Liver transplantation from active COVID-19 donors: Is it ethically justifiable?

The debate on the opportunity to use organs from donors testing positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in recipients with naïve resolved or active COVID-19 is ongoing. We aim to present the ethical analyses underlying the decision to perform liver transplantation (LT) in selected patients with resolved or active COVID-19 in Italy. We used Jonsen, Siegler, and Winslade's Four-Boxes casuistic method, addressing the four topics considered as constitutive of the essential structure of single clinical cases for their ethical analysis (medical indications, patient preferences, quality of life, and contextual features) to enable decision-making on a case-by-case basis. Based on these topics, we elucidate the meaning and balance among the principles of biomedical ethics. Clinical ethics judgment based on the relation between the risk of acquiring SARS-CoV-2 along with its potentially negative effects and the expected benefits of transplant lead to consider LT as clinically appropriate. Shared decision-making allows the integration of clinical options with the patient's subjective preferences and considerations, enabling a valid informed consent specifically tailored to the patients' individual circumstances. The inclusion of carefully selected SARS-CoV-2 positive donors represents an opportunity to offer lifesaving LT to patients who might otherwise have limited opportunities to receive one. COVID-19 positive donor livers are fairly allocated among equals, and respect for fundamental rights of the individual and the broader community in a context of healthcare rationing is guaranteed.The ethical analysis of the decision to perform LT in selected patients shows that the decision is ethically justifiable.

Seroconversion After Coronavirus Disease 2019 Vaccination in Patients Awaiting Liver Transplantation: Fact or Fancy?

Chronic liver disease increased the risk of severe coronavirus disease 2019 (COVID-19). Trials to assess efficacy/safety of COVID-19 vaccines in liver disease are underway. We evaluated the humoral immune response and safety of anti-COVID-19 vaccination among patients waiting liver transplantation (LT). We enrolled all pre-LT adults who completed anti-COVID-19 vaccination between January 2021-August 2021 as study group. Patients with histories of COVID-19 received 1 vaccine dose, and all others received 2 doses. Patients were tested for COVID-19 immunoglobulin G (IgG) within 1 and 2 months after vaccination. Safety was evaluated with telephone interviews/outpatient visits. A control group of 30 healthcare workers who underwent vaccination in January 2021 and tested for IgG after 4 months was included. In the 89 pre-LT patients, at T1 (23 days after vaccination), seroconversion rate was 94.4%, and median IgG value was 1980 binding antibody units/mL (interquartile range 646-2080), and at T2 (68 days after vaccination) was 92.0%, with IgG value of 1450 (577-2080); (T1 versus T2, P = 0.38). In the 10/89 patients who received 1 vaccine dose, the median IgG value was 274 (68-548) before vaccine (T0), 2080 (1165-2080) at T1, and 2030 (964-2080) at T2 (T0 versus T1, P = 0.03; T1 versus T2, P = 0.99). All controls tested positive at 4 months after vaccination, with a median value of 847 (509-1165; P < 0.001 versus T1 and P = 0.04 versus T2 in the study group). No serious adverse event was reported in both groups. Our data from 89 pre-LT patients suggest a high rate of immunization (94.4%) after a median time of 23 days from safe COVID-19 vaccine. None of the patients developed COVID-19.

Liver transplantation from active COVID-19 donors: A lifesaving opportunity worth grasping?

COVID-19 pandemic dramatically impacted transplantation landscape. Scientific societies recommend against the use of donors with active SARS-CoV-2 infection. Italian Transplant Authority recommended to test recipients/donors for SARS-CoV-2-RNA immediately before liver transplant (LT) and, starting from November 2020, grafts from deceased donors with active SARS-CoV-2 infection were allowed to be considered for urgent-need transplant candidates with active/resolved COVID-19. We present the results of the first 10 LTs with active COVID-19 donors within an Italian multicenter series. Only two recipients had a positive molecular test at LT and one of them remained positive up to 21 days post-LT. None of the other eight recipients was found to be SARS-CoV-2 positive during follow-up. IgG against SARS-CoV-2 at LT were positive in 80% (8/10) of recipients, and 71% (5/7) showed neutralizing antibodies, expression of protective immunity related to recent COVID-19. In addition, testing for SARS-CoV-2 RNA on donors' liver biopsy at transplantation was negative in 100% (9/9), suggesting a very low risk of transmission with LT. Immunosuppression regimen remained unchanged, according to standard protocol. Despite the small number of cases, these data suggest that transplanting livers from donors with active COVID-19 in informed candidates with SARS-CoV-2 immunity, might contribute to safely increase the donor pool.

COVID-19 in liver transplant candidates: pretransplant and post-transplant outcomes - an ELITA/ELTR multicentre cohort study.

OBJECTIVE: Explore the impact of COVID-19 on patients on the waiting list for liver transplantation (LT) and on their post-LT course. DESIGN: Data from consecutive adult LT candidates with COVID-19 were collected across Europe in a dedicated registry and were analysed. RESULTS: From 21 February to 20 November 2020, 136 adult cases with laboratory-confirmed SARS-CoV-2 infection from 33 centres in 11 European countries were collected, with 113 having COVID-19. Thirty-seven (37/113, 32.7%) patients died after a median of 18 (10-30) days, with respiratory failure being the major cause (33/37, 89.2%). The 60-day mortality risk did not significantly change between first (35.3%, 95% CI 23.9% to 50.0%) and second (26.0%, 95% CI 16.2% to 40.2%) waves. Multivariable Cox regression analysis showed Laboratory Model for End-stage Liver Disease (Lab-MELD) score of ≥15 (Model for End-stage Liver Disease (MELD) score 15-19, HR 5.46, 95% CI 1.81 to 16.50; MELD score≥20, HR 5.24, 95% CI 1.77 to 15.55) and dyspnoea on presentation (HR 3.89, 95% CI 2.02 to 7.51) being the two negative independent factors for mortality. Twenty-six patients underwent an LT after a median time of 78.5 (IQR 44-102) days, and 25 (96%) were alive after a median follow-up of 118 days (IQR 31-170). CONCLUSIONS: Increased mortality in LT candidates with COVID-19 (32.7%), reaching 45% in those with decompensated cirrhosis (DC) and Lab-MELD score of ≥15, was observed, with no significant difference between first and second waves of the pandemic. Respiratory failure was the major cause of death. The dismal prognosis of patients with DC supports the adoption of strict preventative measures and the urgent testing of vaccination efficacy in this population. Prior SARS-CoV-2 symptomatic infection did not affect early post-transplant survival (96%).

Carrying on with liver transplantation during the COVID-19 emergency: Report from piedmont region.

BACKGROUND: The COVID-19 pandemic is an emergency worldwide. In Italy, liver transplant activity was carried on, but despite all efforts, a 25% reduction of procured organs has already been observed during the first 4 weeks of the outbreak. AIMS: To analyze if our strategy and organization of LT pathway during the first two months of the COVID-19 emergency succeeded in keeping a high level of LT activity, comparing the number of LT in the first two months with the same period of time in 2019. METHODS: We compared the liver transplants performed in our Center between February 24th and April 17th, 2020 with liver transplants performed in the same period in 2019. RESULTS: In 2020, 21 patients underwent liver transplantation from deceased donors, exactly as the year before, without statistically significant difference. All patients survived in both groups, and the rate of early graft dysfunction was 24% in 2020 and 33% in 2019. In 2020 Median MELD was higher (17 vs 13). We were able to perform 3 multiorgan transplants and one acute liver failure. Nobody died on waiting list. The performance of our Center, despite the maxi-emergency situation, was steady and this was the result of a tremendous team working within the hospital and in our region. CONCLUSIONS: Team working allowed our Center to maintain its activity level, taking care of patients before and after liver transplantation. Sharing our experience, we hope to be helpful to other Centers that are facing the pandemic and, if another pandemic comes, to be more prepared to deal with it.

Outcome of COVID-19 in liver transplant recipients: A preliminary report from Northwestern Italy.

Covid-19 pandemic is deeply affecting transplant activity worldwide. It is unclear whether solid organ transplant recipients are at increased risk of developing severe complications and how they should be managed, also concerning immunosuppression. This is a report about the course and management of SARS-CoV-2 infection in liver transplant recipients from a single center in Northwestern Italy in the period March-April 2020. Three patients who were treated at our institution are reported in detail, whereas summary data are provided for those managed at peripheral Hospitals. Presentation varied from asymptomatic to rapidly progressive respiratory failure due to bilateral interstitial pneumonia. Accordingly, treatment and changes to immunosuppression were adapted to the severity of the disease. Overall mortality was 20%, whereas Covid-related mortality was 10%. Two cases of prolonged (>2 months) viral carriage were observed in two asymptomatic patients who contracted the infection in the early course after transplant. Besides depicting Covid-19 course and possible treatment scenarios in liver transplant patients, these cases are discussed in relation to the changes in our practice prompted by Covid-19 epidemic, with potential implications for other transplant programs.