Transplanting hepatitis C virus-infected hearts into uninfected recipients: A single-arm trial.
Adult
Aged
Amides
Antiviral Agents
/ therapeutic use
Benzofurans
/ administration & dosage
Carbamates
Cyclopropanes
Female
Genotype
Graft Rejection
Heart Failure
/ complications
Heart Transplantation
/ adverse effects
Heart-Assist Devices
Hepacivirus
/ genetics
Hepatitis C
/ drug therapy
Humans
Imidazoles
/ administration & dosage
Male
Middle Aged
Postoperative Period
Quinoxalines
/ administration & dosage
RNA, Viral
/ analysis
Sulfonamides
Sustained Virologic Response
Time Factors
Tissue and Organ Procurement
Treatment Outcome
Viral Load
Waiting Lists
clinical research/practice
heart (allograft) function/dysfunction
heart failure/injury
heart transplantation/cardiology
infection and infectious agents - viral
organ allocation
organ procurement and allocation
organ transplantation in general
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
20
12
2018
revised:
10
02
2019
accepted:
11
02
2019
pubmed:
16
2
2019
medline:
24
9
2020
entrez:
16
2
2019
Statut:
ppublish
Résumé
The advent of direct-acting antiviral therapy for hepatitis C virus (HCV) has generated tremendous interest in transplanting organs from HCV-infected donors. We conducted a single-arm trial of orthotopic heart transplantation (OHT) from HCV-infected donors into uninfected recipients, followed by elbasvir/grazoprevir treatment after recipient HCV was first detected (NCT03146741; sponsor: Merck). We enrolled OHT candidates aged 40-65 years; left ventricular assist device (LVAD) support and liver disease were exclusions. We accepted hearts from HCV-genotype 1 donors. From May 16, 2017 to May 10, 2018, 20 patients consented for screening and enrolled, and 10 (median age 52.5 years; 80% male) underwent OHT. The median wait from UNOS opt-in for HCV nucleic-acid-test (NAT)+ donor offers to OHT was 39 days (interquartile range [IQR] 17-57). The median donor age was 34 years (IQR 31-37). Initial recipient HCV RNA levels ranged from 25 IU/mL to 40 million IU/mL, but all 10 patients had rapid decline in HCV NAT after elbasvir/grazoprevir treatment. Nine recipients achieved sustained virologic response at 12 weeks (SVR-12). The 10th recipient had a positive cross-match, experienced antibody-mediated rejection and multi-organ failure, and died on day 79. No serious adverse events occurred from HCV transmission or treatment. These short-term results suggest that HCV-negative candidates transplanted with HCV-infected hearts have acceptable outcomes.
Identifiants
pubmed: 30768838
doi: 10.1111/ajt.15311
pii: S1600-6135(22)09228-0
doi:
Substances chimiques
Amides
0
Antiviral Agents
0
Benzofurans
0
Carbamates
0
Cyclopropanes
0
Imidazoles
0
Quinoxalines
0
RNA, Viral
0
Sulfonamides
0
grazoprevir
4O2AB118LA
elbasvir
632L571YDK
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2533-2542Subventions
Organisme : Merck
Pays : International
Informations de copyright
© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.
Références
OPTN/UNOS data. https://unos.org/data/. Accessed November 30, 2018.
Goldberg DS, Blumberg E, McCauley M, Abt P, Levine M. Improving organ utilization to help overcome the tragedies of the opioid epidemic. Am J Transplant. 2016;16(10):2836-2841.
Reese PP, Abt PL, Blumberg EA, Goldberg DS. Transplanting hepatitis C-positive kidneys. N Engl J Med. 2015;373(4):303-305.
Levitsky J, Formica RN, Bloom RD, et al. The American Society of Transplantation Consensus Conference on the use of hepatitis C viremic donors in solid organ transplantation. Am J Transplant. 2017;17(11):2790-2802.
Schlendorf KH, Zalawadiya S, Shah AS, et al. Early outcomes using hepatitis C-positive donors for cardiac transplantation in the era of effective direct-acting anti-viral therapies. J Heart Lung Transplant. 2018;37(6):763-769.
Gasink LB, Blumberg EA, Localio AR, Desai SS, Israni AK, Lautenbach E. Hepatitis C virus seropositivity in organ donors and survival in heart transplant recipients. JAMA. 2006;296(15):1843-1850
Liao C, Massie A, Bae S, Segev D. HCV, acute rejection, and the new direct-acting antivirals in deceased donor kidney transplant recipients. Am J Transplant. 2016;16(suppl 3).
Willicombe M, Moss J, Moran L, et al. Tubuloreticular inclusions in renal allografts associate with viral infections and donor-specific antibodies. J Am Soc Nephrol. 2016;27(7):2188-2195.
Cosio FG, Sedmak DD, Henry ML, et al. The high prevalence of severe early posttransplant renal allograft pathology in hepatitis C positive recipients. Transplantation. 1996;62(8):1054-1059.
Valantine H. Cardiac allograft vasculopathy after heart transplantation: risk factors and management. J Heart Lung Transplant. 2004;23(5):S187-S193.
Caforio AL, Tona F, Fortina AB, et al. Immune and nonimmune predictors of cardiac allograft vasculopathy onset and severity: multivariate risk factor analysis and role of immunosuppression. Am J Transplant. 2004;4(6):962-970.
Di Bisceglie AM, Shiffman ML, Everson GT, et al. Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. N Engl J Med. 2008;359(23):2429-2441.
Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347(13):975-982.
McHutchison JG, Lawitz EJ, Shiffman ML, et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361(6):580-593.
Muir AJ, Bornstein JD, Killenberg PG. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med. 2004;350(22):2265-2271.
Pariante CM, Landau S, Carpiniello B. Interferon alfa-induced adverse effects in patients with a psychiatric diagnosis. N Engl J Med. 2002;347(2):148-149.
Rodriguez-Torres M, Jeffers LJ, Sheikh MY, et al. Peginterferon alfa-2a and ribavirin in Latino and non-Latino whites with hepatitis C. N Engl J Med. 2009;360(3):257-267.
Kim E, Ko HH, Yoshida EM. Treatment issues surrounding hepatitis C in renal transplantation: a review. Ann Hepatol. 2011;10(1):5-14.
Wang BY, Chang HH, Chen IM, Shih CC, Yang AH. Peginterferon alpha-2b and acute allograft failure in a heart transplant recipient. Ann Thorac Surg. 2010;89(5):1645-1647.
Vassalle C, Masini S, Bianchi F, Zucchelli GC. Evidence for association between hepatitis C virus seropositivity and coronary artery disease. Heart. 2004;90(5):565-566.
Goldberg DS, Abt PL, Blumberg EA, et al. Trial of Transplantation of HCV-Infected Kidneys into Uninfected Recipients. N Engl J Med. 2017;376(24):2394-2395.
Reese PP, Abt PL, Blumberg EA, et al. Twelve-month outcomes after transplant of hepatitis C-infected kidneys into uninfected recipients: a single-group trial. Ann Intern Med. 2018;169(5):273-281.
Durand CM, Bowring MG, Brown DM, et al. Direct-acting antiviral prophylaxis in kidney transplantation from hepatitis C virus-infected donors to noninfected recipients: an open-label nonrandomized trial. Ann Intern Med. 2018;168(8):533-540.
Kwong AJ, Wall A, Melcher M, et al. Liver transplantation for HCV non-viremic recipients with HCV viremic donors. Am J Transplant. 2018; https://doi.org/10.1111/ajt.15162
Gentile C, Van Deerlin VM, Goldberg DS, et al. Hepatitis C virus genotyping of organ donor samples to aid in transplantation of HCV-positive organs. Clin Transplant. 2017;32:e13172.
Curry MP, O'Leary JG, Bzowej N, et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med. 2015;373(27):2618-2628.
Feld JJ, Jacobson IM, Hezode C, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med. 2015;373(27):2599-2607.
Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med. 2015;373(27):2608-2617.
Levitsky J, Verna EC, O'Leary JG, et al. Perioperative ledipasvir-sofosbuvir for HCV in liver-transplant recipients. N Engl J Med. 2016;375(21):2106-2108.
Naggie S, Cooper C, Saag M, et al. Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):705-713.
Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):714-725.
Li H, Stoddard MB, Wang S, et al. Elucidation of hepatitis C virus transmission and early diversification by single genome sequencing. PLoS Pathog. 2012;8(8):e1002880.
Gottlieb RL, Sam T, Wada SY, et al. Rational heart transplant from a hepatitis C donor: new antiviral weapons conquer the trojan horse. J Card Fail. 2017;23(10):765-767.
McCauley M, Mussell A, Goldberg D, et al. Race, risk, and willingness of end-stage renal disease patients without hepatitis C virus to accept an HCV-infected kidney transplant. Transplantation. 2018;102(4):e163-e170.
Reau N, Kwo PY, Rhee S, et al. Glecaprevir/pibrentasvir treatment in liver or kidney transplant patients with hepatitis C virus infection. Hepatology. 2018;68(4):1298-1307.
Lo Re V 3rd, Gowda C, Urick PN, et al. Disparities in absolute denial of modern hepatitis C therapy by type of insurance. Clin Gastroenterol Hepatol. 2016;14(7):1035-1043.