膈下逐瘀汤加减联合核苷类药物治疗乙型肝炎肝硬化疗效及安全性的Meta分析
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摘要
目的:评价膈下逐瘀汤加减联合核苷类药物治疗乙型肝炎肝硬化的疗效以及安全性。方法:检索中国知网数据库(CNKI)、重庆维普中文科技期刊数据库(VIP)和万方数字化期刊全文数据库、The Cochrane Library、Pubmed数据库,纳入随机对照试验(randomized controlled trials,RCTs)相关临床试验数据。检索时限为自建库开始至2018年3月10日。分析由2名独立研究者独立选择试验和质量评价后,提取数据并分析。结果:共纳入13个研究,纳入研究对象1151例,其中试验组579例,对照组572例。结果显示:膈下逐瘀汤联合核苷类药物可降低总胆红素指标TBIL[MD=-10.85(95%可信区间(confidence interval,CI)95%CI:-14.67,-7.03),P<0.000 01]、有效改善肝功能ALT[MD=-29.19(95%CI:-37.50,-20.87),P<0.000 01]、AST[MD=-28.72(95%CI:-40.47,-16.97),P<0.000 01],降低肝纤维化指标透明质酸(HA)水平[MD=-57.39(95%CI:-80.80,-33.99),P<0.000 01]、层粘连蛋白(LN)水平[MD=-17.18(95%CI:-19.93,-14.43),P<0.000 01]、Ⅳ型胶原蛋白(Ⅳ-C)水平[MD=-16.73(95%CI:-18.81,-14.66),P<0.000 01]、Ⅲ型前胶原(PCⅢ)水平[MD=-22.60(95%CI:-25.26,-19.94),P<0.000 01],减少Child-Pugh分级评分[MD=-1.33(95%CI:-1.62,-1.05),P<0.000 01],且均优于单纯核苷类药物治疗(P<0.000 01)。结论:膈下逐瘀汤联合核苷酸类药物治疗乙型肝炎肝硬化的疗效优于单用核苷类药物。
Objective:To evaluate the efficacy and safety of Gexia Zhuyu decoction combined with nucleoside drugs in the treatment of hepatitis B cirrhosis. Methods: to search the database of China knowledge Network(CNKI), Chongqing Weipu Chinese Science and Technology periodical Database(VIP) and Wanfang Digital Journals full text Database(The Cochrane Library,Pubmed), which were included in the randomized controlled trial) related clinical trial data. The time limit for retrieval is from the beginning of the library construction to March 10, 2018. The data were extracted and analyzed by two independent researchers. Results: A total of 13 subjects were included in the study, including 579 cases in the experimental group and 572 cases in the control group. The results showed that Gexia Zhuyu decoction combined with nucleoside drugs could reduce the total bilirubin index TBIL [MD=-10.85(95% confidence interval(confidence interval,CI) 95 CI-14.67), P-7.03), P<0.000 01]. Improve liver function effectively ALT [MD=-29.19(95 CI:-37.50-20.87), P<0.000 01], AST [95 CI:-40.47-16.97), P<0.000 01], The level of hyaluronic acid(HA)(MD=-57.39) and laminin(LN)(MD=-17.18) were decreased [MD=-57.39(95 CI:-80.80-33.99), P<0.000 01)] and MD=-17.18(95 CI:-19.93%-14.43). P<0.000 01, MD=-16.73(95 CI:-18.81-14.66), P<0.000 01), MD=-22.60(95 CI:-25.26), PC Ⅲ(P<0.000 01).-19.94), P<0.000 01, MD=-1.33(95 CI:-1.62 U-1.05), P<0.000 01), and all of them were superior to nucleoside drug therapy(P<0.000 01). Conclusion: Gexiazhuyu decoction combined with nucleotides is superior to nucleoside in the treatment of hepatitis B cirrhosis.
Objective:To evaluate the efficacy and safety of Gexia Zhuyu decoction combined with nucleoside drugs in the treatment of hepatitis B cirrhosis. Methods: to search the database of China knowledge Network(CNKI), Chongqing Weipu Chinese Science and Technology periodical Database(VIP) and Wanfang Digital Journals full text Database(The Cochrane Library,Pubmed), which were included in the randomized controlled trial) related clinical trial data. The time limit for retrieval is from the beginning of the library construction to March 10, 2018. The data were extracted and analyzed by two independent researchers. Results: A total of 13 subjects were included in the study, including 579 cases in the experimental group and 572 cases in the control group. The results showed that Gexia Zhuyu decoction combined with nucleoside drugs could reduce the total bilirubin index TBIL [MD=-10.85(95% confidence interval(confidence interval,CI) 95 CI-14.67), P-7.03), P<0.000 01]. Improve liver function effectively ALT [MD=-29.19(95 CI:-37.50-20.87), P<0.000 01], AST [95 CI:-40.47-16.97), P<0.000 01], The level of hyaluronic acid(HA)(MD=-57.39) and laminin(LN)(MD=-17.18) were decreased [MD=-57.39(95 CI:-80.80-33.99), P<0.000 01)] and MD=-17.18(95 CI:-19.93%-14.43). P<0.000 01, MD=-16.73(95 CI:-18.81-14.66), P<0.000 01), MD=-22.60(95 CI:-25.26), PC Ⅲ(P<0.000 01).-19.94), P<0.000 01, MD=-1.33(95 CI:-1.62 U-1.05), P<0.000 01), and all of them were superior to nucleoside drug therapy(P<0.000 01). Conclusion: Gexiazhuyu decoction combined with nucleotides is superior to nucleoside in the treatment of hepatitis B cirrhosis.
引文
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[7] 代巧妹,贾彦,刘宏,等.膈下逐瘀汤抗大鼠免疫性肝纤维化的研究[J].中国实验方剂学杂志,2011,17(22):187-190.
[8] 黄敬泉,王传香.膈下逐瘀汤用于乙肝肝硬化治疗的临床疗效观察[J].江西中医药,2017,11,48(419):44-45.
[9] 李洪,蔡红兵,李滨,等.加味膈下逐瘀汤联合阿德福韦酯治疗瘀血阻络型慢性乙肝42例疗效观察[J].新中医,2008,40(12):30-31.
[10] 麻飞玲,谢冬梅,孙黎明.膈下逐瘀汤联合恩替卡韦片对瘀血阻络型慢乙肝患者血清肝纤维化指标的影响[J].辽宁中医杂志,2015,42(2):344-346.
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[14] 周怀兵,胡咏梅.膈下逐瘀汤联合抗病毒治疗在瘀血阻络型慢性乙肝患者的应用分析[J].北方药学,2015,12(7):155-156.
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[16] 陈炎生,费新应,刘文涛,等.膈下逐瘀汤联合拉米夫定治疗乙型肝炎肝硬化疗效观察[J].湖北中医杂志,2012,34(7):5-6.
[17] 韩曼珠,王芬,李丽,等.拉米夫定联合膈下逐瘀汤对乙型肝炎肝硬化治疗的临床疗效评价[J].中华医院感染学杂志,2014,24(15):3706-3708.
[18] 李庭辉,贾利英.膈下逐瘀汤加味用于慢性乙型肝炎肝硬化患者的临床疗效观察[J].中国肝脏病杂志(电子版),2015,7(2):84-87.
[19] 马雪茹.膈下逐瘀汤+拉米夫定治疗乙型肝炎肝硬化的临床研究[J].中国现代医生,2016,54(22):122-124.
[20] 辛燏.膈下逐瘀汤联合拉米夫定用于乙型肝炎肝硬化治疗的临床研究[J].海峡药学,2016,28(11):189-191.
[21] Martin DJ,Weideman R,Crook T,et al.Relationship of hepatic fibrosis, cirrhosis, and mortality with cholecystectomy in patients with hepatitis C virus infection[J].Eur J Gastroenterol Hepatol,2016,28(2):181-186.
[22] 贾彦,杨婧,刘宏,等.膈下逐瘀汤逆转猪血清诱导大鼠肝纤维化的作用及机制研究[J].中国实验方剂学杂志,2013,19(5):220-224.
[23] Salazar-Montes AM,Hernández-Ortega LD,Lucano-Landeros MS,et al.New gene therapy strategies for hepatic fibrosis[J].World J Gastroentero,2015,21(13):3813-3825.
[24] Priya S,Sudhakaran PR.Cell survival,activation and apoptosis of hepatic stellate cells: modulation by extracellular matrix proteins[J].Hepatol Res,2008,38(12):1221-1232.
[25] Albillos A,Nieto M,Ubeda M,et al.The biological response modifier AM3 attenuates the inflammatory cell response and hepatic fibrosis in rats with biliary cirrhosis[J].Gut,2010,59(7):943-952.
[26] HUANG Y,DENG X,LIANG J.Modulation of hepatic stellate cells and reversibility of hepatic fibrosis[J].Exp Cell Res,2017,352(2):420-426.
[27] Hidvegi T,Ewing M,Hale P,et al. An autophagy-enhancing drug promotes degradation of mutant alpha1-antitrypsin Z and reduces hepatic fibrosis[J].Science,2010,329(5988):229.
[28] 雷娜,郑仕中,陆茵.活血化瘀类中药防治肝纤维化的机制及研究进展[J]. 中华中医药杂志,2010,25(2):265-268.
[29] 刘鸣昊,薛博瑜.近5年来肝纤维化中医证治用药规律的文献研究[J].中国实验方剂学杂志,2011,17(18):279.
[30] 沈龙柱,高虹,吴兆洪,等.辨病辨证治疗肝硬化腹水47例[J].辽宁中医杂志,2004,31(6):473-474.
[31] 刘宏,贾彦,杨婧.膈下逐瘀汤对免疫性肝纤维化大鼠肝组织MMP-9和TIMP-2表达的影响[J].中华中医药杂志,2012,27(2):450-453.
[32] 杨婧,贾彦,刘宏,等.膈下逐瘀汤对大鼠纤维化肝组织α-SMA和TGF-β1表达的影响[J].中国中医基础医学杂志,2012,18(2):158-160.
[2] 梁小立.大黄蛰虫丸治疗病毒性肝炎肝硬化临床观察[J].中外医疗,2009,28(11):129-130.
[3] Li X,Shen J,Zhong Z,et al.Paeoniflorin: a monomer from traditional Chinese medical herb ameliorates Schistosoma japonicum egg-induced hepatic fibrosis in mice[J].J Parasitol,2009,95(6):1520-1524.
[4] Foo NP,Lin SH,Lee YH,et al.α-Lipoic acid inhibits liver fibrosis through the attenuation of ROS-triggered signaling in hepatic stellate cells activated by PDGF and TGF-β[J].Toxicology,2011,282(1-2):39-46.
[5] Maclean KN,Sikora J,Koich V,et al. A novel transgenic mouse model of CBS-deficient homocystinuria does not incur hepatic steatosis or fibrosis and exhibits a hypercoagulative phenotype that is ameliorated by betaine treatment[J].Mol Genet Metab,2010,101(2-3):153-162.
[6] 李季,叶军,薛冬英.中药复方抗肝纤维化作用机制研究概况[J].中医杂志,2011,52(3):253-256.
[7] 代巧妹,贾彦,刘宏,等.膈下逐瘀汤抗大鼠免疫性肝纤维化的研究[J].中国实验方剂学杂志,2011,17(22):187-190.
[8] 黄敬泉,王传香.膈下逐瘀汤用于乙肝肝硬化治疗的临床疗效观察[J].江西中医药,2017,11,48(419):44-45.
[9] 李洪,蔡红兵,李滨,等.加味膈下逐瘀汤联合阿德福韦酯治疗瘀血阻络型慢性乙肝42例疗效观察[J].新中医,2008,40(12):30-31.
[10] 麻飞玲,谢冬梅,孙黎明.膈下逐瘀汤联合恩替卡韦片对瘀血阻络型慢乙肝患者血清肝纤维化指标的影响[J].辽宁中医杂志,2015,42(2):344-346.
[11] 邱亮,赵兴华.膈下逐瘀汤联合恩替卡韦用于乙肝肝硬化的疗效分析[J].临床医药文献杂志,2016,3(48):9632.
[12] 吴小洁.加味膈下逐瘀汤联合恩替卡韦片对治疗瘀血阻络型慢性乙肝临床研究[J].世界中西医结合杂志,2017 ,12(11):1594-1600.
[13] 肖苗苗.膈下逐瘀汤联合恩替卡韦分散片治疗乙型肝炎肝硬化的效果分析[J].世界最新医学信息文摘,2016,16(94):157-158.
[14] 周怀兵,胡咏梅.膈下逐瘀汤联合抗病毒治疗在瘀血阻络型慢性乙肝患者的应用分析[J].北方药学,2015,12(7):155-156.
[15] 常庆雄.膈下逐瘀汤联合拉米夫定用于乙型肝炎肝硬化治疗临床研究[J].中国实用医药,2016,11(11):198-199.
[16] 陈炎生,费新应,刘文涛,等.膈下逐瘀汤联合拉米夫定治疗乙型肝炎肝硬化疗效观察[J].湖北中医杂志,2012,34(7):5-6.
[17] 韩曼珠,王芬,李丽,等.拉米夫定联合膈下逐瘀汤对乙型肝炎肝硬化治疗的临床疗效评价[J].中华医院感染学杂志,2014,24(15):3706-3708.
[18] 李庭辉,贾利英.膈下逐瘀汤加味用于慢性乙型肝炎肝硬化患者的临床疗效观察[J].中国肝脏病杂志(电子版),2015,7(2):84-87.
[19] 马雪茹.膈下逐瘀汤+拉米夫定治疗乙型肝炎肝硬化的临床研究[J].中国现代医生,2016,54(22):122-124.
[20] 辛燏.膈下逐瘀汤联合拉米夫定用于乙型肝炎肝硬化治疗的临床研究[J].海峡药学,2016,28(11):189-191.
[21] Martin DJ,Weideman R,Crook T,et al.Relationship of hepatic fibrosis, cirrhosis, and mortality with cholecystectomy in patients with hepatitis C virus infection[J].Eur J Gastroenterol Hepatol,2016,28(2):181-186.
[22] 贾彦,杨婧,刘宏,等.膈下逐瘀汤逆转猪血清诱导大鼠肝纤维化的作用及机制研究[J].中国实验方剂学杂志,2013,19(5):220-224.
[23] Salazar-Montes AM,Hernández-Ortega LD,Lucano-Landeros MS,et al.New gene therapy strategies for hepatic fibrosis[J].World J Gastroentero,2015,21(13):3813-3825.
[24] Priya S,Sudhakaran PR.Cell survival,activation and apoptosis of hepatic stellate cells: modulation by extracellular matrix proteins[J].Hepatol Res,2008,38(12):1221-1232.
[25] Albillos A,Nieto M,Ubeda M,et al.The biological response modifier AM3 attenuates the inflammatory cell response and hepatic fibrosis in rats with biliary cirrhosis[J].Gut,2010,59(7):943-952.
[26] HUANG Y,DENG X,LIANG J.Modulation of hepatic stellate cells and reversibility of hepatic fibrosis[J].Exp Cell Res,2017,352(2):420-426.
[27] Hidvegi T,Ewing M,Hale P,et al. An autophagy-enhancing drug promotes degradation of mutant alpha1-antitrypsin Z and reduces hepatic fibrosis[J].Science,2010,329(5988):229.
[28] 雷娜,郑仕中,陆茵.活血化瘀类中药防治肝纤维化的机制及研究进展[J]. 中华中医药杂志,2010,25(2):265-268.
[29] 刘鸣昊,薛博瑜.近5年来肝纤维化中医证治用药规律的文献研究[J].中国实验方剂学杂志,2011,17(18):279.
[30] 沈龙柱,高虹,吴兆洪,等.辨病辨证治疗肝硬化腹水47例[J].辽宁中医杂志,2004,31(6):473-474.
[31] 刘宏,贾彦,杨婧.膈下逐瘀汤对免疫性肝纤维化大鼠肝组织MMP-9和TIMP-2表达的影响[J].中华中医药杂志,2012,27(2):450-453.
[32] 杨婧,贾彦,刘宏,等.膈下逐瘀汤对大鼠纤维化肝组织α-SMA和TGF-β1表达的影响[J].中国中医基础医学杂志,2012,18(2):158-160.