key: cord-0779406-hzkcq6i3
authors: Kulkarni, Anand V.; Parthasarathy, Kumarswamy; Kumar, Pramod; Sharma, Mithun; Reddy, Raghuram; Chaitanya Akkaraju Venkata, Krishna; Gupta, Rajesh; Gupta, Anand; Swaroop, Shakti; Giri Vishwanathan, Premkumar; Senapathy, Gayathri; Menon, Palat B.; Reddy, Nageshwar D.; Padaki, Nagaraja R.
title: Early liver transplantation after COVID‐19 infection: The first report
date: 2021-02-15
journal: Am J Transplant
DOI: 10.1111/ajt.16509
sha: 12616ab921e2157dda93ae14a24d5144ef53b290
doc_id: 779406
cord_uid: hzkcq6i3

COVID‐19 (coronavirus disease 2019) has impacted solid organ transplantation (SOT) in many ways. Transplant centers have initiated SOT despite the COVID‐19 pandemic. Although it is suggested to wait for 4 weeks after COVID‐19 infection, there are no data to support or refute the timing of liver transplant after COVID‐19 infection. Here we describe the course and outcomes of COVID‐19‐infected candidates and healthy living liver donors who underwent transplantation. A total of 38 candidates and 33 potential living donors were evaluated from May 20, 2020 until October 30, 2020. Ten candidates and five donors were reverse transcriptase‐polymerase chain reaction (RT‐PCR) positive for severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) pretransplant. Four candidates succumbed preoperatively. Given the worsening of liver disease, four candidates underwent liver transplant after 2 weeks due to the worsening of liver disease and the other two candidates after 4 weeks. Only one recipient died due to sepsis posttransplant. Three donors underwent successful liver donation surgery after 4 weeks of COVID‐19 infection without any postoperative complications, and the other two were delisted (as the candidates expired). This report is the first to demonstrate the feasibility of elective liver transplant early after COVID‐19 infection.

complications, and the other two were delisted (as the candidates expired). This report is the first to demonstrate the feasibility of elective liver transplant early after COVID-19 infection.

clinical research/practice, infection and infectious agents, liver transplantation/hepatology, liver transplantation: living donor acuity of heart-and lung-waitlisted patients and lesser opportunities for organ availability. 1 The American Society of Transplantation (AST) recommends at least 28 days of symptom resolution prior to procuring an organ from a COVID-19-positive donor. However, they do not comment on the duration in the recipient. 2 Further, the AST guidance recommends at least one negative nucleic acid test (NAT) from the respiratory tract within 3 days prior to transplant. 3 Although it is suggested to perform living donor liver transplantation (LDLT) in patients with a high Model for End-Stage Liver Disease score (MELD > 25) or patients with fulminant liver failure, the timing of surgery after COVID-19 infection in a recipient is not known. 4 There are few reports of deceased donor liver transplants 2-70 days after COVID-19 infection. [5] [6] [7] [8] However, there is a paucity of data on managing COVID-19 patients who are awaiting LDLT and the timing of liver transplantation and organ procurement from a living donor.

Here we describe the course and outcomes of COVID-19 candidates and healthy living liver donors who underwent LDLT at our center.

We performed a retrospective analysis of candidates and donors who underwent LDLT from May 20, 2020 until October 30, 2020.

If the candidate or donor had symptoms suggestive of COVID-19 (fever, dyspnea, cough, or any gastrointestinal symptoms of recent onset) anytime while on the waitlist, they were directed to undergo computed tomography (CT) of the chest, SARS-CoV-2 RT-PCR (reverse transcriptase-polymerase chain reaction), and antibody testing. Each donor and candidate would undergo two RT-PCR tests 24 h apart, with CT screening of chest and antibody testing before elective surgery (even in the absence of symptoms). Patients and donors were scheduled for surgery if both the RT-PCR results were negative, CT was normal, and antibodies were negative, or only IgG was positive. If the candidate was RT-PCR positive and/or IgM antibody positive, the surgery was postponed for 14 days. If the donor was positive or both the candidate and donor were positive, and the candidate was stable, the surgery was postponed for 4 weeks. In case the candidate was worsening (rise in MELD score), we would assess for the feasibility of surgery after 2 weeks with RT-PCR testing, symptom assessment, CT chest, and antibody testing ( Figure 1 ).

For RT-PCR, two separate nylon flocked swabs were taken from the nasopharynx and oropharynx into viral transport medium vial. 

A total of 38 candidates and 33 potential living donors were evaluated during the study period. Of them, 10 candidates (Cases #1-10) and five donors were RT-PCR positive for SARS-CoV-2 pretransplant ( Figure 2 ). Of the 10 candidates, four patients were symptomatic for COVID-19, and the rest were diagnosed incidentally prior to surgery (Table 1) Table 2 . 

The mother (donor) of candidate #1 presented with complaints of sore throat and cough for 4 days (8 days prior to surgery). Her RT-PCR was positive. She was isolated and managed conservatively. After 12 days, the candidate (#1) presented with dyspnea on exertion and tense ascites, which was initially thought to be due to COVID-19. His SpO 2 was 97%, and his CT chest was suggestive of no active disease (CO-RADS-1). He had worsening of ascites, rise in bilirubin, and was also found to be RT-PCR positive. Ascitic tapping relieved his dyspnea. He Candidate #5 presented with complaints of cough and fever for 2 days prior to surgery and was found to be RT-PCR positive. His donor (elder sister) was simultaneously detected RT-PCR positive, although she was asymptomatic. The candidate recovered with symptomatic management. As the candidate was stable, we waited for 4 weeks before surgery. Candidate #6 and his donor (wife) were incidentally detected to be COVID-19 positive prior to surgery. Since the candidate was stable, we waited for 4 weeks. The course of four candidates (#6-10) who succumbed pretransplant is shown in Figure 3 .

Intraoperatively, all the six recipients received 10 mg/kg of methylprednisolone, and postoperatively, from day 1, we initiated 1 mg/kg of methylprednisolone and gradually tapered over 8 days to 30 mg oral prednisolone. Tacrolimus was initiated on day 1 after surgery to achieve a trough level of 8-10 ng/ml. Mycophenolate mofetil (MMF) was introduced on day 2 after surgery for all the six recipients at a dose of 0.5 g/day in two divided doses and escalated up to 2 g/day in two divided doses. Recipient #1 did not tolerate the higher dose of MMF (developed cytopenia on 2 g/day) and is on 1 g/day of MMF.

Recipient #2 developed fever and biliary leak. SARS-CoV-2 RT-PCR was negative, and CT chest was normal. He succumbed to sepsis and graft dysfunction at day 24 posttransplant. Recipient #3 developed reactivation of herpes labialis on day 12, for which prednisolone dose was reduced to 10 mg/day, and aciclovir therapy was initiated.

Recipient #4 developed tacrolimus toxicity and is being managed with steroids and MMF. Recipient #5 developed acute cellular rejection on day 42 and was pulsed with steroids after sepsis screening was negative. Postsurgery graft function stabilized in all patients except in candidates #1 and #4, who had a very gradual decline in bilirubin levels ( Figure 4 ).

In this case series, we report the feasibility of early liver transplant infection. 10 Further, it is difficult to postpone the surgery for 4 weeks in LDLT due to organ availability and the ethical concern of transplanting those who might succumb if not transplanted soon enough.

COVID-19 can induce the worsening of liver disease even in the absence of respiratory symptoms. 11 We performed LDLT after 2 weeks for four candidates due to deterioration of liver disease and a rise in week of illness and then gradually declines over the second week. 12, 13 Furthermore, both IgG and IgM antibodies start to increase around day 10 after symptom onset. 12 Liver injury is well known in COVID-19 and is multifactorial. 14, 15 There are some concerns regarding the transmission of the virus from COVID-19-positive donor to the recipient. [16] [17] [18] There is, however, no evidence currently to support the productive infection of the liver with SARS-CoV-2, and liver injury is probably a bystander phenomenon. Hence, the risk of SARS-CoV-2 transmission from asymptomatic or minimally symptomatic donors is likely very low. 19, 20 Although we regularly screened the candidates and donors for However, this report is the first to demonstrate the feasibility and safety of liver transplant early after COVID-19 infection.

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. 

Data available on request due to privacy/ethical restrictions.

Anand V. Kulkarni https://orcid.org/0000-0002-1240-1675

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