Honda Masaki, Sugawara Yasuhiko, Watanabe Takehisa, Tateyama Masakuni, Tanaka Motohiko, Uchida Koushi, Kawabata Seiichi, Yoshii Daiki, Miura Kouhei, Isono Kaori, Hayashida Shintaro, Ohya Yuki, Yamamoto Hidekazu, Sasaki Yutaka, Inomata Yukihiro
Departments of Transplantation/Pediatric Surgery.
Gastroenterology and Hepatology, Postgraduate School of Life Science, Kumamoto University, Kumamoto, Japan.
Hepatol Res. 2017 Oct;47(11):1147-1154. doi: 10.1111/hepr.12853. Epub 2017 Jan 17.
The development of direct-acting oral agents has dramatically changed the treatment strategy of hepatitis C virus (HCV) infection. Here we aimed to reveal the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) for recurrent HCV genotype 1 infection after liver transplantation (LT).
A retrospective study was undertaken on nine patients who underwent a 24-week DCV/ASV treatment regimen for recurrent HCV genotype 1 infection. Five of the patients were men; four had failed treatment with pegylated interferon (Peg-IFN)/ribavirin, two had failed simeprevir/Peg-IFN/ribavirin, one had the resistance-associated variant Y93H in the NS5A region, and one underwent maintenance dialysis.
Median time to treatment initiation following LT was 70 months. Of the nine patients treated with DCV/ASV, eight (88.9%) achieved a sustained viral response 12 weeks after completion of therapy (SVR12). The patient with virologic failure had failed simeprevir/Peg-interferon/ribavirin therapy 4 months before undergoing the DCV/ASV treatment regimen. In addition, a resistance-associated variant D168E in the NS3 region was detected in the patient after discontinuation of the DCV/ASV regimen. The trough level of tacrolimus tended to decrease, and renal function showed no significant changes during treatment. Adverse events occurred in two patients (22.2%), but no severe adverse events occurred during treatment.
The DCV/ASV regimen was well tolerated, resulting in high rates of sustained viral response 12 weeks after completion of therapy for LT patients with recurrent HCV genotype 1 infection.
直接作用口服药物的发展极大地改变了丙型肝炎病毒（HCV）感染的治疗策略。在此，我们旨在揭示达卡他韦（DCV）和阿舒瑞韦（ASV）治疗肝移植（LT）后复发的HCV 1型感染的疗效和安全性。
对9例接受DCV/ASV治疗方案24周以治疗复发的HCV 1型感染的患者进行了一项回顾性研究。其中5例为男性；4例聚乙二醇干扰素（Peg-IFN）/利巴韦林治疗失败，2例simeprevir/Peg-IFN/利巴韦林治疗失败，1例NS5A区域存在与耐药相关的变异Y93H，1例接受维持性透析。
LT后开始治疗的中位时间为70个月。在接受DCV/ASV治疗的9例患者中，8例（88.9%）在完成治疗12周后实现了持续病毒学应答（SVR12）。病毒学失败的患者在接受DCV/ASV治疗方案前4个月simeprevir/Peg-干扰素/利巴韦林治疗失败。此外，在DCV/ASV治疗方案停药后，该患者NS3区域检测到与耐药相关的变异D168E。他克莫司谷浓度有下降趋势，治疗期间肾功能无明显变化。2例患者（22.2%）发生不良事件，但治疗期间未发生严重不良事件。
DCV/ASV治疗方案耐受性良好，使LT后复发HCV 1型感染患者在完成治疗12周后持续病毒学应答率较高。
