Ikeda Hiroki, Watanabe Tsunamasa, Shimizu Hirohito, Hiraishi Tetsuya, Kaneko Rena, Baba Toshiyuki, Takahashi Hideaki, Matsunaga Kotaro, Matsumoto Nobuyuki, Yasuda Hiroshi, Okuse Chiaki, Iwabuchi Shogo, Suzuki Michihiro, Itoh Fumio
Department of Internal Medicine, Division of Gastroenterology and Hepatology, St. Marianna University, school of medicine, Kawasaki, Japan.
Hepato-Biliary-Pancreatic Center, Shonan Fujisawa Tokushukai Hospital, Fujisawa, Japan.
Hepatol Res. 2018 Sep;48(10):802-809. doi: 10.1111/hepr.13074. Epub 2018 May 4.
The therapeutic benefit of adding ribavirin (RBV) to 12 weeks of ledipasvir/sofosbuvir (LDV/SOF) for patients who experienced failure of a previous nonstructural protein (NS) 5A inhibitor-containing regimen is unclear.
A total of 29 genotype 1b HCV patients who had failed prior daclatasvir (DCV) plus asunaprevir (ASV) treatment were retreated for 12 weeks of LDV/SOF, with or without RBV. Antiviral efficacy and predictive factors associating with a sustained virological response at 24 weeks (SVR24) were evaluated retrospectively.
SVR24 was achieved in 67% (10/15) of patients who received LDV/SOF with, and 64% (9/14) without, RBV. The SVR24 rates were 80% in patients with, and 58% without, mild fibrosis (FIB-4 < 3.25). The SVR24 rate was lower with unfavorable IL28B rs8099917 SNP genotypes; specifically, the TT, TG and GG had SVR24 rates of 78%, 50% and 40%. The SVR24 rate was lower with a poor response to prior DCV plus ASV, where relapse, viral breakthrough and no response had SVR24 rates 71%, 58% and 0%. The SVR24 rate was lower with the number of NS5A resistance-associated substitutions (RAS), where 2, 3, 4 and 5 RAS had SVR24 rates of 78%, 67%, 50% and 0%. A patient with an NS5A-P32 deletion, which shows resistance to next-generation NS5A inhibitors, was retreated with LDV/SOF with RBV and achieved SVR24.
The addition of RBV to 12 weeks of LDV/SOF has little therapeutic benefit when retreating patients in whom a prior NS5A inhibitor-containing regimen had failed.
对于既往接受含非结构蛋白（NS）5A抑制剂方案治疗失败的患者，在12周的来迪派韦/索磷布韦（LDV/SOF）治疗中加用利巴韦林（RBV）的治疗益处尚不清楚。
共有29例基因1b型丙型肝炎病毒（HCV）患者，他们先前接受达卡他韦（DCV）联合阿舒瑞韦（ASV）治疗失败，接受了12周的LDV/SOF再治疗，部分患者加用RBV，部分不加用。回顾性评估抗病毒疗效以及与24周持续病毒学应答（SVR24）相关的预测因素。
接受LDV/SOF联合RBV治疗的患者中67%（10/15）实现了SVR24，接受LDV/SOF单药治疗的患者中64%（9/14）实现了SVR24。轻度纤维化（FIB-4＜3.25）的患者中，联合RBV治疗的SVR24率为80%，未联合RBV治疗的为58%。IL28B rs8099917 SNP基因型不佳时SVR24率较低；具体而言，TT、TG和GG基因型的SVR24率分别为78%、50%和40%。对先前DCV联合ASV治疗应答不佳的患者SVR24率较低，复发、病毒突破和无应答的患者SVR24率分别为71%、58%和0%。NS5A耐药相关置换（RAS）数量较多时SVR24率较低，2个、3个、4个和5个RAS的患者SVR24率分别为78%、67%、
