Successful non-directed living liver donor transplant for an infant with biliary atresia during the COVID-19 pandemic

Abstract

Amidst the coronavirus (COVID-19) pandemic, the American Society for Transplant Surgeons has recommended that only urgent liver transplant with deceased donors should occur. However, young pediatric candidates rely on living donors for lifesaving transplant. We present a case of non-directed left lateral lobe living liver donor transplant for a 7-month-old child with biliary atresia experiencing repeated life-threatening episodes of sepsis and cholangitis from infected bile lakes. Using careful preoperative planning among the entire multidisciplinary team, paying meticulous attention to infection control pre- and post-operatively, and taking advantage of robust telehealth technology both in and out of the hospital, a successful transplant was achieved. Amidst the COVID pandemic, non-directed liver transplantation can be safely achieved for pediatric recipients.

1 |. INTRODUCTION

BA is a progressive, fibro-obliterative disorder of the intra- and extrahepatic bile ducts evident that occurs worldwide in approximately 1 in 10 000 live births. A surgical Kasai (hepato-portoenterostomy) may temporarily restore bile flow. Most children with BA will, however, progress to end-stage liver disease over time, rendering BA the most common indication for pediatric liver transplantation. Currently, in the midst of the COVID-19 pandemic, the (ASTS) has recommended that only urgent liver transplants with deceased donors should be undertaken. Similarly, guidance from the American Society of Transplantation’s Infectious Disease Community of Practice states that “during periods of local transmission of (SARS-CoV)-2, temporary suspension of elective living donor transplantation may need to be considered to protect the potential donor as well as the recipient.”¹ We describe the precautions employed for a non-directed living liver donor (ND-LLD) transplant for an infant with BA complicated by severe recurrent infections during a period of community transmission of COVID-19.

2 |. CASE REPORT

A now 7-month-old infant was diagnosed with BA and underwent Kasai at 3.5 weeks of age. Although she demonstrated good bile flow, she developed cholangitis 3 weeks post-Kasai and concurrently was found to have intrahepatic periportal bile lakes on ultrasound. She was treated with 2 weeks of intravenous (IV) ceftriaxone, but was readmitted with recurrent cholangitis within 48 hours of discontinuing IV antibiotics. Enlargement of the previously noted bile lakes and new intrahepatic portal bile lakes were discovered on magnetic resonance cholangiopancreatography. In an effort to control infection of these lakes and subsequent bacteremia, at 3 months of age an exploratory laparotomy with decompression of a 2.8-centimeter bile cyst into the Roux limb was performed; cyst contents grew Enterococcus faecalis. Despite this procedure and continued IV antibiotics, she had numerous episodes of cholangitis, including two episodes associated with Escherichia coli bacteremia. Given her recurrent infections and persistent bile lakes, she was listed for liver transplantation in January 2020. No appropriate deceased grafts were available. A non-directed, blood group compatible, anonymous live liver donor was identified and approved to donate a left lateral segment by our partners from the University of Colorado adult living donor liver transplant team. The organ was allocated to this patient, and the live donor liver transplant was scheduled for the first week in April.

The first appearance of COVID-19 was documented in Colorado on March 13, 2020, approximately 2 weeks before the scheduled ND-LLD transplant.² The multidisciplinary transplant teams at both the donor and the recipient hospitals met repeatedly during this time to discuss whether to proceed with transplant. Given the infant’s history of repeated episodes of sepsis and persistently infected bile lakes, the transplant was deemed to be lifesaving. Telephone conversations with the recipient’s caregivers and the donor emphasized the additional unknown risks of donation and liver transplant coincident with known community spread of COVID-19 in Colorado. Both the recipient’s family and the donor understood these risks and agreed to proceed with transplant. The recipient family and the donor were asked to self-isolate at home for 14 days prior to transplant.

As per standard protocol, the infant was admitted the day before transplant for preoperative preparation. At the time of admission, there were 4 COVID-19 cases admitted at (CHCO). While typically admitted to the surgical floor pretransplant, we electively admitted this patient to the (PICU), where there were no cases of COVID-19. The PICU agreed to place the recipient on a care team that would not be caring for, and was geographically separated from, patients under investigation for or with documented COVID-19. We instituted “special respiratory isolation” precautions, with (PPE) consisting of gown, gloves, N95 mask, and face shield worn by medical providers entering the patient’s room. Entry into the patient’s room was limited to a bedside nurse, PICU attending physician and surgical physician; all other assessments were performed outside the room using iPad-enabled telehealth. The infant underwent nasopharyngeal PCR testing for SARS-CoV-2, the causative agent of COVID-19, using the (CDC) (2019-nCoV) (RT)-PCR Diagnostic Panel 18 hours prior to transplant. Her caregivers also underwent testing after an agreement between the transplant team and CHCO Incident Command that if the recipient or a family caregiver tested positive, the non-related live donor transplant would be canceled due to the potential increased risk posed by concurrent SARS-CoV-2 infection or exposure.

The donor was admitted to a COVID-19 free surgical ward at University of Colorado Hospital the morning of anticipated live donor surgery, and similar special respiratory isolation precautions were instituted. At the time, there were 102 cases of COVID-19 at the adult hospital (53 in the ICU). The donor had undergone preoperative testing 7 days prior to scheduled surgery but SARS-CoV-2 PCR testing was performed the morning of surgery, understanding that if positive, the surgery would be canceled. On April 2, 2020, after the donor’s SARS-CoV-2 testing was confirmed to be negative the donor underwent a separate consent confirming that although his SARS-CoV-2 testing was negative and he was asymptomatic, there was up to a 25% chance that the result could be a false negative and he could in fact be infected with SARS-CoV-2. It was also explained that he could contract SARS-CoV-2 as an inpatient despite best efforts to isolate him from any such risk. He consented to move ahead with the donor operation and was taken to the operating room for an elective living donor left lateral segmentectomy and cholecystectomy through an upper midline incision. The operation was uncomplicated, and the final graft weight was 162 g with a replaced left hepatic artery, normal portal and hepatic venous anatomy, and a single bile duct. He was placed on a COVID-19 free surgical unit post-operatively and had an uneventful hospital course.

After SARS-CoV-2 testing on the patient and family caregivers returned negative, and the donor surgery was underway, the recipient surgery proceeded. Two attending surgeons performed the liver transplant using standard operative PPE, with anesthesia and operating room staff kept to a minimum and no students/observers permitted. The recipient surgery was performed in our standard fashion for a segment 2/3 graft. Outflow was established with a piggyback left hepatic vein to vena cava anastomosis, end-to-end single portal vein anastomosis. A 7-0 interrupted arterial reconstruction of the replaced donor segment 2/3 artery to the recipient right-left branch patch was performed, and the bile duct was reconstructed to the previously created Roux. The recipient’s prior two surgeries necessitated significant lysis of adhesions, but the surgery was otherwise uneventful. She required minimal blood transfusion, and the liver functioned immediately. She received our standard intra-operative immunosuppression (10 mg/kg IV methylprednisolone); we do not induce with T-cell depletion therapy. Post-operatively, the recipient was extubated in the operating room and transferred to the PICU.

Post-operatively, limited staff consisting of a PICU physician, transplant hepatologist, transplant surgeon, and bedside nurse were permitted to enter the recipient’s room. These individuals rounded in-person each day, with the rest of the multidisciplinary team (transplant coordinator, pharmacist, nutritionist, psychologist, social worker, and medical trainees) participating via Zoom. Similarly, a core group of bedside nurses cared for the recipient to minimize potential exposures and conserve PPE. The recipient received our standard immunosuppression post-operatively (methylprednisolone, 1 mg/kg/day; tacrolimus, 0.1 mg/kg/dose twice a day; and mycophenolate, 300 mg/m²). On post-operative day 3, she was transferred to the surgical floor where we continued to limit the staff entering her room, only with PPE. The majority of post-transplant education for the recipient’s family (by social work, pharmacy, nutrition, and transplant coordinators) occurred by iPad-enabled telehealth from outside the patient’s room rather than in-person. In keeping with our standard practice for liver transplant, the infant’s caregivers successfully completed a 24-hour transitional care period prior to discharge, including administration of all medications and central line care, to assure comfort and competency in these areas. Medications for home use after discharge were preprepared to assure that only one visit to the pharmacy was necessary. The recipient was discharged home 10 days post-operatively with excellent graft function. Her outpatient care has occurred using a combination of multidisciplinary telehealth visits, including daily pictures of her abdominal wound submitted to the care team via the electronic medical record, and limited in-person clinical visits. She is now 3 months post-transplant without complication and has no evidence of COVID-19.

3 |. DISCUSSION

The COVID-19 pandemic, with 1 844 863 cases and 117 021 deaths reported worldwide as of April 14, 2020, has critically altered our concept of standard surgical care, with the mandated cancelation of all elective procedures and surgeries in many jurisdictions.³ As of the same date, 361 children are on the United Network for Organ Sharing list awaiting a deceased donor liver transplant, most with life-threatening medical conditions.⁴ As such, liver transplantation cannot be viewed as an elective surgery. Live donor liver transplantation for infants is a necessary option as suitable deceased donors are often unavailable. In 2017, 72 children received living donor liver transplants, representing 12% of all pediatric liver transplants performed in the United States.⁵ Living donor liver transplants have the potential to decrease wait-list morbidity and mortality and improve survival rates for children with end-stage liver diseases.⁶ Amidst the current pandemic, lifesaving transplants must continue for children who are too sick to wait, and we suggest this includes consideration of both directed and non-directed live donation. This case illustrates that with careful recipient evaluation of urgency, effective preoperative planning among the entire multidisciplinary team, and careful attention to infection control preoperatively and post-operatively, supplemented by use of robust telehealth technology both in and out of the hospital, a successful outcome with ND-LLD transplant can be achieved.

The potential for ongoing live donor liver transplantation in the midst of the COVID-19 pandemic requires careful needs assessment, planning, and risk mitigation strategies tailored to conditions at individual transplant centers. Unique patient risk factors and local/regional disease prevalence and resource availability are critical factors in the decision of whether to proceed with transplant.⁷ The question of medical urgency for an individual child should acknowledge the risk of the underlying illness. In this case, a history of repeated cholangitis and bacteremia with infected bile lakes predicted repeated hospitalizations (with potential for increased exposure to SARS-CoV-2) and significantly increased risk of death over the next 3 months.⁸ Waiting for a deceased donor organ could have resulted in deterioration of the infant’s overall condition, jeopardizing the chances of a favorable outcome with transplantation. The added risk to the donor of hospital-acquired SARS-CoV-2 at the time of donation and the increased morbidity if infected while recovering from surgery must also be carefully considered and discussed with the potential donor. This assessment should consider the prevalence of COVID-19 in the community and the number of COVID-19 cases and available capacity in the donor and recipient hospitals. In this case, Colorado had relatively low community transmission at the time of the planned transplant, providing a window of opportunity in which it was believed safe to proceed with transplant. Furthermore, a careful assessment was conducted by both the donor and the recipient hospitals regarding adequate and timely viral testing capability and availability for pre-, intra-, and post-operative care including ICU and hospital beds, medications, ventilators, blood supply, PPE, and transplant-specific staff.

We believe this careful approach allowed us to mitigate but not eliminate the risk of COVID-19 for both the donor and recipient. As such, both donor and recipient underwent an expanded informed consent, including acknowledging that the true risks of COVID-19 were unknown. These include the possibility that SARS-CoV-2 testing might not detect virus present in the recipient, her caregivers, or donor and risk of spread from asymptomatically or presymptomatically infected hospital staff, all in the context of potentially increased severity of resulting COVID-19 secondary to surgery (donor and recipient) and immunosuppression (recipient). Currently, the degree to which immunosuppressed patients may be at increased risk of poor outcomes of COVID-19 is unclear. Emerging data from Italy suggest that both pediatric and adult liver transplant recipients may not be at increased risk of pulmonary disease from COVID-19 compared to the general population.^9,10

The COVID pandemic is predicted to last for months, possibly until widespread vaccination is a reality. The majority of pediatric patients on the liver transplant wait-list are unlikely to remain stable for the duration of this pandemic. As a transplant community, it is imperative that within the constraints of medical and surgical capacity, we develop methods to facilitate liver transplantation as safely as possible. We suggest this includes consideration of live donation when appropriate resources for pre-, peri-, and post-operative management are felt to provide a favorable risk-benefit balance.

Abbreviations:

2019-nCoV

2019 novel coronavirus

ASTS

American Society for Transplant Surgeons

BA

biliary atresia

CDC

centers for disease control and prevention

CHCO

Children’s Hospital Colorado

COVID

coronavirus disease

IV

intravenous

ND-LLD

non-directed living liver donor

PICU

pediatric intensive care unit

PPE

personal protective equipment

RT

real-time reverse transcriptase

SARS-CoV

severe acute respiratory syndrome-associated coronavirus