Published online Jan 27, 2018. doi: 10.4254/wjh.v10.i1.88
Peer-review started: October 2, 2017
First decision: November 27, 2017
Revised: December 6, 2017
Accepted: December 13, 2017
Article in press: December 13, 2017
Published online: January 27, 2018
In a previous study, it was shown that resistance-associated substitutions (RASs) were predictors of direct-acting antiviral (DAA) failure. No significant adverse effect was reported in the DAA treatment in clinical trials. In this study, the prestudy hypothesis was that another predictor might exist concerning about DAA failure. Another hypothesis was that more severe adverse effects must occur in the real world because patients conditions were more severe than those of clinical trials.
DAAs have been approved for the treatment of hepatitis C virus (HCV) genotype 1 and 2 infections in Japan since 2011. In the new era of DAA therapy, predictors who fail to respond to DAA might be compromised by RASs. There have been few reports of daclatasvir/asunaprevir (DCV/ASV) failure because DCV/ASV is limited in Japan. Therefore, it might be important to report these cases for future research and treatment of HCV.
All patients with HCV infection who underwent DAA prescription were enrolled in this study. Overall, 177 participants treated with DAAs and in whom sustained virologic response at 12 wk after therapy (SVR12) was judged between November 2012 and March 2017 at Kanto Rosai Hospital were included.
HCV patients who underwent DAA prescription were enrolled in this study. Resistance analysis was performed by using direct sequencing and cycleave PCR. Multiple regression analysis was performed to evaluate factors related to loss of HCV RNA.
In total, 117 patients participated in the study, including 135 with genotype 1 and 42 with genotype 2. Of the 135 patients with genotype 1, 16 received protease inhibitor + interferon + ribavirin and all achieved SVR. Of the 119 patients who received interferon-free DAA (in different combinations), 102 achieved SVR while 9 failed, including 7/9 who were on DCV/ASV and 2/9 who were on ledipasvir/sofosbuvir. Efficacy analysis was done only for 42 patients who received DCV/ASV. From this analysis, Y93 RASs were significantly correlated with SVR.
The SVR rate was 98% for genotype 1 and 100% for genotype 2. NS5A RASs are most likely to affect the outcomes of DAA therapy in our facility.
The SVR rate was 98% for genotype 1 and 100% for genotype 2. However, caution is needed for HCV NS5A RASs that are selected by HCV NS5A inhibitors because cerebrovascular adverse events are induced by some DAA drugs.