1
|
Willingness of Kidney and Liver Transplant Candidates to Receive HCV-Infected Organs. J Surg Res 2022; 278:342-349. [PMID: 35667277 DOI: 10.1016/j.jss.2022.05.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 04/13/2022] [Accepted: 05/06/2022] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Transplantation of organs exposed to hepatitis C virus (HCV) into uninfected patients has yielded excellent outcomes and more widespread adoption may lead to fewer discarded organs and more transplants. Patient perceptions may shed light on acceptability and likely the uptake of HCV+/HCV- transplantation, gaps in understanding, and perceived benefits/risks. METHODS We surveyed 435 uninfected kidney and liver transplant candidates at four centers about their attitude towards HCV-infected organs. RESULTS The percentage of patients willing to accept HCV-infected organs increased from 58% at baseline, to 86% following education about HCV, direct-acting antiviral agents (DAAs), and HCV+/HCV- transplantation benefits/risks. More willingness to accept an organ from an intravenous drug user (P < 0.001), age >50 y old (P = 0.02), longer waiting time (P = 0.02), more trust in the transplant system (P = 0.03), and previous awareness of DAAs (P = 0.04) were associated with higher willingness to accept an HCV-infected organ. The most important reasons for accepting an HCV-infected organ were a decrease in waiting time (65%), lower mortality and morbidity risk while on the waiting list (63%), effectiveness of DAAs (54%), and a quicker return to higher functional status (51%). CONCLUSIONS Presenting patients with information about HCV+/HCV- transplantation in small doses that are calibrated to account for varying levels of health and numerical literacy is recommended.
Collapse
|
2
|
Alghamdi W, Lotfy K, Weernink C, Alsolami E, Jevnikar A, Luke P, Skaro A, Qumosani K, Brahmania M, Marotta P, Hosseini-Moghaddam SM, Teriaky A. Hepatitis C positive organ transplantation to negative recipients at a multiorgan Canadian transplant centre: ready for prime time. BMC Gastroenterol 2022; 22:34. [PMID: 35078405 PMCID: PMC8787881 DOI: 10.1186/s12876-022-02107-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 01/13/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Transplantation offers the best survival for patients with end stage organ disease. Transplant of hepatitis C virus (HCV) nucleic acid test (NAT) positive organs into negative recipients is a novel strategy that can expand the donor pool. We aim to evaluate our centre's experience. METHODS We preformed a retrospective review of anti-HCV NAT positive and negative organs into negative recipients transplanted over 27 months. Primary outcome was the success rate of eradication of HCV post-transplant. Secondary outcomes were rate of transmission of HCV, treatment adverse events, and graft failure. RESULTS 33 anti-HCV positive organs were transplanted into negative recipients. 22 (66.7%) were NAT positive. Median recipients age was 49 years (interquartile range [IQR] 44.5-62.0) with the majority being males (57.6%). NAT positive organ transplantations included 16 kidneys, 3 livers, 1 kidney-pancreas, 1 liver-kidney, and 1 heart. The most common HCV genotype was 1a (59.1%). The median time to initiating therapy was 41.5 days. SVR12 was 100% in patients who finished therapy. There were no adverse events with therapy and no graft failure. CONCLUSIONS Anti-HCV NAT positive organ transplantation into negative recipients is safe with excellent eradication rates and no significant adverse events or graft failure. This would expand donor pool to close the gap between supply and demand.
Collapse
Affiliation(s)
- Waleed Alghamdi
- Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
- Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada.
- Multiorgan Transplant Program, London Health Sciences Centre, London, ON, Canada.
- Division of Gastroenterology, Department of Medicine, King Abdulaziz University, Building 10, Second Floor, P.O. Box 55603, Jeddah, 21544, Saudi Arabia.
| | - Khaled Lotfy
- Division of Nephrology, Department of Medicine, Western University, London, ON, Canada
- Multiorgan Transplant Program, London Health Sciences Centre, London, ON, Canada
| | - Corinne Weernink
- Multiorgan Transplant Program, London Health Sciences Centre, London, ON, Canada
| | - Enad Alsolami
- Department of Internal Medicine, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia
| | - Anthony Jevnikar
- Division of Nephrology, Department of Medicine, Western University, London, ON, Canada
- Multiorgan Transplant Program, London Health Sciences Centre, London, ON, Canada
| | - Patrick Luke
- Department of Surgery, Western University, London, ON, Canada
- Multiorgan Transplant Program, London Health Sciences Centre, London, ON, Canada
| | - Anton Skaro
- Department of Surgery, Western University, London, ON, Canada
- Multiorgan Transplant Program, London Health Sciences Centre, London, ON, Canada
| | - Karim Qumosani
- Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada
- Multiorgan Transplant Program, London Health Sciences Centre, London, ON, Canada
| | - Mayur Brahmania
- Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada
- Multiorgan Transplant Program, London Health Sciences Centre, London, ON, Canada
| | - Paul Marotta
- Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada
- Multiorgan Transplant Program, London Health Sciences Centre, London, ON, Canada
| | - Syed M Hosseini-Moghaddam
- Division of Infectious Diseases, Department of Medicine, Western University, London, ON, Canada
- Multiorgan Transplant Program, London Health Sciences Centre, London, ON, Canada
| | - Anouar Teriaky
- Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada
- Multiorgan Transplant Program, London Health Sciences Centre, London, ON, Canada
| |
Collapse
|
3
|
Innovations in liver transplantation in 2020, position of the Belgian Liver Intestine Advisory Committee (BeLIAC). Acta Gastroenterol Belg 2021; 84:347-359. [PMID: 34217187 DOI: 10.51821/84.2.347] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver transplantation (LT) remains the only curative option for patients suffering from end-stage liver disease, acute liver failure and selected hepatocellular carcinomas and access to the LT-waiting list is limited to certain strict indications. However, LT has shown survival advantages for patients in certain indications such as acute alcoholic hepatitis, hepatocellular carcinoma outside Milan criteria and colorectal cancer metastases. These newer indications increase the pressure in an already difficult context of organ shortage. Strategies to increase the transplantable organ pool are therefore needed. We will discuss here the use of HCV positive grafts as the use of normothermic isolated liver perfusion. Belgian Liver Intestine Advisory Committee (BeLIAC) from the Belgian Transplant Society (BTS) aims to guarantee the balance between the new indications and the available resources.
Collapse
|
4
|
Bethea E, Arvind A, Gustafson J, Andersson K, Pratt D, Bhan I, Thiim M, Corey K, Bloom P, Markmann J, Yeh H, Elias N, Kimura S, Dageforde LA, Cuenca A, Kawai T, Safa K, Williams W, Gilligan H, Sise M, Fishman J, Kotton C, Kim A, Marks C, Shao S, Cote M, Irwin L, Myoung P, Chung RT. Immediate administration of antiviral therapy after transplantation of hepatitis C-infected livers into uninfected recipients: Implications for therapeutic planning. Am J Transplant 2020; 20:1619-1628. [PMID: 31887236 PMCID: PMC8005111 DOI: 10.1111/ajt.15768] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 12/04/2019] [Accepted: 12/22/2019] [Indexed: 01/25/2023]
Abstract
The practice of transplanting hepatitis C (HCV)-infected livers into HCV-uninfected recipients has not previously been recommended in transplant guidelines, in part because of concerns over uncontrolled HCV infection of the allograft. Direct-acting antivirals (DAAs) provide an opportunity to treat donor-derived HCV-infection and should be administered early in the posttransplant period. However, evidence on the safety and efficacy of an immediate DAA treatment approach, including how to manage logistical barriers surrounding timely DAA procurement, are required prior to broader use of HCV-positive donor organs. We report the results of a trial in which 14 HCV-negative patients underwent successful liver transplantation from HCV-positive donors. Nine patients received viremic (nucleic acid testing [NAT]-positive) livers and started a 12-week course of oral glecaprevir-pibrentasvir within 5 days of transplant. Five patients received livers from HCV antibody-positive nonviremic donors and were followed using a reactive approach. Survival in NAT-positive recipients is 100% at a median follow-up of 46 weeks. An immediate treatment approach for HCV NAT-positive liver transplantation into uninfected recipients is safe and efficacious. Securing payer approval for DAAs early in the posttransplant course could enable need-based allocation of HCV-positive donor organs irrespective of candidate HCV status, while averting chronic HCV allograft infection.
Collapse
Affiliation(s)
- Emily Bethea
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Ashwini Arvind
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Jenna Gustafson
- Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Karin Andersson
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Daniel Pratt
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Irun Bhan
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Michael Thiim
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Kathleen Corey
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Patricia Bloom
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Jim Markmann
- Harvard Medical School, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts,Transplant Surgery Division, Massachusetts General Hospital, Boston Massachusetts
| | - Heidi Yeh
- Harvard Medical School, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts,Transplant Surgery Division, Massachusetts General Hospital, Boston Massachusetts
| | - Nahel Elias
- Harvard Medical School, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts,Transplant Surgery Division, Massachusetts General Hospital, Boston Massachusetts
| | - Shoko Kimura
- Harvard Medical School, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Leigh Anne Dageforde
- Harvard Medical School, Boston, Massachusetts,Transplant Surgery Division, Massachusetts General Hospital, Boston Massachusetts
| | - Alex Cuenca
- Harvard Medical School, Boston, Massachusetts,Transplant Surgery Division, Massachusetts General Hospital, Boston Massachusetts
| | - Tatsuo Kawai
- Harvard Medical School, Boston, Massachusetts,Transplant Surgery Division, Massachusetts General Hospital, Boston Massachusetts
| | - Kassem Safa
- Harvard Medical School, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts,Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Winfred Williams
- Harvard Medical School, Boston, Massachusetts,Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Hannah Gilligan
- Harvard Medical School, Boston, Massachusetts,Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Meghan Sise
- Harvard Medical School, Boston, Massachusetts,Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Jay Fishman
- Harvard Medical School, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts,Infectious Diseases Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Camille Kotton
- Harvard Medical School, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts,Infectious Diseases Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Arthur Kim
- Harvard Medical School, Boston, Massachusetts,Infectious Diseases Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Christin Marks
- Harvard Medical School, Boston, Massachusetts,Massachusetts General Hospital Division of Pharmacy, Boston Massachusetts
| | - Sarah Shao
- Massachusetts General Hospital Transplant Center, Boston, Massachusetts,Massachusetts General Hospital Division of Pharmacy, Boston Massachusetts
| | - Mariesa Cote
- Massachusetts General Hospital Division of Pharmacy, Boston Massachusetts
| | - Linda Irwin
- Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Paul Myoung
- Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Raymond T. Chung
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| |
Collapse
|
5
|
Abstract
INTRODUCTION The recent availability of highly effective hepatitis C medications, with a cure rate approaching 100%, has created a wide range of questions and uncertainties. AREAS COVERED The most recent data around hepatitis C virus (HCV) elimination will be reviewed. In addition, the impact of HCV cure or sustained virologic response (SVR) on the risk for hepatocellular carcinoma (HCC) development will be discussed. Although the terms 'SVR' and 'cure' are used interchangeably, there are little data to support that they are actually the same. In this review, we will shed some light on the status of HCV vaccine development, obstacles, and published experience. Finally, in the face of decreasing HCV patients needing transplantation, and increasing available organs from donors infected with HCV, the question is that, is it possible to transplant an organ infected with HCV to a patient who is not infected? The pros and cons of transplanting HCV-positive organs to HCV-negative recipients will be discussed. EXPERT OPINION Although the new advances in HCV treatment have solved many problems, it created several new issues which the medical community has to deal with and which will likely remain in the near future.
Collapse
Affiliation(s)
- Omar Massoud
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham , Birmingham, AL, USA
| |
Collapse
|
6
|
AASLD-IDSA Hepatitis C Guidance Panel *, Morgan TR, AASLD‐IDSA Hepatitis C Guidance Panel. Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology 2020; 71:686-721. [PMID: 31816111 PMCID: PMC9710295 DOI: 10.1002/hep.31060] [Citation(s) in RCA: 523] [Impact Index Per Article: 104.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 11/21/2019] [Indexed: 02/06/2023]
Affiliation(s)
| | - Timothy R. Morgan
- Chief of Hepatology Veterans Affairs Long Beach Healthcare System Long Beach CA
| | | |
Collapse
|
7
|
Crismale JF, Ahmad J. Expanding the donor pool: Hepatitis C, hepatitis B and human immunodeficiency virus-positive donors in liver transplantation. World J Gastroenterol 2019; 25:6799-6812. [PMID: 31885421 PMCID: PMC6931007 DOI: 10.3748/wjg.v25.i47.6799] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 11/26/2019] [Accepted: 11/29/2019] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) remains the best option for patients with end-stage liver disease but the demand for organs from deceased donors continues to outweigh the available supply. The advent of highly effective anti-viral treatments has reduced the number of patients undergoing LT for hepatitis C (HCV) and hepatitis B (HBV) related liver disease and yet the number of patients waiting for LT continues to increase, driven by an increase in the patients listed with a diagnosis of cirrhosis due to non-alcoholic steatohepatitis and alcohol-related liver disease. In addition, human immunodeficiency virus (HIV) infection, which was previously a contra-indication for LT, is no longer a fatal disease due to the effectiveness of HIV therapy and patients with HIV and liver disease are now developing indications for LT. The rising demand for LT is projected to increase further in the future, thus driving the need to investigate potential means of expanding the pool of potential donors. One mechanism for doing so is utilizing organs from donors that previously would have been discarded or used only in exceptional circumstances such as HCV-positive, HBV-positive, and HIV-positive donors. The advent of highly effective anti-viral therapy has meant that these organs can now be used with excellent outcomes in HCV, HBV or HIV infected recipients and in some cases uninfected recipients.
Collapse
Affiliation(s)
- James F Crismale
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
| | - Jawad Ahmad
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
| |
Collapse
|
8
|
Bethea ED, Gaj K, Gustafson JL, Axtell A, Lebeis T, Schoenike M, Turvey K, Coglianese E, Thomas S, Newton-Cheh C, Ibrahim N, Carlson W, Ho JE, Shah R, Nayor M, Gift T, Shao S, Dugal A, Markmann J, Elias N, Yeh H, Andersson K, Pratt D, Bhan I, Safa K, Fishman J, Kotton C, Myoung P, Villavicencio MA, D'Alessandro D, Chung RT, Lewis GD. Pre-emptive pangenotypic direct acting antiviral therapy in donor HCV-positive to recipient HCV-negative heart transplantation: an open-label study. Lancet Gastroenterol Hepatol 2019; 4:771-780. [PMID: 31353243 DOI: 10.1016/s2468-1253(19)30240-7] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Revised: 06/06/2019] [Accepted: 06/17/2019] [Indexed: 12/26/2022]
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.
Collapse
Affiliation(s)
- Emily D Bethea
- 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
| | - Kerry Gaj
- Massachusetts General Hospital Transplant Center, Massachusetts General Hospital, Boston, MA, USA; Cardiology Division, Massachusetts General Hospital, Boston, MA, USA
| | - Jenna L Gustafson
- Liver Center, Gastrointestinal Division, Massachusetts General Hospital, Boston, MA, USA; Massachusetts General Hospital Transplant Center, Massachusetts General Hospital, Boston, MA, USA
| | - Andrea Axtell
- 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
| | - Taylor Lebeis
- 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
| | - Mark Schoenike
- Cardiology Division, Massachusetts General Hospital, Boston, MA, USA
| | - Karen Turvey
- Massachusetts General Hospital Transplant Center, Massachusetts General Hospital, Boston, MA, USA; Cardiology Division, Massachusetts General Hospital, Boston, MA, USA
| | - Erin Coglianese
- 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
| | - Sunu Thomas
- 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
| | - Christopher Newton-Cheh
- 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
| | - Nasrien Ibrahim
- 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
| | - William Carlson
- 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
| | - Jennifer E Ho
- 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
| | - Ravi Shah
- 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
| | - Matthew Nayor
- 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
| | - Thais Gift
- Division of Pharmacy, Massachusetts General Hospital, Boston, MA, USA
| | - Sarah Shao
- Division of Pharmacy, Massachusetts General Hospital, Boston, MA, USA
| | - Amanda Dugal
- Division of Pharmacy, Massachusetts General Hospital, Boston, MA, USA
| | - James Markmann
- 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
| | - Nahel Elias
- 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
| | - Heidi Yeh
- 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
| | - Karin Andersson
- 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
| | - Daniel Pratt
- 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
| | - Irun Bhan
- 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
| | - Kassem Safa
- 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
| | - Jay Fishman
- 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
| | - Camille Kotton
- 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
| | - Paul Myoung
- Massachusetts General Hospital Transplant Center, Massachusetts General Hospital, Boston, MA, USA
| | - Mauricio A Villavicencio
- 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
| | - David D'Alessandro
- 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
| | - Raymond T Chung
- 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.
| | - Gregory D Lewis
- 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
| |
Collapse
|
9
|
Kwong AJ, Wall A, Melcher M, Wang U, Ahmed A, Subramanian A, Kwo PY. Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors. Am J Transplant 2019; 19:1380-1387. [PMID: 30378723 PMCID: PMC6663314 DOI: 10.1111/ajt.15162] [Citation(s) in RCA: 109] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Revised: 10/15/2018] [Accepted: 10/17/2018] [Indexed: 01/25/2023]
Abstract
In the context of organ shortage, the opioid epidemic, and effective direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV), more HCV-infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor-derived HCV in previously non-viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor-derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing. Seven had a prior diagnosis of HCV and were treated before liver transplantation. All recipients were non-viremic at the time of transplantation. All 10 recipients derived hepatitis C infection from their donor and achieved sustained virologic response at 12 weeks posttreatment with DAA-based regimens, with a median time from transplant to treatment initiation of 43 days (IQR 20-59). There have been no instances of graft loss or death, with median follow-up of 380 days (IQR 263-434) posttransplant. Transplantation of HCV-viremic livers into non-viremic recipients results in acceptable short-term outcomes. Such strategies may be used to expand the donor pool and increase access to liver transplantation.
Collapse
Affiliation(s)
- Allison J. Kwong
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA
- Division of Gastroenterology, University of California, San Francisco, CA
| | - Anji Wall
- Department of Surgery, Stanford University, Stanford, CA
- Division of Transplant Surgery, Baylor University Medical Center, Dallas, TX
| | - Marc Melcher
- Department of Surgery, Stanford University, Stanford, CA
| | - Uerica Wang
- Department of Pharmacy, Stanford Hospital and Clinics, Stanford, CA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA
| | | | - Paul Y. Kwo
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA
| |
Collapse
|
10
|
Use of Hepatitis C-Positive Liver Grafts in Hepatitis C-Negative Recipients. Dig Dis Sci 2019; 64:1110-1118. [PMID: 30560331 DOI: 10.1007/s10620-018-5404-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Accepted: 11/27/2018] [Indexed: 12/18/2022]
Abstract
As the demand for liver transplantation continues to rise, the scarcity of liver donor grafts has led to the use of extended criteria grafts for liver transplantation in select group of patients. Hepatitis C-seropositive liver grafts have been used primarily in hepatitis C-positive recipients, with studies showing non-inferior outcomes when compared to hepatitis C-negative grafts. Studies suggest that hepatitis C serology status of the donor liver does not influence the patient or graft outcomes in the recipient. These results advocate for offering hepatitis C-positive grafts to all patients awaiting liver transplantation regardless of their hepatitis C status. However, some concerns persist regarding the ethics of potentially introducing a new infection into a patient that could progress to chronic liver disease following liver transplantation. The recent approval of direct-acting antiviral therapy offers a solution to this dilemma, as it has changed the landscape of hepatitis C management by making it a curable disease. In this review, we shall discuss the current evidence regarding the use of hepatitis C-seropositive donor grafts in hepatitis C-positive and hepatitis C-negative patients.
Collapse
|
11
|
Abstract
Donor-derived infections are defined as any infection present in the donor that is transmitted to 1 or more recipients. Donor-derived infections can be categorized into 2 groups: "expected" and "unexpected" infections. Expected transmissions occur when the donor is known to have an infection, such as positive serology for cytomegalovirus, Epstein Barr virus, or hepatitis B core antibody, at the time of donation. Unexpected transmissions occur when a donor has no known infection before donation, but 1 or more transplant recipients develop an infection derived from the common donor. Unexpected infections are estimated to occur in far less than 1% of solid organ transplant recipients. We will review the epidemiology, risk factors, and approaches to prevention and management of donor-derived viral infectious disease transmission in liver transplantation.
Collapse
|
12
|
Use of Hepatitis C Virus Antibody-Positive Donor Livers in Hepatitis C Nonviremic Liver Transplant Recipients. J Am Coll Surg 2019; 228:560-567. [DOI: 10.1016/j.jamcollsurg.2018.12.004] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Accepted: 12/10/2018] [Indexed: 01/28/2023]
|
13
|
Bethea ED, Samur S, Kanwal F, Ayer T, Hur C, Roberts MS, Terrault N, Chung RT, Chhatwal J. Cost Effectiveness of Transplanting HCV-Infected Livers Into Uninfected Recipients With Preemptive Antiviral Therapy. Clin Gastroenterol Hepatol 2019; 17:739-747.e8. [PMID: 30138735 PMCID: PMC6382534 DOI: 10.1016/j.cgh.2018.08.042] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 07/26/2018] [Accepted: 08/13/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Guidelines do not recommend transplanting hepatitis C virus (HCV)-infected livers into HCV-uninfected recipients. Direct-acting antivirals (DAAs) can be used to treat donor-derived HCV infection. However, the added cost of DAA therapy is a barrier. We evaluated the cost effectiveness of transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy. METHODS A previously validated Markov-based mathematical model was adapted to simulate a virtual trial of HCV-negative patients on the liver transplant waitlist. The model compared long-term clinical and economic outcomes in patients willing to accept only HCV-negative livers vs those willing to accept any liver (HCV negative or HCV positive). Recipients of HCV-positive livers received 12 weeks of preemptive DAA therapy. The model incorporated data from the United Network for Organ Sharing and published sources. RESULTS For patients with a model for end-stage liver disease (MELD) score ≥ 22, accepting any liver vs waiting for only HCV-negative livers was cost effective, with incremental cost-effectiveness ratios ranging from $56,100 to $91,700/quality-adjusted life-year. For patients with a MELD score of 28 (the median MELD score of patients undergoing transplantation in the United States), accepting any liver was cost effective at an incremental cost-effectiveness ratio of $62,600/quality-adjusted life year. In patients with low MELD scores, which may not accurately reflect disease severity, accepting any liver was cost effective, irrespective of MELD score. CONCLUSIONS Using a Markov-based mathematical model, we found transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy to be a cost-effective strategy that could improve health outcomes.
Collapse
Affiliation(s)
- Emily D Bethea
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Sumeyye Samur
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
| | - Fasiha Kanwal
- Department of Medicine, Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas; Houston Veterans Affairs Health Services Research and Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Turgay Ayer
- Department of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia
| | - Chin Hur
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Mark S Roberts
- Department of Health Policy and Management, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania; University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Norah Terrault
- University of California San Francisco Medical Center, Gastroenterology and Hepatology Division, San Francisco, California
| | - Raymond T Chung
- Harvard Medical School, Boston, Massachusetts; Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Jagpreet Chhatwal
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts.
| |
Collapse
|
14
|
Watson J, Mulvihill MS, Cox ML, Rich L, Wolfe CR, Gray A, Hartwig MG. Early experience with the use of hepatitis C antibody-positive, nucleic acid testing-negative donors in lung transplantation. Clin Transplant 2019; 33:e13476. [PMID: 30609162 DOI: 10.1111/ctr.13476] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 01/02/2019] [Accepted: 01/03/2019] [Indexed: 12/25/2022]
Abstract
Historically, potential lung donors who have detectable antibodies to hepatitis C virus have been declined by most centers due to concern for possible disease transmission. We sought to evaluate hepatitis C viral transmission rates from donors who were known to be HCV Ab positive but HCV NAT negative. We performed a single-center retrospective review of a prospectively collected database for lung transplant recipients at our center including HCV Ab+NAT- donors (approved January 2017). Donor and recipient demographic data were compiled, and records were queried to ascertain rate of seroconversion. During the study period (1/1/17 to 8/9/17), a total of 64 recipients underwent lung transplantation. Thirteen (20%) donors were HCV Ab+NAT-. All recipients of HCV Ab+NAT- grafts were HCV Ab- at the time of transplant. Recipients of grafts from HCV Ab+NAT- donors underwent protocol NAT at 2 and 12 months and all are NAT- to date. One recipient developed reactive HCV Ab at 6 months post-transplant. Follow-up NAT showed HCV RNA to be undetectable. To date, use of HCV Ab+NAT- donors in lung transplantation has yielded favorable outcomes, with evidence of one transient seroconversion suggesting this practice may increase access to life-saving transplantation to those in need.
Collapse
Affiliation(s)
- Joshua Watson
- Department of Surgery, Duke University, Durham, North Carolina
| | | | - Morgan L Cox
- Department of Surgery, Duke University, Durham, North Carolina
| | - Lauren Rich
- Department of Surgery, Duke University, Durham, North Carolina
| | | | - Alice Gray
- University of Colorado Anschultz Medical Campus, Aurora, CO
| | | |
Collapse
|
15
|
Li AA, Cholankeril G, Cheng XS, Tan JC, Kim D, Toll AE, Nair S, Ahmed A. Underutilization of Hepatitis C Virus Seropositive Donor Kidneys in the United States in the Current Opioid Epidemic and Direct-Acting Antiviral Era. Diseases 2018; 6:E62. [PMID: 29996536 PMCID: PMC6165210 DOI: 10.3390/diseases6030062] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 07/05/2018] [Accepted: 07/09/2018] [Indexed: 12/26/2022] Open
Abstract
In recent years, the opioid epidemic and new hepatitis C virus (HCV) treatments have changed the landscape of organ procurement and allocation. We studied national trends in solid organ transplantation (2000⁻2016), focusing on graft utilization from HCV seropositive deceased donors in the pre-2014 (2000⁻2013) versus current (2014⁻2016) eras with a retrospective analysis of the United Network for Organ Sharing database. During the study period, HCV seropositive donors increased from 181 to 661 donors/year. The rate of HCV seropositive donor transplants doubled from 2014 to 2016. Heart and lung transplantation data were too few to analyze. A higher number of HCV seropositive livers were transplanted into HCV seropositive recipients during the current era: 374 versus 124 liver transplants/year. Utilization rates for liver transplantation reached parity between HCV seropositive and non-HCV donors. While the number of HCV seropositive kidneys transplanted to HCV seropositive recipients increased from 165.4 to 334.7 kidneys/year from the pre-2014 era to the current era, utilization rates for kidneys remained lower in HCV seropositive than in non-HCV donors. In conclusion, relative underutilization of kidneys from HCV seropositive versus non-HCV donors has persisted, in contrast to trends in liver transplantation.
Collapse
Affiliation(s)
- Andrew A Li
- Department of Medicine, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
| | - George Cholankeril
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
| | - Xingxing S Cheng
- Division of Nephrology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
| | - Jane C Tan
- Division of Nephrology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
| | - Alice E Toll
- United Network for Organ Sharing, Richmond, VA 23219, USA.
| | - Satheesh Nair
- Department of Transplant Surgery, Methodist University Hospital, University of Tennessee Health Science Center, Memphis, TN 38104, USA.
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
| |
Collapse
|
16
|
Chhatwal J, Samur S, Bethea ED, Ayer T, Kanwal F, Hur C, Roberts MS, Terrault N, Chung RT. Transplanting hepatitis C virus-positive livers into hepatitis C virus-negative patients with preemptive antiviral treatment: A modeling study. Hepatology 2018; 67:2085-2095. [PMID: 29222916 PMCID: PMC5991982 DOI: 10.1002/hep.29723] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2017] [Revised: 10/30/2017] [Accepted: 12/07/2017] [Indexed: 12/11/2022]
Abstract
UNLABELLED Under current guidelines, hepatitis C virus (HCV)-positive livers are not transplanted into HCV-negative recipients because of adverse posttransplant outcomes associated with allograft HCV infection. However, HCV can now be cured post-LT (liver transplant) using direct-acting antivirals (DAAs) with >90% success; therefore, HCV-negative patients on the LT waiting list may benefit from accepting HCV-positive organs with preemptive treatment. Our objective was to evaluate whether and in which HCV-negative patients the potential benefit of accepting an HCV-positive (i.e., viremic) organ outweighed the risks associated with HCV allograft infection. We developed a Markov-based mathematical model that simulated a virtual trial of HCV-negative patients on the LT waiting list to compare long-term outcomes in patients: (1) willing to accept any (HCV-negative or HCV-positive) liver versus (2) those willing to accept only HCV-negative livers. Patients receiving HCV-positive livers were treated preemptively with 12 weeks of DAA therapy and had a higher risk of graft failure than those receiving HCV-negative livers. The model incorporated data from published studies and the United Network for Organ Sharing (UNOS). We found that accepting any liver regardless of HCV status versus accepting only HCV-negative livers resulted in an increase in life expectancy when Model for End-Stage Liver Disease (MELD) was ≥20, and the benefit was highest at MELD 28 (0.172 additional life-years). The magnitude of clinical benefit was greater in UNOS regions with higher HCV-positive donor organ rates, that is, Regions 1, 2, 3, 10, and 11. Sensitivity analysis demonstrated that model outcomes were robust. CONCLUSION Transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy could improve patient survival on the LT waiting list. Our analysis can help inform clinical trials and minimize patient harm. (Hepatology 2018;67:2085-2095).
Collapse
Affiliation(s)
- Jagpreet Chhatwal
- Massachusetts General Hospital Institute for Technology Assessment, Boston, MA,Harvard Medical School, Boston, MA,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA
| | - Sumeyye Samur
- Massachusetts General Hospital Institute for Technology Assessment, Boston, MA,Harvard Medical School, Boston, MA
| | - Emily D. Bethea
- Massachusetts General Hospital Institute for Technology Assessment, Boston, MA,Harvard Medical School, Boston, MA,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA
| | - Turgay Ayer
- Department of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA
| | - Fasiha Kanwal
- Department of Medicine, Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX,Houston Veterans Affairs Health Services Research and Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX
| | - Chin Hur
- Massachusetts General Hospital Institute for Technology Assessment, Boston, MA,Harvard Medical School, Boston, MA,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA
| | - Mark S. Roberts
- Department of Health Policy and Management, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA,University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Norah Terrault
- University of California San Francisco Medical Center, San Francisco, CA
| | - Raymond T. Chung
- Harvard Medical School, Boston, MA,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA
| |
Collapse
|
17
|
Selzner N, Berenguer M. Should organs from hepatitis C-positive donors be used in hepatitis C-negative recipients for liver transplantation? Liver Transpl 2018; 24:831-840. [PMID: 29624894 DOI: 10.1002/lt.25072] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 02/10/2018] [Accepted: 03/10/2018] [Indexed: 02/07/2023]
Abstract
Given the scarcity of donated organs and the frequency of death on the waiting list, strategies that could improve the available supply of high-quality liver grafts are much needed. Direct-acting antiviral agent (DAA) regimens have proved to be highly effective to treat hepatitis C virus (HCV), even in the setting of posttransplantation. The question arises as to whether transplant communities should consider the utilization of HCV-positive donors into HCV-negative recipients. This review summarizes risk of transmission, treatment options with success rate, and ethical considerations for usage of HCV-positive donors. Liver Transplantation 24 831-840 2018 AASLD.
Collapse
Affiliation(s)
- Nazia Selzner
- Multiorgan Transplant Program, University of Toronto, Toronto, Canada
| | - Marina Berenguer
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Universidad de Valencia, Valencia, Spain
| |
Collapse
|
18
|
Somerville L, Doucette K. Hepatitis C: Current Controversies and Future Potential in Solid Organ Transplantation. Curr Infect Dis Rep 2018; 20:18. [PMID: 29789956 DOI: 10.1007/s11908-018-0625-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
PURPOSE OF REVIEW To highlight the changing landscape of hepatitis C virus (HCV) infection in the context of organ transplantation. This focuses on areas of controversy and future potential in the era of highly effective direct-acting antiviral (DAA) agents. RECENT FINDINGS Since the advent of safe and highly effective DAA therapy, HCV infection is now curable in virtually all cases, including organ transplant recipients. Excellent drug tolerability and safety combined with high cure rates across all organ groups means that HCV is no longer a barrier to transplantation or its outcomes. Mounting data demonstrate the safety of using organs from HCV-infected donors with subsequent treatment of HCV in the recipient and a potential to expand the donor pool. Historical data demonstrating inferior survival in transplant recipients with HCV is of limited relevance in the DAA era. Virtually all transplant recipients with HCV infection can be cured, while early data also suggest excellent outcomes in recipients of organs from HCV viremic donors. The optimal timing of HCV therapy in relation to transplantation and the optimal use of organs from HCV viremic donors remain areas of controversy and ongoing research efforts.
Collapse
Affiliation(s)
- Lucy Somerville
- Department of Medicine, Division of Infectious Diseases, University of Alberta, CSB 1-139, 11350 83 Avenue, Edmonton, AB, T6G 2G3, Canada
| | - Karen Doucette
- Department of Medicine, Division of Infectious Diseases, University of Alberta, CSB 1-139, 11350 83 Avenue, Edmonton, AB, T6G 2G3, Canada.
| |
Collapse
|
19
|
Bari K, Luckett K, Kaiser T, Diwan T, Cuffy M, Schoech MR, Safdar K, Blackard JT, Apewokin S, Paterno F, Sherman KE, Zucker SD, Anwar N, Shah SA. Hepatitis C transmission from seropositive, nonviremic donors to non-hepatitis C liver transplant recipients. Hepatology 2018; 67:1673-1682. [PMID: 29205441 DOI: 10.1002/hep.29704] [Citation(s) in RCA: 79] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 11/09/2017] [Accepted: 11/28/2017] [Indexed: 12/11/2022]
Abstract
UNLABELLED Breakthroughs in hepatitis C virus (HCV) treatment and rising rates of intravenous drug use have led to an increase in the number of organ donors who are HCV antibody-positive but serum nucleic acid test (NAT)-negative. The risk of HCV transmission from the liver grafts of these donors to recipients is unknown. To estimate the incidence of HCV transmission, we prospectively followed 26 consecutive HCV antibody-negative (n = 25) or NAT-negative (n = 1) transplant recipients who received a liver graft from donors who were HCV antibody-positive but serum NAT-negative between March 2016 and March 2017. HCV transmission was considered to have occurred if recipients exhibited a positive HCV PCR test by 3 months following transplantation. Drug overdose was listed as the cause of death in 15 (60%) of the donors. One recipient died 18 days after transplantation from primary graft nonfunction and was excluded. Of the remaining 25 recipients, HCV transmission occurred in 4 (16%), at a median follow-up of 11 months, all from donors who died of drug overdose. Three of these patients were treated with direct-acting antiviral therapy, with two achieving a sustained virologic response and one an end-of-treatment response. One patient with HCV transmission died after a complicated postoperative course and did not receive antiviral therapy. CONCLUSION In this prospective cohort of non-HCV liver recipients receiving grafts from HCV antibody-positive/NAT-negative donors, the incidence of HCV transmission was 16%, with the highest risk conferred by donors who died of drug overdose; given the availability of safe and highly effective antiviral therapies, use of such organs could be considered to expand the donor pool. (Hepatology 2018;67:1673-1682).
Collapse
Affiliation(s)
- Khurram Bari
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH
| | - Keith Luckett
- Division of Infectious Diseases, Department of Medicine, University of Cincinnati, Cincinnati, OH
| | - Tiffany Kaiser
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH
| | - Tayyab Diwan
- Division of Transplant Surgery, Department of Surgery, University of Cincinnati, Cincinnati, OH
| | - Madison Cuffy
- Division of Transplant Surgery, Department of Surgery, University of Cincinnati, Cincinnati, OH
| | - Michael R Schoech
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH
| | - Kamran Safdar
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH
| | - Jason T Blackard
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH
| | - Senu Apewokin
- Division of Infectious Diseases, Department of Medicine, University of Cincinnati, Cincinnati, OH
| | - Flavio Paterno
- Division of Transplant Surgery, Department of Surgery, University of Cincinnati, Cincinnati, OH
| | - Kenneth E Sherman
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH
| | - Stephen D Zucker
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH.,Division of Gastroenterology, Hepatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Nadeem Anwar
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH
| | - Shimul A Shah
- Division of Transplant Surgery, Department of Surgery, University of Cincinnati, Cincinnati, OH
| |
Collapse
|
20
|
Vitrone M, Andini R, Mattucci I, Maiello C, Atripaldi L, Durante-Mangoni E, Zampino R. Direct antiviral treatment of chronic hepatitis C in heart transplant recipients. Transpl Infect Dis 2017; 20. [PMID: 29139181 DOI: 10.1111/tid.12813] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Revised: 08/19/2017] [Accepted: 08/29/2017] [Indexed: 12/17/2022]
Abstract
Direct-acting antiviral agents (DAAs) are a safe and effective treatment for chronic hepatitis C (CHC). This may be particularly valuable for patients with severe comorbidities or baseline conditions, including non-liver solid organ transplant. We report cases of two heart transplant recipients with CHC treated with DAAs (sofosbuvir and daclatasvir) achieving sustained virological response. Treatment was well tolerated and no relevant side effects were observed. The drug-drug interactions and graft function were carefully monitored.
Collapse
Affiliation(s)
- Martina Vitrone
- Internal Medicine, University of Campania 'L. Vanvitelli', Napoli, Italy
| | - Roberto Andini
- Internal Medicine, University of Campania 'L. Vanvitelli', Napoli, Italy
| | - Irene Mattucci
- Internal Medicine, University of Campania 'L. Vanvitelli', Napoli, Italy.,Transplant Surgery, AORN Ospedali dei Colli, Ospedale Monaldi, Napoli, Italy
| | - Ciro Maiello
- Transplant Surgery, AORN Ospedali dei Colli, Ospedale Monaldi, Napoli, Italy
| | - Luigi Atripaldi
- Clinical Biochemistry, AORN Ospedali dei Colli, Ospedale Monaldi, Napoli, Italy
| | - Emanuele Durante-Mangoni
- Internal Medicine, University of Campania 'L. Vanvitelli', Napoli, Italy.,Infectious and Transplant Medicine, AORN Ospedali dei Colli, Ospedale Monaldi, Napoli, Italy
| | - Rosa Zampino
- Internal Medicine, University of Campania 'L. Vanvitelli', Napoli, Italy.,Infectious and Transplant Medicine, AORN Ospedali dei Colli, Ospedale Monaldi, Napoli, Italy
| |
Collapse
|
21
|
Kling CE, Perkins JD, Landis CS, Limaye AP, Sibulesky L. Utilization of Organs From Donors According to Hepatitis C Antibody and Nucleic Acid Testing Status: Time for Change. Am J Transplant 2017; 17:2863-2868. [PMID: 28688205 DOI: 10.1111/ajt.14386] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Revised: 05/31/2017] [Accepted: 06/04/2017] [Indexed: 02/06/2023]
Abstract
Previous studies have grouped all donors positive for hepatitis C virus (HCV) antibody (Ab). Only recently has donor HCV nucleic acid testing (NAT) become routine, and the impact of Ab and NAT status on organ utilization is unknown. Using the United Network for Organ Sharing database, we identified 9290 donors from 2015 to 2016 for whom both HCV Ab and NAT data were available and compared organ utilization by HCV status. Overall, 93.8% of donors were Ab negative and NAT negative (Ab-NAT-), 0.15% were Ab negative and NAT positive, 1.8% were Ab positive and NAT negative (Ab+NAT-), and 4.2% were both Ab and NAT positive (Ab+NAT+). Ab-NAT- donors donated at the highest rate for all organs except livers, of which Ab+NAT- donors donated at a higher rate (81.2% vs 73.2%, p = 0.03). Livers were discarded for reasons related to abnormal biopsies in Ab+NAT+ donors, whereas kidneys from Ab- or NAT-positive donors were discarded for reasons related to HCV status. Using a propensity score-matched model, we estimated that using Ab+NAT- donors at the same rate as Ab-NAT- donors could result in 48 more kidney donors, 37 more heart donors, and 15 more lung donors annually. We urge the use of HCV Ab+NAT- donors for appropriately selected and consenting recipients.
Collapse
Affiliation(s)
- C E Kling
- Division of Transplant Surgery, Department of Surgery, University of Washington, Seattle, WA
| | - J D Perkins
- Division of Transplant Surgery, Department of Surgery, University of Washington, Seattle, WA
| | - C S Landis
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Washington, Seattle, WA
| | - A P Limaye
- Division of Allergy and Infectious Disease, Department of Medicine, University of Washington, Seattle, WA
| | - L Sibulesky
- Division of Transplant Surgery, Department of Surgery, University of Washington, Seattle, WA
| |
Collapse
|
22
|
Kim AY. Donor-derived hepatitis C virus infections: Are they “high-risk” anymore? Transpl Infect Dis 2017; 19. [DOI: 10.1111/tid.12679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2017] [Accepted: 02/10/2017] [Indexed: 11/27/2022]
Affiliation(s)
- Arthur Y. Kim
- Division of Infectious Diseases; Massachusetts General Hospital; Harvard Medical School; Boston MA USA
| |
Collapse
|