Introduction: Acute immunological reactions after liver transplantation leading to graft loss or significant deterioration of liver function are extremely uncommon. Significant liver function deterioration related to antibody mediated reaction may occur  between hours and first 20 postoperative days and is often difficult to diagnose and treat. In many cases, it leads to graft loss. This study analyzes cases of early, severe AMR in pediatric liver transplant recipients.
Materials: This retrospective analysis includes all pediatric liver transplants performed at our center from 1997 to 2024. Among 964 transplantations, 12 children (1.24%) experienced early AMR. Patients were aged 1 to 12.1 years (median: 3.98 years). Nine received grafts from living-related donors, three ABO-incompatible transplants. Despite negative classical cross-matches, seven patients had positive cytometric cross-matches.
Clinical and biochemical signs of liver dysfunction emerged between 1 hour and 14 days post-transplantation (median: 8 days). Hyperacute rejection was identified in two explanted grafts. Two patients initially presented with suspected sepsis due to high fever, and one experienced graft rupture. All patients exhibited severe liver dysfunction (markedly elevated transaminases, coagulopathy, impaired blood flow in the portal vein and/or hepatic artery on Doppler ultrasound) and graft edema. Donor-specific antibodies (DSA) targeting HLA class II were detected in five patients.
Five patients required emergency surgical revision due to suspected vascular complications, though no thrombosis was confirmed. Liver biopsy was performed in 8 patients — at graft revision in 4, postmortem in 1, after unsuccessful steroid treatment in 1, and in 2 explanted grafts. Histopathology showed centrilobular or extensive hemorrhagic necrosis in 10 cases, T-cell mediated rejection in 4 cases, and C4d staining was positive in 2 patients at initial biopsy and 2 upon second biopsy.
Therapy included methylprednisolone in 9 patients, plasma exchange in 4, and high-dose intravenous immunoglobulin (IVIG) in 7. One patient received antilymphocyte globulin, and two received rituximab.
Results: Liver failure progressed in 8 patients, necessitating retransplantation. Two patients died on the waiting list, and six underwent retransplantation between 1.12 days and 6.2 months post initial transplantation, with three postoperative deaths. Currently, seven patients are alive with stable graft function, including three post-retransplantation.
Conclusion: Severe early immunological complications after liver transplantation are uncommon in the era of modern immunosuppression. However, when they occur, diagnosis is difficult and treatment may be delayed. Managing these patients remains highly challenging, with a substantial risk of graft loss and mortality. Even with successful intervention, long-term survival remains difficult to predict.