A prospective study of daclatasvir and sofosbuvir in chronic HCV-infected kidney transplant recipients

BMC Nephrol. 2019 Feb 4;20(1):36. doi: 10.1186/s12882-019-1218-0.

Abstract

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.

Keywords: Daclatasvir; Direct-acting antivirals; HCV infection; Kidney transplantation; Sofosbuvir.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Biopsy, Needle
  • Calcineurin Inhibitors / adverse effects
  • Calcineurin Inhibitors / therapeutic use
  • Carbamates / administration & dosage
  • Carbamates / pharmacology
  • Carbamates / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Glucose Intolerance / chemically induced
  • Hepacivirus / drug effects
  • Hepacivirus / isolation & purification
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / pathology
  • Heterocyclic Compounds, 4 or More Rings / administration & dosage
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Heterocyclic Compounds, 4 or More Rings / therapeutic use
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use*
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / therapy
  • Kidney Transplantation*
  • Liver / pathology
  • Macrocyclic Compounds / administration & dosage
  • Macrocyclic Compounds / pharmacology
  • Macrocyclic Compounds / therapeutic use
  • Male
  • Middle Aged
  • Prospective Studies
  • RNA, Viral / blood
  • Salvage Therapy
  • Sofosbuvir / administration & dosage
  • Sofosbuvir / therapeutic use*
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use
  • Treatment Outcome
  • Viral Load
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Viremia / complications
  • Viremia / drug therapy*
  • Viremia / pathology

Substances

  • Antiviral Agents
  • Calcineurin Inhibitors
  • Carbamates
  • Heterocyclic Compounds, 4 or More Rings
  • Imidazoles
  • Macrocyclic Compounds
  • NS-5 protein, hepatitis C virus
  • NS3 protein, hepatitis C virus
  • RNA, Viral
  • Sulfonamides
  • Viral Nonstructural Proteins
  • voxilaprevir
  • velpatasvir
  • daclatasvir
  • Sofosbuvir

Associated data

  • EudraCT/2014-004551-32