Outcome of children on the UK national prioritised paediatric registration tier

P69 Table 1Demographic and transplant data for all 14 prioritised patientsPatient/Sex Centre Age at registration (yrs) Primary liver disease Registered prior to Prioritisation Indication of Prioritization LT Waiting time on prioritised tier/Time on list prior to prioritisation 1/M 1 0 CDG Yes Acute decompensation with presence of encephalopathy Yes/LLS 5/27 2/M 2 1 Cryptogenic Cirrhosis Yes CLD with nodular lesions s/o HCC Yes/LLS 16/48 3/F 1 15 AILD Yes Chronic rejection Yes/whole liver 3/4 4/M 2 0 Biliary Atresia Yes PTLD/HAT/Sepsis Yes/LLS 14/71 5/F 2 4 IFALD No Coagulopathy with active bleeding/Renal impairment Yes/LLS 15/820 6/F 2 0 Biliary Atresia Yes Acute decompensation due to portal hypertension Yes/LLS 37/405 7/M 2 10 NSC Yes Decompensated chronic liver disease/Renal impairment Yes/reduced R lobe 4/7 8/M 3 8 PFIC3 Yes Acute decompensation of Chronic liver disease Yes/LLS 6/51 9/F 1 0 Other (Hepatoblastoma) Intestinal Tx prioritized Acute decompensation of Chronic liver disease Yes/LLS 11/ 10/F 2 0 Biliary atresia Yes Decompensated Chronic Liver Disease with Severe Coagulopathy Yes/LLS 10/120 11/M 1 0 Biliary atresia (Hepatoblastoma) Yes Acute decompensation of Chronic liver disease Yes/LLS 9/4 12/F 3 0 Biliary atresia Yes Acute decompensation of Chronic liver disease Yes/LLS 12/323 13/F 1 17 Hepatic Artery thrombosis Yes Hepatic Artery thrombosis Yes/whole liver 2/ 14/F 2 0 Biliary atresia Yes Acute decompensation of Chronic liver disease Suspended 12/65 PFIC3;Progressive Familial Intrahepatic Cholestasis type 3, LT;Liver transplantation, HCC;Hepatocellular Carcinoma NSC;Neonatal Sclerosing Cholangitis, CDG;Congenital Disorder of Glycosylation, AILD;Autoimmune Liver Disease, IFALD;Intestinal Failure Associated Liver Disease,PTLD;Center 1-Kings;Center2-Birmingham;Center3-Leeds.ConclusionThe national paediatric prioritization tier, introduced during the COVID19 pandemic, has been a pivotal initiative for the UK paediatric LT program, showcasing national collaboration. All patients underwent a LT successfully within a short time from prioritization with 100% patient and graft survival. The intention is to maintain this prioritized paediatric tier beyond the pandemic.

Kidney Transplantation From Deceased Donors With Vaccine-induced Immune Thrombocytopenia and Thrombosis: An Updated Analysis of the UK Experience.

BACKGROUND: The emergence and attendant mortality of vaccine-induced immune thrombocytopenia and thrombosis (VITT) as a consequence of vaccination against severe acute respiratory syndrome coronavirus 2 have resulted in some patients with VITT being considered as deceased organ donors. Outcomes after kidney transplantation in this context are poorly described. Because the disease seems to be mediated by antiplatelet factor 4 antibodies, there is a theoretical risk of transmission via passenger leukocytes within the allograft. METHODS: We analyzed the experience of kidney transplantation from donors with VITT in the United Kingdom between January and June 2021. We followed-up all recipients of kidney-only transplants from donors with VITT to detect major postoperative complications or features of disease transmission and assess graft survival and function. RESULTS: There were 16 kidney donors and 30 single kidney transplant recipients in our study period. Of 11 preimplantation biopsies, 4 showed widespread glomerular microthrombi. After a median of 5 mo, patient and graft survival were 97% and 90%, respectively. The median 3-mo estimated glomerular filtration rate was 51 mL/min/1.73 m 2 . Two recipients had detectable antiplatelet factor 4 antibodies but no evidence of clinical disease after transplantation. Major hemorrhagic complications occurred in 3 recipients, all of whom had independent risk factors for bleeding, resulting in the loss of 2 grafts. The involvement of VITT could not be completely excluded in one of these cases. CONCLUSIONS: The UK experience to date shows that favorable outcomes are possible after kidney transplantation from donors with VITT but highlights the need for ongoing vigilance for donor-related complications in these patients.

The Global Impact of COVID-19 on Solid Organ Transplantation: Two Years Into a Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has had a major global impact on solid organ transplantation (SOT). An estimated 16% global reduction in transplant activity occurred over the course of 2020, most markedly impacting kidney transplant and living donor programs, resulting in substantial knock-on effects for waitlisted patients. The increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection risk and excess deaths in transplant candidates has resulted in substantial effort to prioritize the safe restart and continuation of transplant programs over the second year of the pandemic, with transplant rates returning towards prepandemic levels. Over the past 2 y, COVID-19 mortality in SOT recipients has fallen from 20%-25% to 8%-10%, attributed to the increased and early availability of SARS-CoV-2 testing, adherence to nonpharmaceutical interventions, development of novel treatments, and vaccination. Despite these positive steps, transplant programs and SOT recipients continue to face challenges. Vaccine efficacy in SOT recipients is substantially lower than the general population and SOT recipients remain at an increased risk of adverse outcomes if they develop COVID-19. SOT recipients and transplant teams need to remain vigilant and ongoing adherence to nonpharmaceutical interventions appears essential. In this review, we summarize the global impact of COVID-19 on transplant activity, donor evaluation, and patient outcomes over the past 2 y, discuss the current strategies aimed at preventing and treating SARS-CoV-2 infection in SOT recipients, and based on lessons learnt from this pandemic, propose steps the transplant community could consider as preparation for future pandemics.

A coordinated national UK liver transplant program response, prioritizing waitlist recipients with the highest need, provided excellent outcomes during the first wave of the COVID-19 pandemic.

INTRODUCTION: Healthcare provision has been severely affected by COVID-19, with specific challenges in organ transplantation. Here, we describe the coordinated response to, and outcomes during the first wave, across all UK liver transplant (LT) centers. METHODS: Several policy changes affecting the liver transplant processes were agreed upon. These included donor age restrictions and changes to offering. A "high-urgency" (HU) category was established, prioritizing only those with UKELD > 60, HCC reaching transplant criteria, and others likely to die within 90 days. Outcomes were compared with the same period in 2018 and 2019. RESULTS: The retrieval rate for deceased donor livers (71% vs. 54%; P < .0001) and conversion from offer to completed transplant (63% vs. 48%; P < .0001) was significantly higher. Pediatric LT activity was maintained; there was a significant reduction in adult (42%) and total (36%) LT. Almost all adult LT were super-urgent (n = 15) or HU (n = 133). We successfully prioritized those with highest illness severity with no reduction in 90-day patient (P = .89) or graft survival (P = .98). There was a small (5% compared with 3%; P = .0015) increase in deaths or removals from the waitlist, mainly amongst HU cohort. CONCLUSIONS: We successfully prioritized LT recipients in highest need, maintaining excellent outcomes, and waitlist mortality was only marginally increased.

Real-world Effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S Vaccines Against SARS-CoV-2 in Solid Organ and Islet Transplant Recipients.

BACKGROUND: The clinical effectiveness of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunosuppressed solid organ and islet transplant (SOT) recipients is unclear. METHODS: We linked 4 national registries to retrospectively identify laboratory-confirmed SARS-CoV-2 infections and deaths within 28 d in England between September 1, 2020, and August 31, 2021, comparing unvaccinated adult SOT recipients and those who had received 2 doses of ChAdOx1-S or BNT162b2 vaccine. Infection incidence rate ratios were adjusted for recipient demographics and calendar month using a negative binomial regression model, with 95% confidence intervals. Case fatality rate ratios were adjusted using a Cox proportional hazards model to generate hazard ratio (95% confidence interval). RESULTS: On August 31, 2021, it was found that 3080 (7.1%) were unvaccinated, 1141 (2.6%) had 1 vaccine dose, and 39 260 (90.3%) had 2 vaccine doses. There were 4147 SARS-CoV-2 infections and 407 deaths (unadjusted case fatality rate 9.8%). The risk-adjusted infection incidence rate ratio was 1.29 (1.03-1.61), implying that vaccination was not associated with reduction in risk of testing positive for SARS-CoV-2 RNA. Overall, the hazard ratio for death within 28 d of SARS-CoV-2 infection was 0.80 (0.63-1.00), a 20% reduction in risk of death in vaccinated patients (P = 0.05). Two doses of ChAdOx1-S were associated with a significantly reduced risk of death (hazard ratio, 0.69; 0.52-0.92), whereas vaccination with BNT162b2 was not (0.97; 0.71-1.31). CONCLUSIONS: Vaccination of SOT recipients confers some protection against SARS-CoV-2-related mortality, but this protection is inferior to that achieved in the general population. SOT recipients require additional protective measures, including further vaccine doses, antiviral drugs, and nonpharmaceutical interventions.

A coordinated national response maintained a safe and effective UK liver transplant program during the first year of the COVID-19 pandemic

P091 Figure 1Number of livers from UK deceased doners offered, retrieved and transplanted, 4 February 2020 to 5 April 2021[Figure omitted. See PDF]DiscussionA sophisticated national response has maintained a safe and effective UK LT program throughout the first year of COVID. We adapted our resources, implementing phased donor restrictions and a new category for recipient prioritisation. Patients benefitted from collaborative working, enabling those in most need to be transferred and transplanted in protected centres. Consequently, we mitigated against a significant fall in LT activity. Our collaborative response serves as an as exemplar for other specialist healthcare services.

COVID-19 pandemic and worldwide organ transplantation: a population-based study.

BACKGROUND: Preliminary data suggest that COVID-19 has reduced access to solid organ transplantation. However, the global consequences of the COVID-19 pandemic on transplantation rates and the effect on waitlisted patients have not been reported. We aimed to assess the effect of the COVID-19 pandemic on transplantation and investigate if the pandemic was associated with heterogeneous adaptation in terms of organ transplantation, with ensuing consequences for waitlisted patients. METHODS: In this population-based, observational, before-and-after study, we collected and validated nationwide cohorts of consecutive kidney, liver, lung, and heart transplants from 22 countries. Data were collected from Jan 1 to Dec 31, 2020, along with data from the same period in 2019. The analysis was done from the onset of the 100th cumulative COVID-19 case through to Dec 31, 2020. We assessed the effect of the pandemic on the worldwide organ transplantation rate and the disparity in transplant numbers within each country. We estimated the number of waitlisted patient life-years lost due to the negative effects of the pandemic. The study is registered with ClinicalTrials.gov, NCT04416256. FINDINGS: Transplant activity in all countries studied showed an overall decrease during the pandemic. Kidney transplantation was the most affected, followed by lung, liver, and heart. We identified three organ transplant rate patterns, as follows: countries with a sharp decrease in transplantation rate with a low COVID-19-related death rate; countries with a moderate decrease in transplantation rate with a moderate COVID-19-related death rate; and countries with a slight decrease in transplantation rate despite a high COVID-19-related death rate. Temporal trends revealed a marked worldwide reduction in transplant activity during the first 3 months of the pandemic, with losses stabilising after June, 2020, but decreasing again from October to December, 2020. The overall reduction in transplants during the observation time period translated to 48 239 waitlisted patient life-years lost. INTERPRETATION: We quantified the impact of the COVID-19 pandemic on worldwide organ transplantation activity and revealed heterogeneous adaptation in terms of organ transplantation, both at national levels and within countries, with detrimental consequences for waitlisted patients. Understanding how different countries and health-care systems responded to COVID-19-related challenges could facilitate improved pandemic preparedness, notably, how to safely maintain transplant programmes, both with immediate and non-immediate life-saving potential, to prevent loss of patient life-years. FUNDING: French national research agency (INSERM) ATIP Avenir and Fondation Bettencourt Schueller.

O3 The UK paediatric liver transplant programme during the COVID-19 pandemic

IntroductionThe UK has been severely affected by the COVID-19 pandemic. The impact on the adult population has been disproportionately higher when compared to children with consequent challenges to organ donation and liver transplantation (LT). Across the three UK paediatric liver centres there has only been a very small number of patients who tested positive for COVID-19 and all made a speedy and full recovery. We report here the response during the pandemic across the 3 paediatric LT centres.MethodsA series of nationally agreed policy changes affecting the liver procurement, listing and transplant process were agreed during regular meetings with LT centre directors and NHSE. Actions at a local and national level were agreed to protect and maintain the paediatric LT programmes.Data were collected from 27/03/20 until 26/11/20 and compared with same time period for the years 2016–19.ResultsDuring the study period, there was a significant reduction in the adult population in the mean number of weekly liver offers, donors and LTs compared to before the pandemic with signs of recovery between the 1st and 2nd UK lockdown periods (figure 1). More specifically the number of livers offered nationally was reduced from an average 30–40/week to only <10/week during the 1st wave in the March-April period. The number of children on the LT list during the study period across all 3 centres was 74 in total with 17 (23%) super-urgent and 57(77%) electives, which was comparable to previous years.Overall, 65–80 paediatric LTs are performed annually across the UK’s 3 paediatric centres. From March-November 2020 there were 58(82%) elective and 13(18%) super urgent (acute liver failure & hepatoblastoma) paediatric LTs performed.Donor Brain Dead (DBD) and Donor Cardiac Dead (DCDC) LTs were 54(76%) and 3(4%), respectively. Living related LT (LRLT) programme was sustained comprising 20% of LTs performed.The number of paediatric LTs performed during the pandemic was comparable to those performed yearly since 2016. The number of LT per paediatric centre for King’s College Hospital (KCH), Birmingham Children’s Hospital (BCH) and Leeds Liver Unit were 40 (56%), 15(21%) and 16(23%), respectively with excellent outcome. A 15-year-old girl from KCH diagnosed with Wilson disease presented with liver failure and became COVID-19 positive whilst listed. She underwent LT soon after becoming COVID-19 negative. No perioperative mortality was reported with excellent outcome so far in all.ConclusionThe current COVID-19 pandemic had a significant impact on the UK adult LT programme. The paediatric programme LT was preserved despite a decrease in organ offering and retrieval nationally plus limitations on adult intensive care resources at a regional level. Overall, paediatric LT outcome remained very good.

SARS-CoV-2 infection and early mortality of waitlisted and solid organ transplant recipients in England: A national cohort study.

Patients waitlisted for and recipients of solid organ transplants (SOT) are perceived to have a higher risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and death; however, definitive epidemiological evidence is lacking. In a comprehensive national cohort study enabled by linkage of the UK transplant registry and Public Health England and NHS Digital Tracing services, we examined the incidence of laboratory-confirmed SARS-CoV-2 infection and subsequent mortality in patients on the active waiting list for a deceased donor SOT and recipients with a functioning SOT as of February 1, 2020 with follow-up to May 20, 2020. Univariate and multivariable techniques were used to compare differences between groups and to control for case-mix. One hundred ninety-seven (3.8%) of the 5184 waitlisted patients and 597 (1.3%) of the 46 789 SOT recipients tested positive for SARS-CoV-2. Mortality after testing positive for SARS-CoV-2 was 10.2% (20/197) for waitlisted patients and 25.8% (154/597) for SOT recipients. Increasing recipient age was the only variable independently associated with death after positive SARS-CoV-2 test. Of the 1004 transplants performed in 2020, 41 (4.1%) recipients have tested positive for SARS-CoV-2 with 8 (0.8%) deaths reported by May 20. These data provide evidence to support decisions on the risks and benefits of SOT during the coronavirus disease 2019 pandemic.