Beyond five years: long-term follow-up in pediatric liver transplantation.

Pediatric liver transplant patients are now routinely surviving 10 years or more. Beyond the first year after transplant, surgical biliary or vascular complications are rare, and the incidence of acute rejection episodes falls precipitously. Attention is turning to minimizing the toxicity of immunosuppressive regimens and their potential negative impact on growth, bone health, cognitive development, renal function, and quality of life. Innovative combinations of immunosuppressive medications are being used as initial management after transplantation to minimize acute rejection and allow rapid weaning of corticosteroids and reduction in maintenance levels of calcineurin inhibitors. The substitution of potentially less toxic immunosuppressive agents, such as mycophenolate mofetil and rapamycin, is being studied in patients who develop renal dysfunction. A major current emphasis is on defining the natural history of long-term graft injury and elucidating histopathologic changes that mimic autoimmune chronic active hepatitis but are likely a form of chronic rejection due to production by the recipient of antibodies to foreign graft antigens. As patients survive longer, we are seeing various forms of immune dysregulation engendered by the presence of the graft and chronic immunosuppression of the host. By defining the resulting patterns of graft injury and understanding their immunopathogenesis, we can devise rational adjustments in immunosuppression that will preserve graft function and maximize graft life.