BMC nephrology · 2019
A prospective study of daclatasvir and sofosbuvir in chronic HCV-infected kidney transplant recipients.
Клиническое исследование II фазыСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Duerr Michael, Schrezenmeier Eva V, Lehner Lukas J, Bergfeld Léon, Glander Petra, Marticorena Garcia Stephan R, Althoff Christian E, Sack Ingolf, Brakemeier Susanne, Eckardt Kai-Uwe, Budde Klemens, Halleck Fabian
Аннотация
BACKGROUND: Only a few prospective trials exist regarding the use of novel direct-acting antiviral agents (DAAs) in kidney transplant recipients (KTR) with chronic hepatitis C virus (HCV) infection.
METHODS: This prospective single-center trial evaluated treatment with daclatasvir (DCV) and sofosbuvir (SOF) over 12 weeks in 16 adult chronic HCV infected KTR and eGFR > 30 ml/min/1.73m2. Primary endpoint was sustained virological response 12 weeks after end of therapy (SVR12). Beside baseline liver biopsy, hepatic function and glucose metabolism were regularly assessed.
RESULTS: Four of 16 study patients had previously failed interferon-based HCV treatment. Liver biopsy showed mostly moderate fibrosis score before therapy with DCV/SOF was initiated at a median of 10.3 years after transplantation. In total, 15 of 16 KTR achieved SVR12. One patient showed early viral relapse because of resistance-associated variants (RAVs) in the HCV NS5A region. Rescue treatment with SOF/velpatasvir/voxilaprevir resulted in SVR12. DAAs treatment led to significant improvement of liver metabolism and glucose tolerance accompanied with no therapy-associated major adverse events and excellent tolerability.
CONCLUSIONS: Our study demonstrates safety, efficacy and functional benefit of DCV/SOF treatment in KTR with chronic HCV infection. We provide data on rescue strategies for treatment failures due to present RAVs and amelioration of hepatic function and glucose tolerance.
TRIAL REGISTRATION: Registry name: European Clinical Trials Register; Trial registry number (Eudra-CT): 2014-004551-32 , Registration date: Aug 28th 2015.
METHODS: This prospective single-center trial evaluated treatment with daclatasvir (DCV) and sofosbuvir (SOF) over 12 weeks in 16 adult chronic HCV infected KTR and eGFR > 30 ml/min/1.73m2. Primary endpoint was sustained virological response 12 weeks after end of therapy (SVR12). Beside baseline liver biopsy, hepatic function and glucose metabolism were regularly assessed.
RESULTS: Four of 16 study patients had previously failed interferon-based HCV treatment. Liver biopsy showed mostly moderate fibrosis score before therapy with DCV/SOF was initiated at a median of 10.3 years after transplantation. In total, 15 of 16 KTR achieved SVR12. One patient showed early viral relapse because of resistance-associated variants (RAVs) in the HCV NS5A region. Rescue treatment with SOF/velpatasvir/voxilaprevir resulted in SVR12. DAAs treatment led to significant improvement of liver metabolism and glucose tolerance accompanied with no therapy-associated major adverse events and excellent tolerability.
CONCLUSIONS: Our study demonstrates safety, efficacy and functional benefit of DCV/SOF treatment in KTR with chronic HCV infection. We provide data on rescue strategies for treatment failures due to present RAVs and amelioration of hepatic function and glucose tolerance.
TRIAL REGISTRATION: Registry name: European Clinical Trials Register; Trial registry number (Eudra-CT): 2014-004551-32 , Registration date: Aug 28th 2015.
Предметные рубрики MeSH
AdultAgedAminoisobutyric AcidsAntiviral AgentsBiopsy, NeedleCalcineurin InhibitorsCarbamatesCyclopropanesDrug Therapy, CombinationFemaleGlucose IntoleranceHepacivirusHepatitis C, ChronicHeterocyclic Compounds, 4 or More RingsHumansImidazolesKidney Failure, ChronicKidney TransplantationLactams, MacrocyclicLeucineLiverMacrocyclic CompoundsMaleMiddle AgedProlineProspective StudiesPyrrolidinesQuinoxalinesRNA, ViralSalvage TherapySofosbuvirSulfonamidesTreatment OutcomeValineViral LoadViral Nonstructural ProteinsViremiaSerine EndopeptidasesNucleoside-TriphosphataseDEAD-box RNA HelicasesViral ProteasesRNA-Dependent RNA PolymeraseBenzimidazolesBenzopyrans