Published online Oct 14, 2018. doi: 10.3748/wjg.v24.i38.4304
Peer-review started: July 17, 2018
First decision: July 25, 2018
Revised: August 2, 2018
Accepted: August 24, 2018
Article in press: August 24, 2018
Published online: October 14, 2018
Processing time: 86 Days and 23.1 Hours
Interferon (IFN)-based therapy for hepatitis C virus (HCV) infection has recently been replaced by IFN-free direct-acting antiviral (DAA)-based therapy, which has been established as a 1st line therapy with high efficacy and tolerability due to its reasonable safety profile. Resistance-associated substitutions (RASs) have been a weakness of DAA-based therapy. For example, combination therapy with daclatasvir and asunaprevir (DCV/ASV) is less effective for HCV genotype 1-infected patients with Y93H as a nonstructural protein 5A RAS. However, the problem regarding RASs has been gradually overcome with the advent of recently developed DAAs, such as sofosbuvir-based regimens or combination therapy with glecaprevir and pibrentasvir. Despite the high efficiency of DAA-based therapy, some cases fail to achieve viral eradication. P32 deletion, an NS5A RAS, has been gradually noticed in patients with DCV/ASV failure. P32 deletion has been sporadically reported and the prevalence of this RAS has been considered to be low in patients with DCV/ASV failure. Thus, the picture of P32 deletion has not been fully evaluated. Importantly, currently-commercialized DAA-based combination therapy was not likely to be effective for patients with P32 deletion. Exploring and overcoming this RAS is essential for antiviral therapy for chronic hepatitis C.
Core tip: P32 deletion, as a nonstructural protein 5A resistance-associated substitution (RAS), has been gradually noticed in patients who experience treatment failure associated with daclatasvir and asunaprevir as an antiviral therapy for chronic hepatitis C. Information regarding P32 deletion is very limited at the present. Although the prevalence of this RAS is assumed to be low, it was found to be a new threat to current direct-acting antiviral-based combination therapy. There is an urgent need for further basic and clinical studies on this RAS. Exploring and overcoming this RAS is essential for antiviral therapy for chronic hepatitis C.