title: Impact of HCV kinetics on treatment outcome differs by the type of real-time HCV assay in NS3/4A protease inhibitor-based triple therapy.
abstract: Repeated measurement of the HCV RNA level is essential for properly monitoring treatment efficacy. The aim of this study was to determine the utility of two HCV real-time assays in the evaluation of the impact of hepatitis C virus (HCV) kinetics on the outcome of triple therapy with NS3/4A protease inhibitors (PIs), telaprevir or simeprevir. This study consisted of 171 Japanese patients infected with HCV genotype 1. All 3266 serum samples taken during and post treatment were tested with both the COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) HCV Test v2.0 and the Abbott RealTime (ART) HCV Test. Of the 2597 samples undetectable (lower limit of detection [<LOD]) for HCV RNA by the CAP/CTM assay from the on and post treatment, 400 (15.4%) (369 detectable/less than the lower limitation of quantification [<LLOQ] and 31 quantifiable) were detectable by the ART assay. HCV RNA < LOD within the first four weeks by ART was associated with sustained virological response (SVR) for the difficult-to-treat group that included patients with advanced fibrosis or prior partial/null response. In contrast, for the non-difficult-to-treat group, almost all of the late responders by ART achieved SVR, unlike by CAP/CTM. Despite HCV RNA being once < LOD by ART, 33.1% patients experienced the reappearance of residual HCV RNA (detectable/<LLOQ) during treatment. This event in the first 12 weeks (with PI-treatment period) was not related to treatment failure, however, relapse was observed in all patients with a reappearance of residual HCV RNA after 12 weeks (without PI-treatment period). The superior ability to detect low-level HCV RNA by ART could be useful for predicting SVR by difficult-to-treat patients in the early period and relapse in the late period.
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan. Electronic address: eogawa@gim.med.kyushu-u.ac.jp.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ogawa
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Furusyo
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Murata
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Haru
authors.initials: H
authors.lastname: Mukae
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Toyoda
authors.affiliation: Department of Clinical Chemistry and Laboratory of Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Hotta
authors.affiliation: Department of Clinical Chemistry and Laboratory of Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uchiumi
authors.affiliation: Kyushu General Internal Medicine Center, Haradoi Hospital, Fukuoka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hayashi
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D011480:Protease Inhibitors; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C080107:NS4B protein, flavivirus
keywords: Hepatitis C virus; Pegylated interferon; Protease inhibitor; Real-time PCR; Simeprevir