The Daclatasvir/Asunaprevir/Beclabuvir Combination Therapy for Chronic Hepatitis C Patients Experiencing Failure of IFN-Free DAA-Based Therapies

Background: Daclatasvir/asunaprevir/beclabuvir (DCV/ASV/BCV) combination therapy had been available for the treatment of chronic hepatitis C patients with genotype 1 (CHG1) in Japan. Our aim was to report the efficacy and safety of DCV/ASV/BCV in patients experiencing treatment failure with interferon (IFN)-free direct-acting antiviral agent (DAA)-based therapies, which have not been fully evaluated. Methods: We evaluated the efficacy and safety of 12-week DCV/ASV/BCV combination therapy for CHG1 patients experiencing failure of DCV/ASV and/or sofosbuvir/ledipasvir (SOF/LDV). Results: Nine patients were eligible for inclusion in this study. The previous IFN-free DAA-based therapies included DCV/ASV (n=7). SOF/LDV (n=1) and both DCV/ASV and SOF/LDV (n=1). The sustained virologic response at post-treatment week (PTW) 24 (SVR24) rate was 33.3% (3/9) and an SVR24 was obtained in patients who previously received DCV/ASV. Notably, virologic relapse occurred at PTW16 or 18 in 2 patients. “D168E or D168H in addition to Y93H”, “presumed L31 deletion (L31del) and/or P32del”, and “P29del” might contribute to the resistance to DCV/ASV/BCV combination therapy. One patient developed Grade 3 liver dysfunction but treatment could be completed with dose modification. Conclusions: The efficacy of DCV/ASV/BCV combination therapy in patients who experienced treatment failure with IFN-free DAA-based combination regimens was unsatisfactory, although the therapy was relatively well-tolerated. As virologic relapse occurred after PTW 12 in two cases, an SVR24 might be more suitable for judging viral eradication than an SVR12. The role of resistance-associated substitutions in patients who experience treatment failure with DCV/ASV/BCV combination therapy should be further evaluated.