Sugiura Ayumi, Joshita Satoru, Yamashita Yuki, Yamazaki Tomoo, Fujimori Naoyuki, Kimura Takefumi, Matsumoto Akihiro, Wada Shuichi, Mori Hiromitsu, Shibata Soichiro, Yoshizawa Kaname, Morita Susumu, Furuta Kiyoshi, Kamijo Atsushi, Iijima Akihiro, Kako Satoko, Maruyama Atsushi, Kobayashi Masakazu, Komatsu Michiharu, Matsumura Makiko, Miyabayashi Chiharu, Ichijo Tetsuya, Takeuchi Aki, Koike Yuriko, Gibo Yukio, Tsukadaira Toshihisa, Inada Hiroyuki, Nakano Yoshiyuki, Usuda Seiichi, Kiyosawa Kendo, Tanaka Eiji, Umemura Takeji
Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
Consultation Centers for Hepatic Diseases, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
Biomedicines. 2020 Apr 3;8(4):74. doi: 10.3390/biomedicines8040074.
Glecaprevir/pibrentasvir (G/P) are direct-acting antivirals (DAAs) that achieve a high sustained virological response (SVR) rate for hepatitis C virus (HCV) infection. We investigated G/P effectiveness for HCV patients based on real-world experience and the clinical features of retreatment cases. HCV patients (n = 182) were compared for clinical features and outcomes between first treatment (n = 159) and retreatment (n = 23) G/P groups. Overall, 77 patients (42.3%) were male, the median age was 68 years, and 86/66/1/4 cases had genotype 1/2/1+2/3, respectively. An SVR was achieved in 97.8% (178/182) of cases by intention-to-treat analysis and 99.4% (178/179) of cases by per-protocol analysis. There were no remarkable differences between the first treatment and retreatment groups for male (42.8% vs. 39.1%, p = 0.70), median age (68 vs. 68 years, p = 0.36), prior hepatocellular carcinoma (5.8% vs. 8.7%, p = 0.59), or the fibrosis markers AST-to-platelet ratio index (APRI) (0.5 vs. 0.5, p = 0.80) and fibrosis-4 (FIB-4) index (2.2 vs. 2.6, p = 0.59). The retreatment group had a significantly more frequent history of interferon treatment (12.3% vs. 52.2%, p < 0.01) and the Y93H mutation (25.0% vs. 64.7%, p = 0.02). The number of retreatment patients who had experienced 3, 2, and 1 DAA treatment failures was 1, 3, and 19, respectively, all of whom ultimately achieved an SVR by G/P treatment. In conclusion, G/P was effective and safe for both HCV first treatment and retreatment cases despite the retreatment group having specific resistance mutations for other prior DAAs. As G/P treatment failure has been reported for P32 deletions, clinicians should consider resistance mutations during DAA selection.
格卡瑞韦/哌仑他韦（G/P）是直接作用抗病毒药物（DAA），可使丙型肝炎病毒（HCV）感染获得较高的持续病毒学应答（SVR）率。我们基于真实世界经验和再治疗病例的临床特征，研究了G/P对HCV患者的有效性。比较了HCV患者中初次治疗组（n = 159）和再治疗组（n = 23）的G/P治疗的临床特征和结局。总体而言，77例患者（42.3%）为男性，中位年龄为68岁，分别有86/66/1/4例患者为基因1/2/1+2/3型。意向性分析中97.8%（178/182）的病例和符合方案分析中99.4%（178/179）的病例实现了SVR。初次治疗组和再治疗组在男性比例（42.8%对39.1%，p = 0.70）、中位年龄（68岁对68岁，p = 0.36）、既往肝细胞癌（5.8%对8.7%，p = 0.59）或纤维化指标天冬氨酸转氨酶与血小板比值指数（APRI）（0.5对0.5，p = 0.80）以及纤维化-4（FIB-4）指数（2.2对2.6，p = 0.59）方面无显著差异。再治疗组干扰素治疗史更常见（12.3%对52.2%，p < 0.01）以及Y93H突变更常见（25.0%对64.7%，p = 0.02）。经历过3次、2次和1次DAA治疗失败的再治疗患者人数分别为1例、3例和19例，所有这些患者最终通过G/P治疗均实现了SVR。总之，尽管再治疗组存在对其他既往DAA的特定耐药突变，但G/P对HCV初次治疗和再治疗病例均有效且安全。由于已有P32缺失导致G/P治疗失败的报道，临床医生在选择DAA时应考虑耐药突变。
