Retreatment with sofosbuvir/ledipasvir with or without lead-in interferon- injections in patients infected with genotype 1b hepatitis C virus after unsuccessful daclatasvir/asunaprevir therapy
Retreatment with sofosbuvir/ledipasvir with or without lead-in interferon- injections in patients infected with genotype 1b hepatitis C virus after unsuccessful daclatasvir/asunaprevir therapy
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DOI：
10.1111/hepr.12980
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发表时间：
2018-03-01
影响因子：
4.2
通讯作者：
Mochida, Satoshi
中科院分区：
文献类型：
--
作者：
Uemura, Hayato;Uchida, Yoshihito;Mochida, Satoshi
目的为了提高索非布韦/雷地帕韦（SOF/LDV）治疗daclatasvir/asunaprevir （DCV/ASV）后患者再治疗的疗效，根据基因型1b型丙型肝炎病毒（HCV）非结构蛋白（NS）5A区耐药相关替代（RAS）的类型，制定有或无引入干扰素（IFN）注射的定制治疗方案。方法33例既往DCV/ASV失败患者接受sofv /LDV治疗12周。携带不利NS5A-RAS的HCV患者和/或先前接受西莫普韦治疗的患者给予IFN注射，每天两次，持续2周；采用深度测序法评价注射期间NS5A-RAS的序列变化。结果27例患者未进行铅注射；26例患者获得了持续的病毒应答（SVR），而1例携带NS5A-L28M/R30H/Y93H突变的HCV患者出现了病毒复发。在6例接受引入针注射的患者中，2例存在不利的ifn -3相关基因单核苷酸多态性等位基因的患者出现病毒复发；这两名患者之前都接受过西莫普韦治疗，并且在DCV/ASV之后出现了携带NS5A-L31V/Y93H突变的HCV。深度测序显示，两例患者在引入注射期间，NS5A-RAS谱未发生变化。相反，在一个具有有利等位基因的患者感染了类似的不利HCV株，在注射期间出现了NS5A-L31/Y93野生型株，从而实现了SVR。结论在既往DCV/ASV失败的患者中，采用基于NS5A-RAS基因谱的定制化治疗可获得较高的sofv /LDV后SVR率。对于携带不利NS5A-RAS基因的HCV患者，除了具有有利的IFN-3相关基因等位基因的患者外，引入IFN注射并没有提高疗效。
AimTo improve the therapeutic efficacy of sofosbuvir/ledipasvir (SOF/LDV) for the retreatment of patients after daclatasvir/asunaprevir (DCV/ASV), a customized therapy with or without lead-in interferon (IFN)- injections was formulated according to the types of resistance-associated substitutions (RAS) in the non-structural protein (NS)5A region of genotype 1b hepatitis C virus (HCV).MethodsThirty-three patients failing prior DCV/ASV received SOF/LDV for 12weeks. Patients with HCV carrying unfavorable NS5A-RAS and/or those previously treated with simeprevir were given lead-in IFN- injections twice a day for 2weeks; sequential changes in the NS5A-RAS during the injection period were evaluated using deep sequencing.ResultsLead-in injections were not undertaken in 27 patients; a sustained viral response (SVR) was achieved in 26 patients, while viral relapse occurred in 1 patient with HCV carrying NS5A-L28M/R30H/Y93H mutations. Among the 6 patients receiving lead-in injections, viral relapse occurred in 2 patients who had an unfavorable IFN-3-related gene single nucleotide polymorphism allele; both patients had been previously treated with simeprevir, and HCV carrying NS5A-L31V/Y93H mutations had emerged after DCV/ASV. Deep sequencing revealed no changes in the NS5A-RAS profiles during the lead-in injection period in either patient. In contrast, in a patient with a favorable allele who was infected with similar unfavorable HCV strains, NS5A-L31/Y93 wild-type strains appeared during the injection period, enabling an SVR.ConclusionUsing customized therapies based on the NS5A-RAS profiles, a high SVR rate was obtained after SOF/LDV in patients failing prior DCV/ASV. Lead-in IFN- injections did not improve the efficacy in patients with HCV carrying unfavorable NS5A-RAS except in those with a favorable IFN-3-related gene allele.