益生菌对化疗相关性腹泻防治作用的Meta分析

Probiotics in the Prevention and Treatment of Chemotherap-induced Diarrhea: A Meta analysis

目的:采用Meta分析方法评价益生菌防治化疗相关性腹泻(CID)的安全性、有效性,以及对肠黏膜屏障的保护、修复作用。方法:计算机检索Cochrane Library、Pub Med、Embase、CNKI、VIP、Wan Fang Data,检索时限均为建库至2017年8月31日,全面查找收集益生菌预防和治疗化疗相关性腹泻的随机对照试验(RCTs),提取资料并根据Cochrane工作手册5.0.1版本推荐的"偏倚风险评估"工具对纳入的研究进行偏倚风险评价,采用Stata 12统计软件进行Meta分析。结果:共纳入20个RCTs,包括1 727例患者。Meta分析结果显示,与仅给予常规支持/对症治疗的对照组比较,使用益生菌联合常规支持/对症治疗可以降低CID的总发生率[OR=0.26,95%CI(0.19,0.35),P<0.000 1]和Ⅲ级以上严重CID发生率[OR=0.28,95%CI(0.16,0.52),P<0.000 1],提高治疗CID患者的总有效率[OR=4.25,95%CI(2.78,6.48),P<0.000 1]和显效率[OR=2.16,95%CI(1.60,2.91),P<0.000 1],减少腹泻天数[SMD=-3.57,95%CI(-5.85,-1.29),P=0.002],降低患者血清内毒素[SMD=-0.95,95%CI(-1.21,-0.68),P<0.000 1]、二胺氧化酶[SMD=-1.52,95%CI(-2.73,-0.31),P<0.000 1]、D-乳酸[SMD=-1.92,95%CI(-2.29,-1.55),P<0.000 1]和肿瘤坏死因子-α[SMD=-1.13,95%CI(-1.55,-0.70),P<0.000 1]。结论:化疗前使用益生菌制剂可以有效减少癌症患者CID的发生率;在已发生CID患者的治疗中,辅助使用益生菌制剂可以提高CID治疗的效果,同时可以降低肠黏膜通透性,保护和修复肠黏膜的屏障作用。受纳入研究数量和质量的限制,上述结论尚待更多高质量研究予以验证。

Objective ： To systemically assess the security and efficacy of probiotics in the prevention and treatment of chemotherapy-induced diarrhea （ CID）, as well as the protective and repair effects on intestinal mucosal barrier. Methods：Cochrane Library, PubMed, Embase, CNKI, VIP and WanFang Data were electronically searched up to August 31st 2017. Randomized controlled trials （RCTs） of probiotics for prevention and treatment of chemotherapy-associated diarrhea was comprehensively collected. Extracted relevant material and the bias of the included literature was evaluated methodologically according to the ＂ risk bias assessment＂ tool recommended in the Cochrane manual of version 5.0.1. And the Meta analysis was carried out with Stata 12 statistical software. Results ：A total of 20 RCTs were included, including 1727 pa- tients. Meta analysis showed that compared with the control group, probiotics group could reduce the incidence of CID [ OR =0.26, 95%CI（0.19, 0.35）, P 〈 0.000 1 ] and severe CID in grade Ⅲ and above [OR =0.28, 95% CI（0. 16, 0.52）, P 〈0. 0001 ], improving the total effective rate [ OR =4.25, 95% CI（2.78, 6.48）, P 〈0.000 1] and markedly effective rate of CID patients [ OR = 2.16, 95% CI（ 1.60, 2.91 ）, P 〈 0. 000 1 ] ; reducing the number of diarrhea days [SMD= -3.57, 95%CI（ -5.85, -1.29）, P=0.002]; and reducing serumET [SMD= -0.95, 95%C1 （ -1.21, -0.68）, P〈0.000 1], DAO [SMD= -1.52, 95%CI（-2.73,-0.31）, P〈0.000 1], D-lactate [SMD= -1.92, 95%CI（-2.29, -1.55）,P〈0.000 1] andTNF-α [SMD= -1.13,95%CI（-1.55,-0.70）,P〈0.000 1]. Con- clusion：The incidence of CID in cancer patients could be effectively reduced by taking probiotics before chemotherapy. In the treatment of patients with CID, adjuvant use of probiotics could improve the efficacy of CID treatment, at meanwhile, could reduce the permeability of intestinal mucosa, protecting and repairing the barrier of intestinal mucosa. Due to limitedquantity and quality of the included studies, more high quality studies were need to verify above conclusions.