双歧杆菌活菌制剂联合恩替卡韦治疗乙型肝炎肝硬化临床疗效的meta分析

Meta-analysis of the clinical efficacy of live bifidobacterium bacteria preparation combined with entecavir in the treatment of hepatitis B virus-related cirrhosis

目的系统评价双歧杆菌活菌制剂联合恩替卡韦治疗乙型肝炎肝硬化的疗效。方法计算机检索PubMed、Web of science、中国知网、万方数字化期刊、维普中文科技期刊等数据库,时间截至2020年10月。纳入双歧杆菌活菌制剂联合恩替卡韦治疗乙型肝炎肝硬化相关的随机对照临床试验进行统计分析。计数资料用相对危险度(RR)为效应量。计量资料采用均值差(MD)或标准化均数差(SMD)表示效应量。各效应量均计算95%可信区间(95%CI)。I2统计量和P值用来评估纳入文献的异质性,若I2≤50%,P>0.1,采用固定效应模型进行分析;否则使用随机效应模型进行分析进行meta分析。结果共纳入9篇文献865例患者,其中双歧杆菌活菌制剂联合恩替卡韦治疗组434例,恩替卡韦组431例。结果显示与恩替卡韦组相比,双歧杆菌活菌制剂联合恩替卡韦治疗组能明显降低患者肝纤维4项指标:血清透明质酸(HA)(SMD=-1.87 ng/ml,95%CI:-2.32~1.41,P<0.01)、层黏连蛋白(LN)(SMD=-1.62 ng/ml,95%CI:-2.04~1.19,P<0.01)、Ⅲ型前胶原肽(PC-Ⅲ)(SMD=-0.98,95%CI:-1.26~0.7,P<0.01)、Ⅳ型胶原(Ⅳ-C)(SMD=-1.14 ng/ml,95%CI:-1.73~0.55,P<0.01),降低患者门静脉内径(SMD=-0.91 mm,95%CI:-1.27~0.55,P<0.01)和脾脏厚度(MD=-3.26mm,95%CI:-3.95~2.58,P<0.01),但2组患者的乙型肝炎病毒DNA阴转率差异无统计学意义。结论与恩替卡韦治疗组相比,双歧杆菌活菌制剂联合恩替卡韦治疗可以显著改善乙型肝炎肝硬化患者的肝硬化程度,提高临床疗效。

Objective To systematically evaluate the efficacy of live Bifidobacterium preparations combined with entecavir in the treatment of hepatitis B virus-related cirrhosis.Methods PubMed,Web of Science,CNKI,Wanfang,VIP,and other databases were searched electronically until October 2020.Randomized controlled clinical trials in the treatment of hepatitis B virus-related cirrhosis with live Bifidobacterium preparations combined with entecavir were included for statistical analysis.The relative risk(RR)was used as the effect size for the count data.Measurement data were expressed as mean difference(MD)or standardized mean difference(SMD)to represent the effect size.95%confidence intervals(95%CI)were calculated for each effect size.The I2 statistic and P-values were used to evaluate the heterogeneity of the included literature.The fixed effect model was used for analysis if I2≤50%,P>0.1;otherwise,the random effect model was used for meta-analysis.Results A total of 865 patients from nine studies were included.Among them,434 cases were in the live Bifidobacterium preparation combined with the entecavir treatment group and 431 cases in the entecavir group.The results showed that compared with the entecavir group,the live bifidobacterium preparation combined with the entecavir treatment group had significantly reduced the four indicators of liver fibrosis:serum hyaluronic acid(HA)(SMD=-1.87 ng/ml,95%CI:-2.32~1.41,P<0.01),laminin(LN)(SMD=-1.62 ng/ml,95%CI:-2.04~1.19,P<0.01),type III procollagen peptide(PC-III)(SMD=-0.98,95%CI:-1.26~0.7,P<0.01),type IIIcollagen(III-C)(SMD=-1.14 ng/ml,95%CI:-1.73~0.55,P<0.01),portal vein diameter(SMD=-0.91 mm,95%CI:-1.27~0.55,P<0.01)and spleen thickness(MD=-3.26mm,95%CI:-3.95~2.58,P<0.01).However,there was no statistically significant difference in the negative conversion rate of hepatitis B virus DNA(HBV DNA)between the two groups of patients.Conclusion Compared to the entecavir treatment group,the live Bifidobacterium preparation combined with entecavir showed apparent severity improvement and enhanced clinical efficacy in patients with hepatitis B virus-related cirrhosis.