The Efficacy Of Probiotics On Non-alcoholic Fatty Liver Disease:A Meta-analysis

Background:Non-alcoholic fatty liver disease refers to clinical pathological syndromes characterized by diffuse hepatic macro bubble fat,including non-alcoholic fatty liver,non-alcoholic steatohepatitis and related cirrhosis and hepatocellular carcinoma.At present,NAFLD(especially NASH)has become the leading cause of abnormalities in the world's largest chronic liver disease and cryptogenic liver biochemical indicators due to its high prevalence,aging trend and chronic progression.Therefore,it is very important to actively prevent and control NAFLD.Controlling body quality,improving diet and moderate exercise are recognized as effective prevention and control measures by NAFLD.The use of lipid-lowering drugs,insulin sensitizers,vitamin E and other drugs and metabolic surgery have a certain therapeutic value.Recently,with the introduction and improvement of "intestinal-hepatic axis" theory,maintaining the intestinal micro-ecological balance has become an innovative and complementary treatment in the clinical practice of NAFLD.Probiotics,as a part of the intestinal micro-ecology,have a key regulatory role in the intestinal micro-ecological balance.Largely clinical trials have shown that probiotics have a therapeutic effect on NAFLD,but there are problems such as sample size,evaluation indicators,regional differences,and some research conclusions.Therefore,this article aim to search for the clinical randomized controlled trial for the treatment of NAFLD by bacterial preparations,systematically evaluates the therapeutic value of probiotic preparations.Objective:To systematically evaluate the therapeutic value of probiotics in non-alcoholic fattyliver disease(NAFLD)by a meta-analysis.Methods:Literatures about randomized controlled trials of the treatment on NAFLD with probiotics published in PubMed,the Cochrane Library,Embase,CNKI,VIP and Wanfang database before December 2017 were searched.Two investigators independently selected the literatures with established criteria and evaluated the included literatures by using modified Jadad scale and the Cochrane bias risk scale.The Meta-analysis and forest maps were performed by using Rev Man 5.3 software.At the same time,stata14.0 software was used for heterogeneity and publication bias analysis.Results:1.Literatures retrieval results:initial literatures were gradually selected after weighting,reading topics,abstracts,and full content.Finally,11 articles including 599 subjects were brought into this meta-analysis.All selected articles were published before December 2017,and the modified Jadad scores were?4 points.Among them there are 4 domestic articles,7foreign countries;8 adult articles and 3 children.2.The analysis results:(1)The probiotics obviously decreased the level of alanine aminotransferase(ALT)[MD=-15.23,95%CI:-19.63~-10.82,P<0.00001],aspartate aminotransferase(AST)[MD=-17.08,95%CI :-24.23~-9.92,P<0.00001],gamma glutamyl transpeptidease(GGT)[MD=-20.49,95%CI:-26.23~-14.74,P<0.00001],triglyceride(TG)[MD=-0.12,95%CI :-0.24~-0.01,P=0.04],total-cholesterol(TC)[MD=-0.33,95%CI :-0.56~-0.11,P=0.003],high-density lipoprotein(HDL)[MD=-0.07,95%CI :-0.14~-0.01,P=0.03],tumor necrosis factor-?(TNF-?)[MD=-0.38,95%CI:-0.52~-0.24,P<0.00001,homeostasis model assessment for insulin resistance(HOMA-IR)[MD=-0.39,95%CI:-0.53~-0.24,P<0.00001].(2)The use of probiotics was not associated with changes in body mass index(BMI)[MD=-0.73,95%CI:-1.91~0.46,P=0.23] and low-density lipoprotein(LDL)[MD=-0.30,95%CI:-0.60~0.01,P=0.06] with NAFLD patients.3.The publication bias,sensitivity and heterogeneity analysis:The results of all indicators in this meta-analysis were stable and there was no significant publication bias.Due to the obvious heterogeneity of some indicators,subgroup analysis showed that the published country was not related to heterogeneity,and the study population and intervention time could induce to the heterogeneity.Conclusion:Probiotics can help liver-protecting drugs improve liver transaminases,lipid metabolism,inflammatory factors and insulin resistance in patients with NAFLD,which may have certain therapeutic value for NAFLD.