Milazzo Laura, Magni Carlo, Niero Fosca, Schiavini Monica, Lai Alessia, Cento Valeria, Binda Francesca, Antinori Spinello, Sollima Salvatore
aDepartment of Biomedical and Clinical Sciences L. Sacco, University of Milan bFirst Division of Infectious Diseases, ASST Fatebenefratelli-Sacco, Milan cDepartment of Experimental Medicine and Surgery, University of Rome 'Tor Vergata', Rome, Italy.
Eur J Gastroenterol Hepatol. 2017 Nov;29(11):1231-1234. doi: 10.1097/MEG.0000000000000965.
Few real-life data are available on the retreatment of patients who failed direct-acting antiviral (DAA)-regimens. We reported the outcome of retreatment with approved DAA regimens in a real-life cohort of patients who previously failed an all-oral DAAs combination and we analyzed the association with resistance substitutions (RASs) performed at the time of virological failure.
Next-generation sequencing of the NS3, NS5A, and NS5B regions was performed by Illumina deep sequencing. The sequence reads were analyzed by an in-house pipeline.
Of the 16/759 (2%) patients who failed to achieve a sustained virological response at 12 weeks to all-oral DAAs from December 2014 to January 2016, 10 were retreated with licensed DAAs regimens. In all the patients, retreatment was followed by sustained virological response at 12 weeks. Baseline NS3-RASs before retreatment were observed in two patients who failed a sofosbuvir/simeprevir regimen: D168V RAS was detected in a genotype-4 patient, whereas the complex RAS-pattern Q80K, I170V, R155K, D168E was observed in a genotype-1a patient. Only one of the two patients who previously failed ombitasvir, paritaprevir/ritonavir, and dasabuvir underwent RAS analysis at relapse and showed baseline NS5A RAS (M28V) before retreatment.
These real-life findings indicated a high efficacy of sofosbuvir+NS5A-inihbitors in retreating NS3-experienced patients and also NS5A-experienced patients by using a 24-week course ribavirin-containing regimen. The relevance of hepatitis C virus resistance testing before retreatment remains to be better defined to guide the choice of the new regimen before retreatment in DAA-experienced patients.
关于接受直接抗病毒药物（DAA）方案治疗失败患者的再治疗，现实生活中的数据较少。我们报告了在一个现实生活队列中，对先前接受全口服DAA联合治疗失败的患者使用已获批DAA方案进行再治疗的结果，并分析了与病毒学失败时进行的耐药替代（RAS）的相关性。
通过Illumina深度测序对NS3、NS5A和NS5B区域进行下一代测序。序列读数由内部流程进行分析。
在2014年12月至2016年1月接受全口服DAA治疗12周未实现持续病毒学应答的16/759例（2%）患者中，10例接受了已获批DAA方案的再治疗。所有患者在再治疗后12周均实现了持续病毒学应答。在2例接受索磷布韦/西米普明治疗失败的患者中观察到再治疗前的基线NS3-RAS：在1例4型患者中检测到D168V RAS，而在1例1a型患者中观察到复杂的RAS模式Q80K、I170V、R155K、D168E。先前接受奥比他韦、帕利哌韦/利托那韦和达沙布韦治疗失败的2例患者中，只有1例在复发时进行了RAS分析，且在再治疗前显示基线NS5A RAS（M28V）。
这些现实生活中的发现表明，索磷布韦+NS5A抑制剂在对有NS3治疗史的患者以及有NS5A治疗史的患者进行再治疗时具有较高疗效，采用含利巴韦林的24周疗程方案即可。在DAA治疗经验丰富的患者中，再治疗前丙型肝炎病毒耐药检测的相关性仍有待更好地界定，以指导再治疗前新方案的选择。
