key: cord-0723989-ppa42c9j
authors: Whitsett, Maureen; Ortiz, Vivian; Weinberg, Ethan M.
title: CON: Liver Transplantation in the Times of COVID‐19: Patients with COVID‐19 Infection Should not Undergo Liver Transplantation
date: 2021-11-20
journal: Clin Liver Dis (Hoboken)
DOI: 10.1002/cld.1136
sha: 4d0f4c0754f4e19035d6bf6e99551df7fc36146d
doc_id: 723989
cord_uid: ppa42c9j

nan

review SARS-CoV-2 shortly after undergoing LT. Transplanting an actively infected patient may potentially incur a high risk for postoperative and COVID-19-related complications, graft loss, and death; it also may endanger the health and safety of providers and demands utilization of significant resources in an already resource-strained health system.

The tremendous physiological stress of surgery coupled with active COVID-19 could result in significant postoperative morbidity and mortality in an LT recipient. A large international surgery registry (n = 1128) evaluating the surgical outcomes of SARS-CoV-2-infected patients who require emergent or elective nontransplant surgeries demonstrated a 21% 30-day mortality, with nearly 50% of patients experiencing pulmonary complications. 1 The stress of this surgery can lead to cytokine storm and clinical decline, resulting in possible superimposed infections and graft loss. 2 Ongoing COVID-19 in the early postoperative period could potentially compromise graft and patient health through the development of arterial or venous thromboses, myocarditis or myocardial infarction, renal failure, or respiratory failure. 3-5 SARS-CoV-2 infection can lead to acute hepatitis with aminotransferase elevation to one to three times the upper limit of normal, and acute liver failure with concomitant COVID-19 may be indistinguishable from COVID-induced liver injury. Thus, distinguishing acute rejection from viral-induced hepatitis would be challenging. 5 Pediatric LT recipients with active uncontrolled respiratory viral infection inadvertently contracted at or near the time of LT had higher all-cause graft failure and increased length of stay. 6 Although emerging therapies can potentially mitigate the severity of organ damage incurred from SARS-CoV-2 infection, there is no efficacious antiviral therapy to control and/or eradicate the virus. Active SARS-CoV-2 infection could and should be considered a potential contraindication for LT. 5

There is a dearth of literature that supports transplanting actively infected patients. Outcomes of COVID-19 in LT recipients are poorly defined in patients transplanted within 1 year. 7 It is difficult to extrapolate this information to patients who acquired COVID-19 in the perioperative period or shortly after LT when immunosuppression is typically most intense. Scarce case reports describe the postoperative courses of patients who developed COVID-19 after transplant (Table 1) . [8] [9] [10] In cases of transplantation soon after COVID-19 recovery, the viral polymerase chain reaction (PCR) was negative on more than one test for all patients prior to transplant. [11] [12] [13] [14] Only one case exists of transplantation with a positive PCR. However, in this lung transplant recipient's preoperative swabs, the cycle threshold-the number of amplification cycles needed to detect genetic material of the virus-was persistently high, and virus was not cultured. 15 Lower cycle threshold, indicative of a higher viral load and high levels of viable virus, correlates with risk for progression to severe disease with increased mortality, as well as increased infectivity. 16 saFeTY THreaT TO HealTH Care wOrKers Transmissibility of the virus is an important consideration, because an actively infected patient poses a threat to the health and safety of those involved in patient care. 

Immunosuppressed patients can develop prolonged viral shedding, with a report of a kidney transplant recipient with 6 weeks of nasopharyngeal shedding and even infection recurrence with prolonged shedding after an LT. 13, 17 Establishing an efficient and reliable screening system for donor and recipient is of utmost importance to ensure that neither patient has active, viable virus. In challenging cases with positive PCR or equivocal results, infectious disease experts should be involved in the decision-making process.

Minimization of SARS-CoV-2 hospital transmission rates can be achieved with adequate personal protective equipment (PPE), adequate handwashing, and a health care system that can supply the necessary resources for complex post-LT care. Transplant patients have a greater expected need for high-volume transfusions and longer length of intensive care unit (ICU) stay. 18 Actively infected LT recipients face the challenge of recovery from both LT and COVID-19, potentially increasing the need for additional health care resources. An overwhelmed hospital system at the peak of a pandemic may restrict services, such as imaging and endoscopy, and may not have sufficient ICU space, PPE, blood products, and intravenous medications to adequately care for such a patient. 19 eTHiCal COnsiDeraTiOns

The dilemma of whether to transplant an actively infected patient requires significant ethical considerations for fair allocation of perhaps the scarcest resource of all-the grafted liver. The principle of utility dictates that to achieve maximum transplant benefit, allocation must result in the greatest collective good for both the patient and society. The allocation must be beneficent by optimizing survival and health of patient and graft, and it must also be nonmaleficent by ensuring the transplant does not lead to increased mortality or significant surgical complications, as can occur with severe COVID-19. With the uncertainty regarding outcomes of LT in SARS-CoV-2-infected recipients and the potential for significant illness, graft and patient survival cannot be guaranteed. The principle of justice dictates that scarce health care resources could potentially be used in the care of other patients, and the liver could be transplanted in a more suitable candidate with a higher probability of maximizing the benefit. 20 Although knowledge regarding the virus and impact on LT recipients is rapidly evolving, there is scant evidence to support the safe and successful transplantation of patients with active COVID-19. Despite increasing availability of PPE and medical supplies, the pandemic continues to significantly strain hospital systems throughout the country. The health and safety of hospital personnel must not be jeopardized through constant exposure to a highly infective LT recipient. The ethical principles of justice and utility should guide decision making regarding the just use of resources and the appropriate allocation of organs to those who would derive the maximum benefit. Thus, at this time we cannot recommend LT for patients infected with COVID-19.

Division of Gastroenterology and Hepatology

Factors associated with surgical mortality and complications among patients with and without coronavirus disease 2019 (COVID-19) in Italy

Rates of co-infection between SARS-CoV-2 and other respiratory pathogens

Incidence of venous thromboembolism in hospitalized patients with COVID-19

Cardiology and COVID-19

Clinical best practice advice for hepatology and liver transplant providers during the COVID-19 pandemic: AASLD Expert Panel Consensus Statement

Viral upper respiratory infection at pediatric liver transplantation is associated with hepatic artery thrombosis

Outcomes following SARS-CoV-2 infection in liver transplant recipients: an international registry study

Clinical characteristics and immunosuppressant management of coronavirus disease 2019 in solid organ transplant recipients

Remdesevir plus convalescent plasma for the treatment of COVID-19 in a patient with a recent liver transplant

Liver transplant recipients infected with SARS-CoV-2 in the early postoperative period: lessons from a single center in the epicenter of the pandemic

Liver transplant in a recently COVID-19 positive child with hepatoblastoma

Urgent liver transplantation soon after recovery from COVID-19 in a patient with decompensated liver cirrhosis

Liver transplantation in a patient after COVID-19 -Rapid loss of antibodies and prolonged viral RNA shedding

Successful liver transplantation in a patient recovered from COVID-19

Lung transplantation for COVID-19-associated acute respiratory distress syndrome in a PCR-positive patient

A narrative systematic review of the clinical utility of cycle threshold values in the context of COVID-19

Persistent viral shedding despite seroconversion in a kidney transplant recipient with severe extrapulmonary COVID-19

Risk assessment in high-and low-MELD liver transplantation

COVID-19: a global transplant perspective on successfully navigating a pandemic

Ethical Principles in the Allocation of Human Organs