Expanding the Use of Organs From Hepatitis C-Viremic Donors: The Evidence Continues to Build.
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ABSTRACT:
SUBMITTER: Holscher CM
PROVIDER: S-EPMC5860943 | biostudies-literature | 2018 Apr
REPOSITORIES: biostudies-literature
Publications
Expanding the Use of Organs From Hepatitis C-Viremic Donors: The Evidence Continues to Build.
Holscher Courtenay M CM Durand Christine M CM Desai Niraj M NM
Transplantation 20180401 4
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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.
| S-EPMC8317248 | biostudies-literature
Project description:In the context of organ shortage, the opioid epidemic, and effective direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV), more HCV-infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor-derived HCV in previously non-viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor-derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing. Seven had a prior diagnosis of HCV and were treated before liver transplantation. All recipients were non-viremic at the time of transplantation. All 10 recipients derived hepatitis C infection from their donor and achieved sustained virologic response at 12 weeks posttreatment with DAA-based regimens, with a median time from transplant to treatment initiation of 43 days (IQR 20-59). There have been no instances of graft loss or death, with median follow-up of 380 days (IQR 263-434) posttransplant. Transplantation of HCV-viremic livers into non-viremic recipients results in acceptable short-term outcomes. Such strategies may be used to expand the donor pool and increase access to liver transplantation.
| S-EPMC6663314 | biostudies-literature
Project description:Background and objectivesKidneys 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, & measurementsData 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.ResultsAmong 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).ConclusionsDespite 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.
| S-EPMC7863640 | biostudies-literature
Project description:BackgroundThe advent of direct-acting antiviral therapy for Hepatitis C (HCV) has made using HCV-viremic donors a viable strategy to address the donor shortage in heart transplantation. We employed a large-scale simulation to evaluate the impact and cost-effectiveness of using HCV-viremic donors for heart transplant.MethodsWe simulated detailed histories from time of listing until death for the real-world cohort of all adults listed for heart transplant in the United States from July 2014 to June 2019 (n = 19,346). This population was imputed using historical data and captures "real-world" heterogeneity in geographic and clinical characteristics. We estimated the impact of an intervention in which all candidates accept HCV+ potential donors (n = 472) on transplant volume, waitlist outcomes, and lifetime costs and quality-adjusted life years (QALYs).ResultsThe intervention produced 232 more transplants, 132 fewer delistings due to deterioration, and 50 fewer waitlist deaths within this 5-year cohort and reduced wait times by 3% to 11% (varying by priority status). The intervention was cost-effective, adding an average of 0.08 QALYs per patient at a cost of $124 million ($81,892 per QALY). DAA therapy and HCV care combined account for 11% this cost, with the remainder due to higher costs of transplant procedures and routine post-transplant care. The impact on transplant volume varied by blood type and region and was correlated with donor-to-candidate ratio (ρ = 0.71).ConclusionsTransplanting HCV+ donor hearts is likely to be cost-effective and improve waitlist outcomes, particularly in regions and subgroups experiencing high donor scarcity.
| S-EPMC8973316 | biostudies-literature
Project description:IntroductionUtilization of hepatitis C viremic (HCV+) deceased donor kidneys (DDKT) for aviremic recipients increases opportunities for transplantation with excellent short-term outcomes. Our primary aim was to understand longer-term outcomes, specifically assessing kidney and liver function in the first year posttransplant.MethodsThis was a retrospective single-center study of adult DDKT recipients of HCV+ kidneys (cases) matched 1:1 to recipients of HCV- kidneys (comparators). Between-group outcomes were analyzed using comparisons of means and proportions, survival analysis methods, and multivariable mixed effects models.ResultsSixty-five cases and 65 comparators had statistically comparable demographic and clinical characteristics. There were no between-group differences in serum creatinine or estimated glomerular filtration rate at month 12 (p = .662) or in their trajectories over months 1-12 (p > .292). Within the first 60 days, rates of liver function values >3 times upper limit of normal among cases were comparable to comparators for aspartate aminotransferase (AST) (14% vs. 6%, p = .242) and higher for alanine transaminase (ALT) (23% vs. 6%, p = .011). AST declined during the first 8 weeks (p = .005) and stabilized for both groups (p = .406) during the following 10 months. ALT declined during the first 8 weeks (p < .001), continued to decline over months 3-12 (p = .016), and the trajectory was unrelated to antiviral therapy initiation among cases.ConclusionsAviremic recipients of HCV+ kidneys had comparable kidney outcomes to matched recipients of HCV- kidneys. Despite more HCV+ recipients having an elevation in ALT within the first 60 days, ALT values normalized with no identified liver complications attributed to HCV.
| S-EPMC10922352 | biostudies-literature
Project description: Not available
| S-EPMC8288461 | biostudies-literature
Project description:BackgroundHistorically, many organs from deceased donors with hepatitis C virus (HCV) were discarded. The advent of highly curative direct-acting antiviral (DAA) therapies motivated transplant centers to conduct trials of transplanting HCV-viremic organs (nucleic acid amplification test positive) into HCV-negative recipients, followed by DAA treatment. However, the factors that influence candidates' decisions regarding acceptance of transplant with HCV-viremic organs are not well understood.MethodsTo explore patient-level perceptions, influences, and experiences that inform candidate decision-making regarding transplant with organs from HCV-viremic donors, we conducted a qualitative semistructured interview study embedded within 3 clinical trials investigating the safety and efficacy of transplanting lungs and kidneys from HCV-viremic donors into HCV-negative recipients. The study was conducted from June 2019 to March 2021.ResultsAmong 44 HCV-negative patients listed for organ transplant who were approached for enrollment in the applicable clinical trial, 3 approaches to decision-making emerged: positivist, risk analyses, and instinctual response. Perceptions of risk contributed to conceptualizations of factors influencing decisions. Moreover, most participants relied on multiple decision-making approaches, either simultaneously or sequentially.ConclusionsUnderstanding how different decisional models influence patients' choices regarding transplant with organs from HCV-viremic donors may promote shared decision-making among transplant patients and providers.
| S-EPMC9298473 | biostudies-literature
Project description:ObjectiveThe feasibility and 6-month outcome safety of lung transplants (LTs) from hepatitis C virus (HCV)-viremic donors for HCV-seronegative recipients (R-) were established in 2019, but longer-term safety and uptake of this practice nationally remain unknown.MethodsWe identified HCV-seronegative LT recipients (R-) 2015-2020 using the Scientific Registry of Transplant Recipients. We classified donors as seronegative (D-) or viremic (D+). We used χ2 testing, rank-sum testing, and Cox regression to compare posttransplant outcomes between HCV D+/R- and D-/R- LT recipients.ResultsHCV D+/R- LT increased from 2 to 97/year; centers performing HCV D+/R- LT increased from 1 to 25. HCV D+/R- versus HCV D-/R- LT recipients had more obstructive disease (35.7% vs 23.3%, P < .001), lower lung allocation score (36.5 vs 41.1, P < .001), and longer waitlist time (P = .002). HCV D+/R- LT had similar risk of acute rejection (adjusted odds ratio [aOR], 0.87; P = .58), extracorporeal membranous oxygenation (aOR, 1.94; P = .10), and tracheostomy (aOR, 0.42; P = .16); similar median hospital stay (P = .07); and lower risk of ventilator > 48 hours (aOR, 0.68; P = .006). Adjusting for donor, recipient, and transplant characteristics, risk of all-cause graft failure and mortality were similar at 30 days, 1 year, and 3 years for HCV D+/R- versus HCV D-/R- LT (all P > .1), as well as for high- (≥20/year) versus low-volume LT centers and high- (≥5/year) versus low-volume HCV D+/R- LT centers (all P > .5).ConclusionsHCV D+/R- and HCV D-/R- LT have similar outcomes at 3 years posttransplant. These results underscore the safety of HCV D+/R- LT and the potential benefit of expanding this practice further.
| S-EPMC9989038 | biostudies-literature
Project description:MELODIC trial is an prospective, multicenter, non-randomized, open-label, parallel trial, aimed at assessing the efficacy (in terms of overall survival: OS) of liver transplantation (LT) in unresecable CRC liver-only metastases, compared with a matched cohort of patients bearing the same tumor characteristics, and treated with chemotherapy. Synthesis of Inclusion parameters: "10;10;10;100"
| 2376303 | ecrin-mdr-crc
Project description:ObjectivePublic trust in health systems is pivotal for their effective and efficient functioning. In particular, public trust is essential for personal data use, as demonstrated in debates in many countries, for example, about whether data from COVID-19 contact tracing apps should be pooled or remain on individuals' smartphones. Low levels of public trust pose a risk not only to health system legitimacy but can also harm population health.MethodsSynthesising our previous qualitative and theoretical research in the English National Health Service which enabled us to conceptualise the nature of public trust in health systems, we present guiding principles designed to rebuild public trust, if lost, and to maintain high levels of public trust in personal data use within the health system, if not.ResultsTo build public trust, health system actors need to not rush trust building; engage with the public; keep the public safe; offer autonomy to the public; plan for diverse trust relationships; recognise that trust is shaped by both emotion and rational thought; represent the public interest; and work towards realising a net benefit for the health system and the public.ConclusionsBeyond policymakers and government officials, the guiding principles address a wide range of actors within health systems so that they can work collectively to build public trust. The guiding principles can be used to inform policymaking in health and health care and to analyse the performance of different governments to see if those governments that operate in greater conformity with the guiding principles perform better.
| S-EPMC9297454 | biostudies-literature