We describe a case with viral breakthrough of hepatitis C virus (HCV) during the treatment of daclatasvir/asunaprevir/beclabuvir (DCV/ASV/BCV). The case is a 63-year-old man with HCV-associated cirrhosis, who failed to respond to previous direct-acting antiviral agent (DAA) regimens including DCV/ASV and ledipasvir/sofosbuvir. Sequence analyses of HCV-NS3, NS5A and NS5B regions revealed that he had acquired an additional substitution of P495L in NS5B region at viral breakthrough, with another substitution as C451Y simultaneously. Although the data from phase III clinical trials in Japanese patients infected with HCV genotype 1 displayed no virological failures, our case indicates that retreatment with DCV/ASV/BCV in failures to prior DAA regimens can result in the emergence of a new NS5B resistance-associated substitution like P495L.
