Real-world efficacy of glecaprevir plus pibrentasvir for chronic hepatitis C patient with previous direct-acting antiviral therapy failures

• Published in: Journal of gastroenterology 2019-03, Vol.54 (3), p.291-296
• Main Authors: Osawa, Mitsutaka, Imamura, Michio, Teraoka, Yuji, Uchida, Takuro, Morio, Kei, Fujino, Hatsue, Nakahara, Takashi, Ono, Atsushi, Murakami, Eisuke, Kawaoka, Tomokazu, Miki, Daiki, Tsuge, Masataka, Hiramatsu, Akira, Aikata, Hiroshi, Hayes, C. Nelson, Chayama, Kazuaki
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Aged; Aged, 80 and over; Analysis; Antiviral agents; Antiviral Agents - adverse effects; Antiviral Agents - therapeutic use; Antiviral drugs; Benzimidazoles - therapeutic use; Biliary Tract; Care and treatment; Colorectal Surgery; Drug resistance; Female; Fibrosis; Gastroenterology; Genotype; Genotype & phenotype; Genotypes; Health aspects; Hepacivirus - genetics; Hepatitis; Hepatitis C; Hepatitis C virus; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Hepatology; Humans; Interferon; Japan; Liver; Male; Medicine; Medicine & Public Health; Middle Aged; Original Article—Liver; Pancreas; Patients; Quinoxalines - adverse effects; Quinoxalines - therapeutic use; Recurrence; Retreatment; Sulfonamides - adverse effects; Sulfonamides - therapeutic use; Surgical Oncology; Treatment Failure; Treatment Outcome
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-018-1520-9

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.