Yee Brittany E, Nguyen Nghia H, Jin Minjuan, Lutchman Glen, Lim Joseph K, Nguyen Mindie H
Department of Internal Medicine , University of California San Diego Medical Center , San Diego, California , USA.
Department of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA; Department of Epidemiology and Biostatistics, Zhejiang University School of Public Health, Hang Zhou, China.
BMJ Open Gastroenterol. 2016 Mar 2;3(1):e000056. doi: 10.1136/bmjgast-2015-000056. eCollection 2016.
High sustained virological response at 12 weeks after end of treatment (SVR12) with 12 weeks of simeprevir and sofosbuvir±ribavirin (SMV+SOF±RBV) has been demonstrated in hepatitis C virus genotype 1 (HCV-1) but is based on limited data. Therefore, we performed a meta-analysis of available data evaluating the effectiveness of SMV+SOF±RBV in HCV-1.
We performed a comprehensive literature search in June 2015 to identify randomised controlled trials (RCTs) and observational studies of HCV-1 patients treated with 12 weeks of SMV+SOF±RBV. Original studies with SVR12 data in ≥5 HCV-1 patients were included. We excluded studies on liver transplant recipients and/or patients co-infected with HIV or hepatitis B/D. We estimated pooled effect sizes using a random-effects model and evaluated heterogeneity with Cochrane Q-test, p≤0.10 and I(2) statistic ≥50%.
Pooled SVR12 was 85.6% (CI 81.3% to 89.0%) in 1389 HCV-1 patients from 15 studies. On subgroup analysis, SVR12 was 83.9% (CI 79.4% to 87.5%) in observational studies, which was lower than 93.5% (CI 85.7% to 97.2%) in RCTs. A trend showed SVR12 was higher in mild fibrosis, 93.0% (CI 86.2% to 96.6%) compared with advanced fibrosis, 81.5% (CI 75.7% to 86.1%), OR 2.22 (CI 0.79 to 6.25, p=0.131). There was no significant difference in SVR12 rates between HCV-1a, 89.9% (CI 81.9% to 94.6%) and HCV-1b, 89.0% (CI 78.9% to 94.6%) with OR 1.35 (CI 0.75 to 2.42, p=0.322). The most common pooled side effects were: headache 15.2% (n=55/361), fatigue 12.1% (n=78/646), nausea 9.5% (n=50/527) and rash 9.3% (n=68/728).
SMV+SOF±RBV is an effective regimen in HCV-1 patients. The SVR12 rate in observational studies was lower than that in RCTs, which may reflect the more diverse patient population in real-world settings.
在丙型肝炎病毒1型（HCV - 1）患者中，采用12周的西米普明和索磷布韦±利巴韦林（SMV + SOF±RBV）治疗，在治疗结束后12周实现高持续病毒学应答（SVR12）已得到证实，但相关数据有限。因此，我们对现有数据进行了荟萃分析，以评估SMV + SOF±RBV治疗HCV - 1的有效性。
2015年6月，我们进行了全面的文献检索，以确定接受12周SMV + SOF±RBV治疗的HCV - 1患者的随机对照试验（RCT）和观察性研究。纳入≥5例HCV - 1患者且有SVR12数据的原始研究。我们排除了关于肝移植受者和/或合并感染HIV或乙肝/丁肝患者的研究。我们使用随机效应模型估计合并效应量，并通过Cochrane Q检验、p≤0.10和I²统计量≥50%评估异质性。
来自15项研究的1389例HCV - 1患者的合并SVR12为85.6%（95%CI 81.3%至89.0%）。亚组分析显示，观察性研究中的SVR12为83.9%（95%CI 79.4%至87.5%），低于RCT中的93.5%（95%CI 85.7%至97.2%）。有趋势表明，轻度纤维化患者的SVR12较高，为93.0%（95%CI 86.2%至96.6%），而重度纤维化患者为81.5%（95%CI 75.7%至86.1%），比值比为2.22（95%CI 0.79至6.25，p = 0.131）。HCV - 1a型患者的SVR12率为89.9%（95%CI 81.9%至94.6%），HCV - 1b型患者为89.0%（95%CI 78.9%至94.6%），两者无显著差异，比值比为1.35（95%CI 0.75至2.42，p = 0.322）。最常见的合并副作用为：头痛15.2%（n = 55/361）、疲劳12.1%（n = 78/646）、恶心9.5%（n = 50/527）和皮疹9.3%（n = 68/728）。
SMV + SOF±RBV是治疗HCV - 1患者的有效方案。观察性研究中的SVR12率低于RCT，这可能反映了现实环境中患者群体更加多样化。
