目的:我们评估了泛基因型方案的有效性和安全性,glecaprevir/pibrentasvir(GLE/PIB),sofosbuvir/velpatasvir(SOF/VEL),和sofosbuvir/daclatasvir(SOF/DCV)和其他直接作用的抗病毒药物(DAA)方案,用于治疗丙型肝炎病毒(HCV)感染的青少年(12-18岁),年龄较大的儿童(6-11岁),和幼儿(3-5岁)。本系统评价和荟萃分析的目的是为世界卫生组织(WHO)指南提供信息。
方法:我们纳入了截至2021年8月11日发表的临床试验和观察性研究,这些研究评估了HCV感染青少年的DAA方案,年龄较大的孩子,和年幼的孩子。我们搜索了MEDLINE,EMBASE,以及CENTRAL数据库和关键会议摘要。治疗结束后12周的持续病毒学应答(SVR12),不良事件(AE),和治疗终止是对结局的评估.使用改良版本的ROBINS-I工具评估偏倚风险。使用随机效应模型汇集数据,并使用等级方法评估证据的确定性。
结果:共49项研究,包括1882名青少年,436名年龄较大的儿童,166名儿童被考虑。SVR12为100%(95%置信区间:96-100),96%(90-100),青少年GLE/PIB占96%(83-100),年长的,和年幼的孩子,分别为95%(90-99),93%(86-98),和83%(70-93),对于SOF/VEL,青少年和大龄儿童的SOF/DCV分别为100%(97-100)和100%(94-100),分别。有一个明显的趋势是,任何报告的青少年不良事件的发生率更高(50%),年龄较大的儿童(53%),幼儿(72%)。严重的不良事件和治疗中断在青少年和年龄较大的儿童中不常见(<1%),但在幼儿中略高(3%)。
结论:所有三种泛基因型DAA治疗方案都非常有效且耐受性良好,目前WHO推荐用于成人。青少年,和3岁以下的孩子,这将简化采购和供应链管理。证据主要基于单臂非随机对照研究。此外,还缺少有关关键变量的数据,例如HCV获取途径,是否存在肝硬化,或HIV合并感染,无法评估这些因素对结局的影响。
■CRD42020146752。
OBJECTIVE: We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct-acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)-infected adolescents (12-18 years), older children (6-11 years), and young children (3-5 years). The purpose of this systematic
review and meta-analysis was to inform the World Health Organization (WHO) guidelines.
METHODS: We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV-infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS-I tool. Data were pooled using random-effects models, and certainty of the evidence was assessed using the GRADE approach.
RESULTS: A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96-100), 96% (90-100), and 96% (83-100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90-99), 93% (86-98), and 83% (70-93), for SOF/VEL, respectively; and 100% (97-100) and 100% (94-100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%).
CONCLUSIONS: All three pan-genotypic DAA regimens were highly effective and well-tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single-arm non-randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co-infection that precluded evaluation of the impact of these factors on outcomes.
UNASSIGNED: CRD42020146752.