Retreatment with sofosbuvir/ledipasvir with or without lead-in interferon-β injections in patients infected with genotype 1b hepatitis C virus after unsuccessful daclatasvir/asunaprevir therapy
| Autor: | Manabu Nakazawa, Yukinori Imai, Yoichi Saito, Masamitsu Nakao, Yohei Fujii, Hayato Uemura, Satoshi Mochida, Yoshihito Uchida, Mie Inao, Tomoaki Tomiya, Kayoko Sugawara, Keisuke Shiokawa, Kayoko Naiki, Daisuke Motoya, Shinpei Yamaba, Nobuaki Nakayama, Satsuki Ando, Jun-ichi Kouyama, Hiroshi Uchiya, Akira Fuchigami |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Simeprevir Ledipasvir Daclatasvir Hepatology Sofosbuvir business.industry Hepatitis C virus 030106 microbiology virus diseases medicine.disease_cause Virology digestive system diseases Viral Relapse 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Infectious Diseases chemistry Interferon medicine Asunaprevir 030211 gastroenterology & hepatology business medicine.drug |
| Zdroj: | Hepatology Research. 48:233-243 |
| ISSN: | 1386-6346 |
| DOI: | 10.1111/hepr.12980 |
| Popis: | Aim To improve the therapeutic efficacy of sofosbuvir/ledipasvir (SOF/LDV) for the retreatment of patients after daclatasvir/asunaprevir (DCV/ASV), a customized therapy with or without lead-in interferon (IFN)-β injections was formulated according to the types of resistance-associated substitutions (RAS) in the non-structural protein (NS)5A region of genotype 1b hepatitis C virus (HCV). Methods Thirty-three patients failing prior DCV/ASV received SOF/LDV for 12 weeks. Patients with HCV carrying unfavorable NS5A-RAS and/or those previously treated with simeprevir were given lead-in IFN-β injections twice a day for 2 weeks; sequential changes in the NS5A-RAS during the injection period were evaluated using deep sequencing. Results Lead-in injections were not undertaken in 27 patients; a sustained viral response (SVR) was achieved in 26 patients, while viral relapse occurred in 1 patient with HCV carrying NS5A-L28M/R30H/Y93H mutations. Among the 6 patients receiving lead-in injections, viral relapse occurred in 2 patients who had an unfavorable IFN-λ3-related gene single nucleotide polymorphism allele; both patients had been previously treated with simeprevir, and HCV carrying NS5A-L31V/Y93H mutations had emerged after DCV/ASV. Deep sequencing revealed no changes in the NS5A-RAS profiles during the lead-in injection period in either patient. In contrast, in a patient with a favorable allele who was infected with similar unfavorable HCV strains, NS5A-L31/Y93 wild-type strains appeared during the injection period, enabling an SVR. Conclusion Using customized therapies based on the NS5A-RAS profiles, a high SVR rate was obtained after SOF/LDV in patients failing prior DCV/ASV. Lead-in IFN-β injections did not improve the efficacy in patients with HCV carrying unfavorable NS5A-RAS except in those with a favorable IFN-λ3-related gene allele. |
| Databáze: | OpenAIRE |
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