Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease, University of Birmingham and Queen Elizabeth Hospital, Edgbaston Birmingham B152TT, United Kingdom.
Institute of Liver Studies, MRC Centre for Transplantation, King's College London, London SE5 9RS, United Kingdom.
J Hepatol. 2015 Apr;62(1 Suppl):S170-85. doi: 10.1016/j.jhep.2015.02.042.
The past three decades have seen liver transplantation becoming a major therapeutic approach in the management of end-stage liver diseases. This is due to the dramatic improvement in survival after liver transplantation as a consequence of the improvement of surgical and anaesthetic techniques, of post-transplant medico-surgical management and of prevention of disease recurrence and other post-transplant complications. Improved use of post-transplant immunosuppression to prevent acute and chronic rejection is a major factor in these improved results. The liver has been shown to be more tolerogenic than other organs, and matching of donor and recipients is mainly limited to ABO blood group compatibility. However, long-term immunosuppression is required to avoid severe acute and chronic rejection and graft loss. With the current immunosuppression protocols, the risk of acute rejection requiring additional therapy is 10-40% and the risk of chronic rejection is below 5%. However, the development of histological lesions in the graft in long-term survivors suggest atypical forms of graft rejection may develop as a consequence of under-immunosuppression. The backbone of immunosuppression remains calcineurin inhibitors (CNI) mostly in association with steroids in the short-term and mycophenolate mofetil or mTOR inhibitors (everolimus). The occurrence of post-transplant complications related to the immunosuppressive therapy has led to the development of new protocols aimed at protecting renal function and preventing the development of de novo cancer and of dysmetabolic syndrome. However, there is no new class of immunosuppressive drugs in the pipeline able to replace current protocols in the near future. The aim of a full immune tolerance of the graft is rarely achieved since only 20% of selected patients can be weaned successfully off immunosuppression. In the future, immunosuppression will probably be more case oriented aiming to protect the graft from rejection and at reducing the risk of disease recurrence and complications related to immunosuppressive therapy. Such approaches will include strategies aiming to promote stable long-term immunological tolerance of the liver graft.
过去三十年，肝移植已成为治疗终末期肝病的主要方法。这是因为肝移植术后存活率显著提高，这归因于手术和麻醉技术、移植后医学和外科管理以及预防疾病复发和其他移植后并发症的改善。更好地使用移植后免疫抑制来预防急性和慢性排斥反应是这些改善结果的主要因素。肝脏比其他器官更具有耐受性，供体和受者的匹配主要限于 ABO 血型相容。然而，需要长期免疫抑制以避免严重的急性和慢性排斥反应和移植物丢失。根据目前的免疫抑制方案，需要额外治疗的急性排斥反应风险为 10-40%，慢性排斥反应风险低于 5%。然而，长期存活者移植后移植物中组织学病变的发展表明，由于免疫抑制不足，可能会出现不典型的移植物排斥形式。免疫抑制的基础仍然是钙调神经磷酸酶抑制剂（CNI），短期通常与类固醇联合使用，长期则与霉酚酸酯或 mTOR 抑制剂（依维莫司）联合使用。与免疫抑制治疗相关的移植后并发症的发生导致了新方案的发展，旨在保护肾功能，预防新发癌症和代谢综合征的发生。然而，在可预见的未来，没有新的免疫抑制药物能够替代当前的方案。由于只有 20%的选定患者能够成功地停止免疫抑制，因此，移植后移植物完全免疫耐受的目标很少实现。未来，免疫抑制可能会更加针对具体病例，旨在保护移植物免受排斥反应，并降低与免疫抑制治疗相关的疾病复发和并发症的风险。这些方法将包括旨在促进肝移植稳定长期免疫耐受的策略。
