Published online Sep 8, 2017. doi: 10.4254/wjh.v9.i25.1064
Peer-review started: March 17, 2017
First decision: May 3, 2017
Revised: May 17, 2017
Accepted: July 14, 2017
Article in press: July 17, 2017
Published online: September 8, 2017
Processing time: 174 Days and 5.4 Hours
To investigate daclatasvir (DCV) and asunaprevir (ASV) efficacy in hepatitis C (HCV) patients, with respect to resistance-associated substitutions (RASs).
A total of 392 HCV-infected patients from multiple centers were included in this study. We evaluated their clinical courses and sustained virologic responses (SVR) according to pretreatment factors (gender, age, history of interferon-based regimens, platelet counts, level of viremia, pretreatment NA5A:L31, and Y93 substitutions). We also analyzed the pretreatment and post-treatment major RASs of NS3:D168, NS5A:L31 and Y93 substitutions using a direct-sequencing method in 17 patients who were unable to achieve SVR at 12 wk after treatment completion (SVR12).
The overall SVR12 rate was 88.3%. Thirty-one patients discontinued treatment before 24 wk because of adverse events, 23 of whom achieved SVR12. There were no significant differences in SVR12 rates with respect to gender, age, history of interferon-based regimens, and platelet counts. The SVR12 rate in patients with viral loads of ≥ 6.0 log IU/mL was significantly lower than those with viral loads of < 6.0 log IU/mL (P < 0.001). The SVR12 rate in patients with Y93 substitution-positive was significantly lower than those with Y93 substitution-negative (P < 0.001). The L31 substitution-positive group showed a lower SVR12 rate than the L31 substitution-negative group, but the difference was not statistically significant. Seventeen patients who did not achieve SVR12 and had available pretreatment and post-treatment sera had additional RASs in NS3:D168, NS5:L31, and Y93 substitution at treatment failure.
Combination of DCV and ASV is associated with a high SVR rate. Baseline RASs should be thoroughly assessed to avoid additional RASs after treatment failure.
Core tip: Hepatitis C - infected patients treated with daclatasvir and asunaprevir were evaluated for sustained virological response (SVR) according to pretreatment factors. The overall rate of SVR12 was 88.3%. The SVR12 rate in the ≥ 6.0 log IU/mL group was significantly lower than in the < 6.0 log IU/mL group. The SVR12 rate in Y93 substitution-positive patients was significantly lower than that in non-Y93 substitution patients. The L31 substitution-positive group had a lower SVR 12 rate than the L31 substitution-negative group. Seventeen patients who did not achieve SVR 12 had additional RASs in NS3:D168, NS5:L31, and Y93 post-treatment. Baseline RASs should be thoroughly assessed to avoid additional RASs after treatment failure.