“茵陈-大黄”药对治疗非酒精性脂肪肝的系统评价
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摘要
目的:基于文献荟萃分析(Meta分析)方法,对"茵陈-大黄"药对治疗非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)的疗效及安全性进行系统评价。方法:计算机检索7个中英文数据库,纳入"茵陈-大黄"药对治疗NAFLD的随机对照试验(观察组患者采用"茵陈-大黄"药对组成的复方治疗或与常规治疗联合应用,对照组患者采用安慰剂、常规治疗或其他非中药治疗),评定其方法学质量,并对结局指标进行合成分析。结果:共纳入15篇文献,涉及1 317例患者,所有文献均具有一定的偏倚风险。Meta分析结果显示,观察组患者治疗总有效率明显高于对照组(RR=1.24,95%CI=1.11～1.40,P=0.000 2),血清丙氨酸氨基转移酶(RR=-9.87,95%CI=-13.48～-6.26,P<0.000 1)、天门冬氨酸氨基转移酶(RR=-7.55,95%CI=-11.11～-3.96,P<0.000 1)、γ-谷酰转肽酶水平(RR=-12.32,95%CI=-18.64～-6.00,P=0.000 1)、总胆固醇(RR=-0.53,95%CI=-0.89～-0.18,P=0.003)、三酰甘油(RR=-0.78,95%CI=-1.27～-0.29,P=0.002)及低密度脂蛋白胆固醇(RR=-0.40,95%CI=-0.59～-0.20,P<0.000 1)水平明显低于对照组,差异均有统计学意义;两组患者高密度脂蛋白胆固醇水平的差异无统计学意义(RR=0.08,95%CI=-0.07～0.23,P=0.30);安全性方面,观察组患者无明显不良反应。结论:"茵陈-大黄"药对治疗NAFLD有效且安全,但本研究所纳入的随机对照试验的方法学质量较低,有待进一步采用更严格的随机对照试验对结果提供充分的临床证据,为"茵陈-大黄"药对在临床上的安全、有效应用提供指导。
OBJECTIVE: To systematically evaluate the efficacy and safety of "yinchen-dahuang " drug compatibility in treatment of non-alcoholic fatty liver disease( NAFLD) based on Meta-analysis. METHODS: 7 Chinese and English databases were retrieved to collect randomized controlled trials( RCTs) of "yinchen-dahuang " drug compatibility in treatment of NAFLD( patients in observation group were treated with compound "yinchen-dahuang "drug compatibility or combined with conventional treatment,while the control group received placebo,conventional treatment or other non-traditional Chinese medicine treatment). The methodological quality was assessed and the outcome measures were analyzed synthetically. RESULTS: Totally 15 literature were involved,including 1 317 patients,all literature had a certain risk of bias. The total effective rate of observation group was significantly higher than that of control group( RR = 1. 24,95% CI = 1. 11-1. 40,P = 0. 000 2),the serum alanine aminotransferase( RR =-9. 87,95% CI =-13. 48--6. 26,P < 0. 000 1),aspartate aminotransferase( RR =-7. 55,95% CI =-11. 11--3. 96,P < 0. 000 1),γ-glutamyltranspeptidase level( RR =-12. 32,95% CI =-18. 64--6. 00,P = 0. 000 1),total cholesterol( RR =-0. 53,95% CI =-0. 89--0. 18,P = 0. 003),triacylglycerol( RR =-0. 78,95% CI =-1. 27--0. 29,P = 0. 002) and low-density lipoprotein cholesterol( RR =-0. 40,95% CI =-0. 59--0. 20,P <0. 000 1) of observation group were significantly lower than those of control group,the differences were statistically significant. There was no significant difference in high-density lipoprotein cholesterol levels between two groups( RR =0. 08,95% CI =-0. 07-0. 23,P = 0. 30). In terms of safety,patients in observation group had no obvious adverse drug reactions. CONCLUSIONS: "Yinchen-dahuang"drug compatibility is effective and safe in treatment of NAFLD.However,the methodological quality of RCTs included in this study is relatively low,and more rigorous RCTs areneeded to further provide sufficient clinical evidence for the results,so as to provide guidance for the safe and effective application of "yinchen-dahuang"drug compatibility in clinic.
OBJECTIVE: To systematically evaluate the efficacy and safety of "yinchen-dahuang " drug compatibility in treatment of non-alcoholic fatty liver disease( NAFLD) based on Meta-analysis. METHODS: 7 Chinese and English databases were retrieved to collect randomized controlled trials( RCTs) of "yinchen-dahuang " drug compatibility in treatment of NAFLD( patients in observation group were treated with compound "yinchen-dahuang "drug compatibility or combined with conventional treatment,while the control group received placebo,conventional treatment or other non-traditional Chinese medicine treatment). The methodological quality was assessed and the outcome measures were analyzed synthetically. RESULTS: Totally 15 literature were involved,including 1 317 patients,all literature had a certain risk of bias. The total effective rate of observation group was significantly higher than that of control group( RR = 1. 24,95% CI = 1. 11-1. 40,P = 0. 000 2),the serum alanine aminotransferase( RR =-9. 87,95% CI =-13. 48--6. 26,P < 0. 000 1),aspartate aminotransferase( RR =-7. 55,95% CI =-11. 11--3. 96,P < 0. 000 1),γ-glutamyltranspeptidase level( RR =-12. 32,95% CI =-18. 64--6. 00,P = 0. 000 1),total cholesterol( RR =-0. 53,95% CI =-0. 89--0. 18,P = 0. 003),triacylglycerol( RR =-0. 78,95% CI =-1. 27--0. 29,P = 0. 002) and low-density lipoprotein cholesterol( RR =-0. 40,95% CI =-0. 59--0. 20,P <0. 000 1) of observation group were significantly lower than those of control group,the differences were statistically significant. There was no significant difference in high-density lipoprotein cholesterol levels between two groups( RR =0. 08,95% CI =-0. 07-0. 23,P = 0. 30). In terms of safety,patients in observation group had no obvious adverse drug reactions. CONCLUSIONS: "Yinchen-dahuang"drug compatibility is effective and safe in treatment of NAFLD.However,the methodological quality of RCTs included in this study is relatively low,and more rigorous RCTs areneeded to further provide sufficient clinical evidence for the results,so as to provide guidance for the safe and effective application of "yinchen-dahuang"drug compatibility in clinic.
引文
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[27]刘庆燕.疏肝健脾清热利湿法治疗非酒精性脂肪性肝炎对B超影响的临床研究[D].哈尔滨:黑龙江中医药大学,2009.
[28]刘月艳.疏肝健脾清热利湿法治疗非酒精性脂肪性肝炎中医症候及CT的临床研究[D].哈尔滨:黑龙江中医药大学,2009.
[29]黄志平,林燕萍,张萍,等.茵陈越鞠汤治疗非酒精性脂肪性肝炎的临床观察[J].中华中医药学刊,2008,26(5):1100-1101.
[30]黄志平,李伏娥,朱清云,等.茵陈越鞠汤治疗非酒精性脂肪性肝炎的临床观察[J].中国中医药科技,2004,11(6):371-372.
[31]Wang ZQ,Zhang XH,Yu Y,et al.Artemisia scoparia extract attenuates non-alcoholic fatty liver disease in diet-induced obesity mice by enhancing hepatic insulin and AMPK signaling independently of FGF21 pathway[J].Metabolism,2013,62(9):1239-1249.
[32]Lee J,Narayan VP,Hong EY,et al.Artemisia iwayomogi extract attenuates high-fat diet-induced hypertriglyceridemia in mice:Pote-ntial involvement of the adiponectin-AMPK pathway and very low density lipoprotein assembly in the liver[J].Int J Mol Sci,2017,18(8):E1762.
[33]Jang E,Kim BJ,Lee KT,et al.A Survey of Therapeutic Effects of Artemisia capillaris in Liver Diseases[J].Evid Based Complement Alternat Med,2015:728137.
[34]Wang JB,Zhao HP,Zhao YL,et al.Hepatotoxicity or hepatoprotection?Pattern recognition for the paradoxical effect of the Chinese herb Rheum palmatum L.in treating rat liver injury[J].PLo S One,2011,6(9):e24498.
[35]Ma J,Zheng L,He YS,et al.Hepatotoxic assessment of Polygoni Multiflori Radix extract and toxicokinetic study of stilbene glucoside and anthraquinones in rats[J].J Ethnopharmacol,2015,162:61-68.
[36]吴晓东,张峰,梁瑞峰.大黄素与丹参素合用对四氯化碳诱导大鼠肝纤维化的保护作用[J].天津中医药,2018,35(2):143-146.
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[2]王建,王诗源.中药学[M].北京:中国医药科技出版社,2015:110,151.
[3]Chen Z,Ma X,Zhao Y,et al.Yinchenhao decoction in the treatment of cholestasis:A systematic review and meta-analysis[J].J Ethnopharmacol,2015,168:208-216.
[4]李建缘,刘平,孙明瑜.茵陈蒿汤治疗肝胆病的作用机制研究进展[J].中药药理与临床,2015,31(6):241-244.
[5]许正锯,黄以群,张启华,等.大黄对慢性肝炎抗肝纤维化的临床研究[J].中华传染病杂志,2004,22(3):202-203.
[6]中华医学会肝病学分会脂肪肝和酒精性肝病学组,中国医师协会脂肪性肝病专家委员会.非酒精性脂肪性肝病防治指南:2018年更新版[J].实用肝脏病杂志,2018,21(2):177-186.
[7]李军祥,王允亮,刘敏,等.健脾疏肝方治疗非酒精性脂肪性肝炎多中心、随机、对照的临床研究[J].中国中西医结合杂志,2014,34(1):15-19.
[8]隋晓丹,邓厚波,刘铁军.中医药防治非酒精性脂肪肝病的研究进展[J].世界华人消化杂志,2013,21(18):1708-1713.
[9]Pan J,Wang M,Song H,et al.The efficacy and safety of traditional chinese medicine(jiang zhi granule)for nonalcoholic Fatty liver:a multicenter,randomized,placebo-controlled study[J].Evid Based Complement Alternat Med,2013:965723.
[10]Shi KQ,Fan YC,Liu WY,et al.Traditional Chinese medicines benefit to nonalcoholic fatty liver disease:a systematic review and meta-analysis[J].Mol Biol Rep,2012,39(10):9715-9722.
[11]张良登,魏玮,孙晓红,等.茵陈蒿汤加减治疗非酒精性脂肪肝的随机对照试验系统评价与Meta分析[J].世界华人消化杂志,2014,22(16):2327-2337.
[12]伊凡,马存贞,曾韦苹,等.茵陈蒿汤治疗NAFLD随机对照试验的系统评价[J].新疆医科大学学报,2018,41(2):139-143.
[13]赵嘉晶,汪颖珏,朱永新,等.茵陈蒿汤加减方对非酒精性脂肪肝患者糖、脂及尿酸代谢的影响[J].四川中医,2018,36(3):112-114.
[14]刘丹,李萍,王俊岭,等.茵陈蒿汤治疗非酒精性脂肪性肝炎的临床疗效及对TLR-4表达的影响[J].中西医结合肝病杂志,2017,27(2):80-82.
[15]刘洪敏.泄浊解毒汤对非酒精性脂肪肝病及血清瘦素的临床观察[D].石家庄:河北医科大学,2016.
[16]刘旭东,涂燕云,张红星.祛湿活血中药治疗非酒精性脂肪肝40例[J].陕西中医,2013,34(1):16-18.
[17]陈兴,吴玲,黄廷荣.金丹王合剂治疗非酒精性脂肪性肝炎的临床研究[J].中西医结合肝病杂志,2012,22(2):94-96.
[18]郑羽.强肝消脂胶囊治疗瘀血湿热内阻型非酒精性脂肪性肝炎的临床研究[D].哈尔滨:黑龙江中医药大学,2011.
[19]张博.强肝消脂胶囊治疗非酒精性脂肪肝(瘀血湿热内阻证)临床观察[D].长春:长春中医药大学,2011.
[20]谢军.玉凤汤治疗肝胃郁热型非酒精性脂肪性肝炎的临床研究[D].长沙:湖南中医药大学,2011.
[21]赵智宏.芪茵颗粒治疗非酒精性脂肪肝肝郁脾虚型的临床研究[D].乌鲁木齐:新疆医科大学,2010.
[22]马建,孙阳,黄荣忠.清肝消脂汤治疗非酒精性脂肪性肝炎疗效观察[J].实用中西医结合临床,2010,10(2):5-6.
[23]林立,张其清.消脂健脾合剂防治非酒精性脂肪性肝炎的临床研究[J].中医药通报,2010,9(4):44-46.
[24]周兵,蔡光先,柏正平,等.利湿活血通络汤治疗非酒精性脂肪性肝炎60例临床观察[J].中医药导报,2009,15(7):13-15.
[25]葛庆红.疏肝健脾清热利湿法对非酒精性脂肪性肝炎肝功ALT、AST、GGT的临床研究[D].哈尔滨:黑龙江中医药大学,2009.
[26]李勇.疏肝健脾清热利湿法对非酒精性脂肪性肝炎血脂TC、TG影响的临床研究[D].哈尔滨:黑龙江中医药大学,2009.
[27]刘庆燕.疏肝健脾清热利湿法治疗非酒精性脂肪性肝炎对B超影响的临床研究[D].哈尔滨:黑龙江中医药大学,2009.
[28]刘月艳.疏肝健脾清热利湿法治疗非酒精性脂肪性肝炎中医症候及CT的临床研究[D].哈尔滨:黑龙江中医药大学,2009.
[29]黄志平,林燕萍,张萍,等.茵陈越鞠汤治疗非酒精性脂肪性肝炎的临床观察[J].中华中医药学刊,2008,26(5):1100-1101.
[30]黄志平,李伏娥,朱清云,等.茵陈越鞠汤治疗非酒精性脂肪性肝炎的临床观察[J].中国中医药科技,2004,11(6):371-372.
[31]Wang ZQ,Zhang XH,Yu Y,et al.Artemisia scoparia extract attenuates non-alcoholic fatty liver disease in diet-induced obesity mice by enhancing hepatic insulin and AMPK signaling independently of FGF21 pathway[J].Metabolism,2013,62(9):1239-1249.
[32]Lee J,Narayan VP,Hong EY,et al.Artemisia iwayomogi extract attenuates high-fat diet-induced hypertriglyceridemia in mice:Pote-ntial involvement of the adiponectin-AMPK pathway and very low density lipoprotein assembly in the liver[J].Int J Mol Sci,2017,18(8):E1762.
[33]Jang E,Kim BJ,Lee KT,et al.A Survey of Therapeutic Effects of Artemisia capillaris in Liver Diseases[J].Evid Based Complement Alternat Med,2015:728137.
[34]Wang JB,Zhao HP,Zhao YL,et al.Hepatotoxicity or hepatoprotection?Pattern recognition for the paradoxical effect of the Chinese herb Rheum palmatum L.in treating rat liver injury[J].PLo S One,2011,6(9):e24498.
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