Sato Ken, Hosonuma Kenichi, Yamazaki Yuichi, Kobayashi Takeshi, Takakusagi Satoshi, Horiguchi Norio, Kakizaki Satoru, Kusano Motoyasu, Ohnishi Hiroshi, Okamoto Hiroaki, Yamada Masanobu
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine.
Tohoku J Exp Med. 2017 Jan;241(1):45-53. doi: 10.1620/tjem.241.45.
Hepatitis C virus (HCV) infection is common in dialysis patients worldwide and nosocomial HCV spread within dialysis facilities continues to develop. Combination therapy with daclatasvir and asunaprevir (DCV/ASV) that has proven efficacy for dialysis patients infected with genotype 1b HCV (HCV/1b) has several concerns in Japan. The recently available combination therapy with ombitasvir, paritaprevir, and ritonavir (OBV/PTV/r) is not contraindicated in patients with chronic renal failure and has more safety profile and shorter treatment period than that with DCV/ASV. We evaluated the effects of combination therapy with OBV/PTV/r in four dialysis patients infected with HCV/1b, who were eligible for our study. On-treatment assessments included standard laboratory testing, serum HCV RNA and symptom-directed physical examinations. Three patients had a sustained virological response at 12 weeks after treatment, but one remaining patient had viral breakthrough. Notably, the patient with viral breakthrough had been coinfected with HCV/1b and HCV/2b; namely, HCV/2b with resistance-associated variations was not eradicated by the combination therapy. Among the three patients responsive to the combination therapy, one patient complained of appetite loss and itching, while in another patient the therapy was discontinued due to itching, exacerbation of wamble, and a falling tendency probably due to interaction with valsartan. These AEs were ameliorated or disappeared after the completion of the therapy. The significance of our study is persuasive virological evaluation associated to the combination therapy and reasonable interpretation of AEs. In conclusion, combination therapy with OBV/PTV/r may have promise as an efficacious therapy, but caution regarding AEs should be practiced.
丙型肝炎病毒（HCV）感染在全球透析患者中很常见，透析机构内的医院获得性HCV传播仍在持续。在日本，对于感染1b型HCV（HCV/1b）的透析患者已证实有效的达卡他韦和阿舒瑞韦联合疗法（DCV/ASV）存在一些问题。最近可用的奥比他韦、帕利哌韦和利托那韦联合疗法（OBV/PTV/r）对慢性肾衰竭患者无禁忌，且与DCV/ASV相比具有更高的安全性和更短的治疗周期。我们评估了OBV/PTV/r联合疗法对4例符合研究条件的感染HCV/1b的透析患者的疗效。治疗期间的评估包括标准实验室检测、血清HCV RNA检测和症状导向的体格检查。3例患者在治疗12周后获得持续病毒学应答，但仍有1例患者出现病毒突破。值得注意的是，出现病毒突破的患者同时感染了HCV/1b和HCV/2b；也就是说，联合疗法未能根除具有耐药相关变异的HCV/2b。在对联合疗法有反应的3例患者中，1例患者抱怨食欲不振和瘙痒，而另1例患者因瘙痒、胃部不适加重以及可能与缬沙坦相互作用导致的体重下降趋势而停止治疗。这些不良事件在治疗结束后得到改善或消失。我们研究的意义在于对联合疗法进行有说服力的病毒学评估以及对不良事件进行合理解释。总之，OBV/PTV/r联合疗法可能有望成为一种有效的治疗方法，但应谨慎对待不良事件。
