益生菌对轻微肝性脑病疗效的Meta分析

Efficacy of probiotics on minimal hepatic encephalopathy:a Meta-analysis

目的系统评价益生菌治疗轻微肝性脑病(minimal hepatic encephalopathy,MHE)的有效性。方法计算机检索PubMed、EMbase、Cochrane Central Register of Controlled Trials、中国知网、万方、中国生物医学文献数据库和维普数据库,检索益生菌制剂治疗MHE的随机对照试验(randomized controlled trial,RCT),检索时限均为建库至2020年7月26日。检索美国临床试验注册平台(ClinicalTrials.gov)进行文献补充。由2名研究人员独立筛选文献、提取数据、评价纳入研究的偏倚风险,采用RevMan 5.3进行Meta分析。结果共纳入13篇RCT,Meta分析表明益生菌治疗组在降低血氨水平(SMD=-0.79,95%CI:-1.20~-0.37,P=0.0002)、缩短数字连接试验-A型(number connection test-type A,NCT-A)反应时间(MD=-16.31,95%CI:-22.09~-10.53,P<0.001)、降低显性肝性脑病发生率(RR=-0.26,95%CI:0.12~0.56,P=0.0007)、提高MHE逆转率(RR=1.48,95%CI:1.11~1.97,P=0.008)和提高数字符号试验(digit symbol test,DST)分数(SMD=0.61,95%CI:0.35~0.86,P<0.001)方面均显著优于对照组。益生菌治疗组与对照组的内毒素水平(SMD=-0.58,95%CI:-2.29~1.13,P=0.51)和丙氨酸氨基转移酶水平(MD=-36.18,95%CI:-86.65~14.29,P=0.16)差异均无统计学意义。结论益生菌可改善MHE患者认知功能,提高MHE逆转率,降低显性肝性脑病发生率,有望成为临床治疗MHE的新选择。

Objective To systematically evaluate the effects of probiotics in treatment of minimal hepatic encephalopathy(MHE).Methods PubMed,EMbase,The Cochrane Central Register of Controlled Trials,CNKI,Wanfang,CBM and Viper databases were electronically searched to collect randomized controlled trial(RCT)of the treatment of MHE by probiotics from inception to July 26th,2020.US clinical trial registration platform(ClinicalTrials.gov)was also searched for supplementary literature.Two reviewers screened literature,extracted data and assessed the risk of bias of included studies independently.Meta-analysis was performed by RevMan 5.3 software.Results A total of 13 RCT were included.The results of Meta-analysis indicated that probiotics treatment group was superior to control group on blood ammonia level(SMD=-0.79,95%CI:-1.20~-0.37,P=0.0002),time of number connection test-type A(NCT-A)(MD=-16.31,95%CI:-22.09~-10.53,P<0.001),incidence of overt hepatic encephalopathy(RR=-0.26,95%CI:0.12~0.56,P=0.0007),reversal rate of MHE(RR=1.48,95%CI:1.11~1.97,P=0.008)and score of digital symbol test(DST)(SMD=0.61,95%CI:0.35~0.86,P<0.001).There were no significant differences in endotoxin level(SMD=-0.58,95%CI:-2.29~1.13,P=0.51)and the alanine transaminase(ALT)level(MD=-36.18,95%CI:-86.65~14.29,P=0.16)of patients between two groups.Conclusions Probiotics can improve cognitive function of patients with MHE,increase the reversal rate of MHE and reduce the incidence of overt hepatic encephalopathy,which may become a new measure of clinical treatment in future.