Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA.
Departments of Medicine and Surgery, Baylor College of Medicine, Houston, TX, USA.
J Viral Hepat. 2020 Nov;27(11):1222-1233. doi: 10.1111/jvh.13357. Epub 2020 Aug 10.
Direct-acting antiviral treatments for chronic hepatitis C virus (HCV) infection are generally safe; however, understanding the safety profile of each regimen is essential for their continued use. Safety data were pooled from 12 clinical trials of elbasvir/grazoprevir (EBR/GZR) that enrolled adult participants with HCV infection. Pooled analyses are presented for participants receiving EBR/GZR for 12 weeks and those receiving EBR/GZR plus ribavirin (RBV) for 16-18 weeks. Safety data are also presented for participants with comorbidities receiving EBR/GZR for 12 weeks in individual clinical trials (chronic kidney disease [CKD] stage 4/5, inherited blood disorders [IBLD] or receiving opioid agonist therapy [OAT]). Among 1743 participants receiving EBR/GZR for 12 weeks, 1068 (61.3%) reported ≥1 adverse event (AE) and 491 had AEs (28.2%) considered drug-related. The most frequent AEs were headache (10.6%), fatigue (8.7%), nasopharyngitis (5.8%), nausea (5.1%) and diarrhoea (5.0%). Serious AEs were reported by 37 participants (2.1%), and 12 (0.7%) discontinued treatment due to an AE. In populations with CKD 4/5 or IBLD or receiving OAT, safety was similar in participants receiving EBR/GZR for 12 weeks and those receiving placebo. Some AEs occurred at higher frequencies in participants receiving RBV compared with those receiving EBR/GZR alone: fatigue (32.7% vs 8.7%); headache (21.6% vs 10.6%); and nausea (15.8% vs 5.1%). Safety was similar in participants with and those without cirrhosis. Grade 3/4 alanine aminotransferase elevations were reported in 0.7% participants. EBR/GZR is a safe treatment option for individuals with HCV genotype (GT) 1 or GT4 infections, even those with challenging comorbidities such as CKD or IBLD and those receiving OAT.
直接作用抗病毒药物治疗慢性丙型肝炎病毒（HCV）感染通常是安全的；然而，了解每种方案的安全性概况对于它们的持续使用至关重要。安全性数据来自 12 项纳入 HCV 感染成年参与者的格拉瑞韦/格卡瑞韦（EBR/GZR）临床试验的汇总分析。报告了接受 EBR/GZR 治疗 12 周和接受 EBR/GZR 加利巴韦林（RBV）治疗 16-18 周的参与者的汇总分析。还报告了在个别临床试验中接受 EBR/GZR 治疗 12 周的伴有合并症的参与者的安全性数据（慢性肾脏病[CKD] 4/5 期、遗传性血液疾病[IBLD]或接受阿片类药物激动剂治疗[OAT]）。在接受 EBR/GZR 治疗 12 周的 1743 名参与者中，1068 名（61.3%）报告了≥1 例不良事件（AE），491 名有 AE（28.2%）被认为与药物相关。最常见的 AE 是头痛（10.6%）、疲劳（8.7%）、鼻咽炎（5.8%）、恶心（5.1%）和腹泻（5.0%）。37 名参与者（2.1%）报告了严重 AE，12 名（0.7%）因 AE 而停止治疗。在 CKD 4/5 期或 IBLD 或接受 OAT 的人群中，接受 EBR/GZR 治疗 12 周的参与者与接受安慰剂的参与者的安全性相似。与单独接受 EBR/GZR 治疗的参与者相比，接受 RBV 治疗的参与者出现一些 AE 的频率更高：疲劳（32.7% vs 8.7%）；头痛（21.6% vs 10.6%）；恶心（15.8% vs 5.1%）。在有或没有肝硬化的参与者中，安全性相似。0.7%的参与者报告了 3/4 级丙氨酸氨基转移酶升高。EBR/GZR 是 HCV 基因 1 或基因 4 感染个体的安全治疗选择，即使是那些有挑战性的合并症，如 CKD 或 IBLD，以及那些接受 OAT 的个体。
