Significance of variants associated with resistance to NS5A inhibitors in Japanese patients with genotype 1b hepatitis C virus infection as evaluated using cycling-probe real-time PCR combined with direct sequencing

Abstract

NS5A-Y93H mutation was associated with sex, serum AFP levels, and IL28B-related gene polymorphisms in patients infected with genotype 1b HCV. The indications for NS5A inhibitor use should be determined based on these factors, since mutant strains seem to be sensitive to interferon.

A case of genotype‐3b hepatitis C virus in which the whole genome was successfully analyzed using third‐generation nanopore sequencing

“…Illumina sequencing is also useful to clarify viral factors involved in virologic failure in patients with HCV receiving DAA therapies. Recently, we reported “reversi‐type virologic failure” involved in the development of NS5A RASs in patients with genotype 1b HCV carrying no signature RASs at baseline of DAA therapies, using Illumina sequencing in combination with cycling‐probe real‐time polymerase chain reaction (PCR) . Moreover, Illumina sequencing revealed that rare NS5A RASs showing extreme tolerance against NS5A replication complex inhibitors could develop during DAA therapies through a two‐hit mechanism .…”

Development of rare resistance‐associated variants that are extremely tolerant against NS5A inhibitors during daclatasvir/asunaprevir therapy by a two‐hit mechanism

“…Also, all patients receiving previous triple therapy with telaprevir achieved SVR12. Recently, we reported that HCV strains with NS5A‐Y93H mutation were more sensitive to IFN/Peg‐IFN than wild‐type HCV strains . In the present study, NS5A‐Y93H mutant HCV strains were found less frequently among patients with previous IFN/Peg‐IFN therapy (5/100; 5.0%) than among the treatment‐naïve patients (17/106; 16.0%) ( P = 0.01).…”

“…Thus, we developed a simple assay procedure to quantify the percentage of HCV‐RNA levels of NS5A‐Y93H mutant strains and NS5A‐Y93 wild‐type strains relative to the total HCV‐RNA levels using cycling‐probe real‐time polymerase chain reaction (PCR) and established a diagnostic system in combination with direct sequencing to evaluate NS5A‐RAVs, including L31M/V and Y93H/C mutations . This novel system revealed that mixed NS5A‐Y93 wild‐type and NS5A‐Y93H mutant HCV strains were found in 11.9% and exclusive NS5A‐Y93H mutant HCV strains were found in 8.7% of 444 Japanese patients with genotype‐1b HCV.…”

“…This novel system revealed that mixed NS5A‐Y93 wild‐type and NS5A‐Y93H mutant HCV strains were found in 11.9% and exclusive NS5A‐Y93H mutant HCV strains were found in 8.7% of 444 Japanese patients with genotype‐1b HCV. Exclusive NS5A‐L31M/V mutant HCV strains and both NS5A‐Y93H and NS5A‐L31M mutant HCV strains were found in only 1.8% and 0.4%, respectively, and other RAVs in NS5A regions were not detected …”

Mechanisms of Virologic Failure in Hepatitis C and Strategies for Treatment Failure

“…Virologic failure during dual oral therapy may develop more frequently among women than among men. The TT allele was detected more frequently among female patients than male patients [21]. An elevated body mass index and GT1a disease have emerged as the most important factors limiting treatment success in the general population [15].…”