Long term management of liver transplant rejection in children

The current management of hepatic allograft rejection after liver transplan tation in children requires effective baseline immunosuppression to prevent rejection and rapid diagnosis and treatment to manage acute rejection epis odes. The subsequent impact on chronic rejection is dependent on the combin ation of adequate prevention and the treatment of acute rejection. Tacrolimus is a macrolide lactone that inhibits the signal transduction of interleukin-2 (IL-2) via calcineurin inhibition. Introduced in 1989, tacrol imus was first used in the salvage of refractory acute or chronic rejection under cyclosporin or to rescue patients with significant cyclosporin-relat ed complications. The majority of paediatric transplant centres use a combi nation of steroids with tacrolimus as a basic immunosuppressant regimen fol lowing paediatric liver transplantation. This combination has allowed the a cute cellular rejection-free rare to increase to between 30 and 60%, while lowering the rate of refractory rejection to less than 5%. Corticosteroid-r esistant rejection is commonly treated with monoclonal (muromonab CD3) or p olyclonal preparations. Although most episodes of acute cellular rejection occur during the first 6 weeks after liver transplant, the appearance of la te acute liver allograft rejection must raise the question of noncompliance , especially in the adolescent population. Chronic rejection is becoming in creasingly rare under tacrolimus-based immunosuppression. Tacrolimus is eff ective in reversing refractory acute cellular rejection or early chronic re jection in patients initially treated with cyclosporin-based regimens. Pati ents with a history of noncompliance as well as children with auto-immune l iver disease are at risk of chronic rejection. Retransplantation therapy fo r chronic rejection has, fortunately, become more rare in the tacrolimus er a with only 3% of retransplants being performed for this indication. Newer immunosuppressive agents are further modifying the long term manageme nt of liver allograft rejection. These include mycophenolate mofetil, rapam ycin and IL-2 antibodies such as daclizumab. The development of these agent s is allowing patient-specific immunosuppressive management to minimise rej ection as well as the complications related to immunosuppression.