کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6088406 1207703 2015 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Liver, Pancreas and Biliary TractKinetics of hepatitis C virus RNA decay, quasispecies evolution and risk of virological failure during telaprevir-based triple therapy in clinical practice
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی غدد درون ریز، دیابت و متابولیسم
پیش نمایش صفحه اول مقاله
Liver, Pancreas and Biliary TractKinetics of hepatitis C virus RNA decay, quasispecies evolution and risk of virological failure during telaprevir-based triple therapy in clinical practice
چکیده انگلیسی

BackgroundThe used first generation protease inhibitors may be hampered by virological failure in partially interferon-sensitive patients.AimTo investigate early hepatitis C virus (HCV)-RNA decay and quasispecies modifications, and disclose viral dynamics underlying failure.MethodsViraemia decay at early time-points during telaprevir treatment was modelled according to Neumann et al. (1998). NS3-sequences were obtained by population-sequencing and ultradeep-454-pyrosequencing.Results13 treatment-experienced (8 non-responders, 5 relapsers), and two cirrhotic naïve patients, received telaprevir + pegylated-interferon-α + ribavirin.Viraemia decay was biphasic. In all patients, first-phase was rapid and consistent, with a median [interquartile-range] viraemia decay of 2.8 [2.6-3.2] log IU/ml within 48 h. Second-phase decay was slower, especially in failing patients: 3/3 showed <1 log IU/ml decay between 48 h and 2 weeks, and HCV-RNA >100 IU/ml at week 2. Only one patient experiencing sustained viral response showed similar kinetics.By pyrosequencing, mutational freeze was observed in all 15 patients within the first 24 h, but only in patients with sustained response afterwards. Indeed, 2/2 failing patients showed early resistance, as minor (V36A-T54A: prevalence <26% at 48 h) or major (V36M/A-R155K: prevalence, 99.8% at week 2) variants.ConclusionsFollowing telaprevir administration, first-phase HCV-RNA decay is consistent with mutational freeze and limited/no viral replication, while second-phase is significantly slower in failing patients (with appearance of resistance), suggesting the usefulness of early HCV-RNA monitoring.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Digestive and Liver Disease - Volume 47, Issue 3, March 2015, Pages 233-241
نویسندگان
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