帕利普韦、利托那韦、奥比他韦、达沙布韦和/无利巴韦林治疗慢性HCV感染疗效及安全性的Meta分析

Efficacy and safety of Paritaprevir,Ritonavir,Ombitasvir,Dasabuvir with/without Ribavirin in treatment of chronic HCV infection: a Meta-analysis

目的探讨帕利普韦、利托那韦、奥比他韦、达沙布韦和/无利巴韦林治疗慢性丙型肝炎病毒(hepatitis C virus,HCV)感染的疗效及安全性。方法计算机检索2014年1月至2017年6月在Medline、Pub Med、CNKI全文数据库、万方数据库等公开发表的中、英文文献。采用Meta分析方法合并RR值及其95%CI。采用Q检验法分析各研究之间的异质性,对纳入的文献进行质量评价及数据提取,采用Rev Man 5.3统计软件进行Meta分析。结果共收集帕利普韦、利托那韦、奥比他韦、达沙布韦和/无利巴韦林治疗慢性HCV感染相关文献4篇,累计病例805例,其中PROD(帕利普韦、利托那韦、奥比他韦、达沙布韦)组共379例,PROD-R(帕利普韦、利托那韦、奥比他韦、达沙布韦、利巴韦林)组426例。对4项研究进行异质性检验,结果显示P>0.05,I2<56%,提示异质性不显著,采用固定效应模型。对比分析结果显示,PROD治疗慢性HCV感染12周可获得较高持续病毒学应答(SVR)发生率,加用利巴韦林后的疗效无显著提高(Z=0.18,P=0.85)。4项研究中共有3例发生病毒复发,均为GT1b型,均位于PROD-R组。PROD-R组治疗相关不良反应发生率与PROD组比较,差异有统计学意义(P<0.05)。普通不良事件中乏力、瘙痒、恶心、失眠、皮疹、烦躁发生率两组比较,差异有统计学意义(P<0.05)。实验室检验异常以贫血最为常见,其次是胆红素升高,差异有统计学意义(P<0.05)。结论 PROD治疗慢性HCV感染效果好,特别是GT1b型,加用利巴韦林疗效无显著提高,但不良反应明显增加;对于GT1a、GT4型慢性丙型肝炎(CHC)及肝硬化患者,由于本Meta分析所涉及病例较少,无法进行亚组分析,结果显示似乎没必要加用利巴韦林,需进一步资料积累分析。

Objective To investigate the efficacy and safety of Paritaprevir,Ritonavir,Ombitasvir,Dasabuvir with/without Ribavirin（ PROD ± R） in treatment of patients with chronic hepatitis C virus（ HCV） infection. Methods A literature search that combined terms and subject headings for hepatitis C with terms ＂Paritaprevir,Ritonavir,Ombitasvir or Dasabuvir＂was performed across Medline,Pub Med,CNKI and Wan Fang Data from Jan. 2014 to Jun. 2017.Rev Man 5. 3 was used to perfrom a Meta-analysis. Results Four literatures were selected and total 805 patients were involved,379 of them received Paritaprevir,Ritonavir,Ombitasvir,Dasabuvir（ PROD group）,426 cases received Paritaprevir,Ritonavir,Ombitasvir,Dasabuvir and Ribavirin（ PROD-R group）. There was no significant heterogeneity among four studies（ P〈0. 05,I2 56%） and fixed effect of analysis model was used. Rate of SVR12 achieved in PROD group was high enough,no significant improvement of antiviral efficiency was observed in PROD-R group（ Z =0. 18,P = 0. 85）. Only 3 patients were observed having viral relapse,all of them were genotype 1 b in PROD-R group.The pooled incidences of adverse events associated with therapy were 84. 51%（ 360 patients）,72. 82%（ 276 patients）in PROD,PROD-R group,respectively. There was significant difference between two groups（ P〈0. 05）. The pooled incidences of general adverse events in PROD-R group and PROD group were fatigue,pruritus,nausea,insomnia,rash and irritability,there were significant differences between two groups（ P〈0. 05）. Conclusion The antiviral effect of PROD against chronic HCV infection is efficient enough,especially against GT1 b HCV. No improvement in antiviral efficiency,but the incidence of adverse events is obtained after adding Ribavivin. For patients with chronic hepatitis C of GT1 a,GT4 and cirrhosis,it seems unnecessary to add Ribavirin. Yet more data should be collected and analyzed.