益生菌对轻微型肝性脑病患者显性肝性脑病发生率影响的Meta分析

姚俞昊; 张嘉鑫; 夏潇; 朱顺; 李小科; 叶永安

doi:10.3969/j.issn.1001-5256.2022.11.013

益生菌对轻微型肝性脑病患者显性肝性脑病发生率影响的Meta分析

DOI: 10.3969/j.issn.1001-5256.2022.11.013

姚俞昊^{1, 2},
张嘉鑫^{2, 3},
夏潇⁴,
朱顺²,
李小科^{2, 3, , ,},
叶永安^{2, 3, , ,}

1.
北京中医药大学第一临床医学院，北京 100029
2.
北京中医药大学东直门医院，北京 100700
3.
北京中医药大学中医肝病研究院，北京 100700
4.
中国中医科学院广安门医院，北京 100053

基金项目:

国家自然科学基金项目 (82174341);

国家中医药管理局科研基金项目 (JDZX2015300);

北京中医药大学新教师启动基金项目 (2022-JYB-XJSJJ-050)

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：叶永安、李小科对研究思路、设计有关键贡献；姚俞昊起草了文章；姚俞昊、夏潇、朱顺参与了研究数据的获取分析解释过程；李小科、张嘉鑫对文章关键内容进行了修改。

详细信息

通信作者:
李小科，lixiaoke@vip.163.com

叶永安，yeyongan@vip.163.com

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出版历程
- 收稿日期: 2022-04-06
- 录用日期: 2022-05-10
- 出版日期: 2022-11-20

Effect of probiotics in preventing overt hepatic encephalopathy in patients with minimal hepatic encephalopathy: A Meta-analysis

Yuhao YAO^{1, 2},
Jiaxin ZHANG^{2, 3},
Xiao XIA⁴,
Shun ZHU²,
Xiaoke LI^{2, 3
, ,
,},
Yong'an YE^{2, 3
, ,
,}

1.
First School of Clinical Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
2.
Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
3.
Liver Diseases Academy of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100700, China
4.
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China

Research funding:

National Natural Science Foundation of China (82174341);

National Administration of Traditional Chinese Medicine Research Fund (JDZX2015300);

Beijing University of Traditional Chinese Medicine Start-up Fund (2022-JYB-XJSJJ-050)

More Information

Corresponding author: LI Xiaoke, lixiaoke@vip.163.com(ORCID: 0000-0002-1775-3063); YE Yong'an, yeyongan@vip.163.com(ORCID: 0000-0001-9765-4665)

摘要

摘要: 目的评价使用益生菌干预对轻微型肝性脑病患者显性肝性脑病发生率的影响。方法本研究根据PRISMA指南完成，PROSPERO注册号为CRD42022303995。检索PubMed、Web of Science、Cochrane Library、知网、万方数据库，收集建库至2021年11月有关益生菌干预治疗轻微型肝性脑病的研究。用RevMan 5.4进行Meta分析，不能合并的数据采用描述性分析。选择危险比(RR)和95%CI作为汇总指标。结果共纳入6篇文献，均为随机对照研究，共404例轻微型肝性脑病患者。结果表明益生菌干预可使轻微型肝性脑病患者显性肝性脑病的发生率降低54%(RR=0.46，95%CI：0.26~0.81，P=0.007)，并且能增加轻微型肝性脑病患者疾病的逆转率(RR=4.94，95%CI：2.82~8.66，P＜0.000 01)。结论益生菌能够降低轻微型肝性脑病患者显性肝性脑病的发生率，增加轻微型肝性脑病的逆转率，对轻微型肝性脑病患者预防显性肝性脑病的发生具有积极意义，为益生菌治疗轻微型肝性脑病提供了新的证据。
- 肝性脑病 /
- 益生菌 /
- Meta分析
Abstract: Objective To review and analyze the effect of probiotics in preventing the overt hepatic encephalopathy (OHE) in patients with minimal hepatic encephalopathy (MHE). Methods Studies about this subject were searched in PubMed, Web of Science, Cochrane Library, Chinese journal full-text database (CNKI), WanFang data knowledge service platform (WanFang Data) from their establishment to November 2021. Meta-analysis was performed using RevMan 5.4. Description analysis was used for data that could not be pooled. The relative risk (RR) and 95% confidence interval (CI) were used to present pooled data. Results Six RCT studies with a total of 404 patients were included in this meta-analysis. The results showed probiotics users had a significant reduction of the OHE incidence, as compared with the controls (RR=0.46, 95%CI: 0.26 - 0.81; P=0.007), but an increase in the reversal MHE rate (RR=4.94, 95%CI: 2.82-8.66; P < 0.000 01). Conclusion This finding demonstrated that probiotics were able to effectively reduce the OHE incidence and improve the reversal MHE rate in the patients with MHE. This study could provide novel evidence for probiotics treatment of MHE.
- Hepatic Encephalopathy /
- Probiotics /
- Meta-Analysis

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图 1 文献筛选流程

Figure 1. Flowchart of selection of trials

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图 2 质量评价结果

Figure 2. Methodological quality of the included trials

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图 3 益生菌与MHE患者OHE发生率的Meta分析结果

Figure 3. Incidence of OHE with the treatment of probiotics or controlled

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图 4 益生菌与MHE患者逆转率的Meta分析结果

Figure 4. Reversal of MHE with the treatment of probiotics or controlled

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表 1 纳入文献的基本特征

Table 1. Characteristics of the included trials

纳入研究及时间	干预措施			研究时间	结局指标
罗兰^[19](2019)	干预组：枯草杆菌二联活菌肠溶胶囊250 mg/粒，2粒，3次/d 对照组：肝硬化常规治疗			4周	①③④⑤⑧⑨ B11
Bajaj等^[14](2014)	干预组：乳酸菌(＞5×10¹⁰ CFU/g) 对照组：安慰剂			8周	①③④⑥⑦⑩ B11
Vlachogiannakos等^[18](2014)	干预组：乳酸菌对照组：安慰剂			12周	①②③④
Lunia等^[15](2013)	干预组：益生菌(1.1×10¹¹ CFU/粒) 1粒，3次/d 对照组：无治疗			12周	①②③④
Mittal等^[17](2011)	干预组：益生菌(1.1×10¹¹ CFU)次/d 对照组：肝硬化常规治疗			12周	①②③④⑦
Bajaj等^[13](2008)	干预组：酸奶12盎司/d 对照组：无治疗			8周	①②③④⑥⑦⑧⑨

纳入研究及时间	地区	研究类型	研究人数(E∶C)	MHE诊断指标
罗兰^[19](2019)	中国	RCT	109(56∶53)	NCT、DST
Bajaj等^[14](2014)	美国	RCT	37(18∶19)	NCT、DST、BDT
Vlachogiannakos等^[18](2014)	希腊	RCT	72(37∶35)	NCT、BEAP
Lunia等^[15](2013)	印度	RCT	81(42∶39)	PHES≤5
Mittal等^[17](2011)	印度	RCT	80(40∶40)	NCT、FCT
Bajaj等^[13](2008)	美国	RCT	25(17∶8)	NCT、BDT、DST
注：E，干预组；C，对照组；NCT，数字连接测试；DST，数字符号试验；BDT，block design test；PHES，HE智力测试评分；BEAP，brainstem auditory evoked potentials；FCT，figure connection test。结局指标包括①OHE发生率；②MHE逆转率；③神经心理学测试；④血氨；⑤ALT、AST；⑥炎性指标；⑦生活质量；⑧Child-Pugh评分；⑨MELD评分；⑩肠道菌群；B11不良事件发生。

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表 2 OHE发生率的亚组分析

Table 2. Summary of subgroup analysis of OHE incidence

亚组	研究数目	RR(95%CI)	异质性		P值
亚组	研究数目	RR(95%CI)	P值	I²值	P值
地域					0.36
东方^{[15, 17, 19]}	3	0.55(0.28~1.05)	0.55	0
西方^{[13-14, 18]}	3	0.29(0.09~0.92)	0.76	0
益生菌使用时间					0.75
≤8周^{[13-14, 19]}	3	0.56(0.16~1.94)	0.82	0
8~12周^{[15, 17-18]}	3	0.44(0.23~0.83)	0.48	0

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