索菲布韦、雷迪帕韦联合或者不联合利巴韦林治疗基因1型慢性丙型肝炎患者安全性及疗效的Meta分析

发布时间：2018-06-06 04:26

本文选题：索菲布韦 + 雷迪帕韦　；参考：《昆明医科大学》2017年硕士论文

【摘要】：[目的]通过Meta分析对比索菲布韦、雷迪帕韦联合或者不联合利巴韦林两种治疗方案对基因1型慢性丙型肝炎患者的安全性和疗效。[方法]选择 PubMed、SpringerLink、EMBASE、The Cochrane Library、Medline、Science Direct数据库进行检索,时间从2013年12月至2016年11月,收集随机对照试验中包含索菲布韦、雷迪帕韦两联组(LED+SOF)以及索菲布韦、雷迪帕韦、利巴韦林三联组(LED+SOF+RBV)治疗基因1型慢性丙型肝炎(CHC)患者对比的相关文献,并收集相关数据,进行质量评价,使用RevMan 5.0软件对其进行Meta分析。主要结局指标持续病毒学应答率(SVR12,既在治疗结束后12周HCVRNA不可测)、不良反应发生率,次要结局指标有病毒反弹和突破率、因不良反应引起的停药率以及5种常见不良反应的发生率。[结果]纳入了 7个研究,总共包括2626名基因1型CHC患者。1、比较LED+SOF组与LED+SOF+RBV组SVR12无明显统计学差异(RR=1.00,95%CI 0.99～1.01,P=0.99),在亚组分析中 LED+SOF+RBV 组较 LED+SOF组治疗 8 周(RR=1.00,95%CI0.96～1.05,P=0.87)、12 周(RR=0.99,95%CI 0.97～1.01,P=0.53)、24 周(RR=0.99,95%CI0.97～1.01,P=0.49)SVR12 无明显升高,联合或者不联合RBV对于初治无肝硬化患者(RR=1.03,95%CI 0.99～1.07,P=0.20)和经治有肝硬化患者(RR=0.99,95%CI 0.93～1.05,P=0.66)SVR12无明显差异。2、比较LED+SOF组与LED+SOF+RBV组病毒反弹和突破率无明显统计学差异(RR=1.35,95%CI 0.81～2.25,P=0.25)。在亚组分析中 LED+SOF+RBV 组较LED+SOF 组治疗 8 周(RR=1.33,95%CI 0.58～3.02,P=0.50)、24 周(RR=1.51,95%CI0.25～9.05,P=0.65)病毒反弹和突破率无明显升高,但LED+SOF组在治疗12周的病毒反弹和突破率明显大于LED+SOF+RBV组(RR=2.32,95%CI 1.02～5.25,P=0.04)。联合或不联合RBV对于初治无肝硬化患者(RR=0.87,95%CI 0.40～1.91,P=0.93)及经治伴有肝硬化患者(RR=1.23,95%CI 0.50～3.03,P=0.66)在病毒反弹和突破发生率上无明显差异。3、LED+SOF+RBV组较LED+SOF组不良反应发生率明显升高(RR=0.88,95%CI0.84～0.92,P=0.00001)。4、LED+SOF+RBV组与LED+SOF组在因不良反应引起的停药率上无明显统计学差异(RR=0.67,95%CI 0.26-1.70,P=0.40)。5、LED+SOF组在疲乏、恶心、失眠、皮疹发生率上明显小于LED+SOF+RBV组(疲乏:RR=0.60,95%CI0.41～0.86,P=0.006;恶心:RR=0.51,95%CI 0.41-0.62,P0.00001;失眠:RR=0.43,95%CI 0.30-0.60,P0.00001;皮疹:RR=0.36,95%CI0.27～0.49,P0.00001),在头痛的发生率 LED+SOF 与LED+SOF+RBV治疗组之间无明显差异(RR=0.77,95%CI 0.59～1.02,P=0.07)。[结论]1.Meta结果显示LED+SOF在治疗基因1型慢性丙型肝炎患者的疗效并不次于LED+SOF+RBV,且在不同治疗时间、不同治疗背景下疗效相似,但在治疗12周时加上RBV有利于减少病毒反弹和突破发生率。2.LED+SOF+RBV组的不良反应发生率明显高于LED+SOF组。
[Abstract]:[objective] to compare the safety and efficacy of sofebuvir combined with or without ribavirin in patients with chronic hepatitis C type 1 by Meta analysis. [methods] the Cochrane Library Direct database was selected to search the Cochrane Library Direct from December 2013 to November 2016. The randomized controlled trials included Sofibuvir, Redipravir, Sofibuvir and Redipavir. The relative literature of ribavirin triple group in the treatment of chronic hepatitis C type 1 (CHC1) patients was compared, and the relevant data were collected, the quality was evaluated, and Meta was analyzed by RevMan 5.0 software. The main outcome measure was persistent virological response rate (SVR12). After 12 weeks of treatment, HCVRNA was undetectable, the incidence of adverse reactions and secondary outcome indicators were virus rebound and breakthrough rate. The withdrawal rate due to adverse reactions and the incidence of 5 common adverse reactions. [results] included in seven studies, A total of 2626 patients with type 1 CHC were included. There was no significant difference in SVR12 between the LED SOF group and the LED SOF RBV group. In the subgroup analysis, there was no significant increase in RRN 1.00 ~ 95CI0.965P0.8712 weeks in the LED SOF RBV group as compared with that in the LED SOF group. There was no significant difference between RBV combined with or without RBV in the initial treatment of cirrhotic patients with or without liver cirrhosis. There was no significant difference between the two groups. There was no significant difference in the rate of virus rebound and breakthrough between the LED SOF group and the LED SOF RBV group. There was no significant difference in the rate of virus rebound and breakthrough between the LED SOF group and the LED SOF RBV group (RRR1.35 / 95CI 0.81 / 2.25P0. 25) and that in the meridian liver cirrhosis patients (CI 0.931.05 / 95) was not significantly different from that in the control group (P = 0.25), and there was no significant difference between the LED SOF group and the LED SOF RBV group in the rate of virus rebound and breakthrough. In the subgroup analysis, there was no significant increase in the rebound and breakthrough rate of the virus in the LED SOF RBV group compared with that in the LED SOF group at 8 weeks after treatment (CI 0.583.02 ~ 0.50), but the rate of virus rebound and breakthrough in the LED SOF group at 12 weeks was significantly higher than that in the LED SOF RBV group (RRN 2.3295 CI 1.025.250.45). There was no significant difference in the incidence of virus rebound and breakthrough in patients with or without liver cirrhosis treated with or without RBV. The incidence of adverse reactions in the SOF RBV group was significantly higher than that in the LED SOF group. The incidence of adverse reactions in the SOF RBV group was significantly higher than that in the LED SOF group, and the incidence of adverse reactions was significantly higher in the patients with cirrhosis than in the LED SOF group (CI 0.40 1.91P0.93) and the patients with liver cirrhosis treated with CI 0.500.2395% CI 0.503.03P0.66). The incidence of adverse reactions in the 3LED SOF RBV group was significantly higher than that in the LED SOF group. The incidence of adverse reactions in the SOF RBV group was significantly higher than that in the LED SOF group. The incidence of adverse reactions was significantly higher in the SOF RBV group than in the LED SOF group. There was no significant difference between LED SOF group and LED SOF group in drug withdrawal rate caused by adverse reactions. The incidence of nausea, insomnia and rash in the LED SOF RBV group was significantly lower than that in the LED SOF RBV group. There was no significant difference in the incidence of headache between the LED SOF group and the LED SOF RBV treatment group (RR0.7795CI 0.597.95CI 0.30-0.60P0.00001; RRR 0.3795CI 0.300.60P0.00001; the incidence of headache between the LED SOF group and the LED SOF RBV treatment group was 0.59795CI 0.59795CI 0.59795CI 0.592P0.00001). [conclusion] 1.Meta results showed that the efficacy of LED SOF in the treatment of chronic hepatitis C type 1 was not inferior to that of LED SOF RBV,. But after 12 weeks of treatment, the incidence of adverse reactions in LED SOF RBV group was significantly higher than that in LED SOF group.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R512.63

【参考文献】