| Abstract: | Daclatasvir is a novel NS5A inhibitor of hepatitis C virus (HCV). Daclatasvir combined with peginterferon α-2a and ribavirin in Japanese patients infected with genotype 1b HCV achieved sustained virological response (SVR) in 100% of treatment-naïve patients, due to high rates of favorable IL28B allele and genotype 1b. SVR 24 was achieved by asunaprevir and daclatasvir in 87.4% of intolerant and 80.5% of nonresponder patients. Baseline NS5A-resistant variants were detected and they failed to achieve SVR. Most patients with genotype 1a experienced virological breakthrough by dual oral treatment, and should be treated QUAD or replaced by all oral regimens that are more potent and have fewer side effects. IFN-free regimens including daclatasvir and asunaprevir for genotype 1 null responders should be tailored to subtype, and preexisting NS5A-resistant variants should be evaluated carefully before choosing the drugs. This regimen alone is unlikely to move forward without additional agents. |
