五种保肝药物对药物性肝损害的疗效分析:一项网状Meta分析研究
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摘要
目的:运用网状Meta分析方法比较双环醇、异甘草酸镁等5种保肝药物治疗药物性肝损害的疗效差异。方法:检索中国期刊网数据库(CNKI)、万方数据平台、EMBASE、PubMed数据库,收集相关的临床试验文献,对文献进行质量评价,使用STATA14软件network程序包实现网状meta分析。结果:共纳入20篇文献,1798例DILI患者入选,网状Meta分析结果显示,与还原型谷胱甘肽相比,有效率方面各干预药物无显著性差异。异甘草酸镁在降低ALT水平方面一致性模型的拟合结果(MD=-23.38,95%CI=-35.24,-11.52],P<0.05)显著优于还原型谷胱甘肽。在降低AST水平方面,异甘草酸镁同样显著优于还原型谷胱甘肽(MD=-18.73,95%CI=-29.52,-7.95], P <0.05)。对于TBIL下降程度,一致性模型拟合结果未见显著性差异。概率排序为,有效率由高到低的顺序为:硫普罗宁>双环醇>还原型谷胱甘肽>甘草酸二铵≈异甘草酸镁。降低ALT水平的顺序为:异甘草酸镁>双环醇>硫普罗宁>甘草酸二铵≈还原型谷胱甘肽。降低AST水平的顺序为:异甘草酸镁>硫普罗宁>双环醇>甘草酸二铵≈还原型谷胱甘肽。降低TBIL水平的顺序为:双环醇>硫普罗宁>还原型谷胱甘肽>异甘草酸镁>甘草酸二铵。结论:五种保肝药物中硫普罗宁的有效率最高,异甘草酸镁在降低ALT、AST水平方面的作用强于其他四种药物,双环醇降低TBIL作用最强。可见,异甘草酸镁更擅长调控ALT、AST水平,双环醇更擅长对TBIL的调控。
OBJECTIVE To evaluate the effect of five kinds of hepatoprotective drugs such as bicyclol and magnesium isoglycyrrhizinate in patients with drug induced liver injury. METHODS CNKI, WANFANG, Embase and Pubmed were searched to collect clinical trial literatures. After assessing these literatures, Meta-analysis was conducted by STATA 14.RESULTS Totally 20 clinical trial literatures and 1 798 patients were involved in this network meta-analysis. Results of network Meta-analysis showed that, compared with reduced glutathione, there was no significant difference in effective rate among all intervention drugs. Magnesium isoglycyrrhizinate(MD =-23.38, 95% CI=[-35.24,-11.52], P <0.05) was superior to reduced glutathione in reducing ALT level. Magnesium glutathione(MD =-18.73, 95%, CI = [-29.52,-7.95],P < 0.05) was also superior to reduced glutathione in reducing AST level. In the degree of TBIL decline, there was no significant difference among all intervention drugs. The probability ranking of effective rate: tiopronin > bicyclol > reduced glutathione > diammonium glycyrrhizinate ≈ magnesium isoglycyrrhizinate. The probability ranking of the ability to reduce ALT:magnesium isoglycyrrhizinate > bicyclol > tiopronin > diammonium glycyrrhizinate ≈ reduced glutathione.The probability ranking of the ability to reduce AST:magnesium isoglycyrrhizinate > tiopronin > bicyclol > diammonium glycyrrhizinate ≈ reduced glutathione. The probability ranking of the ability to reduce TBIL: bicyclol > tiopronin >reduced glutathione >magnesium isoglycyrrhizinate > diammonium glycyrrhizinate. CONCLUSION Tiopronin has the highest efficiency. Magnesium isoglycyrrhizinate significantly decreases the levels of ALT and AST compared with the other four drugs. Bicyclol significantly decreases the level of TBIL.
OBJECTIVE To evaluate the effect of five kinds of hepatoprotective drugs such as bicyclol and magnesium isoglycyrrhizinate in patients with drug induced liver injury. METHODS CNKI, WANFANG, Embase and Pubmed were searched to collect clinical trial literatures. After assessing these literatures, Meta-analysis was conducted by STATA 14.RESULTS Totally 20 clinical trial literatures and 1 798 patients were involved in this network meta-analysis. Results of network Meta-analysis showed that, compared with reduced glutathione, there was no significant difference in effective rate among all intervention drugs. Magnesium isoglycyrrhizinate(MD =-23.38, 95% CI=[-35.24,-11.52], P <0.05) was superior to reduced glutathione in reducing ALT level. Magnesium glutathione(MD =-18.73, 95%, CI = [-29.52,-7.95],P < 0.05) was also superior to reduced glutathione in reducing AST level. In the degree of TBIL decline, there was no significant difference among all intervention drugs. The probability ranking of effective rate: tiopronin > bicyclol > reduced glutathione > diammonium glycyrrhizinate ≈ magnesium isoglycyrrhizinate. The probability ranking of the ability to reduce ALT:magnesium isoglycyrrhizinate > bicyclol > tiopronin > diammonium glycyrrhizinate ≈ reduced glutathione.The probability ranking of the ability to reduce AST:magnesium isoglycyrrhizinate > tiopronin > bicyclol > diammonium glycyrrhizinate ≈ reduced glutathione. The probability ranking of the ability to reduce TBIL: bicyclol > tiopronin >reduced glutathione >magnesium isoglycyrrhizinate > diammonium glycyrrhizinate. CONCLUSION Tiopronin has the highest efficiency. Magnesium isoglycyrrhizinate significantly decreases the levels of ALT and AST compared with the other four drugs. Bicyclol significantly decreases the level of TBIL.
引文
[1] Yu LC, Mao YM, Chen CW. CSH Clinical Guideline:The diagnosis and management of drug-induced liver injury[J].J Pract Hepatol(实用肝脏病杂志),2017(2):257-274.
[2] Wei XC, Zhu LQ, Wang CG, et al. Network meta-analysisof efficacy of 3 kinds of Chinese medicine injections in preventing oxaliplatin-induced peripheral neurotoxicity in cancer patients[J]. Chin Hosp Pharm J(中国医院药学杂志),2016, 36(18):1567-1571.
[3] Liang Y, Guan W,Liu Q, et al. Clinical control study of magnesium isoglycyrrhizinate in the treatment of liver function impairment caused by chemotherapy[J]. Chin J Cancer Prevent Treat(中华肿瘤防治杂志),2017(7):42-43.
[4] Xiao B. Influence on clinical efficacy and serological indexes of magnesium isoglycyrrhizinate in patients with drug-induced hepatitis[J]. Anti Inf Pharm(抗感染药学),2016(06):1329-1331.
[5] Chen LH, Wang JH, Li CM. The clinical effect of magnesium isoglycyrrhizinate in the treatment of antitubercular druginduced liver injuries[J].J Bethune Mil Med Coll(白求恩医志杂志),2016(3):317-318.
[6] Chu GJ. Clinical effect comparison of tiopronin and diammonium glycyrrhizinate in treating antitubercular drug-induced liver injuries[J]. Med J Chin People's Health(中国民康医学),2016(11):47-48.
[7] Zhao JR, Peng GC, Xie RH. Clinical observation of Bicyclol Tablets in treatment of chronic HIV infection with antiviral treatment related drug-induced liver injury[J]. Chin Hepatol(肝脏), 2015(10):798-802.
[8] Xiong XQ. Treatment of 71 cases of liver damage caused by anti-tuberculosis drugs by magnesium isoglycyrrhizinate[J].Jiangxi J Trad Chin Med(江西中医药),2015(11):53-54.
[9] Wu XX, Xing CX, Li XY, et al. Efficacy of magnesium isoglycyrrhizinate in the treatment of drug-induced hepatitis caused by anti-tuberculosis drugs[J]. Mod Diagn Treat(现代诊断与治疗),2015(6):1272-1274.
[10] Liang YP. Clinical analysis of the efficacy of tiopronin and diammonium glycyrrhizinate in the treatment of antitubercular drug-induced liver disease[J]. Shenzhen J Int Trad Chin West Med(深圳中西医结合杂志),2015(19):9-11.
[11] Cao YH. Clinical analysis of Bicyclol Tablets in treating192 cases of liver damage caused by antitubercular drug[J].Shanxi Med J(山西医药杂志),2014(7):793-795.
[12] Liu GD, Hu Y, Zhang YF, et al. Clinical analysis of magnesium isoglycyrrhizinate injection in the treatment of drug-induced liver injury[J]. Mod J Int Trad Chin West Med(现代中西医结合杂志),2014(24):2680-2681.
[13] Liu YF, Yang GB. Effect of magnesium isoglycyrrhizinate on liver damage induced by chemotherapeutic drugs[J].Chin Med Equip(中国医学装备), 2014(S1):393-394.
[14] Cheng XD, Mi D, Li JC. Effect study of tiopronin and diammonium glycyrrhizinate on anti-tuberculosis druginduced liver disease[J]. Chin Med Herald(中国医药导报),2013(23):83-85.
[15] Shu DY. Clinical analysis of bicyclol in the treatment of liver damage caused by anti-TB drugs[J]. Mod Diagn Treat(现代诊断与治疗),2013(10):2209-2210.
[16] Guo XZ, Chen Y, Cheng JW, et al. Randomized doubleblinded and active drug-controlled clinical study of magnesium isoglycyrrhizinate injection in the treatment of antitubercular drug-indeed acute hepatic dysfunction[J].J Micr Infect(微生物与感染),2013(3):157-162.
[17] Tu Y, Wan YY. Therapeutic and prophylactic effect of bicyclol on drug-induced liver injury for lung cancer patients[J]. J Med Res(医学研究杂志),2012(7):156-158.
[18] Hu XP, Ying H, Wang W, et al. Efficacy of bicyclol tablets in the treatment of drug-induced liver injury after renal transplantation[J]. Chin J Gastroenterol Hepatol(胃肠病学和肝病学杂志,2012(4):342-344.
[19] Jia YH, Zhang YQ. Comparison of the efficacy of tiopronin and diammonium glycyrrhizinate in the treatment of antitubercular drug-induced liver disease[J]. Chin J Gerontol(中国老年学杂志),2012(24):5432-5433.
[20] Chen T, Deng YC. Clinical observation of magnesium isoglycyrrhizinate in the treatment of antitubercular druginduced liver injuries[J]. Chin Comm Doct(中国社区医师:医学专业),2010(13):45-46.
[21] Ni HC, Qi YY, Feng WD. Effect of magnesium isoglycyrrhizinate in the treatment of the hepatotoxicity caused by anti-tumor agents in cancer patients[J]. Anhui Med Pharmaceut J(安徽医药),2009(9):1099-1100.
[22] Chen YQ, Gao TJ, Chi J, et al. Analysis of clinical efficacy and safety of bicyclol tablets in treating liver damage caused by anti-tuberculosis drugs[J]. Infect Dis Informat(传染病信息), 2005(4):188-189.
[23] Li ZL. Clinical efficacy of magnesium isoglycyrrhizinate in the treatment of antitubercular drug-induced liver injuries[J]. World Latest Med Informat(世界最新医学信息文摘),2017(32):79.
[24] Chen H, Liu M. Clinical observation of magnesium isoglycyrrhizinate in the treatment of antitubercular druginduced liver injuries[J].J Clin Med Liter(临床医药文献电子杂志),2017(59):11636-11637.
[25] Ruan ST, Xia GY. Application of magnesium glycyrrhizinate and reduced glutathione in treatment of patients with antirheumatoid arthritis-induced liver injuries[J]. J Pract Hepatol(实用肝脏病杂志), 2017(5):608-609.
[26] Zeng XT Zhang C Guang XX et al. Software for network meta-analysis a usage-based comparative study[J]. Chin J Evid Based Med(中国循证医学杂志)2014(10):1270-1275.
[27] Zhang TS. A suite of network commands in Stata for network meta-analysis[J]. Chin J Evid Based Med(中国循证医学杂志),2015(11):1352-1356.
[2] Wei XC, Zhu LQ, Wang CG, et al. Network meta-analysisof efficacy of 3 kinds of Chinese medicine injections in preventing oxaliplatin-induced peripheral neurotoxicity in cancer patients[J]. Chin Hosp Pharm J(中国医院药学杂志),2016, 36(18):1567-1571.
[3] Liang Y, Guan W,Liu Q, et al. Clinical control study of magnesium isoglycyrrhizinate in the treatment of liver function impairment caused by chemotherapy[J]. Chin J Cancer Prevent Treat(中华肿瘤防治杂志),2017(7):42-43.
[4] Xiao B. Influence on clinical efficacy and serological indexes of magnesium isoglycyrrhizinate in patients with drug-induced hepatitis[J]. Anti Inf Pharm(抗感染药学),2016(06):1329-1331.
[5] Chen LH, Wang JH, Li CM. The clinical effect of magnesium isoglycyrrhizinate in the treatment of antitubercular druginduced liver injuries[J].J Bethune Mil Med Coll(白求恩医志杂志),2016(3):317-318.
[6] Chu GJ. Clinical effect comparison of tiopronin and diammonium glycyrrhizinate in treating antitubercular drug-induced liver injuries[J]. Med J Chin People's Health(中国民康医学),2016(11):47-48.
[7] Zhao JR, Peng GC, Xie RH. Clinical observation of Bicyclol Tablets in treatment of chronic HIV infection with antiviral treatment related drug-induced liver injury[J]. Chin Hepatol(肝脏), 2015(10):798-802.
[8] Xiong XQ. Treatment of 71 cases of liver damage caused by anti-tuberculosis drugs by magnesium isoglycyrrhizinate[J].Jiangxi J Trad Chin Med(江西中医药),2015(11):53-54.
[9] Wu XX, Xing CX, Li XY, et al. Efficacy of magnesium isoglycyrrhizinate in the treatment of drug-induced hepatitis caused by anti-tuberculosis drugs[J]. Mod Diagn Treat(现代诊断与治疗),2015(6):1272-1274.
[10] Liang YP. Clinical analysis of the efficacy of tiopronin and diammonium glycyrrhizinate in the treatment of antitubercular drug-induced liver disease[J]. Shenzhen J Int Trad Chin West Med(深圳中西医结合杂志),2015(19):9-11.
[11] Cao YH. Clinical analysis of Bicyclol Tablets in treating192 cases of liver damage caused by antitubercular drug[J].Shanxi Med J(山西医药杂志),2014(7):793-795.
[12] Liu GD, Hu Y, Zhang YF, et al. Clinical analysis of magnesium isoglycyrrhizinate injection in the treatment of drug-induced liver injury[J]. Mod J Int Trad Chin West Med(现代中西医结合杂志),2014(24):2680-2681.
[13] Liu YF, Yang GB. Effect of magnesium isoglycyrrhizinate on liver damage induced by chemotherapeutic drugs[J].Chin Med Equip(中国医学装备), 2014(S1):393-394.
[14] Cheng XD, Mi D, Li JC. Effect study of tiopronin and diammonium glycyrrhizinate on anti-tuberculosis druginduced liver disease[J]. Chin Med Herald(中国医药导报),2013(23):83-85.
[15] Shu DY. Clinical analysis of bicyclol in the treatment of liver damage caused by anti-TB drugs[J]. Mod Diagn Treat(现代诊断与治疗),2013(10):2209-2210.
[16] Guo XZ, Chen Y, Cheng JW, et al. Randomized doubleblinded and active drug-controlled clinical study of magnesium isoglycyrrhizinate injection in the treatment of antitubercular drug-indeed acute hepatic dysfunction[J].J Micr Infect(微生物与感染),2013(3):157-162.
[17] Tu Y, Wan YY. Therapeutic and prophylactic effect of bicyclol on drug-induced liver injury for lung cancer patients[J]. J Med Res(医学研究杂志),2012(7):156-158.
[18] Hu XP, Ying H, Wang W, et al. Efficacy of bicyclol tablets in the treatment of drug-induced liver injury after renal transplantation[J]. Chin J Gastroenterol Hepatol(胃肠病学和肝病学杂志,2012(4):342-344.
[19] Jia YH, Zhang YQ. Comparison of the efficacy of tiopronin and diammonium glycyrrhizinate in the treatment of antitubercular drug-induced liver disease[J]. Chin J Gerontol(中国老年学杂志),2012(24):5432-5433.
[20] Chen T, Deng YC. Clinical observation of magnesium isoglycyrrhizinate in the treatment of antitubercular druginduced liver injuries[J]. Chin Comm Doct(中国社区医师:医学专业),2010(13):45-46.
[21] Ni HC, Qi YY, Feng WD. Effect of magnesium isoglycyrrhizinate in the treatment of the hepatotoxicity caused by anti-tumor agents in cancer patients[J]. Anhui Med Pharmaceut J(安徽医药),2009(9):1099-1100.
[22] Chen YQ, Gao TJ, Chi J, et al. Analysis of clinical efficacy and safety of bicyclol tablets in treating liver damage caused by anti-tuberculosis drugs[J]. Infect Dis Informat(传染病信息), 2005(4):188-189.
[23] Li ZL. Clinical efficacy of magnesium isoglycyrrhizinate in the treatment of antitubercular drug-induced liver injuries[J]. World Latest Med Informat(世界最新医学信息文摘),2017(32):79.
[24] Chen H, Liu M. Clinical observation of magnesium isoglycyrrhizinate in the treatment of antitubercular druginduced liver injuries[J].J Clin Med Liter(临床医药文献电子杂志),2017(59):11636-11637.
[25] Ruan ST, Xia GY. Application of magnesium glycyrrhizinate and reduced glutathione in treatment of patients with antirheumatoid arthritis-induced liver injuries[J]. J Pract Hepatol(实用肝脏病杂志), 2017(5):608-609.
[26] Zeng XT Zhang C Guang XX et al. Software for network meta-analysis a usage-based comparative study[J]. Chin J Evid Based Med(中国循证医学杂志)2014(10):1270-1275.
[27] Zhang TS. A suite of network commands in Stata for network meta-analysis[J]. Chin J Evid Based Med(中国循证医学杂志),2015(11):1352-1356.