**TITLE**:
The impact of treatment with silymarin in patients with non alcoholic fatty liver disease: a systematic review and meta-analysis
***Review question:***
The aim of this study is to systematically review the current literature and to make a meta-analysis about the efficacy of treatment with silymarin in patients with Non-alcoholic Fatty Liver Disease (NAFLD).
***Materials and methods:***
The study protocol is conducted according to the Preferred Reporting Items for Systematic reviews and Met-analyses (PRISMA) statement(1).
**1. Study eligibility criteria**
-Patients- population:
Inclusion criteria :
- Patients with NAFLD diagnosed by liver sonography, radiography, or histology in liver biopsy according to the international criteria for
the diagnosis of NAFLD with daily alcohol intake less than 20 g/day
for women and less tha 30g/day for men. (2)
- Patients older than 18 years old
Exclusion criteria:
- Patients having any history of alcohol abuse
- Severe cardiac, pulmonary or renal comorbidities
-Pregnacy
- Chronic liver disease such as chronic hepatitis b,c, autoimmune hepatitis, Wilson disease, hemochromatosis, alpha-1 antitrypsin deficiency and others
-Patients on medication with hepatotoxic medicines.
-Study design
Type of included studies:
Randomized controlled trials of duration at least 8 weeks of treatment with silymarin.
-Intervention-Comparator:
Studies evaluating the efficacy of oral silymarin treatment as monotherapy in patients with NAFLD versus treatment with placebo .
• Outcomes
Primary outcomes:
changes in pre and after treatment values in ALT , AST ,
Secondary outcomes: changes in BMI,liver histology parameters when available
**2. Search strategy and sources**
A search will be conducted till Novemeber 2019.
The search strategy will be accomplished by two members of the group(GK , AS). A basic search strategy will be developed for PubMed and modified accordingly for other engines. Discrepancies will be solved with discussion between the two researchers and, if needed, with the help of a third one(CA).
The search strategy of our study will use relevant terms for Non-alcoholic Fatty Liver Disease and Silymarin.
Medline/Pubmed , Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE will be used for systematic search for the studies of interest.
Clinicaltrials.gov will be screened for more evidence.
We will also search PROSPERO to check if similar meta-analyses are conducted in order to avoid duplicates.
Conference abstracts will be searched in order to identify potential unpublished studies.
**3. Study selection**
Studies identified from the search in the three databases( Pubmed, CENTRAL, Embase) will be imported into reference manager software. After duplicate removal , the eligible studies will be screened by two independent reviewers(GK ,AS) in two phases , firstly on title and abstract and then on full text screening. The screening will be conducted with the help of an online screening software . Any disagreements of the two reviewers will be resolved with the help of a third senior reviewer(CA).
**4. Data collection and extraction**
Two independently-working reviewers(GK,AS) will collect and extract data from each eligible study with the help of a standardized tool . A common pre-decided data form will be used from the two reviewers . Any disagreements will be resolved with the help of a third senior reviewer(CA). In case of missing data important for the meta-analysis , authors of the studies chosen will be contacted for further information.
**5. Quality assesment**
Two independently working reviewers(GK,AS) will perform risk of bias assessment using the revised Cochraine’s Collaboration Risk of Bias Tool 2.0 (4). Any disagreements will be resolved with the help of a third senior reviewer (CA). Individual studies will be classified at low, some concerns or high risk of bias .
**6. Data synthesis strategy-Statistical analysis**
-"RevMan 5.3 " will be used for all the statistical analyses (5)
-Data synthesis will be performed with random-effects or fixed-effects models.
-Statistical significant difference value is set when P<0.05 (a)
-We will use weighted mean difference and 95% confidence interval (95% CI) for continuous data and relative risk and 95% CI for dichotomous data.
- Cochrane chi-square test will be used to estimate the statistical heterogeneity and I2 statistics to estimate the degree of heterogeneity . Values greater than 60 % will be rated high , where as values lower than 30% will be rated low.
-If necessary subgroup analyses will be conducted to reduce heterogenity
Funding Sources
None
Conflicts of interest
None
Language
English
Country
Greece
References:
1)Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Annals of internal medicine. 2009;151(4):264-9, w64
2)Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012;55:2005–2023
3)Biedermann D, Vavrikova E, Cvak L, et al. Chemistry of silybin. Nat Prod Rep 2014;31:1138–57
4)Higgins JPT, Sterne JAC, Savović J, Page MJ, Hróbjartsson A, Boutron I, Reeves B, Eldridge S. A revised tool for assessing risk of bias in randomized trials In: Chandler J, McKenzie J, Boutron I, Welch V (editors). Cochrane Methods. Cochrane Database of Systematic Reviews 2016, Issue 10 (Suppl 1).
5)Review Manager (RevMan) [Computer program]. Version [insert version number]. Copenhagen: The Nordic Cochrane Centre TCC, 2014
