Tamai Hideyuki, Shingaki Naoki, Ida Yoshiyuki, Shimizu Ryo, Maeshima Shuya, Okamura Junpei, Kawashima Akira, Nakao Taisei, Hara Takeshi, Matsutani Hiroyoshi, Nishikawa Izumi, Higashi Katsuhiko
Department of Hepatology Wakayama Rosai Hospital Wakayama-shi Japan.
Second Department of Internal Medicine Wakayama Medical University Wakayama-shi Japan.
JGH Open. 2018 Sep 19;2(6):300-306. doi: 10.1002/jgh3.12088. eCollection 2018 Dec.
In September 2015, sofosbuvir and ledipasvir were approved for clinical use in Japan for patients infected with genotype 1 hepatitis C virus. We conducted a postmarketing prospective cohort study to elucidate the safety and efficacy of this therapy in a real-world setting.
We treated 509 patients using standard doses of sofosbuvir and ledipasvir for 12 weeks. As sustained virological response (SVR) in 2 patients could not be evaluated, 507 patients were finally analyzed. Patients with daclatasvir plus asunaprevir failure were excluded.
Four patients (0.8%) discontinued treatment due to adverse events. SVR rates for the overall cohort, patients <65 years old, ≥65 and <75 years old, and ≥75 years old were 98% (495/507), 98% (161/163), 96% (179/186), and 98% (155/158), respectively. SVR rates among cirrhotic patients, patients with moderate chronic kidney disease (CKD), patients with a history of hepatocellular carcinoma (HCC) treatment, patients with protease inhibitor (PI) triple therapy failure, and patients with resistance-associated substitutions (RASs) to nonstructural protein 5A (NS5A) were 97% (228/235), 98% (117/119), 95% (95/100), 94% (46/49), and 92% (44/48), respectively. In the comparison of factors between patients with and without SVR, high body weight, discontinuation of therapy, and NS5A RASs were significantly associated with non-SVR.
In this real-world setting, sofosbuvir and ledipasvir were a safe treatment even in patients ≥75 years old. When patients without pre-existing NS5A RASs and daclatasvir plus asunaprevir failure are selected, extremely high SVR rates can be achieved irrespective of age.
2015年9月，索磷布韦和来迪派韦在日本被批准用于治疗基因1型丙型肝炎病毒感染患者。我们开展了一项上市后前瞻性队列研究，以阐明该疗法在实际临床环境中的安全性和疗效。
我们使用标准剂量的索磷布韦和来迪派韦治疗了509例患者，疗程为12周。由于2例患者的持续病毒学应答（SVR）无法评估，最终对507例患者进行了分析。排除了接受达卡他韦加利匹韦林治疗失败的患者。
4例患者（0.8%）因不良事件停药。整个队列、年龄<65岁、年龄≥65岁且<75岁以及年龄≥75岁患者的SVR率分别为98%（495/507）、98%（161/163）、96%（179/186）和98%（155/158）。肝硬化患者、中度慢性肾脏病（CKD）患者、有肝细胞癌（HCC）治疗史患者、蛋白酶抑制剂（PI）三联疗法失败患者以及对非结构蛋白5A（NS5A）有耐药相关替代（RAS）患者的SVR率分别为97%（228/235）、98%（117/119）、95%（95/100）、94%（46/49）和92%（44/48）。在有和没有SVR的患者之间的因素比较中，高体重、停药和NS5A RAS与未实现SVR显著相关。
在这一实际临床环境中，索磷布韦和来迪派韦即使在年龄≥75岁的患者中也是一种安全的治疗方法。当选择没有预先存在的NS5A RAS且未接受达卡他韦加利匹韦林治疗失败的患者时，无论年龄如何，均可实现极高的SVR率。
