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de la Plaza Llamas R, Ortega Azor L, Hernández Yuste M, Gorini L, Latorre-Fragua RA, Díaz Candelas DA, Al Shwely Abduljabar F, Gemio del Rey IA. Quality-adjusted life years and surgical waiting list: Systematic review of the literature. World J Gastrointest Surg 2024; 16:1155-1164. [PMID: 38690041 PMCID: PMC11056653 DOI: 10.4240/wjgs.v16.i4.1155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 01/26/2024] [Accepted: 02/25/2024] [Indexed: 04/22/2024] Open
Abstract
BACKGROUND The quality-adjusted life year (QALY) is a metric that is increasingly used today in the field of health economics to evaluate the value of different medical treatments and procedures. Surgical waiting lists (SWLs) represent a pressing problem in public healthcare. The QALY measure has rarely been used in the context of surgery. It would be interesting to know how many QALYs are lost by patients on SWLs. AIM To investigate the relationship between QALYs and SWLs in a systematic review of the scientific literature. METHODS The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. An unlimited search was carried out in PubMed, updated on January 19, 2024. Data on the following variables were investigated and analyzed: Specialty, country of study, procedure under study, scale used to measure QALYs, the use of a theoretical or real-life model, objectives of the study and items measured, the economic value assigned to the QALY in the country in question, and the results and conclusions published. RESULTS Forty-eight articles were selected for the study. No data were found regarding QALYs lost on SWLs. The specialties in which QALYs were studied the most in relation to the waiting list were urology and general surgery, with 15 articles each. The country in which the most studies of QALYs were carried out was the United States (n = 21), followed by the United Kingdom (n = 9) and Canada (n = 7). The most studied procedure was organ transplantation (n = 39), including 15 kidney, 14 liver, 5 heart, 4 lung, and 1 intestinal. Arthroplasty (n = 4), cataract surgery (n = 2), bariatric surgery (n = 1), mosaicplasty (n = 1), and septoplasty (n = 1) completed the surgical interventions included. Thirty-nine of the models used were theoretical (the most frequently applied being the Markov model, n = 34), and nine were real-life. The survey used to measure quality of life in 11 articles was the European Quality of Life-5 dimensions, but in 32 articles the survey was not specified. The willingness-to-pay per QALY gained ranged from $100000 in the United States to €20000 in Spain. CONCLUSION The relationship between QALYs and SWLs has only rarely been studied in the literature. The rate of QALYs lost on SWLs has not been determined. Future research is warranted to address this issue.
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Affiliation(s)
- Roberto de la Plaza Llamas
- Department of General and Digestive Surgery, Hospital Universitario de Guadalajara, Guadalajara 19002, Spain
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares 28871, Madrid, Spain
| | - Lorena Ortega Azor
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares 28871, Madrid, Spain
| | - Marina Hernández Yuste
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares 28871, Madrid, Spain
| | - Ludovica Gorini
- Department of General and Digestive Surgery, Hospital Universitario de Guadalajara, Guadalajara 19002, Spain
| | - Raquel Aránzazu Latorre-Fragua
- Department of General and Digestive Surgery, Hospital Universitario de Guadalajara, Guadalajara 19002, Spain
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares 28871, Madrid, Spain
| | | | - Farah Al Shwely Abduljabar
- Department of General and Digestive Surgery, Hospital Universitario de Guadalajara, Guadalajara 19002, Spain
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares 28871, Madrid, Spain
| | - Ignacio Antonio Gemio del Rey
- Department of General and Digestive Surgery, Hospital Universitario de Guadalajara, Guadalajara 19002, Spain
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares 28871, Madrid, Spain
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2
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Shah KK, Wyld M, Hedley JA, Waller KMJ, De La Mata N, Webster AC, Morton RL. Cost-effectiveness of Kidney Transplantation From Donors at Increased Risk of Blood-borne Virus Infection Transmission. Transplantation 2023; 107:2028-2042. [PMID: 37211651 DOI: 10.1097/tp.0000000000004632] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
BACKGROUND Demand for donor kidneys outstrips supply. Using kidneys from selected donors with an increased risk of blood-borne virus (BBV) transmission (hepatitis B virus and hepatitis C virus [HCV], human immunodeficiency virus) may expand the donor pool, but cost-effectiveness of this strategy is uncertain. METHODS A Markov model was developed using real-world evidence to compare healthcare costs and quality-adjusted life years (QALYs) of accepting kidneys from deceased donors with potential increased risk of BBV transmission, because of increased risk behaviors and/or history of HCV, versus declining these kidneys. Model simulations were run over a 20-y time horizon. Parameter uncertainty was assessed through deterministic and probabilistic sensitivity analyses. RESULTS Accepting kidneys from donors at increased risk of BBVs (2% from donors with increased-risk behaviors and 5% from donors with active or past HCV infection) incurred total costs of 311 303 Australian dollars with a gain of 8.53 QALYs. Foregoing kidneys from these donors incurred total costs of $330 517 and a gain of 8.44 QALYs. A cost-saving of $19 214 and additional 0.09 QALYs (~33 d in full health) per person would be generated compared with declining these donors. Increasing the availability of kidneys with increased risk by 15% led to further cost-savings of $57 425 and additional 0.23 QALY gains (~84 d in full health). Probabilistic sensitivity analysis using 10 000 iterations showed accepting kidneys from donors at increased risk led to lower costs and higher QALY gains. CONCLUSIONS Shifting clinical practice to accept increased BBV risk donors would likely produce lower costs and higher QALYs for health systems.
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Affiliation(s)
- Karan K Shah
- Health Economics and Health Technology Assessment, NHMRC Clinical Trials Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Melanie Wyld
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
- Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW, Australia
| | - James A Hedley
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Karen M J Waller
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Nicole De La Mata
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Angela C Webster
- Health Economics and Health Technology Assessment, NHMRC Clinical Trials Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
- Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW, Australia
| | - Rachael L Morton
- Health Economics and Health Technology Assessment, NHMRC Clinical Trials Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
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3
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Hedley JA, Kelly PJ, Wyld M, Shah K, Morton RL, Byrnes J, Rosales BM, De La Mata NL, Wyburn K, Webster AC. Cost-effectiveness of Interventions to Increase Utilization of Kidneys From Deceased Donors With Primary Brain Malignancy in an Australian Setting. Transplant Direct 2023; 9:e1474. [PMID: 37090124 PMCID: PMC10118354 DOI: 10.1097/txd.0000000000001474] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 01/26/2023] [Accepted: 01/28/2023] [Indexed: 04/25/2023] Open
Abstract
Kidneys from potential deceased donors with brain cancer are often foregone due to concerns of cancer transmission risk to recipients. There may be uncertainty around donors' medical history and their absolute transmission risk or risk-averse decision-making among clinicians. However, brain cancer transmissions are rare, and prolonging waiting time for recipients is harmful. Methods We assessed the cost-effectiveness of increasing utilization of potential deceased donors with brain cancer using a Markov model simulation of 1500 patients waitlisted for a kidney transplant, based on linked transplant registry data and with a payer perspective (Australian government). We estimated costs and quality-adjusted life-years (QALYs) for three interventions: decision support for clinicians in assessing donor risk, improved cancer classification accuracy with real-time data-linkage to hospital records and cancer registries, and increased risk tolerance to allow intermediate-risk donors (up to 6.4% potential transmission risk). Results Compared with current practice, decision support provided 0.3% more donors with an average transmission risk of 2%. Real-time data-linkage provided 0.6% more donors (1.1% average transmission risk) and increasing risk tolerance (accepting intermediate-risk 6.4%) provided 2.1% more donors (4.9% average transmission risk). Interventions were dominant (improved QALYs and saved costs) in 78%, 80%, and 87% of simulations, respectively. The largest benefit was from increasing risk tolerance (mean +18.6 QALYs and AU$2.2 million [US$1.6 million] cost-savings). Conclusions Despite the additional risk of cancer transmission, accepting intermediate-risk donors with brain cancer is likely to increase the number of donor kidneys available for transplant, improve patient outcomes, and reduce overall healthcare expenditure.
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Affiliation(s)
- James A. Hedley
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia
| | - Patrick J. Kelly
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia
| | - Melanie Wyld
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia
- Centre for Transplant and Renal Research, Westmead Hospital, New South Wales, Australia
| | - Karan Shah
- National Health and Medical Research Council Clinical Trials Centre, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia
| | - Rachael L. Morton
- National Health and Medical Research Council Clinical Trials Centre, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia
| | - Juliet Byrnes
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia
| | - Brenda M. Rosales
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia
| | - Nicole L. De La Mata
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia
| | - Kate Wyburn
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia
- Renal Unit, Royal Prince Alfred Hospital, New South Wales, Australia
| | - Angela C. Webster
- Collaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia
- Centre for Transplant and Renal Research, Westmead Hospital, New South Wales, Australia
- National Health and Medical Research Council Clinical Trials Centre, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia
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Woolley AE, Gandhi AR, Jones ML, Kim JJ, Mallidi HR, Givertz MM, Baden LR, Mehra MR, Neilan AAM. The Cost-effectiveness of Transplanting Hearts From Hepatitis C-infected Donors Into Uninfected Recipients. Transplantation 2023; 107:961-969. [PMID: 36525554 PMCID: PMC10065819 DOI: 10.1097/tp.0000000000004378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 07/29/2022] [Accepted: 08/13/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND The DONATE HCV trial demonstrated the safety and efficacy of transplanting hearts from hepatitis C viremic (HCV+) donors. In this report, we examine the cost-effectiveness and impact of universal HCV+ heart donor eligibility in the United States on transplant waitlist time and life expectancy. METHODS We developed a microsimulation model to compare 2 waitlist strategies for heart transplant candidates in 2018: (1) status quo (SQ) and (2) SQ plus HCV+ donors (SQ + HCV). From the DONATE HCV trial and published national datasets, we modeled mean age (53 years), male sex (75%), probabilities of waitlist mortality (0.01-0.10/month) and transplant (0.03-0.21/month) stratified by medical urgency, and posttransplant mortality (0.003-0.052/month). We assumed a 23% increase in transplant volume with SQ + HCV compared with SQ. Costs (2018 United States dollar) included waitlist care ($2200-190 000/month), transplant ($213 400), 4-wk HCV treatment ($26 000), and posttransplant care ($2500-11 300/month). We projected waitlist time, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs [$/QALY, discounted 3%/year]; threshold ≤$100 000/QALY). RESULTS Compared with SQ, SQ + HCV decreased waitlist time from 8.7 to 6.7 months, increased undiscounted life expectancy from 8.9 to 9.2 QALYs, and increased discounted lifetime costs from $671 400/person to $690 000/person. Four-week HCV treatment comprised 0.5% of lifetime costs. The ICER of SQ + HCV compared with SQ was $74 100/QALY and remained ≤$100 000/QALY with up to 30% increases in transplant and posttransplant costs. CONCLUSIONS Transplanting hearts from HCV-infected donors could decrease waitlist times, increase life expectancy, and be cost-effective. These findings were robust within the context of current high HCV treatment costs.
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Affiliation(s)
- Ann E Woolley
- Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA
- Harvard Medical School, Boston, MA
| | - Aditya R Gandhi
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA
| | - Michelle L Jones
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA
| | - Jane J Kim
- Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Hari R Mallidi
- Harvard Medical School, Boston, MA
- Division of Thoracic and Cardiac Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA
| | - Michael M Givertz
- Harvard Medical School, Boston, MA
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA
| | - Lindsey R Baden
- Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA
- Harvard Medical School, Boston, MA
| | - Mandeep R Mehra
- Harvard Medical School, Boston, MA
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA
| | - And Anne M Neilan
- Harvard Medical School, Boston, MA
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA
- Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA
- Division of General Academic Pediatrics, Department of Pediatrics, Massachusetts General Hospital, Boston, MA
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5
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Zaphiros NH, Nie J, Chang S, Shah V, Kareem S, Zaaroura A, Kayler LK. Broad organ acceptance and equitable access to early kidney transplantation. Clin Transplant 2023; 37:e14916. [PMID: 36638138 DOI: 10.1111/ctr.14916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 12/23/2022] [Accepted: 01/10/2023] [Indexed: 01/14/2023]
Abstract
BACKGROUND Broad organ acceptance can increase early kidney transplantation (KTX) within <1-year of dialysis initiation while improving access inequity. METHODS Single-center data of adult isolated deceased-donor KTX recipients between 2013 and 2020 were stratified into three 2.5-year periods before-, early after-, and late after our center's deceased-donor organ acceptance practice change, excluding a 6-month implementation period. Outcomes were assessed within five recipient subgroups based on demographic and clinical characteristics. RESULTS Of 704 recipients, the frequency of early KTX was 22% pre-change, 36% early post-change, and 34% late post-change. Given similar post-change frequencies of early KTX, post-change eras were combined to improve analytic power of subgroup analyses. After the organ acceptance practice change (vs. pre-change), the likelihood of early KTX increased variably within historically underserved groups, including recipients who were older (37%-39%, p = .859), Black (10%-21%, p = .136), female (21%-37%, p = .034), diabetic (13%-32%, p = .010), and BMI≥35 kg/m2 (20%-34%, p = .007). Despite the practice change, Black recipients continued to experience less early KTX compared to non-Black recipients. The likelihood of delayed graft function was significantly increased (p < .001), and 1-year creatinine was significantly higher (p < .001) post-practice change, but between-era risk-adjusted death-censored graft survival was similar. CONCLUSIONS Transition to broader donor acceptance was associated with more early KTXs among historically underserved patient subgroups. However, the effect was non-significant among Black recipients, suggesting the need for additional strategies to impact early transplant access for this population. Studies of broad organ acceptance are needed to examine both access and outcomes.
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Affiliation(s)
- Nikolas H Zaphiros
- Department of Surgery, University at Buffalo, Buffalo, New York, USA.,Transplant and Kidney Care Regional Center of Excellence, Erie County Medical Center, Buffalo, New York, USA
| | - Jing Nie
- Department of Epidemiology and Environmental Health, University at Buffalo School of Public Health and Health Professions, Buffalo, New York, USA
| | - Shirley Chang
- Transplant and Kidney Care Regional Center of Excellence, Erie County Medical Center, Buffalo, New York, USA.,Department of Medicine, University at Buffalo, Buffalo, New York, USA
| | - Vaqar Shah
- Transplant and Kidney Care Regional Center of Excellence, Erie County Medical Center, Buffalo, New York, USA.,Department of Medicine, University at Buffalo, Buffalo, New York, USA
| | - Samer Kareem
- Transplant and Kidney Care Regional Center of Excellence, Erie County Medical Center, Buffalo, New York, USA.,Department of Medicine, University at Buffalo, Buffalo, New York, USA
| | - Ahmad Zaaroura
- Department of Surgery, University at Buffalo, Buffalo, New York, USA.,Transplant and Kidney Care Regional Center of Excellence, Erie County Medical Center, Buffalo, New York, USA
| | - Liise K Kayler
- Department of Surgery, University at Buffalo, Buffalo, New York, USA.,Transplant and Kidney Care Regional Center of Excellence, Erie County Medical Center, Buffalo, New York, USA.,Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, New York, USA
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6
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Yaghoubi M, Cressman S, Edwards L, Shechter S, Doyle-Waters MM, Keown P, Sapir-Pichhadze R, Bryan S. A Systematic Review of Kidney Transplantation Decision Modelling Studies. APPLIED HEALTH ECONOMICS AND HEALTH POLICY 2023; 21:39-51. [PMID: 35945483 DOI: 10.1007/s40258-022-00744-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 06/19/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Genome-based precision medicine strategies promise to minimize premature graft loss after renal transplantation, through precision approaches to immune compatibility matching between kidney donors and recipients. The potential adoption of this technology calls for important changes to clinical management processes and allocation policy. Such potential policy change decisions may be supported by decision models from health economics, comparative effectiveness research and operations management. OBJECTIVE We used a systematic approach to identify and extract information about models published in the kidney transplantation literature and provide an overview of the status of our collective model-based knowledge about the kidney transplant process. METHODS Database searches were conducted in MEDLINE, Embase, Web of Science and other sources, for reviews and primary studies. We reviewed all English-language papers that presented a model that could be a tool to support decision making in kidney transplantation. Data were extracted on the clinical context and modelling methods used. RESULTS A total of 144 studies were included, most of which focused on a single component of the transplantation process, such as immunosuppressive therapy or donor-recipient matching and organ allocation policies. Pre- and post-transplant processes have rarely been modelled together. CONCLUSION A whole-disease modelling approach is preferred to inform precision medicine policy, given its potential upstream implementation in the treatment pathway. This requires consideration of pre- and post-transplant natural history, risk factors for allograft dysfunction and failure, and other post-transplant outcomes. Our call is for greater collaboration across disciplines and whole-disease modelling approaches to more accurately simulate complex policy decisions about the integration of precision medicine tools in kidney transplantation.
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Affiliation(s)
- Mohsen Yaghoubi
- Department of Pharmacy Practice, Mercer University College of Pharmacy, Atlanta, USA
| | - Sonya Cressman
- Faculty of Health Sciences, Simon Fraser University, School of Population and Public Health, University of British Columbia, Vancouver, Canada
| | - Louisa Edwards
- School of Population and Public Health, University of British Columbia, Vancouver, V6T 1Z3, Canada
| | - Steven Shechter
- Sauder School of Business, University of British Columbia, Vancouver, Canada
| | - Mary M Doyle-Waters
- Centre for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, Canada
| | - Paul Keown
- Department of Medicine, Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
| | | | - Stirling Bryan
- School of Population and Public Health, University of British Columbia, Vancouver, V6T 1Z3, Canada.
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7
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Sawinski D, Rosenblatt RE, Morales JM. Renal transplantation using kidneys from hepatitis C-infected donors: A review of 30-years' experience. Nefrologia 2022:S2013-2514(22)00178-X. [PMID: 36564226 DOI: 10.1016/j.nefroe.2022.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Accepted: 04/18/2022] [Indexed: 06/17/2023] Open
Abstract
Kidney transplantation is the optimal therapy for end-stage kidney disease but limited by the available number of organs. Using HCV+ donors, both in HCV+ and HCV- recipients, is a rational response to the organ shortage. We review the historic experience using HCV+ donors in HCV+ recipients and assess long-term results. We also discuss contemporary practices, including the transplantation of HCV-viremic kidneys into HCV- recipients with different approaches to posttransplant HCV therapy.
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Affiliation(s)
- Deirdre Sawinski
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Russel E Rosenblatt
- Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
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8
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Doherty DT, Athwal V, Moinuddin Z, Augustine T, Prince M, van Dellen D, Khambalia HA. Kidney Transplantation From Hepatitis-C Viraemic Donors:Considerations for Practice in the United Kingdom. Transpl Int 2022; 35:10277. [PMID: 35592447 PMCID: PMC9110637 DOI: 10.3389/ti.2022.10277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 03/11/2022] [Indexed: 12/01/2022]
Abstract
Background: Donor hepatitis-C (HCV) infection has historically represented a barrier to kidney transplantation (KT). However, direct-acting antiviral (DAA) medications have revolutionised treatment of chronic HCV infection. Recent American studies have demonstrated that DAA regimes can be used safely peri-operatively in KT to mitigate HCV transmission risk. Methods: To formulate this narrative review, a comprehensive literature search was performed to analyse results of existing clinical trials examining KT from HCV-positive donors to HCV-negative recipients with peri-operative DAA regimes. Results: 13 studies were reviewed (11 single centre, four retrospective). Outcomes for 315 recipients were available across these studies. A sustained virological response at 12 weeks (SVR12) of 100% was achieved in 11 studies. One study employed an ultra-short DAA regime and achieved an SVR12 of 98%, while another achieved SVR12 of 96% due to treatment of a missed mixed genotype. Conclusion: HCV+ KT is safe and may allow increased utilisation of organs for transplantation from HCV+ donors, who often have other favourable characteristics for successful donation. Findings from US clinical trials can be applied to the United Kingdom transplant framework to improve organ utilisation as suggested by the NHSBT vision strategy "Organ Donation and Transplantation 2030: meeting the need".
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Affiliation(s)
- Daniel T. Doherty
- Department of Renal and Pancreatic Transplantation, Manchester University NHS Foundation Trust, Manchester, United Kingdom
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Varinder Athwal
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
- Department of Hepatology, Manchester University NHS Foundation Trust, Manchester, United Kingdom
| | - Zia Moinuddin
- Department of Renal and Pancreatic Transplantation, Manchester University NHS Foundation Trust, Manchester, United Kingdom
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Titus Augustine
- Department of Renal and Pancreatic Transplantation, Manchester University NHS Foundation Trust, Manchester, United Kingdom
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Martin Prince
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
- Department of Hepatology, Manchester University NHS Foundation Trust, Manchester, United Kingdom
| | - David van Dellen
- Department of Renal and Pancreatic Transplantation, Manchester University NHS Foundation Trust, Manchester, United Kingdom
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Hussein A. Khambalia
- Department of Renal and Pancreatic Transplantation, Manchester University NHS Foundation Trust, Manchester, United Kingdom
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
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9
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Kuntzen C, Bagha Z. The Use of Hepatitis C Virus-Positive Organs in Hepatitis C Virus-Negative Recipients. Clin Liver Dis 2022; 26:291-312. [PMID: 35487612 DOI: 10.1016/j.cld.2022.01.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The use of hepatitis C virus (HCV) -positive organs in HCV-negative recipients with posttransplant antiviral treatment has increasingly been studied since the introduction of new direct-acting antivirals. This article reviews existing experience in liver and kidney transplant. Fifteen studies with 218 HCV D+/R- liver transplants, with 182 from viremic donors, show a sustained viral response for 12 weeks (SVR12) rate of 99.5%. Nine studies involving 204 HCV donor-positive recipient-negative kidney transplant recipients had an SVR12 rate of 99.5%. Complications are infrequent. Preemptive treatment in kidney transplant of for only 4 weeks or even 4 days showed surprising success rates.
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Affiliation(s)
- Christian Kuntzen
- Hofstra University at Northwell Health, 300 Community Drive, Manhasset, NY 11030, USA.
| | - Zohaib Bagha
- Hofstra University at Northwell Health, 300 Community Drive, Manhasset, NY 11030, USA
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10
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Sawinski D, Rosenblatt RE, Morales JM. Renal transplantation using kidneys from hepatitis C-infected donors: A review of 30-years’ experience. Nefrologia 2022. [DOI: 10.1016/j.nefro.2022.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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11
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Czarnecka P, Czarnecka K, Tronina O, Baczkowska T, Durlik M. Utilization of HCV viremic donors in kidney transplantation: a chance or a threat? Ren Fail 2022; 44:434-449. [PMID: 35260039 PMCID: PMC8920354 DOI: 10.1080/0886022x.2022.2047069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Kidney transplantation is the treatment of choice in end-stage renal disease. The main issue which does not allow to utilize it fully is the number of organs available for transplant. Introduction of highly effective oral direct-acting antivirals (DAAs) to the treatment of chronic hepatitis C virus infection (HCV) enabled transplantation of HCV viremic organs to naive recipients. Despite an increasing number of reports on the satisfying effects of using HCV viremic organs, including kidneys, they are more often rejected than those from HCV negative donors. The main reason is the presence of HCV viremia and not the quality of the organ. The current state of knowledge points to the fact that a kidney transplant from an HCV nucleic acid testing positive (NAT+) donor to naive recipients is an effective and safe solution to the problem of the insufficient number of organs available for transplantation. It does not, however, allow to draw conclusions as to the long-term consequence of such an approach. This review analyzes the possibilities and limitations of the usage of HCV NAT + donor organs. Abbreviations: DAA: direct-acting antivirals; HCV: hepatitis C virus; NAT: nucleic acid testing; OPTN: Organ Procurement and Transplantation Network; KDIGO: Kidney Disease: Improving Global Outcomes; Ab: antigen; eGFR: estimated glomerular filtration rate; D: donor; R: recipient; CMV: cytomegalovirus; HBV: hepatitis B virus; UNOS: United Network for Organ Sharing; PHS: Public Health Service; EBR/GZR: elbasvir/grazoprevir; SVR: sustained virologic response; RAS: resistance-associated substitutions; SOF: soforbuvir; GLE/PIB: glecaprevir/pibrentasvir; ACR: acute cellular rejection; AR: acute rejection; DSA: donor-specific antibodies; KTR: kidney transplant recipients; AASLD: American Association for the Study of Liver Disease; IDSA: Infectious Diseases Society of America; PPI: proton pump inhibitors; CKD: chronic kidney disease; GN: glomerulonephritis; KAS: The Kidney Allocation system.
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Affiliation(s)
- Paulina Czarnecka
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Kinga Czarnecka
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Olga Tronina
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Teresa Baczkowska
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Magdalena Durlik
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
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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.
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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
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Abstract
In the 1970s, an unknown virus was suspected for documented cases of transfusion-associated hepatitis, a phenomenon called non-A, non-B hepatitis. In 1989, the infectious transmissible agent was identified and named hepatitis C virus (HCV) and, soon enough, the first diagnostic HCV antibody test was developed, which led to a dramatic decrease in new infections. Today, HCV infection remains a global health burden and a major cause of liver cirrhosis, hepatocellular carcinoma and liver transplantation. However, tremendous advances have been made over the decades, and HCV became the first curable, chronic viral infection. The introduction of direct antiviral agents revolutionized antiviral treatment, leading to viral eradication in more than 98% of all patients infected with HCV. This Perspective discusses the history of HCV research, which reads like a role model for successful translational research: starting from a clinical observation, specific therapeutic agents were developed, which finally were implemented in national and global elimination programmes.
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Affiliation(s)
- Michael P. Manns
- grid.10423.340000 0000 9529 9877Hannover Medical School, Hannover, Germany
| | - Benjamin Maasoumy
- grid.10423.340000 0000 9529 9877Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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14
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Kim M, Stern J, Robalino R, Weldon EP, Ali N, Mehta SA, Stewart ZA, Lonze BE. Caregiver exposure to hepatitis C virus following transplantation with hepatitis C viremic donor organs: A case series. Transpl Infect Dis 2021; 24:e13775. [PMID: 34910839 DOI: 10.1111/tid.13775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 11/12/2021] [Accepted: 11/29/2021] [Indexed: 11/29/2022]
Abstract
INTRODUCTION Direct acting antiviral (DAA) therapeutics have ushered in an era in which transplanting organs from donors infected with hepatitis C virus (HCV+) into recipients without (HCV-) is an increasingly common practice. Rare but potentially life-threatening events have been reported in recipients of HCV+ organs. METHODS Since 2018 at our institution, 182 HCV- patients have received HCV+ donor organs. Here, we retrospectively reviewed cases in which recipients' family member caregivers reported sustaining needlestick exposures at home following discharge of the transplant recipient from the hospital. RESULTS Caregiver needlestick exposures were passively reported in three cases of HCV+ into HCV- transplants (1.64% of such cases at our center). In all instances, the exposed individuals were aiding in diabetic management and the exposure occurred via lancets or insulin needles. In one case, the recipient viral load was undetectable at the time of the exposure but in the other two, recipients were viremic, putting their family members at risk to contract HCV infection. Surveillance for the exposed individuals was undertaken and no transmissions occurred. DISCUSSION For centers performing HCV+ into HCV- transplants, it is important that informed consent includes discussion of potential secondary risks to family members and caregivers. Further, protocols for post-exposure surveillance and for the acquisition of DAA treatment in the event of a secondary transmission should be in place. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Michelle Kim
- Transplant Institute, New York University Langone Health, New York, NY, USA
| | - Jeffrey Stern
- Transplant Institute, New York University Langone Health, New York, NY, USA
| | - Ryan Robalino
- Transplant Institute, New York University Langone Health, New York, NY, USA
| | - Elaina P Weldon
- Transplant Institute, New York University Langone Health, New York, NY, USA
| | - NicoleM Ali
- Transplant Institute, New York University Langone Health, New York, NY, USA
| | - Sapna A Mehta
- Transplant Institute, New York University Langone Health, New York, NY, USA
| | - Zoe A Stewart
- Transplant Institute, New York University Langone Health, New York, NY, USA
| | - Bonnie E Lonze
- Transplant Institute, New York University Langone Health, New York, NY, USA
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15
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Edmonds C, Carver A, DeClercq J, Choi L, Peter M, Schlendorf K, Perri R, Forbes RC, Concepcion BP. Access to hepatitis C direct-acting antiviral therapy in hepatitis C-positive donor to hepatitis C-negative recipient solid-organ transplantation in a real-world setting. Am J Surg 2021; 223:975-982. [PMID: 34548142 DOI: 10.1016/j.amjsurg.2021.09.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Revised: 08/20/2021] [Accepted: 09/06/2021] [Indexed: 01/08/2023]
Abstract
BACKGROUND Emerging data supports expanding the solid organ donor pool with transplantation from hepatitis C virus (HCV)-positive donors into HCV-negative recipients. However, concerns exist regarding the ability to access direct-acting antivirals (DAAs) post-transplant in a real-world setting. METHODS This single-center, retrospective study evaluated DAA access rates, time to first dose, and patient cost in donor-derived HCV solid-organ transplant recipients utilizing an integrated specialty pharmacy process. RESULTS Among 91 patients, all accessed DAAs through prescription insurance (97%) or patient assistance programs (3%). Of those who received DAAs through insurance, only 65% received approval on initial insurance submission. Median time from transplant to first dose was 45d [IQR 34-66]. The on-site specialty pharmacy was used by 69% of patients. Copay assistance programs reduced the median monthly patient cost from $1914 [range $7-7536] to $0 [range $0-5]. CONCLUSION Our findings indicate that access to DAAs in donor-derived HCV post-transplant is achievable and affordable; however, significant added administrative efforts may be required for insurance approval as well as obtaining copay assistance, which is a limited resource.
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Affiliation(s)
- Cori Edmonds
- Vanderbilt Specialty Pharmacy, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Alicia Carver
- Vanderbilt Specialty Pharmacy, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Josh DeClercq
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Leena Choi
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Megan Peter
- Vanderbilt Specialty Pharmacy, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Kelly Schlendorf
- Section of Heart Failure and Cardiac Transplantation, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Roman Perri
- Department of Medicine, Division of Hepatology, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Rachel C Forbes
- Department of Surgery, Division of Kidney and Pancreas Transplantation, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Beatrice P Concepcion
- Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN, USA.
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Kidney Transplantation From Hepatitis C Viremic Deceased Donors to Aviremic Recipients in a Real-world Setting. Transplant Direct 2021; 7:e761. [PMID: 34514116 PMCID: PMC8425827 DOI: 10.1097/txd.0000000000001217] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 07/23/2021] [Indexed: 01/09/2023] Open
Abstract
Background. Transplantation of hepatitis C viremic (HCV+) deceased donor kidney transplants (DDKT) into aviremic (HCV–) recipients is a strategy to increase organ utilization. However, there are concerns around inferior recipient outcomes due to delayed initiation of direct-acting antiviral (DAA) therapy and sustained HCV replication when implemented outside of a research setting. Methods. This was a retrospective single-center matched cohort study of DDKT recipients of HCV+ donors (cases) who were matched 1:1 to recipients of HCV– donors (comparators) by age, gender, race, presence of diabetes, kidney donor profile index, and calculated panel-reactive antibody. Data were analyzed using summary statistics, t-tests, and chi-square tests for between-group comparisons, and linear mixed-effects models for longitudinal data. Results. Each group consisted of 50 recipients with no significant differences in baseline characteristics. The 6-mo longitudinal trajectory of serum creatinine and estimated glomerular filtration rate did not differ between groups. All recipients had similar rates of acute rejection and readmissions (all P > 0.05). One case lost the allograft 151 d posttransplant because of acute rejection, and 1 comparator died on postoperative day 7 from cardiac arrest. HCV+ recipients initiated DAA on average 29 ± 11 d posttransplant. Ninety-eight percent achieved sustained virologic response at 4 and 12 wks with the first course of therapy; 1 patient had persistent HCV infection and was cured with a second course of DAA. Conclusions. Aviremic recipients of HCV+ DDKT with delayed DAA initiation posttransplant had similar short-term outcomes compared with matched recipient comparators of HCV– donors.
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17
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Cuvelier S, Van Caeseele P, Kadatz M, Peterson K, Sun S, Dodd N, Werestiuk K, Koulack J, Nickerson P, Ho J. Expanding the Deceased Donor Pool in Manitoba Using Hepatitis C-Viremic Donors: Program Report. Can J Kidney Health Dis 2021; 8:20543581211033496. [PMID: 34367648 PMCID: PMC8317248 DOI: 10.1177/20543581211033496] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 06/07/2021] [Indexed: 11/25/2022] Open
Abstract
Purpose of program: The ongoing shortage of organs for transplant combined with Manitoba having the highest prevalence of end-stage renal disease (ESRD) in Canada has resulted in long wait times on the deceased donor waitlist. Therefore, the Transplant Manitoba Adult Kidney Program has ongoing quality improvement initiatives to expand the deceased donor pool. This clinical transplant protocol describes the use of prophylactic pan-genotypic direct-acting anti-viral agents (DAA) for transplanting hepatitis C (HCV)-viremic kidneys (HCV antibody positive/nucleic acid [nucleic acid amplification testing, NAT] positive) to HCV-naïve recipients as routine standard of care. We will evaluate the provincial implementation of this protocol as a prospective observational cohort study. Sources of information: Scoping literature review and key stakeholder engagement with interdisciplinary health care providers and health system leaders/decision markers. Methods: Patients will be screened pre-transplant for eligibility and undergo a multilevel education and consent process to participate in this expanded donor program. Incident adult HCV-naïve recipients of an HCV-viremic kidney transplant will be treated prophylactically with glecaprevir-pibrentasvir with the first dose administered on call to the operation. Glecaprevir-pibrentasvir will be used for 8 weeks with viral monitoring and hepatology follow-up. Primary outcomes are sustained virologic response (SVR) at 12 weeks and the tolerability of DAA therapy. Secondary outcomes within the first year post-transplant are patient and graft survival, graft function, biopsy-proven rejection, HCV transmission to recipient (HCV NAT positive), and HCV nonstructural protein 5A (NS5A) resistance. Safety outcomes within the first year post-transplant include fibrosing cholestatic hepatitis, acute liver failure, primary and secondary DAA treatment failure, HCV transmission to a recipient’s partner, elevated liver enzymes ≥2-fold, abnormal international normalized ratio (INR), angioedema, anaphylaxis, cirrhosis, and hepatocellular carcinoma. Key findings: This program successfully advocated for and obtained hospital formulary, provincial Exceptional Drug Status (EDS), and Non-Insured Health Benefits (NIHB) to provide prophylactic DAA therapy for this indication, and this information may be useful to other provincial transplant organizations seeking to establish an HCV-viremic kidney transplant program with prophylactic DAA drug coverage. Limitations: (1) Patient engagement was not undertaken during the program design phase, but patient-reported experience measures will be obtained for continuous quality improvement. (2) Only standard criteria donors (optimal kidney donor profile index [KDPI] ≤60) will be used. If this approach is safe and feasible, then higher KDPI donors may be included. Implications: The goal of this quality improvement project is to improve access to kidney transplantation for Manitobans. This program will provide prophylactic DAA therapy for HCV-viremic kidney transplant to HCV-naïve recipients as routine standard of care outside a clinical trial protocol. We anticipate this program will be a safe and effective way to expand kidney transplantation from a previously unutilized donor pool.
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Affiliation(s)
- Susan Cuvelier
- Section of Hepatology, Department of Internal Medicine, University of Manitoba, Winnipeg, Canada
| | | | - Matthew Kadatz
- Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, Canada
| | - Kathryn Peterson
- Transplant Manitoba Adult Kidney Program, Winnipeg, Manitoba, Canada
| | - Siyao Sun
- Transplant Manitoba Adult Kidney Program, Winnipeg, Manitoba, Canada
| | - Nancy Dodd
- Transplant Manitoba Adult Kidney Program, Winnipeg, Manitoba, Canada
| | - Kim Werestiuk
- Transplant Manitoba Adult Kidney Program, Winnipeg, Manitoba, Canada
| | - Joshua Koulack
- Section of Vascular Surgery, Department of Surgery, University of Manitoba, Winnipeg, Canada
| | - Peter Nickerson
- Transplant Manitoba Adult Kidney Program, Winnipeg, Manitoba, Canada.,Section of Nephrology, Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.,Department of Immunology, University of Manitoba, Winnipeg, Canada
| | - Julie Ho
- Transplant Manitoba Adult Kidney Program, Winnipeg, Manitoba, Canada.,Section of Nephrology, Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.,Department of Immunology, University of Manitoba, Winnipeg, Canada
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18
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Daloul R, Pesavento T, Goldberg DS, Reese PP. A review of kidney transplantation from HCV-viremic donors into HCV-negative recipients. Kidney Int 2021; 100:1190-1198. [PMID: 34237327 DOI: 10.1016/j.kint.2021.06.034] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 06/17/2021] [Accepted: 06/18/2021] [Indexed: 12/29/2022]
Abstract
The safety and efficacy of direct-acting antiviral therapies have allowed the transplantation of organs from hepatitis C virus (HCV)-viremic donors into uninfected recipients. This novel strategy contrasts with the previous standard-of-care practice of limiting the transplantation of HCV infected-donor organs to HCV-infected recipients, or all too often, discarding viable organs. In this review, we summarize the published literature about the safety and feasibility of transplanting organs from HCV-viremic donors, the challenges that hinder wider adoption of this strategy, and future research needs.
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Affiliation(s)
- Reem Daloul
- The Ohio State University Medical Center, Columbus, Ohio, USA.
| | - Todd Pesavento
- The Ohio State University Medical Center, Columbus, Ohio, USA
| | - David S Goldberg
- University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Peter P Reese
- Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Biostatistics, Epidemiology & Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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19
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Eckman MH, Adejare AA, Duncan H, Woodle ES, Thakar CV, Alloway RR, Sherman KE. Incorporating Patients' Values and Preferences Into Decision Making About Transplantation of HCV-Naïve Recipients With Kidneys From HCV-Viremic Donors: A Feasibility Study. MDM Policy Pract 2021; 6:23814683211056537. [PMID: 34734119 PMCID: PMC8558609 DOI: 10.1177/23814683211056537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 10/05/2021] [Indexed: 11/16/2022] Open
Abstract
Introduction. While use of (hepatitis C virus) HCV-viremic kidneys may result in net benefit for the average end-stage kidney disease (ESKD) patient awaiting transplantation, patients may have different values for ESKD-related health states. Thus, the best decision for any individual may be different depending on the balance of these factors. Our objective was to explore the feasibility of sampling health utilities from hemodialysis patients in order to perform patient-specific decision analyses considering various transplantation strategies. Study Design. We assessed utilities on a convenience sample of hemodialysis patients for health states including hemodialysis, and transplantation with either an HCV-uninfected kidney or an HCV-viremic kidney. We performed patient-specific decision analyses using each patient's age, race, gender, dialysis vintage, and utilities. We used a Markov state transition model considering strategies of continuing hemodialysis, transplantation with an HCV-unexposed kidney, and transplantation with an HCV-viremic kidney and HCV treatment. We interviewed 63 ESKD patients from four dialysis centers (Dialysis Clinic Inc., DCI) in the Cincinnati metropolitan area. Results. Utilities for ESKD-related health states varied widely from patient to patient. Mean values were highest for -transplantation with an HCV-uninfected kidney (0.89, SD: 0.18), and were 0.825 (SD: 0.231) and 0.755 (SD: 0.282), respectively, for hemodialysis and transplantation with an HCV-viremic kidney. Patient-specific decision analyses indicated 37 (59%) of the 63 ESKD patients in the cohort would have a net gain in quality-adjusted life years from transplantation of an HCV-viremic kidney, while 26 would have a net loss. Conclusions. It is feasible to gather dialysis patients' health state utilities and perform personalized decision analyses. This approach could be used in the future to guide shared decision-making discussions about transplantation strategies for ESKD patients.
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Affiliation(s)
- Mark H. Eckman
- Division of General Internal Medicine and the Center for Clinical Effectiveness, University of Cincinnati, Cincinnati, Ohio
| | - Adeboye A. Adejare
- Department of Biomedical Informatics, University of Cincinnati, Cincinnati, Ohio
| | - Heather Duncan
- Division of Nephrology, University of Cincinnati, Cincinnati, Ohio
| | - E. Steve Woodle
- Division of Transplantation, Department of Surgery, University of Cincinnati, Cincinnati, Ohio
| | | | - Rita R. Alloway
- Division of Nephrology, University of Cincinnati, Cincinnati, Ohio
| | - Kenneth E. Sherman
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, Ohio
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20
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Scholte M, Rovers MM, Grutters JPC. The Use of Decision Analytic Modeling in the Evaluation of Surgical Innovations: A Scoping Review. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2021; 24:884-900. [PMID: 34119087 DOI: 10.1016/j.jval.2020.11.020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 11/05/2020] [Accepted: 11/30/2020] [Indexed: 06/12/2023]
Abstract
OBJECTIVES The main objective of this review was to map how decision analytic models are used in surgical innovation (in which research phase, with what aim) and to understand how challenges related to the assessment of surgical interventions are incorporated. METHODS We systematically searched PubMed, Embase, and the Cochrane Library for studies published in 2018. We included original articles using a decision analytic model to compare surgical strategies. We included modeling studies of surgical innovations. General, innovation, and modeling characteristics were extracted, as were outcomes, recommendations, and handling of challenges related to the assessment of surgical interventions (learning curve, incremental innovation, dynamic pricing, quality variation, organizational impact). RESULTS We included 46 studies. The number of studies increased with each research phase, from 4% (n = 2) in the preclinical phase to 40% (n = 20) in phase 3 studies. Eighty-one studies were excluded because they investigated established surgical procedures, indicating that modeling is predominantly applied after the innovation process. Regardless of the research stage, the aim to determine cost-effectiveness was most frequently identified (n = 40, 87%), whereas exploratory aims (eg, exploring when a strategy becomes cost-effective) were less common (n = 9, 20%). Most challenges related to the assessment of surgical interventions were rarely incorporated in models (eg, learning curve [n = 1, 2%], organizational impact [n = 2, 4%], and incremental innovation [n = 1, 2%]), except for dynamic pricing (n = 10, 22%) and quality variation (n = 6, 13%). CONCLUSIONS In surgical innovation, modeling is predominantly used in later research stages to assess cost-effectiveness. The exploratory use of modeling seems still largely overlooked in surgery; therefore, the opportunity to inform research and development may not be optimally used.
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Affiliation(s)
- Mirre Scholte
- Department of Operating Rooms, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
| | - Maroeska M Rovers
- Department of Operating Rooms, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands; Department for Health Evidence, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands
| | - Janneke P C Grutters
- Department of Operating Rooms, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands; Department for Health Evidence, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands
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21
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Schold JD, Mohan S, Huml A, Buccini LD, Sedor JR, Augustine JJ, Poggio ED. Failure to Advance Access to Kidney Transplantation over Two Decades in the United States. J Am Soc Nephrol 2021; 32:913-926. [PMID: 33574159 PMCID: PMC8017535 DOI: 10.1681/asn.2020060888] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 12/02/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Extensive research and policies have been developed to improve access to kidney transplantation among patients with ESKD. Despite this, wide variation in transplant referral rates exists between dialysis facilities. METHODS To evaluate the longitudinal pattern of access to kidney transplantation over the past two decades, we conducted a retrospective cohort study of adult patients with ESKD initiating ESKD or placed on a transplant waiting list from 1997 to 2016 in the United States Renal Data System. We used cumulative incidence models accounting for competing risks and multivariable Cox models to evaluate time to waiting list placement or transplantation (WLT) from ESKD onset. RESULTS Among the study population of 1,309,998 adult patients, cumulative 4-year WLT was 29.7%, which was unchanged over five eras. Preemptive WLT (prior to dialysis) increased by era (5.2% in 1997-2000 to 9.8% in 2013-2016), as did 4-year WLT incidence among patients aged 60-70 (13.4% in 1997-2000 to 19.8% in 2013-2016). Four-year WLT incidence diminished among patients aged 18-39 (55.8%-48.8%). Incidence of WLT was substantially lower among patients in lower-income communities, with no improvement over time. Likelihood of WLT after dialysis significantly declined over time (adjusted hazard ratio, 0.80; 95% confidence interval, 0.79 to 0.82) in 2013-2016 relative to 1997-2000. CONCLUSIONS Despite wide recognition, policy reforms, and extensive research, rates of WLT following ESKD onset did not seem to improve in more than two decades and were consistently reduced among vulnerable populations. Improving access to transplantation may require more substantial interventions.
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Affiliation(s)
- Jesse D. Schold
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio,Center for Populations Health Research, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - Sumit Mohan
- Department of Medicine, Division of Nephrology, Columbia University Vagelos College of Physicians & Surgeons, New York, New York,Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York
| | - Anne Huml
- Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio
| | - Laura D. Buccini
- Center for Populations Health Research, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - John R. Sedor
- Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio
| | | | - Emilio D. Poggio
- Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio
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22
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Weinfurtner K, Reddy KR. Hepatitis C viraemic organs in solid organ transplantation. J Hepatol 2021; 74:716-733. [PMID: 33212088 DOI: 10.1016/j.jhep.2020.11.014] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 11/04/2020] [Accepted: 11/06/2020] [Indexed: 02/07/2023]
Abstract
Although rates of organ donation and solid organ transplantation have been increasing over the last few decades, demand for organs still greatly exceeds supply. Several strategies have been utilised to increase organ supply, including utilisation of high-risk (e.g. HCV antibody-positive) donors. In this context, organs from HCV antibody-positive donors have been used in recipients with chronic HCV since the early 1990s. Recently, transplantation of HCV-viraemic organs into HCV-naïve recipients has garnered significant interest, owing to the development of safe and highly effective direct-acting antivirals and increased experience of treating HCV in the post-transplant setting. Preliminary studies based largely in the US have shown excellent outcomes in kidney, liver, heart, and lung transplantation. This practice has the potential to significantly increase transplantation rates and decrease waitlist mortality; however, intentionally transmitting an infectious disease to recipients has important practical and ethical implications. Further, the generalisability of the US experience to other countries is limited by significant differences in HCV-viraemic donor populations. This review summarises the current data on this practice, discusses barriers to implementation, and highlights areas that warrant further study.
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Affiliation(s)
- Kelley Weinfurtner
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania.
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23
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Chang SH, Merzkani M, Lentine KL, Wang M, Axelrod DA, Anwar S, Schnitzler MA, Wellen J, Chapman WC, Alhamad T. Trends in Discard of Kidneys from Hepatitis C Viremic Donors in the United States. Clin J Am Soc Nephrol 2021; 16:251-261. [PMID: 33451990 PMCID: PMC7863640 DOI: 10.2215/cjn.10960720] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Accepted: 11/17/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND OBJECTIVES Kidneys from hepatitis C virus (HCV) viremic donors have become more commonly accepted for transplant, especially after effective direct-acting antiviral therapy became available in 2014. We examined the contemporary trend of kidney discard from donors with HCV seropositivity and viremia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Data from the Organ Procurement and Transplantation Network were used to identify deceased donor kidneys recovered for transplant. The exposure was donor HCV antibody status in the first analyses, and donor HCV antibody and viremia status in the second analyses. Multilevel, multivariable logistic regression was used to assess the association of these HCV exposure measures with kidney discard, adjusted for donor characteristics. Multilevel analyses were conducted to account for similar kidney discard pattern within clusters of organ procurement organizations and regions. RESULTS Among 225,479 kidneys recovered from 2005 to 2019, 5% were from HCV seropositive donors. Compared with HCV seronegative kidneys, the odds of HCV seropositive kidney discard gradually declined, from a multivariable-adjusted odds ratio (aOR) of 7.06 (95% confidence interval [95% CI], 5.65 to 8.81) in 2014, to 1.20 (95% CI, 1.02 to 1.42) in 2019. Among 82,090 kidneys with nucleic acid amplification test results in 2015-2019, 4% were from HCV viremic donors and 2% were from aviremic seropositive donors. Compared with HCV aviremic seronegative kidneys, the odds of HCV viremic kidney discard decreased from an aOR of 4.89 (95% CI, 4.03 to 5.92) in 2018, to 1.48 (95% CI, 1.22 to 1.81) in 2019. By 2018 and 2019, aviremic seropositive status was not associated with higher odds of discard (2018: aOR, 1.13; 95% CI, 0.88 to 1.45; and 2019: aOR, 0.97; 95% CI, 0.76 to 1.23). CONCLUSIONS Despite the decrease in kidney discard in recent years, kidneys from viremic (compared with aviremic seronegative) donors still had 48% higher odds of discard in 2019. The potential of these discarded organs to provide successful transplantation should be explored.
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Affiliation(s)
- Su-Hsin Chang
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
| | - Massini Merzkani
- Division of Nephrology, Washington University School of Medicine, St. Louis, Missouri,Transplant Epidemiology Research Collaboration, Institute of Public Health, Washington University School of Medicine, St. Louis, Missouri
| | - Krista L. Lentine
- Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, Missouri
| | - Mei Wang
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
| | | | - Siddiq Anwar
- Division of Nephrology, Seha Kidney Care, Abu Dhabi, United Arab Emirates
| | - Mark A. Schnitzler
- Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, Missouri
| | - Jason Wellen
- Department of Surgery, Washington University in St. Louis, St. Louis, Missouri
| | - William C. Chapman
- Department of Surgery, Washington University in St. Louis, St. Louis, Missouri
| | - Tarek Alhamad
- Division of Nephrology, Washington University School of Medicine, St. Louis, Missouri,Transplant Epidemiology Research Collaboration, Institute of Public Health, Washington University School of Medicine, St. Louis, Missouri
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24
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Puttarajappa CM, Mehta R, Roberts MS, Smith KJ, Hariharan S. Economic analysis of screening for subclinical rejection in kidney transplantation using protocol biopsies and noninvasive biomarkers. Am J Transplant 2021; 21:186-197. [PMID: 32558153 PMCID: PMC7744316 DOI: 10.1111/ajt.16150] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 06/03/2020] [Accepted: 06/08/2020] [Indexed: 02/07/2023]
Abstract
Subclinical rejection (SCR) screening in kidney transplantation (KT) using protocol biopsies and noninvasive biomarkers has not been evaluated from an economic perspective. We assessed cost-effectiveness from the health sector perspective of SCR screening in the first year after KT using a Markov model that compared no screening with screening using protocol biopsy or biomarker at 3 months, 12 months, 3 and 12 months, or 3, 6, and 12 months. We used 12% subclinical cellular rejection and 3% subclinical antibody-mediated rejection (SC-ABMR) for the base-case cohort. Results favored 1-time screening at peak SCR incidence rather than repeated screening. Screening 2 or 3 times was favored only with age <35 years and with high SC-ABMR incidence. Compared to biomarkers, protocol biopsy yielded more quality-adjusted life years (QALYs) at lower cost. A 12-month biopsy cost $13 318/QALY for the base-case cohort. Screening for cellular rejection in the absence of SC-ABMR was less cost effective with 12-month biopsy costing $46 370/QALY. Screening was less cost effective in patients >60 years. Using biomarker twice or thrice was cost effective only if biomarker cost was <$700. In conclusion, in KT, screening for SCR more than once during the first year is not economically reasonable. Screening with protocol biopsy was favored over biomarkers.
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Affiliation(s)
- Chethan M. Puttarajappa
- Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania,Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Rajil Mehta
- Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania,Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Mark S. Roberts
- Department of Health Policy and Management, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Kenneth J. Smith
- Department of Medicine, Section of Decision Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Sundaram Hariharan
- Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania,Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
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25
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Lentine KL, Peipert JD, Alhamad T, Caliskan Y, Concepcion BP, Forbes R, Schnitzler M, Chang SH, Cooper M, Bloom RD, Mannon RB, Axelrod DA. Survey of Clinician Opinions on Kidney Transplantation from Hepatitis C Virus Positive Donors: Identifying and Overcoming Barriers. ACTA ACUST UNITED AC 2020; 1:1291-1299. [PMID: 33251523 DOI: 10.34067/kid.0004592020] [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] [Indexed: 12/11/2022]
Abstract
Background Transplant practices related to use of organs from Hepatitis C virus infected donors (DHCV+) is evolving rapidly. Methods We surveyed U.S. kidney transplant programs by email and professional society listserv postings between 7/19-1/20 to assess attitudes, management strategies, and barriers related to use of viremic (nucleic acid testing (NAT)+) donor organs in HCV uninfected recipients. Results Staff at 112 unique programs responded, representing 54% of U.S. adult kidney transplant programs and 69% of adult deceased donor kidney transplant volume in 2019. Most survey respondents were transplant nephrologists (46%) or surgeons (43%). Among responding programs, 67% currently transplant DHCV antibody+/NAT- organs under a clinical protocol or as standard of care. By comparison, only 58% offer DHCV NAT+ kidney transplant to HCV- recipients, including 35% under clinical protocols, 14% as standard of care, and 9% under research protocols. Following transplant of DHCV NAT+ organs to uninfected recipients, 53% start direct acting antiviral agent (DAA) therapy after discharge and documented viremia. Viral monitoring protocols after DHCV NAT+ to HCV uninfected recipient kidney transplantation varied substantially. 56% of programs performing these transplants report having an institutional plan to provide DAA treatment if declined by the recipient's insurance. Respondents felt a mean decrease in waiting time of ≥18 months (range 0-60) justifies the practice. Program concerns related to use of DHCV NAT+ kidneys include insurance coverage concerns (72%), cost (60%), and perceived risk of transmitting resistant infection (44%). Conclusions Addressing knowledge about safety and logistical/financial barriers related to use of DHCV NAT+ kidney transplantation for HCV uninfected recipients may help reduced discards and expand the organ supply.
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Affiliation(s)
- Krista L Lentine
- Saint Louis University Center for Abdominal Transplantation, St. Louis, MO
| | - John D Peipert
- Northwestern University, Feinberg School of Medicine, Chicago, IL.,Northwestern University Transplant Outcomes Research Core, Chicago, IL
| | | | - Yasar Caliskan
- Saint Louis University Center for Abdominal Transplantation, St. Louis, MO
| | | | | | - Mark Schnitzler
- Saint Louis University Center for Abdominal Transplantation, St. Louis, MO
| | | | | | - Roy D Bloom
- University of Pennsylvania, Philadelphia, PA
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26
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Financial Evaluation of Kidney Transplant With Hepatitis C Viremic Donors to Uninfected Recipients. Transplant Direct 2020; 6:e627. [PMID: 33204825 PMCID: PMC7665247 DOI: 10.1097/txd.0000000000001056] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 07/17/2020] [Accepted: 08/04/2020] [Indexed: 02/07/2023] Open
Abstract
Kidney transplantation with hepatitis C viremic (dHCV+) donors appears safe for recipients without HCV when accompanied by direct acting antiviral (DAA) treatment. However, US programs have been reluctant to embrace this approach due to concern about insurance coverage. While the cost of DAA treatment is currently offset by the reduction in waiting time, increased competition for dHCV+ organs may reduce this advantage. This analysis sought to demonstrate the financial benefit of dHCV+ transplant for third-party health insurers to expand coverage availability. Methods An economic analysis was developed using a Markov model for 2 decisions: first, to accept a dHCV+ organ versus wait for a dHCV uninfected organ; or second, accept a high kidney donor profile index (KDPI) (>85) organ versus wait for a better quality dHCV+ organ. The analysis used Medicare payments, historical survival data, cost report data, and an estimated cost of DAA of $29 874. Results In the first analysis, using dHCV+ kidneys reduced the cost of end-stage kidney disease care if the wait for a dHCV uninfected organ exceeded 11.5 months. The financial breakeven point differed according to the cost of DAA treatment. In the second analysis, declining a high-KDPI organ in favor of a waiting dHCV+ organ was marginally clinically beneficial if waiting times were <12 months but not cost effective. Conclusions dHCV+ transplant appears to be economically and clinically advantageous compared with waiting for dHCV-uninfected transplant but should not replace high-KDPI transplant when appropriate. Despite the high cost of DAA therapy, health insurers benefit financially from dHCV+ transplant within 1 year.
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27
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Sise ME, Goldberg DS, Kort JJ, Schaubel DE, Alloway RR, Durand CM, Fontana RJ, Brown RS, Friedewald JJ, Prenner S, Landis JR, Fernando M, Phillips CC, Woodle ES, Rike-Shields A, Sherman KE, Elias N, Williams WW, Gustafson JL, Desai NM, Barnaba B, Norman SP, Doshi M, Sultan ST, Aull MJ, Levitsky J, Belshe DS, Chung RT, Reese PP. Multicenter Study to Transplant Hepatitis C-Infected Kidneys (MYTHIC): An Open-Label Study of Combined Glecaprevir and Pibrentasvir to Treat Recipients of Transplanted Kidneys from Deceased Donors with Hepatitis C Virus Infection. J Am Soc Nephrol 2020; 31:2678-2687. [PMID: 32843477 DOI: 10.1681/asn.2020050686] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 07/06/2020] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Single-center trials and retrospective case series have reported promising outcomes using kidneys from donors with hepatitis C virus (HCV) infection. However, multicenter trials are needed to determine if those findings are generalizable. METHODS We conducted a prospective trial at seven centers to transplant 30 kidneys from deceased donors with HCV viremia into HCV-uninfected recipients, followed by 8 weeks of once-daily coformulated glecaprevir and pibrentasvir, targeted to start 3 days posttransplant. Key outcomes included sustained virologic response (undetectable HCV RNA 12 weeks after completing treatment with glecaprevir and pibrentasvir), adverse events, and allograft function. RESULTS We screened 76 patients and enrolled 63 patients, of whom 30 underwent kidney transplantation from an HCV-viremic deceased donor (median kidney donor profile index, 53%) in May 2019 through October 2019. The median time between consent and transplantation of a kidney from an HCV-viremic donor was 6.3 weeks. All 30 recipients achieved a sustained virologic response. One recipient died of complications of sepsis 4 months after achieving a sustained virologic response. No severe adverse events in any patient were deemed likely related to HCV infection or treatment with glecaprevir and pibrentasvir. Three recipients developed acute cellular rejection, which was borderline in one case. Three recipients developed polyomavirus (BK) viremia near or >10,000 copies/ml that resolved after reduction of immunosuppression. All recipients had good allograft function, with a median creatinine of 1.2 mg/dl and median eGFR of 57 ml/min per 1.73 m2 at 6 months. CONCLUSIONS Our multicenter trial demonstrated safety and efficacy of transplantation of 30 HCV-viremic kidneys into HCV-negative recipients, followed by early initiation of an 8-week regimen of glecaprevir and pibrentasvir.
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Affiliation(s)
- Meghan E Sise
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - David S Goldberg
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida
| | - Jens J Kort
- Global Medical Affairs Research and Development, AbbVie Inc., North Chicago, Illinois
| | - Douglas E Schaubel
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Rita R Alloway
- Division of Nephrology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Christine M Durand
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Robert J Fontana
- Division of Gastroenterology and Hepatology, University of Michigan Medical School, Ann Arbor, Michigan
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York
| | - John J Friedewald
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Stacey Prenner
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - J Richard Landis
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Melissa Fernando
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Caitlin C Phillips
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - E Steve Woodle
- Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Adele Rike-Shields
- Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio.,The Christ Hospital, Cincinnati, Ohio
| | - Kenneth E Sherman
- Division of Digestive Disease, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Nahel Elias
- Transplant Center and Division of Transplant Surgery, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Winfred W Williams
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Jenna L Gustafson
- Gastrointestinal Division, Department of Medicine, Liver Center, Massachusetts General Hospital, Boston, Massachusetts
| | - Niraj M Desai
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Brittany Barnaba
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Silas P Norman
- Division of Nephrology, Michigan Medicine, Ann Arbor, Michigan
| | - Mona Doshi
- Division of Nephrology, Michigan Medicine, Ann Arbor, Michigan
| | - Samuel T Sultan
- Division of Transplant Surgery, New York-Presbyterian/Weill Cornell Medicine, New York, New York
| | - Meredith J Aull
- Division of Transplant Surgery, New York-Presbyterian/Weill Cornell Medicine, New York, New York
| | - Josh Levitsky
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.,Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Dianne S Belshe
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Raymond T Chung
- Gastrointestinal Division, Department of Medicine, Liver Center, Massachusetts General Hospital, Boston, Massachusetts
| | - Peter P Reese
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.,Renal-Electrolyte and Hypertension Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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Abstract
INTRODUCTION Hepatitis C virus (HCV) infection is associated with an increased incidence and progression of chronic kidney disease (CKD), as well as higher mortality in CKD and renal transplant patients. Direct acting antiviral agents (DAAs) have revolutionized the treatment of HCV, with viral eradication attained in 90-100% of treated patients. DAAs have an excellent safety and tolerability profile in CKD and renal transplant patients. AREAS COVERED In this review, we discuss the association of HCV with incidence and progression of CKD as well as its effect on outcomes and mortality. We also discuss the available treatment options in patients with CKD and renal transplant and in HCV-associated glomerular disease. EXPERT OPINION The availability of newly available direct acting anti-viral agents has revolutionized the treatment of HCV in persons with advanced CKD and undergoing dialysis. With these regimens, viral eradication can be attained in 90-100% of the treated patients. The safety, tolerability, and efficacy of these drugs in renal transplant patients have also made it possible to use HCV-infected grafts and successful virus eradication at a later stage.
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Affiliation(s)
- Muhammad Umair Khan
- Department of Medicine, Division of Gastroenterology, Hamad Medical Corporation , Doha, Qatar
| | - Mohamed Ibrahim Mahmoud
- Department of Medicine, Division of Gastroenterology, Hamad Medical Corporation , Doha, Qatar
| | - Adeel A Butt
- Weill Cornell Medical College , New York, Qatar.,Department of Medicine, Hamad Medical Corporation , Doha, Qatar
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29
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Senanayake S, Graves N, Healy H, Baboolal K, Kularatna S. Cost-utility analysis in chronic kidney disease patients undergoing kidney transplant; what pays? A systematic review. COST EFFECTIVENESS AND RESOURCE ALLOCATION 2020; 18:18. [PMID: 32477010 PMCID: PMC7236510 DOI: 10.1186/s12962-020-00213-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Accepted: 05/13/2020] [Indexed: 12/14/2022] Open
Abstract
Background Health systems are under pressure to deliver more effective care without expansion of resources. This is particularly pertinent to diseases like chronic kidney disease (CKD) that are exacting substantial financial burden to many health systems. The aim of this study is to systematically review the Cost Utility Analysis (CUA) evidence generated across interventions for CKD patients undergoing kidney transplant (KT). Methods A systemic review of CUA on the interventions for CKD patients undergoing KT was carried out using a search of the MEDLINE, CINAHL, EMBASE, PsycINFO and NHS-EED. The CHEERS checklist was used as a set of good practice criteria in determining the reporting quality of the economic evaluation. Quality of the data used to inform model parameters was determined using the modified hierarchies of data sources. Results A total of 330 articles identified, 16 met the inclusion criteria. Almost all (n = 15) the studies were from high income countries. Out of the 24 characteristics assessed in the CHEERS checklist, more than 80% of the selected studies reported 14 of the characteristics. Reporting of the CUA were characterized by lack of transparency of model assumptions, narrow economic perspective and incomplete assessment of the effect of uncertainty in the model parameters on the results. The data used for the economic model were satisfactory quality. The authors of 13 studies reported the intervention as cost saving and improving quality of life, whereas three studies were cost increasing and improving quality of life. In addition to the baseline analysis, sensitivity analysis was performed in all the evaluations except one. Transplanting certain high-risk donor kidneys (high risk of HIV and Hepatitis-C infected kidneys, HLA mismatched kidneys, high Kidney Donor Profile Index) and a payment to living donors, were found to be cost-effective. Conclusions The quality of economic evaluations reviewed in this paper were assessed to be satisfactory. Implementation of these strategies will significantly impact current systems of KT and require a systematic implementation plan and coordinated efforts from relevant stakeholders.
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Affiliation(s)
- Sameera Senanayake
- 1Australian Centre for Health Services Innovation, School of Public Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, Brisbane, QLD 4059 Australia
| | - Nicholas Graves
- 1Australian Centre for Health Services Innovation, School of Public Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, Brisbane, QLD 4059 Australia
| | - Helen Healy
- 2Royal Brisbane Hospital for Women, Brisbane, Australia.,3School of Medicine, University of Queensland, Brisbane, Australia
| | - Keshwar Baboolal
- 2Royal Brisbane Hospital for Women, Brisbane, Australia.,3School of Medicine, University of Queensland, Brisbane, Australia
| | - Sanjeewa Kularatna
- 1Australian Centre for Health Services Innovation, School of Public Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, Brisbane, QLD 4059 Australia
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30
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Reddy YNV, Reddy KP, Sise ME. HCV-Infected Deceased Donor Kidney Transplantation-Time to Take Up the Offer. Am J Kidney Dis 2020; 75:827-829. [PMID: 32317120 DOI: 10.1053/j.ajkd.2020.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Accepted: 01/27/2020] [Indexed: 11/11/2022]
Affiliation(s)
- Yuvaram N V Reddy
- Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA.
| | - Krishna P Reddy
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA; Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA
| | - Meghan E Sise
- Harvard Medical School, Boston, MA; Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA
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31
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Howard RJ. We listed patients and we should transplant them. Clin Transplant 2020; 34:e13882. [PMID: 32294274 DOI: 10.1111/ctr.13882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 03/19/2020] [Accepted: 04/07/2020] [Indexed: 11/27/2022]
Abstract
Twenty percent of kidneys recovered for transplantation are discarded. The most common reason for not transplanting these kidneys is to organ quality and biopsy findings. Yet, organ quality measures are not associated with discard rates and kidneys with poorer quality measures lead to greater life span for the recipient compared to staying on dialysis. Biopsy findings are not correlated with graft survival in most cases. The risk aversion of transplant centers from using "high-risk" kidneys can be, in part at least, attributed to negative consequences of poor graft survival with possible program sanctions or possible loss of insurance contracts. CMS has taken a first step by eliminating short-term graft survival as a performance measure for transplant centers. Many of the discarded kidneys will provide good results if transplanted and would recognize that patients value getting a transplant above graft survival.
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32
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Successful Treatment of a Reinfected Liver Graft Because of Receipt of a HCV-Positive Kidney. ACG Case Rep J 2020; 7:e00341. [PMID: 32337307 PMCID: PMC7162115 DOI: 10.14309/crj.0000000000000341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Accepted: 01/08/2020] [Indexed: 11/17/2022] Open
Abstract
Transplantation of hepatitis C virus (HCV)-positive organs has undergone a paradigm shift because of the advent of direct-acting antivirals. We present the case of a 57-year-old man successfully treated initially with pegylated interferon and ribavirin after HCV recurrence postliver transplantation. He subsequently developed end-stage renal disease and received a genotype 1a HCV-positive kidney transplant. A 12-week course of ledipasvir/sofosbuvir and low-dose ribavirin was initiated and sustained virologic response was achieved. This constitutes the first reported case of a patient successfully treated for HCV a second time after receiving an HCV-positive organ.
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Eckman MH, Woodle ES, Thakar CV, Alloway RR, Sherman KE. Cost-effectiveness of Using Kidneys From HCV-Viremic Donors for Transplantation Into HCV-Uninfected Recipients. Am J Kidney Dis 2020; 75:857-867. [PMID: 32081494 DOI: 10.1053/j.ajkd.2019.11.005] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 11/13/2019] [Indexed: 12/19/2022]
Abstract
RATIONALE & OBJECTIVE Less than 4% of patients with kidney failure receive kidney transplants. Although discard rates of hepatitis C virus (HCV)-viremic kidneys are declining, ~39% of HCV-viremic kidneys donated between 2018 and 2019 were discarded. Highly effective antiviral agents are now available to treat chronic HCV infection. Thus, our objective was to examine the cost-effectiveness of transplanting kidneys from HCV-viremic donors into HCV-uninfected recipients. STUDY DESIGN Markov state transition decision model. Data sources include Medline search results, bibliographies from relevant English language articles, Scientific Registry of Transplant Recipients, and the US Renal Data System. SETTING & POPULATION US patients receiving maintenance hemodialysis who are on kidney transplant waiting lists. INTERVENTION(S) Transplantation with an HCV-unexposed kidney versus transplantation with an HCV-viremic kidney and HCV treatment. OUTCOMES Effectiveness measured in quality-adjusted life-years and costs measured in 2018 US dollars. MODEL, PERSPECTIVE, AND TIMEFRAME We used a health care system perspective with a lifelong time horizon. RESULTS In the base-case analysis, transplantation with an HCV-viremic kidney was more effective and less costly than transplantation with an HCV-unexposed kidney because of the longer waiting times for HCV-unexposed kidneys, the substantial excess mortality risk while receiving dialysis, and the high efficacy of direct-acting antiviral agents for HCV infection. Transplantation with an HCV-viremic kidney was also preferred in sensitivity analyses of multiple model parameters. The strategy remained cost-effective unless waiting list time for an HCV-viremic kidney exceeded 3.1 years compared with the base-case value of 1.56 year. LIMITATIONS Estimates of waiting times for patients willing to accept an HCV-viremic kidney were based on data for patients who received HCV-viremic kidney transplants. CONCLUSIONS Transplanting kidneys from HCV-viremic donors into HCV-uninfected recipients increased quality-adjusted life expectancy and reduced costs compared with a strategy of transplanting kidneys from HCV-unexposed donors.
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Affiliation(s)
- Mark H Eckman
- Division of General Internal Medicine and the Center for Clinical Effectiveness, University of Cincinnati Medical Center, Cincinnati, OH.
| | - E Steve Woodle
- Division of Transplantation, Department of Surgery, University of Cincinnati Medical Center, Cincinnati, OH
| | - Charuhas V Thakar
- Division of Nephrology, University of Cincinnati Medical Center, Cincinnati, OH
| | - Rita R Alloway
- Division of Nephrology, University of Cincinnati Medical Center, Cincinnati, OH
| | - Kenneth E Sherman
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH
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Abstract
Multiple strategies have been implemented to increase the donor pool to avoid transplant wait-list mortality. The approval of highly effective direct-acting antiviral regimens for the treatment of hepatitis C virus (HCV) has enabled expansion of the donor pool by allowing the transplantation of organs from HCV-viremic donors to HCV-negative recipients. Multiple centers have recently published data on outcomes of heart transplantation from HCV-viremic heart donors to HCV-negative recipients, with acceptable posttransplant outcomes. However, areas of uncertainty remain, particularly in the long-term risks of intentional HCV transmission, as well as the possibility that sustained virologic response may not be achieved. In this article, we review the literature illustrating both the risks and benefits of transplantation of organs from HCV-viremic donors to HCV-negative recipients. We also present the data collected at our institution regarding this special patient population.
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Ariyamuthu VK, Sandikci B, AbdulRahim N, Hwang C, MacConmara MP, Parasuraman R, Atis A, Tanriover B. Trends in utilization of deceased donor kidneys based on hepatitis C virus status and impact of public health service labeling on discard. Transpl Infect Dis 2019; 22:e13204. [DOI: 10.1111/tid.13204] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Accepted: 10/20/2019] [Indexed: 12/26/2022]
Affiliation(s)
| | | | - Nashila AbdulRahim
- Division of Nephrology University of Texas Southwestern Medical Center Dallas TX USA
| | - Christine Hwang
- Department of Surgery University of Texas Southwestern Medical Center Dallas TX USA
| | | | | | - Ahsen Atis
- Biological Sciences University of Texas at Dallas Richardson TX USA
| | - Bekir Tanriover
- Division of Nephrology University of Texas Southwestern Medical Center Dallas TX USA
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Couri T, Aronsohn A. When Theory Becomes Reality: Navigating the Ethics of Transplanting Hepatitis C Virus-Positive Livers Into Negative Recipients. Clin Liver Dis (Hoboken) 2019; 14:131-134. [PMID: 31709040 PMCID: PMC6832093 DOI: 10.1002/cld.849] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 05/16/2019] [Indexed: 02/06/2023] Open
Affiliation(s)
- Thomas Couri
- Department of Internal MedicineUniversity of Chicago Medical CenterChicagoIL
| | - Andrew Aronsohn
- Center for Liver DiseasesUniversity of Chicago Medical CenterChicagoIL
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Hoz RML, Sandıkçı B, Ariyamuthu VK, Tanriover B. Short-term outcomes of deceased donor renal transplants of HCV uninfected recipients from HCV seropositive nonviremic donors and viremic donors in the era of direct-acting antivirals. Am J Transplant 2019; 19:3058-3070. [PMID: 31207073 PMCID: PMC6864234 DOI: 10.1111/ajt.15496] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Revised: 05/21/2019] [Accepted: 06/07/2019] [Indexed: 01/25/2023]
Abstract
The United States opioid use epidemic over the past decade has coincided with an increase in hepatitis C virus (HCV) positive donors. Using propensity score matching, and the Organ Procurement Transplant Network data files from January 2015 to June 2019, we analyzed the short-term outcomes of adult deceased donor kidney transplants of HCV uninfected recipients with two distinct groups of HCV positive donors (HCV seropositive, nonviremic n = 352 and viremic n = 196) compared to those performed using HCV uninfected donors (n = 36 934). Compared to the reference group, the transplants performed using HCV seropositive, nonviremic and viremic donors experienced a lower proportion of delayed graft function (35.2 vs 18.9%; P < .001 [HCV seropositive, nonviremic donors] and 36.2 vs 16.8% ; P < .001[HCV viremic donors]). The recipients of HCV viremic donors had better allograft function at 6 months posttransplant (eGFR [54.1 vs 68.3 mL/min/1.73 m2; P = .004]. Furthermore, there was no statistical difference in the overall graft failure risk at 12 months posttransplant by propensity score matched multivariable Cox proportional analysis (HR = 0.60, 95% CI 0.23 to 1.29 [HCV seropositive, nonviremic donors] and HR = 0.85, 95% CI 0.25 to 2.96 [HCV viremic donors]). Further studies are required to determine the long-term outcomes of these transplants and address unanswered questions regarding the use of HCV viremic donors.
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Affiliation(s)
- Ricardo M. La Hoz
- Division of Infectious Diseases and Geographic Medicine, University of Texas Southwestern Medical Center, Dallas, TX
| | | | | | - Bekir Tanriover
- Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX
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Molnar MZ, Nair S, Cseprekal O, Yazawa M, Talwar M, Balaraman V, Podila PSB, Mas V, Maluf D, Helmick RA, Campos L, Nezakatgoo N, Eymard C, Horton P, Verma R, Jenkins AH, Handley CR, Snyder HS, Cummings C, Agbim UA, Maliakkal B, Satapathy SK, Eason JD. Transplantation of kidneys from hepatitis C-infected donors to hepatitis C-negative recipients: Single center experience. Am J Transplant 2019; 19:3046-3057. [PMID: 31306549 DOI: 10.1111/ajt.15530] [Citation(s) in RCA: 101] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2019] [Revised: 07/02/2019] [Accepted: 07/05/2019] [Indexed: 01/25/2023]
Abstract
Our aim was to evaluate the safety of transplanting kidneys from HCV-infected donors in HCV-uninfected recipients. Data collected from 53 recipients in a single center, observational study included donor and recipient characteristics, liver and kidney graft function, new infections and de novo donor-specific antibodies and renal histology. Treatment with a direct-acting antiviral regimen was initiated when HCV RNA was detected. The mean ± SD age of recipients was 53 ± 11 years, 34% were female, 19% and 79% of recipients were white and African American, respectively. The median and interquartile range (IQR) time between transplant and treatment initiation was 76 (IQR: 68-88) days. All 53 recipients became viremic (genotype: 1a [N = 34], 1b [N = 1], 2 [N = 3], and 3 [N = 15]). The majority (81%) of recipients did not experience clinically significant increases (>3 times higher than upper limit of the normal value) in aminotransferase levels and their HCV RNA levels were in the 5 to 6 log range. One patient developed fibrosing cholestatic hepatitis with complete resolution. All recipients completed antiviral treatment and 100% were HCV RNA-negative and achieved 12-week sustained virologic response. The estimated GFRs at end of treatment and 12-week posttreatment were 67 ± 21 mL/min/1.73 m2 and 67 ± 17 mL/min/1.73 m2 , respectively. Four recipients developed acute rejection. Kidney transplantation from HCV-infected donors to HCV-negative recipients should be considered in all eligible patients.
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Affiliation(s)
- Miklos Z Molnar
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
- Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary
| | - Satheesh Nair
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Orsolya Cseprekal
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
- Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary
| | - Masahiko Yazawa
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
- Divison of Nephrology and Hypertension, St. Marianna University School of Medicine, Tokyo, Japan
| | - Manish Talwar
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Vasanthi Balaraman
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Pradeep S B Podila
- Faith & Health Division, Methodist Le Bonheur Healthcare, Memphis, Tennessee
- Division of Health Systems Management & Policy, School of Public Health, The University of Memphis, Memphis, Tennessee
| | - Valeria Mas
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Daniel Maluf
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Ryan A Helmick
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Luis Campos
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Nosratollah Nezakatgoo
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Corey Eymard
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Peter Horton
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Rajanshu Verma
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Ann Holbrook Jenkins
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
| | - Charlotte R Handley
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
| | - Heather S Snyder
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
| | - Carolyn Cummings
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
| | - Uchenna A Agbim
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Benedict Maliakkal
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Sanjaya K Satapathy
- Sandra Atlas Bass Center for Liver Diseases & Transplantation, Zucker School of Medicine at Hofstra, Department of Medicine, Northshore University Hospital/Northwell Health, Manhasset, New York
| | - James D Eason
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
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Chan S, Isbel NM, Hawley CM, Campbell SB, Campbell KL, Morrison M, Francis RS, Playford EG, Johnson DW. Infectious Complications Following Kidney Transplantation-A Focus on Hepatitis C Infection, Cytomegalovirus Infection and Novel Developments in the Gut Microbiota. ACTA ACUST UNITED AC 2019; 55:medicina55100672. [PMID: 31590269 PMCID: PMC6843315 DOI: 10.3390/medicina55100672] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 09/24/2019] [Accepted: 09/30/2019] [Indexed: 12/19/2022]
Abstract
The incidence of infectious complications, compared with the general population and the pre-transplant status of the recipient, increases substantially following kidney transplantation, causing significant morbidity and mortality. The potent immunosuppressive therapy given to prevent graft rejection in kidney transplant recipients results in an increased susceptibility to a wide range of opportunistic infections including bacterial, viral and fungal infections. Over the last five years, several advances have occurred that may have changed the burden of infectious complications in kidney transplant recipients. Due to the availability of direct-acting antivirals to manage donor-derived hepatitis C infection, this has opened the way for donors with hepatitis C infection to be considered in the donation process. In addition, there have been the development of medications targeting the growing burden of resistant cytomegalovirus, as well as the discovery of the potentially important role of the gastrointestinal microbiota in the pathogenesis of post-transplant infection. In this narrative review, we will discuss these three advances and their potential implications for clinical practice.
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Affiliation(s)
- Samuel Chan
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia; (N.M.I.); (C.M.H.); (S.B.C.); (R.S.F.); (D.W.J.)
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD 4102, Australia; (K.L.C.); (E.G.P.)
- Translational Research Institute, Brisbane, QLD 4102, Australia
- Correspondence: ; Tel.: +61-7-3176-5080
| | - Nicole M Isbel
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia; (N.M.I.); (C.M.H.); (S.B.C.); (R.S.F.); (D.W.J.)
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD 4102, Australia; (K.L.C.); (E.G.P.)
- Translational Research Institute, Brisbane, QLD 4102, Australia
| | - Carmel M Hawley
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia; (N.M.I.); (C.M.H.); (S.B.C.); (R.S.F.); (D.W.J.)
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD 4102, Australia; (K.L.C.); (E.G.P.)
| | - Scott B Campbell
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia; (N.M.I.); (C.M.H.); (S.B.C.); (R.S.F.); (D.W.J.)
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD 4102, Australia; (K.L.C.); (E.G.P.)
- Translational Research Institute, Brisbane, QLD 4102, Australia
| | - Katrina L Campbell
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD 4102, Australia; (K.L.C.); (E.G.P.)
- Centre for Applied Health Economics, Menzies Research Institute, Griffith University, Brisbane, QLD 4102, Australia
| | - Mark Morrison
- The University of Queensland Diamantina Institute, Faculty of Medicine, University of Queensland, Woolloongabba, QLD 4102, Australia;
| | - Ross S Francis
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia; (N.M.I.); (C.M.H.); (S.B.C.); (R.S.F.); (D.W.J.)
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD 4102, Australia; (K.L.C.); (E.G.P.)
- Translational Research Institute, Brisbane, QLD 4102, Australia
| | - E Geoffrey Playford
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD 4102, Australia; (K.L.C.); (E.G.P.)
- Infection Management Services, Department of Microbiology, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia
| | - David W Johnson
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia; (N.M.I.); (C.M.H.); (S.B.C.); (R.S.F.); (D.W.J.)
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD 4102, Australia; (K.L.C.); (E.G.P.)
- Translational Research Institute, Brisbane, QLD 4102, Australia
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Waller KM, De La Mata NL, Kelly PJ, Ramachandran V, Rawlinson WD, Wyburn KR, Webster AC. Residual risk of infection with blood-borne viruses in potential organ donors at increased risk of infection: systematic review and meta-analysis. Med J Aust 2019; 211:414-420. [PMID: 31489635 DOI: 10.5694/mja2.50315] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 06/06/2019] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To estimate the prevalence and incidence of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) among people at increased risk of infection in Australia; to estimate the residual risk of infection among potential solid organ donors in these groups when their antibody and nucleic acid test results are negative. STUDY DESIGN Systematic review and meta-analysis of reports of the incidence and prevalence of HIV, HCV, and HBV in groups at increased risk of infection in Australia. DATA SOURCES MEDLINE, government and agency reports, Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine conference abstracts, the Australian New Zealand Clinical Trial Registry, and National Health and Medical Research Council grants published 1 January 2000 - 14 February 2019; personal communications. DATA SYNTHESIS Residual risk of HIV infection was highest among men who have sex with men (4.8 [95% CI, 2.7-6.9] per 10 000 antibody-negative persons; 1.5 [95% CI, 0.9-2.2] per 10 000 persons who are both antibody- and nucleic acid-negative). Residual risk of HCV infection was highest among injecting drug users (289 [95% CI, 191-385] per 10 000 antibody-negative persons; 20.9 [95% CI, 13.8-28.0] per 10 000 antibody- and nucleic acid-negative persons). Residual risk for HBV infection was highest among injecting drug users (98.6 [95% CI, 36.4-213] per 10 000 antibody-negative people; 49.4 [95% CI, 18.2-107] per 10 000 persons who were also nucleic acid-negative). CONCLUSIONS Absolute risks of window period viral infections are low in people from Australian groups at increased risk but with negative viral test results. Accepting organ donations by people at increased risk of infection but with negative viral test results could be considered as a strategy for expanding the donor pool. REGISTRATION International Prospective Register of Systematic Reviews (PROSPERO), CRD42017069820.
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Affiliation(s)
| | | | | | - Vidiya Ramachandran
- NSW Health Pathology, Prince of Wales Hospital and Community Health Services, Sydney, NSW
| | - William D Rawlinson
- NSW Health Pathology, Prince of Wales Hospital and Community Health Services, Sydney, NSW.,University of New South Wales, Sydney, NSW
| | - Kate R Wyburn
- Royal Prince Alfred Hospital, Sydney, NSW.,Sydney Medical School, University of Sydney, Sydney, NSW
| | - Angela C Webster
- University of Sydney, Sydney, NSW.,Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW
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Bowring MG, Shaffer AA, Massie AB, Cameron A, Desai N, Sulkowski M, Garonzik-Wang J, Segev DL. Center-level trends in utilization of HCV-exposed donors for HCV-uninfected kidney and liver transplant recipients in the United States. Am J Transplant 2019; 19:2329-2341. [PMID: 30861279 PMCID: PMC6658335 DOI: 10.1111/ajt.15355] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 02/15/2019] [Accepted: 03/05/2019] [Indexed: 01/25/2023]
Abstract
Several single-center reports of using HCV-viremic organs for HCV-uninfected (HCV-) recipients were recently published. We sought to characterize national utilization of HCV-exposed donors for HCV- recipients (HCV D+/R-) in kidney transplantation (KT) and liver transplantation (LT). Using SRTR data (April 1, 2015-December 2, 2018) and Gini coefficients, we studied center-level clustering of 1193 HCV D+/R- KTs and LTs. HCV-viremic (NAT+) D+/R- KTs increased from 1/month in 2015 to 22/month in 2018 (LTs: 0/month to 12/month). HCV-aviremic (Ab+/NAT-) D+/R- KTs increased from < 1/month in 2015 to 26/month in 2018 (LTs: <1/month to 8/month). HCV- recipients of viremic and aviremic kidneys spent a median (interquartile range [IQR]) of 0.7 (0.2-1.6) and 1.6 (0.4-3.5) years on the waitlist versus 1.8 (0.5-4.0) among HCV D-/R-. HCV- recipients of viremic and aviremic livers had median (IQR) MELD scores of 24 (21-30) and 25 (21-32) at transplantation versus 29 (23-36) among HCV D-/R-. 12 KT and 14 LT centers performed 81% and 76% of all viremic HCV D+/R- transplants; 11 KT and 13 LT centers performed 76% and 69% of all aviremic HCV D+/R- transplants. There have been marked increases in HCV D+/R- transplantation, although few centers are driving this practice; centers should continue to weigh the risks and benefits of HCV D+/R- transplantation.
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Affiliation(s)
- Mary G Bowring
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ashton A Shaffer
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Allan B Massie
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Andrew Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Niraj Desai
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Mark Sulkowski
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Jacqueline Garonzik-Wang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Dorry L Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- Scientific Registry of Transplant Recipients, Minneapolis, Minnesota
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Listing practices and graft utilization of hepatitis C-positive deceased donors in liver and kidney transplant. Surgery 2019; 166:102-108. [PMID: 31072671 DOI: 10.1016/j.surg.2019.03.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 02/22/2019] [Accepted: 03/15/2019] [Indexed: 01/25/2023]
Abstract
BACKGROUND The opioid epidemic has resulted in increasing the incidence of hepatitis C virus in the general population and more deceased organ donors with hepatitis C in the United States. We aim to describe how the changing donor landscape affects patterns of liver and kidney transplantation among donors, waitlist candidates, and transplanted recipients. METHODS Using data supplied by the United Network for Organ Sharing, we examined donor hepatitis C virus antibody (Ab) and nucleic acid testing (NAT) status, center waitlist patterns, and liver and kidney transplants and discards between 2015 and 2017 by 6-month periods. RESULTS We observed an increase in donors with any marker of the hepatitis C virus (n = 283 [6.2%] in period 1 to n = 384 [7.4%] in period 5, P = .008) and antibody positive nucleic acid testing negative donors (n = 81 [1.8%] in period 1 to n = 131 [2.5%] in period 5, P < .001). We observed a significant increase in aviremic recipients of liver transplants from antibody positive nucleic acid testing negative donors (n = 1 [1.7%] in period 1, to n = 27 [31.0%] in period 5, P = .005) and a significant decrease in the antibody positive nucleic acid testing positive liver discard rate (P = .01). By the end of the study, 75.8% (n = 97) of recipients of antibody positive nucleic acid testing negative kidneys were hepatitis C virus negative, an increase from 10.6% (n = 5) in period 1. CONCLUSION The number of donors with the hepatitis C virus is increasing. We observed a concomitant increase in the transplantation of kidneys and livers from aviremic donors, and the recipient population of these organs is increasingly hepatitis C virus negative.
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Franco A, Moreso F, Merino E, Sancho A, Kanter J, Gimeno A, Balibrea N, Rodriguez M, Perez Contreras F. Renal transplantation from seropositive hepatitis C virus donors to seronegative recipients in Spain: a prospective study. Transpl Int 2019; 32:710-716. [PMID: 30773693 DOI: 10.1111/tri.13410] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2018] [Revised: 08/11/2018] [Accepted: 02/11/2019] [Indexed: 01/03/2023]
Abstract
Hepatitis C virus (HCV) positive donors are identified in Spain by antibody detection (HCV-Ab) techniques while a HCV nuclear acid-testing (HCV-NAT) is not mandatory. Since it has been shown that HCV-Ab positive HCV-NAT negative donors do not universally transmit the infection, we designed a protocol based on the identification of viremia in HCV-Ab positive donors to start treatment if needed. HCV-Ab-positive donors were identified and we performed HCV-NAT immediately. Donors coinfected with HIV were excluded. Recipients with a low chance to receive a transplant, with no history of liver disease and who were negative for HCV-Ab were selected after informed consent was signed. Kidney recipients from HCV-NAT-positive donors received glecaprevir and pibrentasvir from 6 h before the transplant until 8 weeks after. Recipients from HCV-NAT-negative donors were not treated. Regular monitoring by HCV-NAT was performed to initiate antiviral treatment. We included 11 recipients from six deceased donors Four recipients received grafts from HCV-NAT-positive donors and seven patients received grafts from HCV-NAT-negative donors. None of our recipients exhibited HCV-NAT positivity during the minimum follow-up period of 6 months. Recipients from HCV-NAT-positive donors exhibited sustained virologic response at 12 weeks. One recipient from an HCV-NAT-negative donor lost his graft via a process thought to be unrelated to HCV. The remaining 10 patients had a stable functioning graft at the end of the follow-up period. Our preliminary data suggest that renal transplantation from HCV-Ab- positive donors to HCV-Ab negative recipients is safe when only the recipients of organs from HCV-NAT-positive donors are treated.
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Affiliation(s)
- Antonio Franco
- Department of Nephrology, Hospital General Alicante, Alicante, Spain
| | - Francesc Moreso
- Department of Nephrology, Hospital Universitari Vall Hebron Barcelona, Barcelona, Spain
| | - Esperanza Merino
- Department of Internal Medicine, Hospital General Alicante, Alicante, Spain
| | - Asunción Sancho
- Department of Nephrology, Hospital Dr Pesset, Valencia, Spain
| | - Julia Kanter
- Department of Nephrology, Hospital Dr Pesset, Valencia, Spain
| | - Adelina Gimeno
- Department of Microbiology, Hospital General Alicante, Alicante, Spain
| | - Noelia Balibrea
- Department of Nephrology, Hospital General Alicante, Alicante, Spain
| | - Maria Rodriguez
- Department of Hepatology, Hospital General Alicante, Alicante, Spain
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Angeletti A, Cantarelli C, Cravedi P. HCV-Associated Nephropathies in the Era of Direct Acting Antiviral Agents. Front Med (Lausanne) 2019; 6:20. [PMID: 30800660 PMCID: PMC6376251 DOI: 10.3389/fmed.2019.00020] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2018] [Accepted: 01/23/2019] [Indexed: 12/11/2022] Open
Abstract
Hepatitis C virus (HCV) infection is a systemic disorder that frequently associates with extrahepatic manifestations, including nephropathies. Cryoglobulinemia is a typical extrahepatic manifestation of HCV infection that often involves kidneys with a histological pattern of membranoproliferative glomerulonephritis. Other, less common renal diseases related to HCV infection include membranous nephropathy, focal segmental glomerulosclerosis, IgA nephropathy, fibrillary and immunotactoid glomerulopathy. Over the last decades, the advent of direct-acting antiviral therapies has revolutionized treatment of HCV infection, dramatically increasing the rates of viral clearance. In patients where antiviral therapy alone fails to induce renal disease remission add-on B-cell depleting agents represent an alternative to counteract the synthesis of pathogenic antibodies. Immunosuppressive therapies, such as steroids, alkylating agents, and plasma exchanges, may still represent an effective option to inhibit immune-complex driven inflammatory response, but the potentially associated increase of HCV replication and worsening of liver disease represent a serious limitation to their use.
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Affiliation(s)
- Andrea Angeletti
- Nephrology Dialysis and Renal Transplantation Unit, S. Orsola University Hospital, Bologna, Italy
| | - Chiara Cantarelli
- Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Paolo Cravedi
- Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
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Sharif A. Transplanting Kidneys From Hepatitis C-Infected Donors Into Uninfected Recipients: Ready for the Mainstream. Ann Intern Med 2018; 169:341-342. [PMID: 30083764 DOI: 10.7326/m18-1781] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Adnan Sharif
- Queen Elizabeth Hospital and University of Birmingham, Birmingham, United Kingdom (A.S.)
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