Haga Yuki, Kanda Tatsuo, Yasui Shin, Nakamura Masato, Ooka Yoshihiko, Takahashi Koji, Wu Shuang, Nakamoto Shingo, Arai Makoto, Chiba Tetsuhiro, Maruyama Hitoshi, Yokosuka Osamu, Takada Nobuo, Moriyama Mitsuhiko, Imazeki Fumio, Kato Naoya
Department of Gastroenterology, Chiba University, Graduate School of Medicine, Inohana, Chuo-ku, Chiba, Japan.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan.
Oncotarget. 2017 Dec 29;9(4):5509-5513. doi: 10.18632/oncotarget.23768. eCollection 2018 Jan 12.
Interferon-free treatment results in higher sustained virologic response (SVR) rates, with no serious adverse events in hepatitis C virus (HCV)-infected patients. However, in some patients with treatment-failure in HCV NS5A inhibitor-including interferon-free regimens, the treatment-emergent HCV NS5A resistance-associated variants (RAVs), which are resistant to interferon-free retreatment including HCV NS5A inhibitors, are observed. In HCV-infected Japanese patients with daclatasvir and asunaprevir treatment failure, retreatment with sofosbuvir and ledipasvir could lead to only ∼70% SVR rates.
Three HCV genotype (GT)-1b-infected cirrhotic patients who discontinued the combination of daclatasvir and asunaprevir due to adverse drug reactions within 4 weeks; retreatment with sofosbuvir and ledipasvir combination could result in SVR in these patients without RAVs. One HCV GT-1b-infected cirrhotic patient who discontinued the combination of daclatasvir and asunaprevir due to viral breakthrough at week 10; retreatment with sofosbuvir and ledipasvir combination for this patient with the treatment-emergent HCV NS5A RAV-Y93H resulted in viral relapse at week 4 after the end of the treatment.
Retreatment with sofosbuvir and ledipasvir is effective for HCV GT-1b patients who discontinue the combination of daclatasvir and asunaprevir within 4 weeks. The treatment response should be related to the existence of treatment-emergent HCV NS5A RAVs, but may not be related to the short duration of treatment.
无干扰素治疗可带来更高的持续病毒学应答（SVR）率，且丙型肝炎病毒（HCV）感染患者无严重不良事件发生。然而，在一些接受含HCV NS5A抑制剂的无干扰素方案治疗失败的患者中，可观察到治疗中出现的对包括HCV NS5A抑制剂在内的无干扰素再治疗耐药的HCV NS5A耐药相关变异（RAV）。在HCV感染的日本患者中，达卡他韦和阿舒瑞韦治疗失败后，使用索磷布韦和来迪帕司韦再治疗的SVR率仅约为70%。
3例HCV基因（GT）-1b感染的肝硬化患者在4周内因药物不良反应停用达卡他韦和阿舒瑞韦联合治疗；使用索磷布韦和来迪帕司韦联合再治疗可使这些患者获得无RAV的SVR。1例HCV GT-1b感染的肝硬化患者在第10周因病毒突破停用达卡他韦和阿舒瑞韦联合治疗；该出现治疗中HCV NS5A RAV-Y93H的患者使用索磷布韦和来迪帕司韦联合再治疗，在治疗结束后第4周出现病毒复发。
对于在4周内停用达卡他韦和阿舒瑞韦联合治疗的HCV GT-1b患者，使用索磷布韦和来迪帕司韦再治疗有效。治疗反应应与治疗中出现的HCV NS5A RAV的存在有关，但可能与治疗时间短无关。
