益生菌制剂治疗肝硬化的meta分析
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摘要
背景:肠道菌群失调在肝硬化及其并发症的发生中起重要作用。近年来益生菌制剂在肝硬化治疗中的应用引起了广泛关注。目的:评价益生菌制剂治疗肝硬化的疗效。方法:检索PubMed、Springer Link、Wiley Online Library、MEDLINE、Web of Science、The Cochrane Library以及CNKI、维普、万方数据库,选取关于益生菌制剂治疗肝硬化的随机对照试验(RCTs),应用RevMan 5.1软件进行meta分析。二分类变量和连续变量分别采用相对危险度(RR)和加权均数差(WMD)或标准化均数差(SMD)进行评估。结果:共27项RCTs满足纳入和排除标准。与对照组相比,益生菌制剂可显著降低肝硬化患者的外周血ALT(WMD=15.08,95%CI:6.67~23.49,P=0.000 4)、AST(WMD=5.24,95%CI:0.75~9.73,P=0.02)水平和血氨(SMD=0.35,95%CI:0.16~0.54,P=0.000 3)、内毒素(SMD=0.75,95%CI:0.55~0.96,P<0.000 01)含量,升高血清白蛋白水平(WMD=0.97,95%CI:0.47~1.48,P=0.000 1),缩短数字连接试验(NCT)反应时间(WMD=24.03,95%CI:4.06~44.00,P=0.02),降低肝性脑病(HE)(RR=0.48,95%CI:0.26~0.89,P=0.02)和自发性细菌性腹膜炎(SBP)(RR=0.53,95%CI:0.38~0.74,P=0.000 2)发生率。对肝硬化合并HE的亚组分析显示,益生菌制剂可显著降低HE患者的血氨和内毒素含量。结论:益生菌制剂可明显改善肝硬化患者的临床症状和生化指标,降低HE和SBP的发生风险,对肝硬化合并HE有明显治疗作用。
Background;Alteration of intestinal flora is considered playing a key role in disease progression and development of complications in liver cirrhosis.Therefore,probiotics have attracted wide attention in the treatment of liver cirrhosis.Aims.- To evaluate the efficacy of probiotics in the treatment of liver cirrhosis.Methods;PubMed,Springer Link,Wiley Online Library,MEDLINE,Web of Science and The Cochrane Library,as well as CNKI,CQVIP and Wanfang Database were searched to retrieve the randomized controlled trials(RCTs) evaluating the efficacy of probiotics in treating liver cirrhosis.Meta analysis was performed by using RevMan 5.1 software.Categorical variables and continuous variables were assessed by relative risk(RR) and weighted mean difference(WMD) or standardized mean difference(SMD),respectively.Results;Twenty-seven RCTs fulfilling the inclusion and exclusion criteria were enrolled.Compared with the control group,probiotics significantly decreased peripheral levels of ALT(WMD = 15.08,95%CI;6.67-23.49,P =0.000 4),AST(WMD =5.24,95%CI:0.75-9.73,P = 0.02),ammonia(SMD =0.35,95%CI:0.16-0.54,P =0.0003) and endotoxin(SMD = 0.75,95%CI:0.55-0.96,P <0.000 01),raised serum albumin level(WMD = 0.97,95%CI;0.47-1.48,P =0.000 1),shortened completion time of number connection test(NCT)(WMD =24.03,95%CI:4.06-44.00,P=0.02),and reduced morbidities of hepatic encephalopathy(HE)(RR=0.48,95%CI;0.26-0.89,P=0.02) and spontaneous bacterial peritonitis(SBP)(RR=0.53,95%CI:0.38-0.74,P = 0.000 2) in cirrhotic patients.Subgroup analysis showed that probiotics significantly reduced ammonia and endotoxin levels in cirrhotic patients complicated with HE.Conclusions:Probiotics is effective for improving clinical and biochemical parameters and decreasing risks of HE and SBP in cirrhotic patients,and is significantly beneficial for patients complicated with HE.
Background;Alteration of intestinal flora is considered playing a key role in disease progression and development of complications in liver cirrhosis.Therefore,probiotics have attracted wide attention in the treatment of liver cirrhosis.Aims.- To evaluate the efficacy of probiotics in the treatment of liver cirrhosis.Methods;PubMed,Springer Link,Wiley Online Library,MEDLINE,Web of Science and The Cochrane Library,as well as CNKI,CQVIP and Wanfang Database were searched to retrieve the randomized controlled trials(RCTs) evaluating the efficacy of probiotics in treating liver cirrhosis.Meta analysis was performed by using RevMan 5.1 software.Categorical variables and continuous variables were assessed by relative risk(RR) and weighted mean difference(WMD) or standardized mean difference(SMD),respectively.Results;Twenty-seven RCTs fulfilling the inclusion and exclusion criteria were enrolled.Compared with the control group,probiotics significantly decreased peripheral levels of ALT(WMD = 15.08,95%CI;6.67-23.49,P =0.000 4),AST(WMD =5.24,95%CI:0.75-9.73,P = 0.02),ammonia(SMD =0.35,95%CI:0.16-0.54,P =0.0003) and endotoxin(SMD = 0.75,95%CI:0.55-0.96,P <0.000 01),raised serum albumin level(WMD = 0.97,95%CI;0.47-1.48,P =0.000 1),shortened completion time of number connection test(NCT)(WMD =24.03,95%CI:4.06-44.00,P=0.02),and reduced morbidities of hepatic encephalopathy(HE)(RR=0.48,95%CI;0.26-0.89,P=0.02) and spontaneous bacterial peritonitis(SBP)(RR=0.53,95%CI:0.38-0.74,P = 0.000 2) in cirrhotic patients.Subgroup analysis showed that probiotics significantly reduced ammonia and endotoxin levels in cirrhotic patients complicated with HE.Conclusions:Probiotics is effective for improving clinical and biochemical parameters and decreasing risks of HE and SBP in cirrhotic patients,and is significantly beneficial for patients complicated with HE.
引文
1 Guerrero Hernandez I,Torre Delgadillo A,Vargas Vorackova F,et al.Intestinal flora,probiotics,and cirrhosis f J].Ann Hepatol,2008,7(2):120-124.
2 Bajaj JS,Saeian K,Christensen KM,et al.Probiotic yogurt for the treatment of minimal hepatic encephalopathy[J].Am J Gastroenterol,2008,103(7):1707-1715.
3 Liu Q,Duan ZP,Ha DK,et al.Synbiotic modulation of gut flora;effect on minimal hepatic encephalopathy in patients with cirrhosis[J].Hepatology,2004,39(5):1441-1449.
4 Malaguarnera M,Gargante MP,Malaguarnera G,et al.Bifidobacterium combined with fructo-oligosaccharide versus lactulose in the treatment of patients with hepatic encephalopathy[J].Eur J Gastroenterol Hepatol,2010,22(2):199-206.
5 Mittal W,Sharma BC,Sharma P,et al.A randomized controlled trial comparing lactulose,probiotics,and Lomithine L-aspartate in treatment of minimal hepatic encephalopathy[J].Eur J Gastroenterol Hepatol,2011,23(8):725-732.
6 Pande C,Kumar A,Sarin SK.Addition of probiotics to norfloxacin does not improve efficacy in the prevention of spontaneous bacterial peritonitis:a double-blind placebocontrolled randomized-controlled trial[J].Eur J Gastroenterol Hepatol,2012,24(7):831-839.
7 Pereg D,Kotliroff A,Gadoth N,et al.Probiotics for patients with compensated liver cirrhosis;a double-blind placebocontrolled study[J].Nutrition,2011,27(2):177-181.
8 Saji S,Kumar S,Thomas V.A randomized double blind placebo controlled trial of probiotics in minimal hepatic encephalopathy[J].Trop Gastroenterol,2011,32(2):128-132.
9 Sharma P,Sharma BC,Puri V,et al.An open-label randomized controlled trial of lactulose and probiotics in the treatment of minimal hepatic encephalopathy[J].Eur J Gastroenterol Hepatol,2008,20(6):506-511.
10 Zhao HY,Wang HJ,Lu Z,et al.Intestinal microflora in patients with liver cirrhosis[J].Chin J Dig Dis,2004,5(2):64-67.
11刘旭华,何伟锋,翁伟君.益生菌在自发性细菌性腹膜炎中的应用[J].中国医药导报,2010,7(23):27-28.
12刘晚珍.美常安对肝硬化内毒素血症及肝性脑病的作用[J].中国厂矿医学,2009,22(3):296-297.
13叶瑞华,叶子,阮冰.培菲康对肝硬化患者内毒素、血氨水平以及数字连接试验的影响[J].中国微生态学杂志,2006,18(3):245-246.
14吴晨曲.肠道益生菌对肝硬化患者肠道屏障及肝功能状态的影响[D].上海:上海交通大学,2008.
15周红宇,周国华,陈叶青,等.益生菌预防肝硬化自发性腹膜炎的疗效[J].实用药物与临床,2011,14(4):292-294.
16宋家锋,严荣华,刘建辉.益生菌防治自发性细菌性腹膜炎的疗效观察[J].胃肠病学和肝病学杂志,2004,13(2):150.
17宋爱玲,江海,郭玉婷.调整肠道菌群对肝硬化患者血浆内毒素及肝功能的影响[J].胃肠病学和肝病学杂志,2010,19(8):746-748.
18庄见齐.益生菌治疗肝硬化高血氨症38例临床观察[J].临床和实验医学杂志,2009,8(9):81,84.
19李书印.益生菌治疗肝硬化肠屏障功能障碍的初步临床研究[J].中国社区医师·医学专业半月刊,2009,11(18):62.
20李咏梅,贺俊花.益生菌预防肝硬化自发性腹膜炎疗效观察[J].中国误诊学杂志,2009,9(3):576-577.
21杨莉丽,邹兵,王俊萍,等.乳果糖和益生菌制剂预防肝性脑病的临床疗效观察[J].中国医药导报,2011,8(22):75-76.
22潘小娟,黄月霞.双歧三联活菌胶囊对肝硬化患者血浆内毒素和炎症因子的影响[J].中国药物与临床,2011,11(9):1056-1057.
23范妮,田字彬,孔心涓,等.益生菌对肝硬化患者肠黏膜通透性的影响[J].世界华人消化杂志,2009,17(36):3745-3748.
24蔡丽蓉,王雯.地衣芽孢杆菌治疗肝硬化并自发性细菌性腹膜炎的临床疗效研究[J].中国微生态学杂志,2012,24(1):49-51.
25谢凯元,吕小萍.口服酪酸梭菌活菌片对肝硬化患者肠道通透性的影响[J].中国药物与临床,2011,11(11):1314-1315.
26陈诗焕.益生菌制剂对预防和治疗肝硬化患者发生并发症的影响[J].中国微生态学杂志,2008,20(3):277.
27 Schnabl B.Linking intestinal homeostasis and liver disease[J].Curr Opin Gastroenterol,2013,29(3):264-270.
28 Mangell P,Nejdfors P,Wang M,et al.Lactobacillus plantarum299v inhibits Escherichia coli-induced intestinal permeability[J].Dig Dis Sci,2002,47(3):511-516.
29 Chiva M,Soriano G,Rochat I,et al.Effect d Lactobacillus johnsonii La1 and antioxidants on intestinal flora and bacterial translocation in rats with experimental cirrhosis[J].J Hepatol,2002,37(4):456-162.
30 Shukla S,Shukla A,Mehboob S,et al.Meta-analysis:the effects of gut flora modulation using prebiotics,probiotics and synbiotics on minimal hepatic encephalopathy[J].Aliment Pharmacol Ther,2011,33(6):662-671.
2 Bajaj JS,Saeian K,Christensen KM,et al.Probiotic yogurt for the treatment of minimal hepatic encephalopathy[J].Am J Gastroenterol,2008,103(7):1707-1715.
3 Liu Q,Duan ZP,Ha DK,et al.Synbiotic modulation of gut flora;effect on minimal hepatic encephalopathy in patients with cirrhosis[J].Hepatology,2004,39(5):1441-1449.
4 Malaguarnera M,Gargante MP,Malaguarnera G,et al.Bifidobacterium combined with fructo-oligosaccharide versus lactulose in the treatment of patients with hepatic encephalopathy[J].Eur J Gastroenterol Hepatol,2010,22(2):199-206.
5 Mittal W,Sharma BC,Sharma P,et al.A randomized controlled trial comparing lactulose,probiotics,and Lomithine L-aspartate in treatment of minimal hepatic encephalopathy[J].Eur J Gastroenterol Hepatol,2011,23(8):725-732.
6 Pande C,Kumar A,Sarin SK.Addition of probiotics to norfloxacin does not improve efficacy in the prevention of spontaneous bacterial peritonitis:a double-blind placebocontrolled randomized-controlled trial[J].Eur J Gastroenterol Hepatol,2012,24(7):831-839.
7 Pereg D,Kotliroff A,Gadoth N,et al.Probiotics for patients with compensated liver cirrhosis;a double-blind placebocontrolled study[J].Nutrition,2011,27(2):177-181.
8 Saji S,Kumar S,Thomas V.A randomized double blind placebo controlled trial of probiotics in minimal hepatic encephalopathy[J].Trop Gastroenterol,2011,32(2):128-132.
9 Sharma P,Sharma BC,Puri V,et al.An open-label randomized controlled trial of lactulose and probiotics in the treatment of minimal hepatic encephalopathy[J].Eur J Gastroenterol Hepatol,2008,20(6):506-511.
10 Zhao HY,Wang HJ,Lu Z,et al.Intestinal microflora in patients with liver cirrhosis[J].Chin J Dig Dis,2004,5(2):64-67.
11刘旭华,何伟锋,翁伟君.益生菌在自发性细菌性腹膜炎中的应用[J].中国医药导报,2010,7(23):27-28.
12刘晚珍.美常安对肝硬化内毒素血症及肝性脑病的作用[J].中国厂矿医学,2009,22(3):296-297.
13叶瑞华,叶子,阮冰.培菲康对肝硬化患者内毒素、血氨水平以及数字连接试验的影响[J].中国微生态学杂志,2006,18(3):245-246.
14吴晨曲.肠道益生菌对肝硬化患者肠道屏障及肝功能状态的影响[D].上海:上海交通大学,2008.
15周红宇,周国华,陈叶青,等.益生菌预防肝硬化自发性腹膜炎的疗效[J].实用药物与临床,2011,14(4):292-294.
16宋家锋,严荣华,刘建辉.益生菌防治自发性细菌性腹膜炎的疗效观察[J].胃肠病学和肝病学杂志,2004,13(2):150.
17宋爱玲,江海,郭玉婷.调整肠道菌群对肝硬化患者血浆内毒素及肝功能的影响[J].胃肠病学和肝病学杂志,2010,19(8):746-748.
18庄见齐.益生菌治疗肝硬化高血氨症38例临床观察[J].临床和实验医学杂志,2009,8(9):81,84.
19李书印.益生菌治疗肝硬化肠屏障功能障碍的初步临床研究[J].中国社区医师·医学专业半月刊,2009,11(18):62.
20李咏梅,贺俊花.益生菌预防肝硬化自发性腹膜炎疗效观察[J].中国误诊学杂志,2009,9(3):576-577.
21杨莉丽,邹兵,王俊萍,等.乳果糖和益生菌制剂预防肝性脑病的临床疗效观察[J].中国医药导报,2011,8(22):75-76.
22潘小娟,黄月霞.双歧三联活菌胶囊对肝硬化患者血浆内毒素和炎症因子的影响[J].中国药物与临床,2011,11(9):1056-1057.
23范妮,田字彬,孔心涓,等.益生菌对肝硬化患者肠黏膜通透性的影响[J].世界华人消化杂志,2009,17(36):3745-3748.
24蔡丽蓉,王雯.地衣芽孢杆菌治疗肝硬化并自发性细菌性腹膜炎的临床疗效研究[J].中国微生态学杂志,2012,24(1):49-51.
25谢凯元,吕小萍.口服酪酸梭菌活菌片对肝硬化患者肠道通透性的影响[J].中国药物与临床,2011,11(11):1314-1315.
26陈诗焕.益生菌制剂对预防和治疗肝硬化患者发生并发症的影响[J].中国微生态学杂志,2008,20(3):277.
27 Schnabl B.Linking intestinal homeostasis and liver disease[J].Curr Opin Gastroenterol,2013,29(3):264-270.
28 Mangell P,Nejdfors P,Wang M,et al.Lactobacillus plantarum299v inhibits Escherichia coli-induced intestinal permeability[J].Dig Dis Sci,2002,47(3):511-516.
29 Chiva M,Soriano G,Rochat I,et al.Effect d Lactobacillus johnsonii La1 and antioxidants on intestinal flora and bacterial translocation in rats with experimental cirrhosis[J].J Hepatol,2002,37(4):456-162.
30 Shukla S,Shukla A,Mehboob S,et al.Meta-analysis:the effects of gut flora modulation using prebiotics,probiotics and synbiotics on minimal hepatic encephalopathy[J].Aliment Pharmacol Ther,2011,33(6):662-671.