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. Issue 4 (20th October 2017)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Hepatology research. Volume 48:Issue 4(2018)
• Page Start: 233
• Page End: 243
• Publication Date: 2017-10-20
• Subjects: asunaprevir -- daclatasvir -- interferon‐β -- ledipasvir -- NS5A‐RAS -- sofosbuvir; Liver -- Diseases -- Periodicals; Liver Diseases -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1111/hepr.12980
• Languages: English
• ISSNs: 1386-6346

Abstract

Abstract : 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.