摘要
Interferon(IFN)-based therapy for hepatitis C virus(HCV) infection has recently been replaced by IFNfree direct-acting antiviral(DAA)-based therapy, which has been established as a 1^(st) line therapy with high efficacy and tolerability due to its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.
Interferon(IFN)-based therapy for hepatitis C virus(HCV) infection has recently been replaced by IFNfree direct-acting antiviral(DAA)-based therapy, which has been established as a 1^(st) line therapy with high efficacy and tolerability due to its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.
作者简介
Correspondence to:Ken Sato,MD,PhD,Associate Professor,Doctor,Department of Gastroenterology and Hepatology,Gunma University Graduate School of Medicine,3-39-22 Showa-machi,Maebashi,Gunma 371-8511,Japan.satoken@gunma-u.ac.jp Telephone:+81-272-208127 Fax:+81-272-208127.
