Atsukawa Masanori, Tsubota Akihito, Koushima Yohei, Ikegami Tadashi, Watanabe Kouji, Shimada Noritomo, Sato Shinichi, Kato Keizo, Abe Hiroshi, Okubo Tomomi, Arai Taeang, Itokawa Norio, Kondo Chisa, Mikami Shigeru, Asano Toru, Chuganji Yoshimichi, Matsuzaki Yasushi, Iwakiri Katsuhiko
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.
Hepatol Res. 2017 Dec;47(13):1429-1437. doi: 10.1111/hepr.12910. Epub 2017 May 30.
From a pharmacokinetic viewpoint, the use of ombitasvir/paritaprevir/ritonavir, one of the standards of care for genotype 1b chronic hepatitis C in Japan, could be possible in patients with impaired renal function. The aim of this study was to assess the efficacy and safety of this combination that have not yet been addressed in patients undergoing dialysis.
A retrospective, multicenter study evaluated the outcome of 12-week ombitasvir (non-structural protein [NS]5A inhibitor)/paritaprevir (NS3/4A protease inhibitor)/ritonavir combination therapy for dialysis patients. The primary end-point was sustained virologic response 12 weeks after therapy (SVR12).
The subjects were 31 patients with a median age of 64 years (range, 49-85 years), including 10 cirrhotic patients. All of the 31 patients had an estimated glomerular filtration rate level <15 mL/min/1.73 m , defined as end-stage renal disease (ESRD). Pre-existing resistance-associated substitutions at position L31 and Y93 of the NS5A region were detected in 0% and 3.6% (1/28), respectively. The rates of rapid virologic response, end-of-treatment response, and SVR12 were 93.5% (29/31), 100% (31/31), and 96.8% (30/31), respectively. The incidence of adverse events was 35.5% (11/31). Of the 11 patients, one discontinued the treatment due to erythema multiforme and thereafter relapsed. The most frequent adverse event was pruritus (6.5%; 2/31).
The present study suggests that ombitasvir/paritaprevir/ritonavir combination therapy is effective and safe for genotype 1b chronic hepatitis C patients undergoing dialysis due to ESRD.
从药代动力学角度来看，在日本，作为基因1b型慢性丙型肝炎治疗标准之一的奥比他韦/帕利瑞韦/利托那韦，对于肾功能受损患者或许是可用的。本研究旨在评估这种联合用药在透析患者中尚未得到探讨的疗效和安全性。
一项回顾性多中心研究评估了透析患者接受12周的奥比他韦（非结构蛋白[NS]5A抑制剂）/帕利瑞韦（NS3/4A蛋白酶抑制剂）/利托那韦联合治疗的结果。主要终点为治疗12周后的持续病毒学应答（SVR12）。
受试者为31例患者，中位年龄64岁（范围49 - 85岁），其中10例为肝硬化患者。所有31例患者的估计肾小球滤过率水平均<15 mL/min/1.73 m²，定义为终末期肾病（ESRD）。NS5A区域L31和Y93位点预先存在的耐药相关替代分别在0%和3.6%（1/28）的患者中检测到。快速病毒学应答率、治疗结束时应答率和SVR12率分别为93.5%（29/31）、100%（31/31）和96.8%（30/31）。不良事件发生率为35.5%（11/31）。在这11例患者中，1例因多形性红斑停药，之后复发。最常见的不良事件是瘙痒（6.5%；2/31）。
本研究表明，奥比他韦/帕利瑞韦/利托那韦联合治疗对于因ESRD接受透析的基因1b型慢性丙型肝炎患者是有效且安全的。
