A prospective study of daclatasvir and sofosbuvir in chronic HCV-infected kidney transplant recipients.
Adult
Aged
Aminoisobutyric Acids
Antiviral Agents
/ administration & dosage
Biopsy, Needle
Calcineurin Inhibitors
/ adverse effects
Carbamates
/ administration & dosage
Cyclopropanes
Drug Therapy, Combination
Female
Glucose Intolerance
/ chemically induced
Hepacivirus
/ drug effects
Hepatitis C, Chronic
/ complications
Heterocyclic Compounds, 4 or More Rings
/ administration & dosage
Humans
Imidazoles
/ administration & dosage
Kidney Failure, Chronic
/ complications
Kidney Transplantation
Lactams, Macrocyclic
Leucine
/ analogs & derivatives
Liver
/ pathology
Macrocyclic Compounds
/ administration & dosage
Male
Middle Aged
Proline
/ analogs & derivatives
Prospective Studies
Pyrrolidines
Quinoxalines
RNA, Viral
/ blood
Salvage Therapy
Sofosbuvir
/ administration & dosage
Sulfonamides
/ administration & dosage
Treatment Outcome
Valine
/ analogs & derivatives
Viral Load
Viral Nonstructural Proteins
/ antagonists & inhibitors
Viremia
/ complications
Daclatasvir
Direct-acting antivirals
HCV infection
Kidney transplantation
Sofosbuvir
Journal
BMC nephrology
ISSN: 1471-2369
Titre abrégé: BMC Nephrol
Pays: England
ID NLM: 100967793
Informations de publication
Date de publication:
04 02 2019
04 02 2019
Historique:
received:
10
10
2018
accepted:
17
01
2019
entrez:
6
2
2019
pubmed:
6
2
2019
medline:
8
2
2020
Statut:
epublish
Résumé
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. 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/1.73m 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. 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. Registry name: European Clinical Trials Register; Trial registry number (Eudra-CT): 2014-004551-32 , Registration date: Aug 28th 2015.
Sections du résumé
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/1.73m
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.
Identifiants
pubmed: 30717681
doi: 10.1186/s12882-019-1218-0
pii: 10.1186/s12882-019-1218-0
pmc: PMC6360788
doi:
Substances chimiques
Aminoisobutyric Acids
0
Antiviral Agents
0
Calcineurin Inhibitors
0
Carbamates
0
Cyclopropanes
0
Heterocyclic Compounds, 4 or More Rings
0
Imidazoles
0
Lactams, Macrocyclic
0
Macrocyclic Compounds
0
NS3 protein, hepatitis C virus
0
Pyrrolidines
0
Quinoxalines
0
RNA, Viral
0
Sulfonamides
0
Viral Nonstructural Proteins
0
voxilaprevir
0570F37359
Proline
9DLQ4CIU6V
NS-5 protein, hepatitis C virus
EC 2.7.7.48
Leucine
GMW67QNF9C
Valine
HG18B9YRS7
velpatasvir
KCU0C7RS7Z
daclatasvir
LI2427F9CI
Sofosbuvir
WJ6CA3ZU8B
Banques de données
EudraCT
['2014-004551-32']
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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