Late cellular rejection in paediatric liver transplantation: Aetiology and outcome

Background. Acute cellular rejection, though mostly encountered during the first 3 months after liver transplant, may occur later on. Clinical features and outcome of children experiencing late cellular rejection (LCR) have not been described to date. Patients and Methods. A total of 20 children who developed acute rejection 6 months or more after liver transplant were studied for history of early rejection, levels of immunosuppression, causes of low immunosuppression, viral infections, signs of autoimmunity, and HLA mismatch. All liver biopsies were reviewed. Fifteen patients with no history of LCR were randomly selected as controls. Results. Of 20 children 5 were appropriately immunosuppressed, although 15 were not. Causes of low immunosuppression were: unknown (seven), poor compliance (three), posttransplant lymphoproliferative disease, (two), hepatocellular carcinoma recurrence (one), tuberculosis (one), gastroenteritis (one). Of 20 patients early rejection occurred in 13 and cytomegalovirus infection in 5. At last follow-up 10 children have persistent graft dysfunction, of whom 5 have progressed to de novo autoimmune hepatitis, 2 to chronic rejection, one has persistent graft dysfunction with recurrent cytomegalovirus activation, one has hepatic artery thrombosis and one is likely to have persistent poor compliance. None of the 15 controls developed de novo autoimmune hepatitis or any other form of persistent graft dysfunction at the time of last follow-up. Conclusion. Late cellular rejection in children is usually due to low or decreased immunosuppression and is associated with long-term complications. Prompt intervention to correct inadequate immunosuppression and careful follow-up of the other patients to identify other treatable conditions is essential.