异甘草酸镁注射液治疗药物性肝损伤有效性与安全性的Meta分析
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摘要
目的系统评价异甘草酸镁用于治疗药物性肝损伤(drug-induced liver injury,DILI)的有效性及安全性,完善其循证医学证据。方法计算机检索PubMed、The Cochrane Library、CNKI、VIP和WanFang Data数据库,纳入异甘草酸镁用于治疗DILI的随机对照试验(randomized controlled trials,RCT),检索时限2004年1月至2017年12月,筛查文献、提取资料并进行质量评价后,采用Rev Man 5.3统计软件进行Meta分析。结果共纳入20项RCT,纳入DILI患者1 709例。Meta分析结果显示,异甘草酸镁治疗DILI的总有效率及显效率优于对照组[RR=1.15,95%CI(1.08,1.22),P<0.01]及[RR=1.56,95%CI(1.31,1.85),P<0.01],降低DILI患者ALT水平优于对照组[MD=-31.25,95%CI(-38.97,-23.54),P<0.01];异甘草酸镁ADR发生率低于其他甘草酸制剂[RR=0.29,95%CI(0.16,0.52),P<0.01],但对比非甘草酸类药物差异无统计学意义。结论异甘草酸镁治疗DILI的有效性优于其他常用护肝药物,尤其是能够显著降低DILI患者ALT水平,短期应用安全性较好。受纳入研究方法学质量的限制,该结论有待大样本、高质量的RCT进一步验证。
OBJECTIVE To systematically evaluate the efficacy and safety of magnesium isoglycyrrhizinate in the treatment of drug-induced liver injury( DILI). METHODS We searched PubMed,The Cochrane Library,CNKI,VIP and WanFang data from Jan 2004 to Dec 2017 to collect randomized controlled trials( RCT) of magnesium isoglycyrrhizinate for the treatment of drug-induced liver injury( DILI). Two reviewers independently screened literature,extracted data including basic information,demographic data and clinical characteristics,intervention details,outcome indicators,and so on. Assessed the risk of bias of included studies. Then,Metaanalysis was performed using RevMan 5.3 software. RESULTS A total of 20 RCTs involving 1 709 DILI patients were included. The results of Meta-analysis showed that,the overall response rate and normalized rate of magnesium isoglycyrrhizinate for DILI were significantly higher than control [RR = 1. 15,95% CI( 1. 08,1. 22),P < 0. 01] and [RR = 1. 56,95% CI( 1. 31,1. 85),P < 0. 01].Magnesium isoglycyrrhizinate could significantly lower ALT level than control[MD =-31.25,95%CI(-38.97,-23.54),P< 0.01]. The occurrence rate of ADR was significantly lower in the magnesium isoglycyrrhizinate group compared with other glycyrrhizin subgroup[RR= 0. 29,95% CI( 0. 16,0. 52),P < 0. 01] and was not different from non-glycyrrhizin subgroup. CONCLUSION Magnesium isoglycyrrhizinate treating DILI is superior to other common liver-protecting drugs,especially in lowering ALT level and safety in short term. However,limited to the quality of the included trials,clinical trials of bigger sample size and higher quality is needed to validate this result.
OBJECTIVE To systematically evaluate the efficacy and safety of magnesium isoglycyrrhizinate in the treatment of drug-induced liver injury( DILI). METHODS We searched PubMed,The Cochrane Library,CNKI,VIP and WanFang data from Jan 2004 to Dec 2017 to collect randomized controlled trials( RCT) of magnesium isoglycyrrhizinate for the treatment of drug-induced liver injury( DILI). Two reviewers independently screened literature,extracted data including basic information,demographic data and clinical characteristics,intervention details,outcome indicators,and so on. Assessed the risk of bias of included studies. Then,Metaanalysis was performed using RevMan 5.3 software. RESULTS A total of 20 RCTs involving 1 709 DILI patients were included. The results of Meta-analysis showed that,the overall response rate and normalized rate of magnesium isoglycyrrhizinate for DILI were significantly higher than control [RR = 1. 15,95% CI( 1. 08,1. 22),P < 0. 01] and [RR = 1. 56,95% CI( 1. 31,1. 85),P < 0. 01].Magnesium isoglycyrrhizinate could significantly lower ALT level than control[MD =-31.25,95%CI(-38.97,-23.54),P< 0.01]. The occurrence rate of ADR was significantly lower in the magnesium isoglycyrrhizinate group compared with other glycyrrhizin subgroup[RR= 0. 29,95% CI( 0. 16,0. 52),P < 0. 01] and was not different from non-glycyrrhizin subgroup. CONCLUSION Magnesium isoglycyrrhizinate treating DILI is superior to other common liver-protecting drugs,especially in lowering ALT level and safety in short term. However,limited to the quality of the included trials,clinical trials of bigger sample size and higher quality is needed to validate this result.
引文
[1]中华医学会肝病学分会药物性肝病学组.药物性肝损伤诊治指南[J].实用肝脏病杂志,2017,20(2):257-274.
[2]房澍名,龚新雷,秦叔逵.新型甘草酸制剂防治抗肿瘤药物肝损伤的现状和进展[J].临床肿瘤学杂志,2013,18(9):833-841.
[3]滝川一,恩地森一,高森賴雪.DDW-J2004ヮ—クショップ药物性肝障害诊断基准の提案[J].肝臓,2005,46(2):85-90.
[4]Maria V A J,Victorino R M M. Development and validation of a clinical scale for the diagnosis of drug induced hepatitis[J].Hepatology,1997,26(3):664-669.
[5]Danan G,Benichou C. Causality assessment of adverse reactions to drugs-IA novel method based on the conclusions of international consensus meetings:application to drug-induced liver injuries[J].Journal of Clinical Epidemiology,1993,46(11):1323-1330.
[6]中华医学会消化病学分会肝胆疾病协作组.急性药物性肝损伤诊治建议草案[J].中华消化杂志,2007,27(11):765-767.
[7]王吉耀.现代肝病诊断与治疗[M].上海:复旦大学出版社,2007:192-193.
[8]葛均波,许永健.内科学[M].北京:人民卫生出版社,2013:416.
[9]熊延军,李东方,孙红.异甘草酸镁治疗抗结核药物性肝损害的效果分析[J].中国当代医药,2014,21(5):68-69.
[10]刘超.异甘草酸镁治疗药物性肝损害36例[J].中国药业,2013,22(7):80.
[11]郭换珍,安纪红,倪文,等.异甘草酸镁治疗药物性肝损害的临床疗效探讨[J].实用临床医药杂志,2011,15(13):75-76.
[12]罗冬生.药物性肝损害治疗的比较研究[J].海峡药学,2017,29(10):130-132.
[13]阮圣霆,夏光云.异甘草酸镁与还原型谷胱甘肽治疗抗类风湿药物诱发的药物性肝损伤患者疗效比较[J].实用肝脏病杂志,2017,20(5):608-609.
[14]潘洁,周胜利,储永良,等.异甘草酸镁治疗类风湿关节炎伴肝功能异常的临床疗效[J].江苏医药,2016,42(10):1126-1128.
[15]吴小霞,辛朝雄,李晓云,等.异甘草酸镁治疗抗结核药引起的药物性肝炎的疗效分析[J].现代诊断与治疗,2015,26(6):1272-1274.
[16]吴潮清,熊礼佳,贺红光,等.异甘草酸镁治疗难治性肾病综合征患者环磷酰胺所致肝损伤的疗效观察[J].广西医学,2014,36(4):432-435.
[17]郭新枝,陈裕,程俊伟,等.异甘草酸镁注射液治疗抗结核药物所致急性肝损伤的临床研究[J].微生物与感染,2013,8(3):157-162.
[18]汤丽娜,林峰,沈赞,等.异甘草酸镁治疗抗肿瘤药物引起的急性药物性肝损伤的Ⅲ期临床试验[J].肿瘤,2012,32(9):738-743.
[19]肖波.异甘草酸镁对药物性肝炎患者的疗效与血清学指标的影响[J].抗感染药学,2016,13(6):1329-1331.
[20]孙丽霞,徐国民.异甘草酸镁治疗难治性肾病综合征患者药物所致肝损伤的临床疗效[J].药物评价研究,2016,39(5):835-838.
[21]聂琦,袁冶,陶立轩,等.异甘草酸镁治疗抗结核药物性肝损害例[J].实用药物与临床,2015,18(12):1488-1490.
[22]林健梅,杨仁国,耿晓霞,等.异甘草酸镁治疗药物性肝损害的临床疗效观察[J].四川医学,2012,33(12):2076-2078.
[23]陈咏萍,姜锡平,常庆华,等.异甘草酸镁治疗药物性肝损害[J].临床荟萃,2012,27(22):1993-1994.
[24]丁锷.异甘草酸镁治疗何首乌致药物性肝损伤临床分析[J].内蒙古中医药,2012,31(11):15-16.
[25]章志学.异甘草酸镁与复方甘草酸单胺治疗血液肿瘤化疗后药物性肝损害的疗效比较[J].实用临床医药杂志,2011,15(13):18-20.
[26]欧阳龙明.异甘草酸镁注射液在治疗药物性肝损伤中的作用[J].实用临床医学,2010,11(12):36-37.
[27]倪鸿昌,契燕燕,冯为东.异甘草酸镁治疗化疗药物性肝损害疗效观察[J].安徽医药,2009,13(9):1099-1100.
[28]吕叶,袁明,林峰,等.异甘草酸镁治疗药物性肝损害例效果观察[J].交通医学,2008,22(2):152-153.
[29]胡琴.保肝药物治疗药物性肝损伤系统评价的再评价[J].中国药房,2016,27(9):1214-1218.
[30]张世洪.Meta分析应合理设置亚组分析与敏感性分析以准确解释结果[J].中国现代神经疾病杂志,2016,16(1):1-2.
[31]杨巧丽,刘燕,史玉柱,等.毛菊苣水提取物急性毒性及其保肝作用研究[J].中国现代应用药学,2017,34(7):957-963.
[32]吴永琴,王述蓉,余彬,等.124例药物性肝损伤住院患者保肝药应用调查与分析[J].中国医院用药评价与分析,2017,17(1):99-101.
[33]李志强,夏春辉,王雅婧,等.异甘草酸镁注射液对比种常用药物治疗药物性肝损害有效性与安全性的系统评价[J].中国药房,2015,26(33):4678-4681.
[34]Xu R,Xiao Q,Cao Y,et al. Comparison of the exposure of glycyrrhizin and its Metabolites and the pseudoaldosteronism after intravenous administration of alpha and beta-glycyrrhizin in rat[J]. Drug Res,2013,63:620-624.
[35]茅益民,曾民德,陈勇,等.异甘草酸镁治疗ALT升高的慢性肝病的多中心、随机、双盲、多剂量、阳性药物平行对照临床研究[J].中华肝脏病杂志,2009,17(11):847-851.
[2]房澍名,龚新雷,秦叔逵.新型甘草酸制剂防治抗肿瘤药物肝损伤的现状和进展[J].临床肿瘤学杂志,2013,18(9):833-841.
[3]滝川一,恩地森一,高森賴雪.DDW-J2004ヮ—クショップ药物性肝障害诊断基准の提案[J].肝臓,2005,46(2):85-90.
[4]Maria V A J,Victorino R M M. Development and validation of a clinical scale for the diagnosis of drug induced hepatitis[J].Hepatology,1997,26(3):664-669.
[5]Danan G,Benichou C. Causality assessment of adverse reactions to drugs-IA novel method based on the conclusions of international consensus meetings:application to drug-induced liver injuries[J].Journal of Clinical Epidemiology,1993,46(11):1323-1330.
[6]中华医学会消化病学分会肝胆疾病协作组.急性药物性肝损伤诊治建议草案[J].中华消化杂志,2007,27(11):765-767.
[7]王吉耀.现代肝病诊断与治疗[M].上海:复旦大学出版社,2007:192-193.
[8]葛均波,许永健.内科学[M].北京:人民卫生出版社,2013:416.
[9]熊延军,李东方,孙红.异甘草酸镁治疗抗结核药物性肝损害的效果分析[J].中国当代医药,2014,21(5):68-69.
[10]刘超.异甘草酸镁治疗药物性肝损害36例[J].中国药业,2013,22(7):80.
[11]郭换珍,安纪红,倪文,等.异甘草酸镁治疗药物性肝损害的临床疗效探讨[J].实用临床医药杂志,2011,15(13):75-76.
[12]罗冬生.药物性肝损害治疗的比较研究[J].海峡药学,2017,29(10):130-132.
[13]阮圣霆,夏光云.异甘草酸镁与还原型谷胱甘肽治疗抗类风湿药物诱发的药物性肝损伤患者疗效比较[J].实用肝脏病杂志,2017,20(5):608-609.
[14]潘洁,周胜利,储永良,等.异甘草酸镁治疗类风湿关节炎伴肝功能异常的临床疗效[J].江苏医药,2016,42(10):1126-1128.
[15]吴小霞,辛朝雄,李晓云,等.异甘草酸镁治疗抗结核药引起的药物性肝炎的疗效分析[J].现代诊断与治疗,2015,26(6):1272-1274.
[16]吴潮清,熊礼佳,贺红光,等.异甘草酸镁治疗难治性肾病综合征患者环磷酰胺所致肝损伤的疗效观察[J].广西医学,2014,36(4):432-435.
[17]郭新枝,陈裕,程俊伟,等.异甘草酸镁注射液治疗抗结核药物所致急性肝损伤的临床研究[J].微生物与感染,2013,8(3):157-162.
[18]汤丽娜,林峰,沈赞,等.异甘草酸镁治疗抗肿瘤药物引起的急性药物性肝损伤的Ⅲ期临床试验[J].肿瘤,2012,32(9):738-743.
[19]肖波.异甘草酸镁对药物性肝炎患者的疗效与血清学指标的影响[J].抗感染药学,2016,13(6):1329-1331.
[20]孙丽霞,徐国民.异甘草酸镁治疗难治性肾病综合征患者药物所致肝损伤的临床疗效[J].药物评价研究,2016,39(5):835-838.
[21]聂琦,袁冶,陶立轩,等.异甘草酸镁治疗抗结核药物性肝损害例[J].实用药物与临床,2015,18(12):1488-1490.
[22]林健梅,杨仁国,耿晓霞,等.异甘草酸镁治疗药物性肝损害的临床疗效观察[J].四川医学,2012,33(12):2076-2078.
[23]陈咏萍,姜锡平,常庆华,等.异甘草酸镁治疗药物性肝损害[J].临床荟萃,2012,27(22):1993-1994.
[24]丁锷.异甘草酸镁治疗何首乌致药物性肝损伤临床分析[J].内蒙古中医药,2012,31(11):15-16.
[25]章志学.异甘草酸镁与复方甘草酸单胺治疗血液肿瘤化疗后药物性肝损害的疗效比较[J].实用临床医药杂志,2011,15(13):18-20.
[26]欧阳龙明.异甘草酸镁注射液在治疗药物性肝损伤中的作用[J].实用临床医学,2010,11(12):36-37.
[27]倪鸿昌,契燕燕,冯为东.异甘草酸镁治疗化疗药物性肝损害疗效观察[J].安徽医药,2009,13(9):1099-1100.
[28]吕叶,袁明,林峰,等.异甘草酸镁治疗药物性肝损害例效果观察[J].交通医学,2008,22(2):152-153.
[29]胡琴.保肝药物治疗药物性肝损伤系统评价的再评价[J].中国药房,2016,27(9):1214-1218.
[30]张世洪.Meta分析应合理设置亚组分析与敏感性分析以准确解释结果[J].中国现代神经疾病杂志,2016,16(1):1-2.
[31]杨巧丽,刘燕,史玉柱,等.毛菊苣水提取物急性毒性及其保肝作用研究[J].中国现代应用药学,2017,34(7):957-963.
[32]吴永琴,王述蓉,余彬,等.124例药物性肝损伤住院患者保肝药应用调查与分析[J].中国医院用药评价与分析,2017,17(1):99-101.
[33]李志强,夏春辉,王雅婧,等.异甘草酸镁注射液对比种常用药物治疗药物性肝损害有效性与安全性的系统评价[J].中国药房,2015,26(33):4678-4681.
[34]Xu R,Xiao Q,Cao Y,et al. Comparison of the exposure of glycyrrhizin and its Metabolites and the pseudoaldosteronism after intravenous administration of alpha and beta-glycyrrhizin in rat[J]. Drug Res,2013,63:620-624.
[35]茅益民,曾民德,陈勇,等.异甘草酸镁治疗ALT升高的慢性肝病的多中心、随机、双盲、多剂量、阳性药物平行对照临床研究[J].中华肝脏病杂志,2009,17(11):847-851.