Pediatric patients receiving liver transplants for disorders such as Alagille syndrome (ALGS) had increased risks of developing post-transplant lymphoproliferative disorder (PTLD) if they became seropositive for the Epstein-Barr virus (EBV) after their transplant, according to a new study published in Pediatric Transplantation.

The development of primary EBV infection in pediatric patients following liver transplant increased the chances of developing PTLD by 17.1 times compared to patients who were seropositive prior to their surgery, the authors said. The risk was even higher in patients who developed an infection after liver transplants and had EBV viral loads (EBV-VL) above 211,000 IU/mL compared to those with lower loads (odds ratio, 29.8; 3.7–241.1; P <.001).

“Since there is such a significant increase in risk in seronegative patients with high viral load, it seems important to improve efforts to properly catalog the pretransplant serological status of our patients and monitor the post-transplant [EBV],” the authors said. “These higher risk patients may need to follow a specially minimized immunosuppressive regimen in an attempt to decrease the risk of developing a PTLD.”

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The tacrolimus immunosuppressive dose was decreased in 48 out of 50 patients who had EBV >250,000 IU/mL in an effort to increase immune response and reduce the risk of PTLD. The other 2 patients had EBV decreases without the need for immunosuppressant modification.

Of the 48 patients, 14 developed PTLD despite a decrease in viral loads. One patient experienced 2 PTLD episodes 2 years apart. Of the 15 PTLD episodes, 2 were plasmacytic hyperplasia PTLD, 10 were polymorphic PTLD, 2 were monomorphic PTLD, and 1 case was classical Hodgkin lymphoma. Cessation of tacrolimus resulted in PTLD resolution in 8 of the patients.

How Epstein-Barr Virus Changes the Course of ALGS Treatment

For the remaining PTLD episodes, treatment with rituximab was initiated. For the classical Hodgkin lymphoma patient, treatment with rituximab and chemotherapy was given in conjunction with immunosuppressive cessation.


Quintero Bernabeu J, Juamperez J, Mercadal-Hally M, et al. Epstein-Barr virus-associated risk factors for post-transplant lymphoproliferative disease in pediatric liver transplant recipients. Pediatr Transplant. Published online April 24, 2022. doi:10.1111/petr.14292