Direct-acting antiviral prophylaxis in kidney transplantation from hepatitis C virus-infected donors to noninfected recipients an open-label nonrandomized trial

Christine Durand, Mary G. Bowring, Diane M. Brown, Michael Anand Chattergoon, Guido Massaccesi, Nichole Bair, Russell Wesson, Ashraf Reyad, Fizza Naqvi, Darin Bruce Ostrander, Jeremy Sugarman, Dorry Segev, Mark Sulkowski, Niraj M Desai

Research output: Contribution to journalArticle

Abstract

Background: Given the high mortality rate for patients with end-stage kidney disease receiving dialysis and the efficacy and safety of hepatitis C virus (HCV) treatments, discarded kidneys from HCV-infected donors may be a neglected public health resource. Objective: To determine the tolerability and feasibility of using direct-acting antivirals (DAAs) as prophylaxis before and after kidney transplantation from HCV-infected donors to non-HCV-infected recipients (that is, HCV D+/R transplantation). Design: Open-label nonrandomized trial. (ClinicalTrials.gov: NCT02781649) Setting: Single center. Participants: 10 HCV D+/R kidney transplant candidates older than 50 years with no available living donors. Intervention: Transplantation of kidneys from deceased donors aged 13 to 50 years with positive HCV RNA and HCV antibody test results. All recipients received a dose of grazoprevir (GZR), 100 mg, and elbasvir (EBR), 50 mg, immediately before transplantation. Recipients of kidneys from donors with genotype 1 infection continued receiving GZR-EBR for 12 weeks after transplantation; those receiving organs from donors with genotype 2 or 3 infection had sofosbuvir, 400 mg, added to GZR-EBR for 12 weeks of triple therapy. Measurements: The primary safety outcome was the incidence of adverse events related to GZR-EBR treatment. The primary efficacy outcome was the proportion of recipients with an HCV RNA level below the lower limit of quantification 12 weeks after prophylaxis. Results: Among 10 HCV D+/R transplant recipients, no treatment-related adverse events occurred, and HCV RNA was not detected in any recipient 12 weeks after treatment. Limitation: Nonrandomized study design and a small number of patients. Conclusion: Pre- and posttransplantation HCV treatment was safe and prevented chronic HCV infection in HCV D+/R- kidney transplant recipients. If confirmed in larger studies, this strategy should markedly expand organ options and reduce mortality for kidney transplant candidates without HCV infection.

Original languageEnglish (US)
Pages (from-to)523-540
Number of pages18
JournalAnnals of Internal Medicine
Volume168
Issue number8
DOIs
StatePublished - Apr 17 2018

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Hepacivirus
Kidney Transplantation
Antiviral Agents
Tissue Donors
Kidney
Transplantation
Virus Diseases
RNA
Therapeutics
Genotype
Transplants
Safety
Hepatitis C Antibodies
Mortality
Health Resources
Living Donors
Chronic Hepatitis C
Infection
Chronic Kidney Failure
Dialysis

ASJC Scopus subject areas

  • Internal Medicine

Cite this

@article{7f45017fe8e542b39f1ba386059113f0,
title = "Direct-acting antiviral prophylaxis in kidney transplantation from hepatitis C virus-infected donors to noninfected recipients an open-label nonrandomized trial",
abstract = "Background: Given the high mortality rate for patients with end-stage kidney disease receiving dialysis and the efficacy and safety of hepatitis C virus (HCV) treatments, discarded kidneys from HCV-infected donors may be a neglected public health resource. Objective: To determine the tolerability and feasibility of using direct-acting antivirals (DAAs) as prophylaxis before and after kidney transplantation from HCV-infected donors to non-HCV-infected recipients (that is, HCV D+/R transplantation). Design: Open-label nonrandomized trial. (ClinicalTrials.gov: NCT02781649) Setting: Single center. Participants: 10 HCV D+/R kidney transplant candidates older than 50 years with no available living donors. Intervention: Transplantation of kidneys from deceased donors aged 13 to 50 years with positive HCV RNA and HCV antibody test results. All recipients received a dose of grazoprevir (GZR), 100 mg, and elbasvir (EBR), 50 mg, immediately before transplantation. Recipients of kidneys from donors with genotype 1 infection continued receiving GZR-EBR for 12 weeks after transplantation; those receiving organs from donors with genotype 2 or 3 infection had sofosbuvir, 400 mg, added to GZR-EBR for 12 weeks of triple therapy. Measurements: The primary safety outcome was the incidence of adverse events related to GZR-EBR treatment. The primary efficacy outcome was the proportion of recipients with an HCV RNA level below the lower limit of quantification 12 weeks after prophylaxis. Results: Among 10 HCV D+/R transplant recipients, no treatment-related adverse events occurred, and HCV RNA was not detected in any recipient 12 weeks after treatment. Limitation: Nonrandomized study design and a small number of patients. Conclusion: Pre- and posttransplantation HCV treatment was safe and prevented chronic HCV infection in HCV D+/R- kidney transplant recipients. If confirmed in larger studies, this strategy should markedly expand organ options and reduce mortality for kidney transplant candidates without HCV infection.",
author = "Christine Durand and Bowring, {Mary G.} and Brown, {Diane M.} and Chattergoon, {Michael Anand} and Guido Massaccesi and Nichole Bair and Russell Wesson and Ashraf Reyad and Fizza Naqvi and Ostrander, {Darin Bruce} and Jeremy Sugarman and Dorry Segev and Mark Sulkowski and Desai, {Niraj M}",
year = "2018",
month = "4",
day = "17",
doi = "10.7326/M17-2871",
language = "English (US)",
volume = "168",
pages = "523--540",
journal = "Annals of Internal Medicine",
issn = "0003-4819",
publisher = "American College of Physicians",
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TY - JOUR

T1 - Direct-acting antiviral prophylaxis in kidney transplantation from hepatitis C virus-infected donors to noninfected recipients an open-label nonrandomized trial

AU - Durand, Christine

AU - Bowring, Mary G.

AU - Brown, Diane M.

AU - Chattergoon, Michael Anand

AU - Massaccesi, Guido

AU - Bair, Nichole

AU - Wesson, Russell

AU - Reyad, Ashraf

AU - Naqvi, Fizza

AU - Ostrander, Darin Bruce

AU - Sugarman, Jeremy

AU - Segev, Dorry

AU - Sulkowski, Mark

AU - Desai, Niraj M

PY - 2018/4/17

Y1 - 2018/4/17

N2 - Background: Given the high mortality rate for patients with end-stage kidney disease receiving dialysis and the efficacy and safety of hepatitis C virus (HCV) treatments, discarded kidneys from HCV-infected donors may be a neglected public health resource. Objective: To determine the tolerability and feasibility of using direct-acting antivirals (DAAs) as prophylaxis before and after kidney transplantation from HCV-infected donors to non-HCV-infected recipients (that is, HCV D+/R transplantation). Design: Open-label nonrandomized trial. (ClinicalTrials.gov: NCT02781649) Setting: Single center. Participants: 10 HCV D+/R kidney transplant candidates older than 50 years with no available living donors. Intervention: Transplantation of kidneys from deceased donors aged 13 to 50 years with positive HCV RNA and HCV antibody test results. All recipients received a dose of grazoprevir (GZR), 100 mg, and elbasvir (EBR), 50 mg, immediately before transplantation. Recipients of kidneys from donors with genotype 1 infection continued receiving GZR-EBR for 12 weeks after transplantation; those receiving organs from donors with genotype 2 or 3 infection had sofosbuvir, 400 mg, added to GZR-EBR for 12 weeks of triple therapy. Measurements: The primary safety outcome was the incidence of adverse events related to GZR-EBR treatment. The primary efficacy outcome was the proportion of recipients with an HCV RNA level below the lower limit of quantification 12 weeks after prophylaxis. Results: Among 10 HCV D+/R transplant recipients, no treatment-related adverse events occurred, and HCV RNA was not detected in any recipient 12 weeks after treatment. Limitation: Nonrandomized study design and a small number of patients. Conclusion: Pre- and posttransplantation HCV treatment was safe and prevented chronic HCV infection in HCV D+/R- kidney transplant recipients. If confirmed in larger studies, this strategy should markedly expand organ options and reduce mortality for kidney transplant candidates without HCV infection.

AB - Background: Given the high mortality rate for patients with end-stage kidney disease receiving dialysis and the efficacy and safety of hepatitis C virus (HCV) treatments, discarded kidneys from HCV-infected donors may be a neglected public health resource. Objective: To determine the tolerability and feasibility of using direct-acting antivirals (DAAs) as prophylaxis before and after kidney transplantation from HCV-infected donors to non-HCV-infected recipients (that is, HCV D+/R transplantation). Design: Open-label nonrandomized trial. (ClinicalTrials.gov: NCT02781649) Setting: Single center. Participants: 10 HCV D+/R kidney transplant candidates older than 50 years with no available living donors. Intervention: Transplantation of kidneys from deceased donors aged 13 to 50 years with positive HCV RNA and HCV antibody test results. All recipients received a dose of grazoprevir (GZR), 100 mg, and elbasvir (EBR), 50 mg, immediately before transplantation. Recipients of kidneys from donors with genotype 1 infection continued receiving GZR-EBR for 12 weeks after transplantation; those receiving organs from donors with genotype 2 or 3 infection had sofosbuvir, 400 mg, added to GZR-EBR for 12 weeks of triple therapy. Measurements: The primary safety outcome was the incidence of adverse events related to GZR-EBR treatment. The primary efficacy outcome was the proportion of recipients with an HCV RNA level below the lower limit of quantification 12 weeks after prophylaxis. Results: Among 10 HCV D+/R transplant recipients, no treatment-related adverse events occurred, and HCV RNA was not detected in any recipient 12 weeks after treatment. Limitation: Nonrandomized study design and a small number of patients. Conclusion: Pre- and posttransplantation HCV treatment was safe and prevented chronic HCV infection in HCV D+/R- kidney transplant recipients. If confirmed in larger studies, this strategy should markedly expand organ options and reduce mortality for kidney transplant candidates without HCV infection.

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