Management of acute rejection in paediatric liver transplantation

The success of paediatric liver transplantation is attributed to improved surgical techniques and the advent of calcineurin inhibitor-based immunosuppression. Acute rejection (AR) rarely results in graft loss with calcineurin inhibitor immunosuppressive regimens, and the advent of newer agents like interleukin (IL)-2 receptor antibodies. The latter have the benefit of reducing the incidence of AR further and may be of use in patients who are susceptible to recurrent AR, were retransplanted for graft rejection or are in a steroid-sparing regimen. A total of 60 % of all paediatric liver transplants result in AR; however, there is a 75 % response rate to initial steroid therapy. Steroid therapy remains the mainstay of initial AR management, coupled with an increase in baseline immunosuppression. Steroid-resistant rejection (SRR), previously an immediate indication for potent anti-lymphocyte preparations, is now effectively treated with chimeric or humanised IL-2 receptor monoclonal antibodies. Recurrent AR can be treated by adding adjuvant immunosuppressive agents such as mycophenolate mofetil (MMF) or sirolimus. Studies have also demonstrated the efficacy of MMF as rescue therapy for SRR. Anti-lymphocyte preparations such as anti-thymocyte globulin (ATG) and OKT3 are rarely used in SRR but may be of use as rescue therapy for severe SRR. The challenges of the management of AR remain in the management of recurrent AR and SRR. We discuss the pathogenesis, diagnosis and management of AR, including prevention, and specific management of AR and SRR based on current evidence and our own experience at the King's College Paediatric Liver, Gastroenterology and Nutrition Centre in London.