Liver transplantation in children: Case

This case traces the arc of a paediatric liver transplant from listing through immunosuppression to the late complication that defines the Epstein-Barr-virus-seronegative recipient. The girl's pretransplant course, her graft type, and her serostatus together explain why she developed post-transplant lymphoproliferative disorder, and the case turns on recognising it early on surveillance and managing it by the disciplined reduction of immunosuppression. [11]

Pretransplant course and listing

This girl had biliary atresia, the single most common indication for paediatric liver transplantation, accounting for up to half of all cases. Despite a Kasai portoenterostomy in infancy, she developed growth failure, intractable pruritus, and recurrent cholangitis, the accepted indications for transplantation in a child with a failing Kasai. She was listed for deceased-donor transplantation and prioritised by the Paediatric End-stage Liver Disease score, calculated from her bilirubin, international normalised ratio, albumin, growth failure, and age at listing, with growth failure weighted because malnutrition reflects disease severity in children. [3]

Because the smallest infants have the highest waiting-list mortality as size-matched deceased donors are scarce, her father was evaluated as a living donor. He donated a left lateral segment graft, the graft type that fits an infant and shortens waiting time. The donor evaluation was conducted to the same safety standards as a deceased-donor pathway, and the donor hepatectomy carried a small but real morbidity that was disclosed to the family. [1]

Perioperative and early postoperative course

Her graft reperfused well, with bile production within hours and vascular patency confirmed on intraoperative and early Doppler ultrasound, excluding the hepatic artery thrombosis that is the most feared early vascular complication. Her intensive care priorities were haemodynamic stability, the avoidance of hepatic artery spasm with adequate perfusion and antiplatelet aspirin, infection surveillance, and renal protection against calcineurin-inhibitor nephrotoxicity. [1]

She was started on a tacrolimus-based maintenance regimen with a steroid taper, with the tacrolimus dose individualised by whole-blood trough monitoring, targeting around 8 to 12 nanograms per millilitre in the early months. The mechanism by which tacrolimus prevents rejection is the inhibition of calcineurin, which blocks nuclear factor of activated T-cell activation and interleukin-2 transcription, holding the CD8-mediated rejection cascade in check. Because she was Epstein-Barr-virus-seronegative and received a seropositive graft, she entered an active Epstein-Barr viral load surveillance programme, the highest-risk combination for post-transplant lymphoproliferative disorder. [6]

The late complication: post-transplant lymphoproliferative disorder

Eight months after transplant, her routine Epstein-Barr viral load surveillance polymerase chain reaction rose sharply, and she presented with fever and cervical lymphadenopathy. This is the classic presentation of post-transplant lymphoproliferative disorder, the Epstein-Barr-virus-driven B-cell proliferation that emerges under immunosuppression and is concentrated in seronegative recipients of seropositive grafts. The disorder ranges from a reactive polyclonal proliferation to a frank monoclonal lymphoma, and the diagnosis is confirmed by biopsy of an affected node or mass. [11]

The first step in management is reduction of immunosuppression to restore recipient T-cell immune surveillance against the Epstein-Barr-virus-infected B-cells, which alone controls many early cases. The tacrolimus trough was weaned with close monitoring of graft function, because the risk of reducing immunosuppression is acute cellular rejection. When her viral load and lymphadenopathy persisted despite immunosuppression reduction, she was treated with the anti-CD20 monoclonal antibody rituximab, the standard second-line agent, with chemotherapy reserved for aggressive monoclonal lymphoma. Her Epstein-Barr viral load fell and the lymphadenopathy resolved. [11]

Long-term outlook and disposition

This girl now enters the long arc of post-transplant follow-up, in which graft and patient survival are excellent but increasingly limited by the cumulative consequences of immunosuppression. The 30-year European study reports patient survival of around 90 percent at one year and roughly 80 percent at ten years, with graft survival somewhat lower. Her long-term care integrates ongoing Epstein-Barr and cytomegalovirus surveillance, cotrimoxazole prophylaxis against Pneumocystis, growth and nutrition monitoring, inactivated vaccination, adherence support, and a structured transition to adult transplant services as she approaches adolescence, because adolescent non-adherence is a leading preventable cause of late graft loss. [12]

The case carries a clear teaching point for the family and the trainee: the serostatus mismatch at transplant set the stage for this complication, and the active surveillance programme detected it before it became life-threatening. The disciplined reduction of immunosuppression, balanced against the risk of rejection, is the single most important therapeutic principle in post-transplant lymphoproliferative disorder, and it succeeded here. [11]