Immunosuppression in Pediatric Liver Transplantation
The optimal immunosuppression for liver transplantation recipients remains a topic of debate. Excellent results have been reported from a great number of centers utilizing various treatment regimens. The choice of 1 strategy over another is largely physician dependent. With good results obtainable using almost all drug combinations, it becomes important to minimize the toxic side effects related to chronic immunosuppressive drug use. This is even more important in the pediatric population, where undesirable side effects may lead to noncompliance in a population that requires relatively long graft survival.
CsA Microemulsion vs Tacrolimus (TAC) Therapy in Pediatric Liver Transplant Recipients
A multicenter, European trial compared the use of CsA microemulsion (Neoral) to TAC triple therapy in pediatric liver transplantation. No differences in patient or graft survival between the groups were demonstrated. Acute rejection was documented in 45% of patients treated with TAC, compared with 60% of patients treated with Neoral. Furthermore, the incidence of corticosteroid-resistant rejection was lower in the TAC group. Use of Neoral was associated with a higher incidence of hirsutism and gingival hyperplasia, side effects that have been associated with patient noncompliance.
Daclizumab Induction Therapy In Pediatric Liver Transplant Recipients
Induction therapy with daclizumab, a nondepleting antibody, plus delayed institution of TAC therapy (at day 7) was evaluated in a pediatric population. Patients also received corticosteroids and mycophenolate mofetil (MMF). Historical controls received standard TAC-based triple therapy started immediately posttransplantation. Daclizumab induction was associated with a significantly lower risk of acute rejection within the first 30 days posttransplantation, 15% vs 50%, respectively. Early renal function (at 7 days posttransplantation) was improved in the group that received daclizumab. However, 2-year patient and graft survival rates were not significantly different between groups. These findings indicate that this strategy is efficacious and may be beneficial in the child with underlying renal dysfunction at time of liver transplantation.
Long-term Follow-up in Pediatric Patients Treated With TAC-Based Immunosuppressive Therapy
Long-term follow-up (mean = 9 years) of chronic rejection in 166 pediatric liver recipients managed on TAC-based immunosuppression showed that 10-year actuarial patient and graft survival rates were 84% and 80%, respectively.s Only 4 patients had biopsy-proven chronic rejection. Each of these patients had undergone reduction or withdrawal of immunosuppression as treatment for viral infection/PTLD, or were noncompliant. None of the remaining patients maintained on TAC-based immunosuppression had chronic rejection. By comparison, 20% of children on CsA-based maintenance immunosuppression developed chronic rejection. TAC rescue therapy was effective in 70% of these patients, with normalization of liver enzymes and improvement in liver histology. These findings suggest that TAC is an effective drug for long-term maintenance immunosuppression and prevention of chronic rejection in pediatric liver transplant recipients.
Data emerging on immunosuppressive therapies in pediatric patients generally parallel the findings in adult patients. A number of regimens have been found to be effective in preventing or treating rejection. Emphasis now is on reducing or eliminating side effects that either increase morbidity or contribute to noncompliance. Thus, the armamentarium available to the transplant physician is no longer restricted to corticosteroids, azathioprine, and a calcineurin inhibitor. Judicious use of T cell-depleting and nondepleting antibodies, sirolimus, and MMF have allowed reduction or complete withdrawal of some agents without increasing graft loss or complications. As experience is gained with the use of these drugs, regimens will be tailored individually to the patient based on the side effects encountered.