Emily D Bethea1, Kerry Gaj2, Jenna L Gustafson3, Andrea Axtell4, Taylor Lebeis5, Mark Schoenike6, Karen Turvey2, Erin Coglianese5, Sunu Thomas5, Christopher Newton-Cheh5, Nasrien Ibrahim5, William Carlson5, Jennifer E Ho5, Ravi Shah5, Matthew Nayor5, Thais Gift7, Sarah Shao7, Amanda Dugal7, James Markmann8, Nahel Elias8, Heidi Yeh8, Karin Andersson1, Daniel Pratt1, Irun Bhan1, Kassem Safa9, Jay Fishman10, Camille Kotton10, Paul Myoung11, Mauricio A Villavicencio12, David D'Alessandro12, Raymond T Chung13, Gregory D Lewis5. 1. Harvard Medical School, Boston, MA, USA; Liver Center, Gastrointestinal Division, Massachusetts General Hospital, Boston, MA, USA; Massachusetts General Hospital Transplant Center, Massachusetts General Hospital, Boston, MA, USA. 2. Massachusetts General Hospital Transplant Center, Massachusetts General Hospital, Boston, MA, USA; Cardiology Division, Massachusetts General Hospital, Boston, MA, USA. 3. Liver Center, Gastrointestinal Division, Massachusetts General Hospital, Boston, MA, USA; Massachusetts General Hospital Transplant Center, Massachusetts General Hospital, Boston, MA, USA. 4. Harvard Medical School, Boston, MA, USA; Massachusetts General Hospital Transplant Center, Massachusetts General Hospital, Boston, MA, USA; Cardiothoracic Surgery Division, Massachusetts General Hospital, Boston, MA, USA. 5. Harvard Medical School, Boston, MA, USA; Massachusetts General Hospital Transplant Center, Massachusetts General Hospital, Boston, MA, USA; Cardiology Division, Massachusetts General Hospital, Boston, MA, USA. 6. Cardiology Division, Massachusetts General Hospital, Boston, MA, USA. 7. Division of Pharmacy, Massachusetts General Hospital, Boston, MA, USA. 8. Harvard Medical School, Boston, MA, USA; Massachusetts General Hospital Transplant Center, Massachusetts General Hospital, Boston, MA, USA; Transplant Surgery Division, Massachusetts General Hospital, Boston, MA, USA. 9. Harvard Medical School, Boston, MA, USA; Massachusetts General Hospital Transplant Center, Massachusetts General Hospital, Boston, MA, USA; Nephrology Division, Massachusetts General Hospital, Boston, MA, USA. 10. Harvard Medical School, Boston, MA, USA; Massachusetts General Hospital Transplant Center, Massachusetts General Hospital, Boston, MA, USA; Infectious Diseases Division, Massachusetts General Hospital, Boston, MA, USA. 11. Massachusetts General Hospital Transplant Center, Massachusetts General Hospital, Boston, MA, USA. 12. Harvard Medical School, Boston, MA, USA; Massachusetts General Hospital Transplant Center, Massachusetts General Hospital, Boston, MA, USA; Cardiothoracic Surgery Division, Massachusetts General Hospital, Boston, MA, USA; Transplant Surgery Division, Massachusetts General Hospital, Boston, MA, USA. 13. Harvard Medical School, Boston, MA, USA; Liver Center, Gastrointestinal Division, Massachusetts General Hospital, Boston, MA, USA; Massachusetts General Hospital Transplant Center, Massachusetts General Hospital, Boston, MA, USA. Electronic address: rtchung@partners.org.
Abstract
BACKGROUND: Low donor heart availability underscores the need to identify all potentially transplantable organs. We sought to determine whether pre-emptive administration of pangenotypic direct-acting antiviral therapy can safely prevent the development of chronic hepatitis C virus (HCV) infection in uninfected recipients of HCV-infected donor hearts. METHODS: Patients were recruited for this an open-label, single-centre, proof-of-concept study from Nov 1, 2017, to Nov 30, 2018. Following enrolment, the recipient's status on the heart transplantation waiting list was updated to reflect a willingness to accept either an HCV-positive or HCV-negative heart donor. Patients who underwent transplantation with a viraemic donor heart, as determined by nucleic acid testing (NAT), received pre-emptive oral glecaprevir-pibrentasvir before transport to the operating room followed by an 8-week course of glecaprevir-pibrentasvir after transplantation. Patients receiving HCV antibody-positive donor hearts without detectable circulating HCV RNA were followed using a reactive approach and started glecaprevir-pibrentasvir only if they developed viraemia. The primary outcome was achievement of sustained virological response 12 weeks after completion of glecaprevir-pibrentasvir therapy (SVR12). Patients were followed from study enrolment to 1 year after transplantation. This is an interim analysis, initiated after all enrolled patients reached the primary outcome. Results reflect data from Nov 1, 2017, to May 30, 2019. This trial is registered with ClinicalTrials.gov, number NCT03208244. FINDINGS: 55 patients were assessed for eligibility and 52 consented to enrolment. 25 patients underwent heart transplantation with HCV-positive donor hearts (20 NAT-positive, five NAT-negative), three of whom underwent simultaneous heart-kidney transplantation. All 20 recipients of NAT-positive hearts tolerated glecaprevir-pibrentasvir and showed rapid viral suppression (median time to clearance 3·5 days, IQR 0·0-8·3), with the subsequent achievement of SVR12 by all 20. The five recipients of NAT-negative grafts did not become viraemic. Median pre-transplant waiting time for patients following enrolment in the HCV protocol was 20 days (IQR 8-57). Patient and allograft survival were 100% at a median follow-up of 10·7 months (range 6·5-18·0). INTERPRETATION: Pre-emptive administration of glecaprevir-pibrentasvir therapy results in expedited organ transplantation, rapid HCV suppression, prevention of chronic HCV infection, and excellent early allograft function in patients receiving HCV-infected donor hearts. Long-term outcomes are not yet known. FUNDING: American Association for the Study of Liver Diseases, National Institutes of Health, and the Massachusetts General Hospital.
BACKGROUND: Low donor heart availability underscores the need to identify all potentially transplantable organs. We sought to determine whether pre-emptive administration of pangenotypic direct-acting antiviral therapy can safely prevent the development of chronic hepatitis C virus (HCV) infection in uninfected recipients of HCV-infecteddonor hearts. METHODS:Patients were recruited for this an open-label, single-centre, proof-of-concept study from Nov 1, 2017, to Nov 30, 2018. Following enrolment, the recipient's status on the heart transplantation waiting list was updated to reflect a willingness to accept either an HCV-positive or HCV-negative heart donor. Patients who underwent transplantation with a viraemic donor heart, as determined by nucleic acid testing (NAT), received pre-emptive oral glecaprevir-pibrentasvir before transport to the operating room followed by an 8-week course of glecaprevir-pibrentasvir after transplantation. Patients receiving HCV antibody-positive donor hearts without detectable circulating HCV RNA were followed using a reactive approach and started glecaprevir-pibrentasvir only if they developed viraemia. The primary outcome was achievement of sustained virological response 12 weeks after completion of glecaprevir-pibrentasvir therapy (SVR12). Patients were followed from study enrolment to 1 year after transplantation. This is an interim analysis, initiated after all enrolled patients reached the primary outcome. Results reflect data from Nov 1, 2017, to May 30, 2019. This trial is registered with ClinicalTrials.gov, number NCT03208244. FINDINGS: 55 patients were assessed for eligibility and 52 consented to enrolment. 25 patients underwent heart transplantation with HCV-positive donor hearts (20 NAT-positive, five NAT-negative), three of whom underwent simultaneous heart-kidney transplantation. All 20 recipients of NAT-positive hearts tolerated glecaprevir-pibrentasvir and showed rapid viral suppression (median time to clearance 3·5 days, IQR 0·0-8·3), with the subsequent achievement of SVR12 by all 20. The five recipients of NAT-negative grafts did not become viraemic. Median pre-transplant waiting time for patients following enrolment in the HCV protocol was 20 days (IQR 8-57). Patient and allograft survival were 100% at a median follow-up of 10·7 months (range 6·5-18·0). INTERPRETATION: Pre-emptive administration of glecaprevir-pibrentasvir therapy results in expedited organ transplantation, rapid HCV suppression, prevention of chronic HCV infection, and excellent early allograft function in patients receiving HCV-infecteddonor hearts. Long-term outcomes are not yet known. FUNDING: American Association for the Study of Liver Diseases, National Institutes of Health, and the Massachusetts General Hospital.
Authors: Jordan J Feld; Marcelo Cypel; Deepali Kumar; Harel Dahari; Rafaela Vanin Pinto Ribeiro; Nikki Marks; Nellie Kamkar; Ilona Bahinskaya; Fernanda Q Onofrio; Mohamed A Zahoor; Orlando Cerrochi; Kathryn Tinckam; S Joseph Kim; Jeffrey Schiff; Trevor W Reichman; Michael McDonald; Carolina Alba; Thomas K Waddell; Gonzalo Sapisochin; Markus Selzner; Shaf Keshavjee; Harry L A Janssen; Bettina E Hansen; Lianne G Singer; Atul Humar Journal: Lancet Gastroenterol Hepatol Date: 2020-05-06
Authors: Emily Bethea; Ashwini Arvind; Jenna Gustafson; Karin Andersson; Daniel Pratt; Irun Bhan; Michael Thiim; Kathleen Corey; Patricia Bloom; Jim Markmann; Heidi Yeh; Nahel Elias; Shoko Kimura; Leigh Anne Dageforde; Alex Cuenca; Tatsuo Kawai; Kassem Safa; Winfred Williams; Hannah Gilligan; Meghan Sise; Jay Fishman; Camille Kotton; Arthur Kim; Christin C Rogers; Sarah Shao; Mariesa Cote; Linda Irwin; Paul Myoung; Raymond T Chung Journal: Am J Transplant Date: 2020-02-03 Impact factor: 8.086
Authors: Schnegg Bruno; Bart Nicole; Dharan Nila J; Matthews Gail; Nadel James; Macdonald Peter S; Hayward Christopher S Journal: Transplant Direct Date: 2019-08-23