Efficacy of daclatasvir/asunaprevir according to resistance-associated variants in chronic hepatitis C with genotype 1

Abstract

History of SMV therapy and pre-existing NS5A Y93H were associated with virological failure of DCV/ASV therapy, resulting in the emergence of multiple RAVs. Patients with RAVs at baseline should be assessed to optimize future DAA therapies.

Clinical evaluation of sofosbuvir/ledipasvir in patients with chronic hepatitis C genotype 1 with and without prior daclatasvir/asunaprevir therapy

“…In the present study, 32.8% patients had the NS5A 93 and/or 31 variant at baseline, but no correlation was observed between SVR12 and the NS5A Y93H variant status at baseline. However, multiple NS5A RAVs (≥2) emerged after virological failure of SOF/LDV, as experienced after DCV/ASV treatment failure . Among 26 patients with prior DCV/ASV therapy, the prevalence of NS5A multi‐RAVs (≥2) did not differ significantly between responders (SVR12) and non‐responders to SOF/LDV therapy (61.1% vs. 75.0%).…”

“…The DCV and ASV combination therapy was particularly valuable for IFN intolerant or ineligible patients, such as those with depression, LC, the elderly and patients with renal failure, as well as pegylated‐IFN plus ribavirin‐based regimen non‐responders. Although DCV/ASV therapy for 24 weeks improved the efficacy and safety outcomes for patients with HCV infection, approximately 10% of patients could not achieve SVR and, finally, multiple NS5A resistance‐associated variants (RAVs) emerged after DCV/ASV failure . In 2015, sofosbuvir (SOF), an oral nucleotide analog inhibitor of the HCV NS5B polymerase plus ledipasvir (LDV), a second‐in‐class NS5A inhibitor, were approved in Japan.…”

Real-World Experiences with the Combination Treatment of Ledipasvir plus Sofosbuvir for 12 Weeks in HCV Genotype 1-Infected Japanese Patients: Achievement of a Sustained Virological Response in Previous Users of Peginterferon plus Ribavirin with HCV NS3/4A Inhibitors

“…In Japan, HCV genotype 1b (GT1b) occupied 70% of HCV infection and HCV GT1a is rare [8]. The combination of the HCV NS3/4A inhibitor asunaprevir and the HCV NS5A inhibitor daclatasvir for 24 weeks was the first approved interferon-free treatment against HCV GT1b patients in July, 2014 [7,9]. Although several guidelines recommended the measurement of HCV NS5A resistance-associated variants (RAVs) before this treatment, the treatment failure of the combination of asunaprevir and daclatasvir introduced multiple RAVs into the HCV NS3/4A and NS5A regions [10,11].…”

“…Although several guidelines recommended the measurement of HCV NS5A resistance-associated variants (RAVs) before this treatment, the treatment failure of the combination of asunaprevir and daclatasvir introduced multiple RAVs into the HCV NS3/4A and NS5A regions [10,11]. We do not use the combination of asunaprevir and daclatasvir for HCV GT1 patients with peginterferon plus ribavirin with NS3/4A protease simeprevir failure [12], because 66.7% of patients with prior peginterferon plus ribavirin with simeprevir failure had virological failure in the retreatment with the combination of asunaprevir and daclatasvir [9]. …”

Early recurrence of hepatocellular carcinoma in patients with HCV infection followed by transient elastography for two years after successful treatment with daclatasvir plus asunaprevir

“…In Japan, daclatasvir (DCV) plus asunaprevir (ASV) was the first-generation treatment option approved for chronic HCV genotype 1b patients in September 2014 [5]. Without a previous history of simeprevir therapy and pre-existing NS5A Y93H, DCV plus ASV was reported to be approximately 90% effective for patients with HCV genotype 1b [7]. DAA were recently shown to achieve sustained virological responses (SVR) in more than 90% of HCV-infected patients, even those with severe fibrosis.…”