西咪匹韦联合治疗基因1型丙型肝炎疗效与安全性的Meta分析

Efficacy and Safety of Simeprevir Plus Ribavirin/Pegylated-Interferon for the Treatment of Hepatitis C Virus Genotype 1: A Meta Analysis

目的系统评价西咪匹韦治疗基因1型丙型肝炎的疗效与安全性。方法计算机检索Pub Med、the Cochrane Library、EMbase、Wanfang、VIP和CNKI等数据库,收集国内外公开发表的关于西咪匹韦治疗基因1型丙型肝炎的随机对照实验(RCT)。根据纳入与排除标准独立筛选文献,按Cochrane系统评价方法进行资料提取、质量评价,并采用Rev Man 5.2软件进行Meta分析。结果最终纳入8项RCTs,共2 758例患者。Meta分析结果显示,疗程为12周及24周的西咪匹韦联合治疗组在12周续病毒学应答率(SVR12率)及SVR24率方面较PR治疗组均有显著提高[SVR12:OR=3.92,95%CI(2.86,5.39),P<0.000 01]、[SVR24(疗程12周):OR=3.79,95%CI(2.86,5.01),P<0.000 01],[SVR24(疗程24周):OR=4.12,95%CI(2.69,6.30),P<0.000 01];其中疗程为12周的西咪匹韦联合治疗组在严重不良事件发生率方面低于PR治疗组[OR=0.67,95%CI(0.47,0.95),P=0.02];但不良事件导致治疗停止发生率方面,差异无统计学意义[12周:OR=0.85,95%CI(0.54,1.33),P=0.48];疗程为24周的西咪匹韦联合治疗组在严重不良事件发生率[OR=0.65,95%CI(0.32,1.32),P=0.24]及严重不良事件发生率方面[OR=0.82,95%CI(0.42,1.60),P=0.55]差异均无统计学意。结论西咪匹韦联合治疗基因1型丙型肝炎较单纯的PR(聚乙二醇干扰素+利巴韦林)二联疗法能有效提高慢性丙型肝炎患者SVR12率、SVR24率;且疗程为12周的西咪匹韦三联疗法可降低严重不良事件发生率,但不良事件导致治疗停止发生率无显著差异。上述结论还需更多多中心、大规模的临床试验进一步验证。

OBJECTIVE To assess efficacy and safety of simeprevir-based therapy for the treatment of hepatitis C virus geno- type 1. METHODS We searched Pubmed, EMBASE, the Cochrane Library, highwire, CBM, CNKI, Wanfang, VIP Data- base and literature from some relative paper based magazines also be retrieved. Randomised controlled trials（RCTs） of examining simeprevir plus ribavirin （RBV） and pegylated-interferon （peg-IFN） among adults with chronic HCV infection were includ- ed. Select the RCTs according to the inclusion criterion, then appraise them critiically by Cochrane handbook. All outcomes were pooled by the RevManS. 2 software of Cochrane Collaboration. Data were extracted on virological responses including sustained virological response at post-treatment week 12 （SVR12） , SVR24, serious adverse event（SAE） , treat-ment discontinuation due to an adverse event （TDAE）. RESULTS Eight RCTs were finally included involving 2 758 patients who were treated with simeprevir, RBV and peg-IFN. The results of Meta-analysis showed that SVR12 rates was [ OR = 3.92,95 % CI （2.86,5.39） , P 〈0. 000 01 ] , SVR24 rates was[ 12 week：OR = 3.79,95% CI（2. 86,5. 01） , P 〈0. 000 01 ] , [24 week：OR =4.12,95% CI（2. 69,6. 30） , P 〈0. 000 01] , SAE rates was[ 12 week：OR =0.67,95% CI（0. 47,0. 95） ,P = 0.02 ] , TDAE rates was [12 week：OR=0.85, 95%CI（0.54, 1.33）, P=0.48],[24week：OR=0.82,95%CI（0.42,1.60）, P=0.55]. CON- CLUSION Evidence shows that, simeprevir-based treatment （ simeprevir plus ribavirin and pegylated-interferon） for treating genotype 1 chronic HCV infection is better than PR treatment in SVR12 rates, SVR24 rates and SAE rates（ course of treatment is 12 weeks）. However, they are alike in TDAE rates.