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: Uemura, Hayato, Uchida, Yoshihito, Kouyama, Jun‐ichi, Naiki, Kayoko, Yamaba, Shinpei, Fuchigami, Akira, Saito, Yoichi, Shiokawa, Keisuke, Fujii, Yohei, Uchiya, Hiroshi, Nakazawa, Manabu, Ando, Satsuki, Nakao, Masamitsu, Motoya, Daisuke, Sugawara, Kayoko, Inao, Mie, Imai, Yukinori, Nakayama, Nobuaki, Tomiya, Tomoaki, Mochida, Satoshi
Předmět:
Zdroj: Hepatology Research; Mar2018, Vol. 48 Issue 4, p233-243, 11p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje