeuschwander-Tetri, B. A., Loomba, R., Sanyal, A. J., Lavine, J. E., Van Natta, M. L., Abdelmalek, M. F., Chalasani, N., Dasarathy, S., Diehl, A. M., Hameed, B., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61933-4 · Cited by 2,237
Self-citationThe Use of Silymarin in the Treatment of Liver Diseases
Saller, R., Meier, R. F., & Brignoli, R. (2001) · Drugs · doi:10.2165/00003495-200161140-00003 · Cited by 720
Milk thistle in liver diseases: past, present, future
Abenavoli, L., Capasso, R., Milić, N., & Capasso, F. (2010) · Phytotherapy Research · doi:10.1002/ptr.3207 · Cited by 614
Molecular Virology of Hepatitis B Virus
LOCARNINI, S. A. (2004) · Seminars in Liver Disease · doi:10.1055/s-2004-828672 · Cited by 521
(2004) · Seminars in Liver Disease · doi:10.1055/s-2004-823098 · Cited by 481 · cited 1×
“Liver biopsy remains the gold standard for diagnosing and assessing the degree of injury in NASH [1,2].”
BackgroundSelf-citationA randomized trial of silymarin for the treatment of nonalcoholic steatohepatitis
Wah Kheong, C., Nik Mustapha, N. R., & Mahadeva, S. (2017) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2017.04.016 · Cited by 264
Scavenging of reactive oxygen species by silibinin dihemisuccinate
Mira, L., Silva, M. M. P., & Manso, C. (1994) · Biochemical Pharmacology · doi:10.1016/0006-2952(94)90053-1 · Cited by 192
Fried, M. (2012) · JAMA · doi:10.1001/jama.2012.8265 · Cited by 160
Self-citation
Cited by
Sorted by citations
Rinella, M. E., Neuschwander-Tetri, B. A., Siddiqui, M. S., Abdelmalek, M. F., Caldwell, S., Barb, D., Kleiner, D. E., & Loomba, R. (2023) · Hepatology · doi:10.1097/hep.0000000000000323 · Cited by 2,667
Tacke, F., Horn, P., Wai-Sun Wong, V., Ratziu, V., Bugianesi, E., Francque, S., Zelber-Sagi, S., Valenti, L., Roden, M., Schick, F., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.04.031 · Cited by 2,210
(2024) · Obesity Facts · doi:10.1159/000539371 · Cited by 545
Oxidative Stress in Non-alcoholic Fatty Liver Disease. An Updated Mini Review
Bovi, A. P. D., Marciano, F., Mandato, C., Siano, M., Savoia, M., & Vajro, P. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.595371 · Cited by 318
Ferro, D., Baratta, F., Pastori, D., Cocomello, N., Colantoni, A., Angelico, F., & Ben, M. D. (2020) · Nutrients · doi:10.3390/nu12092762 · Cited by 202
Metadata
- Authors
- Navarro, V. J., Belle, S. H., D’Amato, M., Adfhal, N., Brunt, E. M., Fried, M. W., Reddy, K. R., Wahed, A. S., Harrison, S., & on behalf of the Silymarin in NASH and C Hepatitis (SyNCH) Study Group
- Affiliations
- Jefferson Einstein Philadelphia Hospital (US)
- University of Pittsburgh (US)
- Beth Israel Deaconess Medical Center (US)
- Washington University in St. Louis (US)
- University of North Carolina at Chapel Hill (US)
- University of Pennsylvania (US)
- Brooke Army Medical Center (US)
- Corresponding author
- Navarro, Victor J.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2019-09-19
- Volume
- 14
- Issue
- 9
- Pages
- e0221683
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC6752871
- OpenAlex
- W2973727343
- Cited by
- 125
- References
- 14
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 30 · 2023: 16 · 2022: 19 · 2021: 18 · 2020: 9 · 2019: 1
- FWCI
- 8.64
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-10-10)
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- The Medicine Forum (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Rottapharm|Madaus
- Topics
- Health Sciences › Medicine › Hepatology › Silymarin and Mushroom Poisoning
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Complementary and alternative medicine › Nigella sativa pharmacological applications
- Keywords
- silymarin, Silybum marianum, nonalcoholic steatohepatitis, non-cirrhotic liver disease, NAFLD activity score, liver fibrosis, antioxidant therapy, herbal supplement safety, dose comparison, histological improvement
- MeSH terms
- Adult, Antioxidants, Double-Blind Method, Female, Humans, Male, Middle Aged, Silymarin, Treatment Outcome, Intention to Treat Analysis, Non-alcoholic Fatty Liver Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
