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The impact of hepatitis C viremic donor lung allograft characteristics on post-transplantation outcomes.

ABSTRACT: Background:There is a low utilization rate of donated donor lungs. Historically, transplantation of lungs from hepatitis C-viremic donors to hepatitis C (HCV) negative recipients was avoided due to concern for worse graft survival. In the past few years with the advent of direct acting antiviral (DAA) therapy, there are emerging data suggesting the safety and efficacy of transplanting thoracic organs from HCV-viremic donors. This study assessed the differences in donor characteristics and allograft-specific clinical features at the time of organ offer and investigated whether these variables differed in HCV-viremic versus HCV-negative donors and impacted recipient outcomes. Methods:We conducted a single-center, retrospective cohort study of adult patients who underwent a lung transplant at Brigham and Women's Hospital between March 2017 and October 2018. Patients were stratified based on their donor HCV status (HCV-viremic versus HCV-negative). Donor and allograft-specific characteristics and clinical features including chest imaging and bronchoscopy reports, respiratory cultures, and the donor's oxygenation as measured by the arterial partial pressure of oxygen (PaO2) were collected as well as recipient baseline characteristics and transplant outcomes. Results:During the study period, 42 and 57 lung transplants were performed from HCV-viremic and HCV-negative donors, respectively. Donor age was similar in both cohorts. More HCV-viremic donors died from drug intoxication (71% versus 19%, P=0.0001) and had a history of cigarette use (83% versus 5%, P=0.0001) and drug use (76% versus 49%, P=0.007). There were differences in the baseline recipient characteristics including a lower median lung allocation score in the HCV-viremic cohort. The organ-specific clinical characteristics including the terminal PaO2, chest imaging and bronchoscopy findings, and evidence of pulmonary infection were similar between the two cohorts. The recipient outcomes overall were excellent and did not differ significantly in both cohorts in terms of graft and patient survival at 6 and 12 months. Conclusions:Despite a greater proportion of HCV-viremic donors being increased risk with a history of drug and cigarette use and having died as a result of drug intoxication, the quality of the HCV-viremic donor organs did not differ from the HCV-negative donor organs or impact graft and recipient survival. Due to an increasing number of transplants from increased risk donors and in order to develop safe and effective protocols to perform lung transplants from HCV-infected donors, further characterization of the donor and allograft-specific clinical features and longer-term recipient outcomes is greatly needed.

SUBMITTER: Woolley AE

PROVIDER: S-EPMC7049551 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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The impact of hepatitis C viremic donor lung allograft characteristics on post-transplantation outcomes.

Woolley Ann E AE Piechura Laura M LM Goldberg Hilary J HJ Singh Steve K SK Coppolino Antonio A Baden Lindsey R LR Mallidi Hari R HR

Annals of cardiothoracic surgery 20200101 1

<h4>Background</h4>There is a low utilization rate of donated donor lungs. Historically, transplantation of lungs from hepatitis C-viremic donors to hepatitis C (HCV) negative recipients was avoided due to concern for worse graft survival. In the past few years with the advent of direct acting antiviral (DAA) therapy, there are emerging data suggesting the safety and efficacy of transplanting thoracic organs from HCV-viremic donors. This study assessed the differences in donor characteristics an ...[more]

PMID: 32175238

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Project description:BackgroundDonor-characteristics and donor characteristics-based decision algorithms are being progressively used in the decision process whether or not to accept an available donor kidney graft for transplantation. While this may improve outcomes, the performance characteristics of the algorithms remains moderate. To estimate the impact of donor factors of grafts accepted for transplantation on transplant outcomes, and to test whether implementation of donor-characteristics-based algorithms in clinical decision-making is justified, we applied an instrumental variable analysis to outcomes for kidney donor pairs transplanted in different individuals.MethodsThis analysis used (dis)congruent outcomes of kidney donor pairs as an instrument and was based on national transplantation registry data for all donor kidney pairs transplanted in separate individuals in the Netherlands (1990-2018, 2,845 donor pairs), and the United Kingdom (UK, 2000-2018, 11,450 pairs). Incident early graft loss (EGL) was used as the primary discriminatory factor. It was reasoned that a scenario with a dominant impact of donor variables on transplantation outcomes would result in high concordance of EGL in both recipients, whilst dominance of asymmetrical outcomes could indicate a more complex scenario, involving an interaction of donor, procedural and recipient factors.FindingsIncidences of congruent EGL (Netherlands: 1·2%, UK: 0·7%) were slightly lower than the arithmetical (stochastic) incidences, suggesting that once a graft has been accepted for transplantation, donor factors minimally contribute to incident EGL. A long-term impact of donor factors was explored by comparing outcomes for functional grafts from donor pairs with asymmetrical vs. symmetrical outcomes. Recipient survival was similar for both groups, but a slightly compromised graft survival was observed for grafts with asymmetrical outcomes in the UK cohort: (10-years Hazard Ratio for graft loss: 1·18 [1·03-1·35] p<0·018); and 5 years eGFR (48·6 [48·3-49·0] vs. 46·0 [44·5-47·6] ml/min in the symmetrical outcome group, p<0·001).InterpretationOur results suggest that donor factors for kidney grafts deemed acceptable for transplantation impact minimally on transplantation outcomes. A strong reliance on donor factors and/or donor-characteristics-based decision algorithms could result in unjustified rejection of grafts. Future efforts to optimize transplant outcomes should focus on a better understanding of the recipient factors underlying transplant outcomes.FundingNone.

Project description:Purpose of programThe 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 informationScoping literature review and key stakeholder engagement with interdisciplinary health care providers and health system leaders/decision markers.MethodsPatients 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 findingsThis 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.ImplicationsThe 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.

Dataset Information

The impact of hepatitis C viremic donor lung allograft characteristics on post-transplantation outcomes.

Publications

The impact of hepatitis C viremic donor lung allograft characteristics on post-transplantation outcomes.

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