A Systematic Review And Meta-analysis:flavonoids For Non-alcoholic Fatty Liver Disease

Evidence based medicine is a discipline that adheres to the best results of modern medical inquiry and guides medical staff to conduct scientific diagnosis and treatment for patients.Systematic review is a quantitative or qualitative analysis of a specific clinical study.Systematic review is to collect and sort out all the research evidence that the inclusion and exclusion criteria has been established,so as to evaluate the specific problems of a certain research.Systematic review adopts a clear and systematic method to reduce bias,providing more reliable results for medical service providers,consumers,researchers and policy makers,and promoting decision-making.Non-alcoholic Fatty Liver Disease has become the most widespread chronic progressive Liver Disease in modern society,the incidence is increasing year by year,but it has not been recognized as a safe and effective treatment,so the application of traditional Chinese medicine treatment(TCM)may be a new opportunity to treat the Disease.However,TCM has long been questioned.In order to improve the reliability of TCM research,systematic review can be applied to TCM,and more easily be recognized by the international medical arena for the effectiveness and safety of TCM.Objective:The efficacy and safety of flavonoids in the treatment of NAFLD were systematically reviewed.Methods:Computer searchs CNKI,wanfang,VIP,CBM,EMBASE,Cochrane library and Pub Med electronic database.The subjects included in the study were NAFLD patients.The intervention measures were flavonoid compounds or flavonoid compounds plus the same western medicine treatment as the control group,while the control group received placebo or western medicine treatment.The main outcome index was the total effective rate,liver function(ALT,AST,ALP,GGT),the oxidative index(MDA,SOD)and NAFLD fibrosis score.Secondary outcome indicators as lipid metabolism index(TC,TG,LDL,HDL),glucose metabolism index(Fasting blood glucose,HOMA-IR),body measurement index(body weight,BMI),IL-6,TNF-?.Randomized controlled trials or Quasi-randomized controlled trials have been studied.The retrieved literature was screened and data extracted independently by two trained researchers.Meta analysis and risk of bias were performed using the SR method and software Ren Man5.3 provided by Cochrane collaboration.Descriptive analysis was used for those that could not be merged.The test level was ?=0.05.Publication bias was detected by funnel plot.GRADEprofiler software was used to evaluate the recommendation strength of evidence.Results:A total of 3783 literatures were retrieved in this study,and 12 of them were eventually included.Among them,6 were published in English(one of which was for Chinese people)and 6 were published in Chinese.Only one of them had a low risk of bias,while the other 11 had a high risk of bias.The rest were excluded because they were unrelated to the study,did not meet the inclusion and meet the exclusion criteria,and lacked the necessary data.A total of 1016 patients were diagnosed with NAFLD,including 496 patients in the flavonoid group and 520 patients in the control group.Meta analysis results showed that flavonoids have therapeutic effects on ALT [SMD=0.58,95%CI(0.23,0.94),Z=3.24,p=0.001],AST [SMD=0.29,95 % CI(0.10,0.48),Z=2.97,p=0.003]?LDL [MD=0.21,95%CI(0.14,0.28),Z=6.06,p<0.00001] and HDL [MD=-0.05,95%CI(-0.09,-0.02),Z=3.06,p=0.002],the difference was statistically significant.The effects of flavonoids on total effective rate [RR=1.02,95%CI(0.89,1.17),Z=0.29,p=0.77] and incidence of adverse reactions [RR=1.70,95%CI(0.74,3.90),Z=1.25,p=0.21],there was no statistical difference with the control group.But the results of TC and TNF-? were not stable and required further study.Flavonoids had no significant effect on GGT,MAD,SOD,TG,fasting blood glucose,HOMA-IR,IL-6,body weight and BMI.However,after subgroup analysis,compared with the placebo group,flavonoids reduced ALT AST TG LDL and increased HDL in NAFLD patients,and the difference was statistically significant.In the comparison of flavonoids VS western medicine group,the effect of flavonoids on reducing fasting blood glucose and HOMA-IR was not as good as that of western medicine group,and the difference was statistically significant.In the comparison of flavonoid + western medicine VS western medicine group,the combination of flavonoid + western medicine could better treat ALT,AST,MDA,SOD,LDL and HDL fasting blood glucose,HOMA-IR IL-6 and TNF-?,and the difference was statistically significant.Descriptive analysis showed that flavonoids can improve ALP and NAFLD fibrosis score.Funnel plot was used to detect publication bias.The study was asymmetrical and there might be publication bias.GRADEprofiler software was used to evaluate the recommendation strength of evidence for each outcome index.The quality of evidence was very low and the recommendation strength was weak.Conclusion:(1)Flavonoids have therapeutic effects on ALT,AST,LDL and HDL in NAFLD patients.Compared with the control group,flavonoids reduced GGT,MDA,TG,fasting blood glucose,HOMA-IR,IL-6,body weight,BMI,adverse reaction rate and increased SOD and the total effective rate had no effect.Meta analysis results of the effects of flavonoids on TC and TNF-? in NAFLD patients were not stable,which needs to be confirmed by more studies.(2)Flavonoids reduced ALT,AST,TG,LDL and elevated HDL in NAFLD patients better than placebo.The ability of flavonoids to reduce fasting blood glucose and HOMA-IR is not as good as that of western medicine.The combination of flavonoids and western medicine can better treat ALT,AST,MDA,SOD,LDL and HDL fasting blood glucose,HOMA-IR IL-6 and TNF-?.(3)More low risk of bias clinical studies are needed to further prove the long-term validity and security of flavonoids in the treatment of NAFLD.