Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan.
J Gastroenterol. 2019 Mar;54(3):291-296. doi: 10.1007/s00535-018-1520-9. Epub 2018 Oct 17.
Combination therapy with glecaprevir (GLE) and pibrentasvir (PIB) has high efficacy for pan-genotypic hepatitis C virus (HCV)-infected patients. However, the efficacy of the therapy for failures to prior direct-acting antiviral (DAA) regimens in real-world practice is not well known.
Thirty patients infected with HCV genotype 1b, 2a, 2b, or 3a who failed to respond during prior DAA therapies were treated with GLE/PIB for 12 weeks. HCV NS3 and NS5A drug resistance-associated variants (RAVs) were determined by direct sequencing.
Twenty-eight out of 30 patients (93.3%) achieved SVR12 by GLE/PIB treatment. SVR12 rates were similar between patients with and without advanced liver fibrosis (94.7% and 91.0%, respectively). All 9 patients with genotype 2a, 2b, or 3a HCV infection achieved SVR12. However, two genotype 1b HCV-infected patients who failed previous daclatasvir plus asunaprevir treatment experienced HCV relapse after the end of GLE/PIB treatment. Direct sequence analysis showed the presence of NS3-D168E plus NS5A-L31I/P58S/Y93H RAVs in one patient and NS5A-L31F/P32del RAVs in another patient before GLE/PIB treatment. In the former patient, NS3-D168E plus NS5A-L31I/P58S/Y93H RAVs persisted, and additional NS5A-L28M/V75A variants emerged after HCV relapse.
GLE/PIB treatment for HCV-infected patients who did not respond to prior DAA treatments was highly effective regardless of liver fibrosis stage. However, some genotype 1b HCV-infected patients, especially those with NS5A-P32del, may have low susceptibility to the treatment.
格拉瑞韦（GLE）和比蓬特韦（PIB）联合治疗对泛基因型丙型肝炎病毒（HCV）感染患者具有高效性。然而，在真实世界实践中，对于先前直接作用抗病毒（DAA）治疗方案失败的患者，该疗法的疗效尚不清楚。
30 名感染 HCV 基因型 1b、2a、2b 或 3a 的患者，在先前的 DAA 治疗中未出现应答，使用 GLE/PIB 治疗 12 周。通过直接测序确定 HCV NS3 和 NS5A 耐药相关变异（RAV）。
28 名患者（93.3%）在 GLE/PIB 治疗后获得了 SVR12。有和无晚期肝纤维化的患者 SVR12 率相似（分别为 94.7%和 91.0%）。所有 9 名基因型 2a、2b 或 3a HCV 感染的患者均获得了 SVR12。然而，两名先前接受达拉他韦联合asunaprevir 治疗失败的基因型 1b HCV 感染患者在 GLE/PIB 治疗结束后出现 HCV 复发。直接序列分析显示，在一名患者中存在 NS3-D168E 加 NS5A-L31I/P58S/Y93H RAV，在另一名患者中存在 NS5A-L31F/P32del RAV。在前者患者中，NS3-D168E 加 NS5A-L31I/P58S/Y93H RAV 持续存在，HCV 复发后出现了额外的 NS5A-L28M/V75A 变异。
对于先前 DAA 治疗失败的 HCV 感染患者，GLE/PIB 治疗是非常有效的，无论肝纤维化阶段如何。然而，一些基因型 1b HCV 感染患者，特别是那些存在 NS5A-P32del 的患者，对该治疗可能具有较低的敏感性。
