Mitsutaka Osawa1,2, Michio Imamura1,2, Yuji Teraoka1,2, Takuro Uchida1,2, Kei Morio1,2, Hatsue Fujino1,2, Takashi Nakahara1,2, Atsushi Ono1,2, Eisuke Murakami1,2, Tomokazu Kawaoka1,2, Daiki Miki1,2, Masataka Tsuge2,3, Akira Hiramatsu1,2, Hiroshi Aikata1,2, C Nelson Hayes1,2, Kazuaki Chayama4,5. 1. Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. 2. Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan. 3. Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan. 4. Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. chayama@hiroshima-u.ac.jp. 5. Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan. chayama@hiroshima-u.ac.jp.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: Combination therapy with glecaprevir (GLE) and pibrentasvir (PIB) has high efficacy for pan-genotypic hepatitis C virus (HCV)-infectedpatients. However, the efficacy of the therapy for failures to prior direct-acting antiviral (DAA) regimens in real-world practice is not well known. METHODS: Thirty patientsinfected with HCV genotype 1b, 2a, 2b, or 3a who failed to respond during prior DAA therapies were treated with GLE/PIB for 12 weeks. HCVNS3 and NS5A drug resistance-associated variants (RAVs) were determined by direct sequencing. RESULTS: 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-infectedpatients 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. CONCLUSIONS:GLE/PIB treatment for HCV-infectedpatients who did not respond to prior DAA treatments was highly effective regardless of liver fibrosis stage. However, some genotype 1b HCV-infectedpatients, especially those with NS5A-P32del, may have low susceptibility to the treatment.
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