Safety and efficacy of daclatasvir and asunaprevir in hepatitis C virus infected patients with renal impairment
Safety and efficacy of daclatasvir and asunaprevir in hepatitis C virus infected patients with renal impairment
复制标题
达卡他韦和阿舒瑞韦治疗丙型肝炎病毒感染肾功能不全患者的安全性和有效性
DOI：
10.1111/hepr.12851
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发表时间：
2017
期刊：
影响因子：
4.2
通讯作者：
Sakamoto N;
中科院分区：
文献类型：
--
作者：
Suda G;Nagasaka A;Yamamoto Y;Furuya K;Kumagai K;Kudo M;Terashita K;Kobayashi T;Tsunematsu I;Yoshida J;Meguro T;Kimura M;Ito J;Umemura M;Izumi T;Tsunematsu S;Sato F;Tsukuda Y;Nakai M;Sho T;Natsuizaka M;Morikawa K;Ogawa K;Sakamoto N;
目的丙型肝炎病毒(HCV)感染是终末期肾病、肾移植衰竭和血液透析患者死亡的危险因素。然而，直接作用的抗病毒治疗对合并肾损害的丙型肝炎病毒感染患者的疗效尚不清楚。此外，前景看好的NS5B抑制剂索索布韦并未被推荐用于严重肾损害的患者。在这项前瞻性的多中心研究中，我们评估了达拉塔韦和阿索奈韦联合治疗的有效性和安全性，重点是肾损害患者。方法研究包括322名接受达拉塔韦和阿索奈韦联合治疗的1型丙型肝炎病毒感染者。结果322例慢性肾脏病患者中，慢性肾脏病G3b期(估计肾小球滤过率30~44 mL/min/1.73 mm2)占5%(16/322)，G4/5期(15~29 mL/min/1.73 m2)占2.5%(8/322)。在EGFR和EGFR>；45亿毫升/分/1.73百万米2和EGFR>；45亿毫升/分/1.73百万米2的患者中，NS5A耐药相关变异、以前的西美普韦治疗和丙型肝炎病毒RNA滴度的基线存在是相似的，这些都是持续病毒应答的预测因素。值得注意的是，12周的持续病毒应答率与EGFR>；45亿毫升/分钟/1.73百万米2的患者(100%，24/24)和EGFR>；45亿毫升/分钟/1.73百万平方米的患者(88.9%，265/298；P= 0.07)相当。两组患者的停药率及丙氨酸氨基转移酶升高、贫血、肾功能障碍等不良反应相似。结论达拉他韦联合阿昔洛韦治疗肾功能不全安全有效。
AimHepatitis C virus (HCV) infection is a risk factor for end‐stage renal disease, renal graft failure, and hemodialysis patient mortality. However, the efficacy of direct‐acting antiviral therapy for HCV‐infected patients with renal impairment is unclear. Additionally, the promising NS5B inhibitor sofosbuvir has not been recommended for patients with severe renal impairment. In this prospective, multicenter study, we evaluated the efficacy and safety of daclatasvir and asunaprevir combination therapy, with a focus on patients with renal impairment.MethodsThe study included 322 genotype 1 HCV‐infected patients who received daclatasvir and asunaprevir combination therapy. The safety and sustained virological response was examined at 12 weeks after the end of treatment and safety was evaluated according to renal function.ResultsOf 322 patients, 5% (16/322) and 2.5% (8/322) had chronic kidney disease stage G3b (estimated glomerular filtration rate [eGFR], 30–44 mL/min/1.73 m2) and stage G4/5 (eGFR, 15–29/<15 mL/min/1.73 m2), respectively. Baseline presence of the NS5A resistance‐associated variant, previous simeprevir treatment, and HCV RNA titers, which were predictors of a sustained viral response, were similar between patients with eGFR <45 mL/min/1.73 m2and eGFR >45 mL/min/1.73 m2. Notably, the 12‐week sustained viral response rate was comparable in patients with eGFR <45 mL/min/1.73 m2(100%, 24/24) and those with eGFR >45 mL/min/1.73 m2(88.9%, 265/298;P= 0.07). Treatment discontinuation rates and adverse events, including alanine aminotransferase elevation, anemia, and renal disorders, were similar between the two groups.ConclusionDaclatasvir and asunaprevir combination therapy for patients with renal dysfunction was highly effective and safe.