甘草酸二铵制剂治疗药物性肝损害有效性与安全性的系统评价
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摘要
目的系统评价甘草酸二铵制剂治疗药物性肝损害(drug-inducedliverinjury,DILI)的有效性与安全性。方法检索PubMed、EMBase、Cochrane Library、CNKI、Sinomed、万方数据库和维普数据库公开发表的研究,纳入甘草酸二铵制剂治疗DILI的随机对照试验(randomized controlled trials,RCTs),检索时间从建库到2018年2月,采用Rev Man 5.3统计软件进行meta分析。结果最终纳入24项RCTs,合计2 116例患者。meta分析结果显示:与对照组相比,甘草酸二铵制剂组的治疗有效率更高,RR=1.20,[95%CI(1.12,1.28),P<0.0001]。肝功能指标ALT、AST水平显著下降,WMD_((ALT))=-20.01,[95%CI(-29.00,-11.02),P<0.000 1];WMD_((AST))=-64.36,[95%CI(-92.77,-35.96),P<0.000 1]。且甘草酸二铵组的TBIL和ALT指标复常时间明显快于对照组(P<0.05)。但2组在降低TBIL、ALB、GGT水平和不良反应发生率方面均无统计学意义。结论甘草酸二铵制剂能够有效治疗DILI,不良反应发生率较其他保肝药差异无统计学意义。
OBJECTIVE To system assess the clinical efficacy and safety of diammonium glycyrrhizinate against drug-induced liver injury(DILI). METHODS Studies in Pubmed, EMBase, Cochrane Library, CNKI, Sinomed, Vip and Wanfang database were searched to collect randomized controlled trials(RCTs) regarding the treatment of DILI by diammonium glycyrrhizinate from initial to February 2018. Meta-analysis was conducted by using Rev Man 5.3 statistical software. RESULTS A total of 2 116 patients from 24 RCTs were included. Meta-analysis result showed that compared with control group, diammonium glycyrrhizinate group had higher clinical effective rate, RR=1.20, [95% CI(1.12, 1.28), P<0.000 1]. And it was superior in reduction of biochemical indicators such as ALT, AST, WMD_((ALT))=-20.01, [95% CI(-29.00,-11.02), P<0.000 1]; WMD_((AST))=-64.36, [95%CI(-92.77,-35.96), P<0.000 1]. Also, it was superior in the recovery time for TBIL and AST compared with control group(P<0.05). But there was no statistical significance in reduction of TBIL, ALB, GGT and the rate of drug adverse reaction. CONCLUSION Diammonium glycyrrhizinate is effective in treatment of DILI patients, there is no statistical significance in the rate of drug adverse reaction compared with other protection drugs.
OBJECTIVE To system assess the clinical efficacy and safety of diammonium glycyrrhizinate against drug-induced liver injury(DILI). METHODS Studies in Pubmed, EMBase, Cochrane Library, CNKI, Sinomed, Vip and Wanfang database were searched to collect randomized controlled trials(RCTs) regarding the treatment of DILI by diammonium glycyrrhizinate from initial to February 2018. Meta-analysis was conducted by using Rev Man 5.3 statistical software. RESULTS A total of 2 116 patients from 24 RCTs were included. Meta-analysis result showed that compared with control group, diammonium glycyrrhizinate group had higher clinical effective rate, RR=1.20, [95% CI(1.12, 1.28), P<0.000 1]. And it was superior in reduction of biochemical indicators such as ALT, AST, WMD_((ALT))=-20.01, [95% CI(-29.00,-11.02), P<0.000 1]; WMD_((AST))=-64.36, [95%CI(-92.77,-35.96), P<0.000 1]. Also, it was superior in the recovery time for TBIL and AST compared with control group(P<0.05). But there was no statistical significance in reduction of TBIL, ALB, GGT and the rate of drug adverse reaction. CONCLUSION Diammonium glycyrrhizinate is effective in treatment of DILI patients, there is no statistical significance in the rate of drug adverse reaction compared with other protection drugs.
引文
[1]LIU X Q,WU W X,GENG X C,et al.Research progress of biomarkers of drug-induced liver injury[J].Chin J New Drugs(中国新药杂志),2018,27(1):47-52.
[2]CHALASANI N P,HAYASHI P H,BONKOVSKY H L,et al.ACG clinical guideline:the diagnosis and management of idiosyncratic drug-induced liver injury[J].Am J Gastroenterol,2014,109(7):950-966.
[3]CHEN F,CHEN Z,ZHANG J,et al.Advances in clinical epidemiology of drug-induced liver injury[J].Chin JPharmacoepidemiol(药物流行病学杂志),2016,25(12):69-72,77.
[4]DAVERN T J,CHALASANI N.Drug-induced liver injury in clinical trials:as rare as hens'teeth[J].Am J Gastroenterol,2009,104(5):1159-1161.
[5]ZHAO R,LYU L.Pharmacological research and clinical development of diammonium glycyrrhizinate[J].Asia-pacific Tradit Med(亚太传统医药),2008,4(3):31-36.
[6]Study of Drug Induced Liver Disease of Chinese Medical Association.[Diagnosis and treatment guideline on drug-induced liver injury][J].Chin J Hepatol(中华肝脏病杂志),2015,20(10):750-765.
[7]LI Q Z,Duan J L.Systematic review of diammonium glycyrrhizinate in the treatment of drug-induced liver injury[J].China Pharm(中国药房),2010,21(12):1100-1105.
[8]LI R P,ZHANG Q S,XIE Y N,et al.Protective effect of Trillium tschonoskii Maxim.alcohol extract on acute liver injury rats based on NF-κB signaling pathway[J]..Chin J Mod Appl Pharm(中国现代应用药学),2018,35(3):314-318.
[9]ZHU F P,LEI Z B.Retrospect analysis of adverse drug reactions of diammonium glycyrrhizinate[J].World Clin Drugs(世界临床药物),2014,35(9):550-552.
[10]张龙跃,徐艳卿,张俊秀.甘利欣致低血糖反应2例[J].医用放射技术杂志,2007(8):88.
[11]张艳辉.甘草酸二铵致过敏性休克1例[J].现代医药卫生,2013,29(2):213.
[12]钱瑾.不同护肝药在肺结核合并肝功能异常中的作用观察[J].中外医学研究,2013,11(24):168-169.
[13]CHENG X D,MI D,LI J C.Effect study of tiopronin and diammonium glycyrrhizinate on anti-tuberculosis drug-induced liver disease[J].China Med Herald(药物与临床),2013,10(23):83-85.
[14]HIGGINS JPT,GREEN S.Cochrane handbook for systematic reviews of interventions 5.1.0[EB/OL].(2011)[2014-11-10].http://handbook.cochrane.org.
[15]MA J,LIU Y,ZHONG L P,et al.Comparison between Jadad scale and Cochrane collaboration's tool for assessing risk of bias on the quality and risk of bias evaluation in randomized controlled trials[J].Chin J Oral Maxillofac Surg(中国口腔颌面外科杂志),2012,10(5):417-422.
[16]刘钦,刘良珍,谢新园,等.草酸二铵治疗抗精神病药所致肝损害疗效观察[C].临床心身疾病杂志学研讨会综合刊.2014.
[17]HUANG Q W,HUANG Z M,XIANG X U.Observing clinical effect of glycyrrhizin in treating liver injury resulted from antituberculosis drugs[J].Youjiang Med J(右江医学),2004,32(4):310-312.
[18]李爽,孙力,丛登立.甘利欣治疗抗结核药物所致肝损害的临床疗效观察[J].中国防痨杂志,2011,33(6):385-386.
[19]党海燕.甘利欣治疗抗结核药物性肝炎的疗效观察[J].中国医学创新,2010,7(29):85-87.
[20]丁卫民,杨俊行,郑继海.三种复方甘草酸制剂治疗肺结核抗结核化疗过程中肝功能损害对比观察[J].中国药物与临床,2005,5(7):548-550.
[21]ZHANG L,MENG N.Clinical observation on effect of Gan Li Xin in treating drug-induced hepatitis[J].J Jilin Med Coll(吉林医药学院学报),2005,26(2):89-90.
[22]郭堑,韦启援,曾菲.甘利欣治疗乙肝病毒感染者抗结核药物所致肝损害的疗效观察[J].应用预防医学,2003,9(3):172-173.
[23]周荷.甘利欣对抗结核药物致肝损害疗效观察[J].海峡药学,2012,24(5):176-177.
[24]WANG P,W U L H.Clinical observation of diammonium glycyrrhizinate in the treatment of drug-induced hepatitis causeded by antituberculosis drugs[J].J Inner Mongol Univ National(Nat Sci)(内蒙古民族大学学报自然科学版),2009,24(6):699-700.
[25]张分明.甘利欣对老年药物性肝损伤的疗效观察[J].中原医刊,2007,34(11):82.
[26]赖道丽,胡卫平,吴波.甘草酸二胺胶囊防治抗精神病药物致肝损害的临床观察[J].医学信息,2015,28(10):171.
[27]吴东.甘利欣胶囊治疗抗精神病药物所致肝损害效果分析[J].当代医学,2014,34(369):132-133.
[28]徐爱东.甘利欣对抗痨药物引起肝损的治疗作用[J].现代中西医结合杂志,1999,8(4):556-557.
[29]覃永红,吴才林.甘利欣治疗药物致肝功能异常的临床研究[J].广西医学,2005,27(6):830-831.
[30]钱伟明.甘草酸二铵治疗急性药物性肝损伤的疗效观察[J].中国卫生产业,2014(10):127,129.
[31]张增康.甘草酸二胺治疗药物性肝损害80例临床观察[J].中外健康文摘,2011,8(41):177-178.
[32]YANG Q L,ZHOU T,LU H J,et al.Ganlixin injection solution in treatment of hepatic-lesion caus ed by chemotheraphy[J].J Bengbu Med Coll(蚌埠医学院学报),2005,30(5):433-434.
[33]刘思纯,马博.甘草酸二铵治疗急性药物性肝损伤的疗效观察[J].中国处方药,2006,10(55):62-64.
[34]ZHANG T,HE W H,ZHOU P L,et al.Curative effect analysis of ganlixin in liver dysfunction caused by antitb drugs[J].Mod Pre Med(现代预防医学),2011,38(11):2172-2173,2175.
[35]殷玲丽,黄春英,雷向盈,等.甘利欣治疗抗结核药物所致肝损害的疗效观察[J].医药前沿,2016,6(29):162-163.
[36]ZHAO X L,LIU D F,ZHANG B Q,et al.Effect of glycyrrhizic acid diamine capsules and compound ammonium glycyrrhetate on liver protection in patients with leukemia undergoing chemotherapy[J].Hainan Med J(海南医学),2015,26(24):3598-3600.
[37]张盛,熊枝繁.甘草酸二铵治疗抗精神病药物所致的肝功能损伤52例[J].医药导报,2013,32(12):1602-1603.
[38]MOLLICA L,MARCHIS F D,SPITALERI A,et al.Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities[J].Chem Biol,2007,14(4):431-441.
[39]CAVONE L,CUPPARI C,MANTI S,et al.Increase in the level of proinflammatory cytokine hmgb1 in nasal fluids of patients with rhinitis and its sequestration by glycyrrhizin induces eosinophil cell death[J].Clin Exp Otorhinolaryngol,2015,8(2):123-128.
[40]刘蔚红,李成建,代晓燕.甘草酸二铵所致不良反应文献概述[J].中国药物滥用防治杂志,2013,19(5):292-293.
[41]白金丽,李怡莹.甘草酸二铵致不良反应259例分析[J].现代医药卫生,2011,27(8):1251-1252.
[2]CHALASANI N P,HAYASHI P H,BONKOVSKY H L,et al.ACG clinical guideline:the diagnosis and management of idiosyncratic drug-induced liver injury[J].Am J Gastroenterol,2014,109(7):950-966.
[3]CHEN F,CHEN Z,ZHANG J,et al.Advances in clinical epidemiology of drug-induced liver injury[J].Chin JPharmacoepidemiol(药物流行病学杂志),2016,25(12):69-72,77.
[4]DAVERN T J,CHALASANI N.Drug-induced liver injury in clinical trials:as rare as hens'teeth[J].Am J Gastroenterol,2009,104(5):1159-1161.
[5]ZHAO R,LYU L.Pharmacological research and clinical development of diammonium glycyrrhizinate[J].Asia-pacific Tradit Med(亚太传统医药),2008,4(3):31-36.
[6]Study of Drug Induced Liver Disease of Chinese Medical Association.[Diagnosis and treatment guideline on drug-induced liver injury][J].Chin J Hepatol(中华肝脏病杂志),2015,20(10):750-765.
[7]LI Q Z,Duan J L.Systematic review of diammonium glycyrrhizinate in the treatment of drug-induced liver injury[J].China Pharm(中国药房),2010,21(12):1100-1105.
[8]LI R P,ZHANG Q S,XIE Y N,et al.Protective effect of Trillium tschonoskii Maxim.alcohol extract on acute liver injury rats based on NF-κB signaling pathway[J]..Chin J Mod Appl Pharm(中国现代应用药学),2018,35(3):314-318.
[9]ZHU F P,LEI Z B.Retrospect analysis of adverse drug reactions of diammonium glycyrrhizinate[J].World Clin Drugs(世界临床药物),2014,35(9):550-552.
[10]张龙跃,徐艳卿,张俊秀.甘利欣致低血糖反应2例[J].医用放射技术杂志,2007(8):88.
[11]张艳辉.甘草酸二铵致过敏性休克1例[J].现代医药卫生,2013,29(2):213.
[12]钱瑾.不同护肝药在肺结核合并肝功能异常中的作用观察[J].中外医学研究,2013,11(24):168-169.
[13]CHENG X D,MI D,LI J C.Effect study of tiopronin and diammonium glycyrrhizinate on anti-tuberculosis drug-induced liver disease[J].China Med Herald(药物与临床),2013,10(23):83-85.
[14]HIGGINS JPT,GREEN S.Cochrane handbook for systematic reviews of interventions 5.1.0[EB/OL].(2011)[2014-11-10].http://handbook.cochrane.org.
[15]MA J,LIU Y,ZHONG L P,et al.Comparison between Jadad scale and Cochrane collaboration's tool for assessing risk of bias on the quality and risk of bias evaluation in randomized controlled trials[J].Chin J Oral Maxillofac Surg(中国口腔颌面外科杂志),2012,10(5):417-422.
[16]刘钦,刘良珍,谢新园,等.草酸二铵治疗抗精神病药所致肝损害疗效观察[C].临床心身疾病杂志学研讨会综合刊.2014.
[17]HUANG Q W,HUANG Z M,XIANG X U.Observing clinical effect of glycyrrhizin in treating liver injury resulted from antituberculosis drugs[J].Youjiang Med J(右江医学),2004,32(4):310-312.
[18]李爽,孙力,丛登立.甘利欣治疗抗结核药物所致肝损害的临床疗效观察[J].中国防痨杂志,2011,33(6):385-386.
[19]党海燕.甘利欣治疗抗结核药物性肝炎的疗效观察[J].中国医学创新,2010,7(29):85-87.
[20]丁卫民,杨俊行,郑继海.三种复方甘草酸制剂治疗肺结核抗结核化疗过程中肝功能损害对比观察[J].中国药物与临床,2005,5(7):548-550.
[21]ZHANG L,MENG N.Clinical observation on effect of Gan Li Xin in treating drug-induced hepatitis[J].J Jilin Med Coll(吉林医药学院学报),2005,26(2):89-90.
[22]郭堑,韦启援,曾菲.甘利欣治疗乙肝病毒感染者抗结核药物所致肝损害的疗效观察[J].应用预防医学,2003,9(3):172-173.
[23]周荷.甘利欣对抗结核药物致肝损害疗效观察[J].海峡药学,2012,24(5):176-177.
[24]WANG P,W U L H.Clinical observation of diammonium glycyrrhizinate in the treatment of drug-induced hepatitis causeded by antituberculosis drugs[J].J Inner Mongol Univ National(Nat Sci)(内蒙古民族大学学报自然科学版),2009,24(6):699-700.
[25]张分明.甘利欣对老年药物性肝损伤的疗效观察[J].中原医刊,2007,34(11):82.
[26]赖道丽,胡卫平,吴波.甘草酸二胺胶囊防治抗精神病药物致肝损害的临床观察[J].医学信息,2015,28(10):171.
[27]吴东.甘利欣胶囊治疗抗精神病药物所致肝损害效果分析[J].当代医学,2014,34(369):132-133.
[28]徐爱东.甘利欣对抗痨药物引起肝损的治疗作用[J].现代中西医结合杂志,1999,8(4):556-557.
[29]覃永红,吴才林.甘利欣治疗药物致肝功能异常的临床研究[J].广西医学,2005,27(6):830-831.
[30]钱伟明.甘草酸二铵治疗急性药物性肝损伤的疗效观察[J].中国卫生产业,2014(10):127,129.
[31]张增康.甘草酸二胺治疗药物性肝损害80例临床观察[J].中外健康文摘,2011,8(41):177-178.
[32]YANG Q L,ZHOU T,LU H J,et al.Ganlixin injection solution in treatment of hepatic-lesion caus ed by chemotheraphy[J].J Bengbu Med Coll(蚌埠医学院学报),2005,30(5):433-434.
[33]刘思纯,马博.甘草酸二铵治疗急性药物性肝损伤的疗效观察[J].中国处方药,2006,10(55):62-64.
[34]ZHANG T,HE W H,ZHOU P L,et al.Curative effect analysis of ganlixin in liver dysfunction caused by antitb drugs[J].Mod Pre Med(现代预防医学),2011,38(11):2172-2173,2175.
[35]殷玲丽,黄春英,雷向盈,等.甘利欣治疗抗结核药物所致肝损害的疗效观察[J].医药前沿,2016,6(29):162-163.
[36]ZHAO X L,LIU D F,ZHANG B Q,et al.Effect of glycyrrhizic acid diamine capsules and compound ammonium glycyrrhetate on liver protection in patients with leukemia undergoing chemotherapy[J].Hainan Med J(海南医学),2015,26(24):3598-3600.
[37]张盛,熊枝繁.甘草酸二铵治疗抗精神病药物所致的肝功能损伤52例[J].医药导报,2013,32(12):1602-1603.
[38]MOLLICA L,MARCHIS F D,SPITALERI A,et al.Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities[J].Chem Biol,2007,14(4):431-441.
[39]CAVONE L,CUPPARI C,MANTI S,et al.Increase in the level of proinflammatory cytokine hmgb1 in nasal fluids of patients with rhinitis and its sequestration by glycyrrhizin induces eosinophil cell death[J].Clin Exp Otorhinolaryngol,2015,8(2):123-128.
[40]刘蔚红,李成建,代晓燕.甘草酸二铵所致不良反应文献概述[J].中国药物滥用防治杂志,2013,19(5):292-293.
[41]白金丽,李怡莹.甘草酸二铵致不良反应259例分析[J].现代医药卫生,2011,27(8):1251-1252.