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

• Published in: Hepatology research Vol. 48; no. 4; pp. 233 - 243
• Main 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
• Format: Journal Article
• Language: English
• Published: Netherlands Wiley Subscription Services, Inc 01-03-2018
• Subjects: Alleles; asunaprevir; daclatasvir; Gene polymorphism; Genotypes; Hepatitis; Hepatitis C; Injection; Interferon; interferon‐β; ledipasvir; Mutation; NS5A‐RAS; Patients; Single-nucleotide polymorphism; sofosbuvir; Strains (organisms); ledipasvir; sofosbuvir; NS5A-RAS; asunaprevir; interferon-β; daclatasvir
• ISSN: 1386-6346; 1872-034X
• DOI: 10.1111/hepr.12980

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.