Moser Michael A J
Multi-Organ Transplant Program, London Health Sciences Center, 339 Windermere Road, London, Ontario N6A 5A5, Canada.
Drugs. 2002;62(7):995-1011. doi: 10.2165/00003495-200262070-00002.
Immunosuppression administered in the early postoperative period following liver transplantation plays a crucial role in the survival of the graft and the patient. The introduction of cyclosporin was an important landmark in transplantation, and to this day, calcineurin inhibitors form the basis of most induction immunosuppression regimens. New drugs are being developed which are more specifically targeted to prevention of rejection, and multiple drug combinations have been proposed as a means of reducing the adverse effects of individual drugs. Azathioprine and the newer antimetabolite mycophenolate mofetil have been added to calcineurin inhibitor-based regimens with varying amounts of success. Antibody induction has evolved as a potent form of immunosuppression as well as a means of avoiding certain adverse effects, particularly nephrotoxicity. The numerous adverse effects encountered with polyclonal preparations have been reduced with the development of more specific monoclonal antibodies such as muromonab CD3 (OKT3) or interleukin (IL)-2 receptor (IL-2R) antagonists. The anti-IL-2R antibody preparations basiliximab and daclizumab have shown excellent early results due to their potent yet highly targeted immunosuppressive effect and minimal adverse effects. Further study is needed to determine the most appropriate dosage, timing and patient population for these new drugs in the setting of liver transplantation. Although a number of different induction regimens have been described, no single protocol is suitable for all liver transplant recipients. Rather, certain regimens have advantages that could favour their use in a specific subgroup of patients. A number of clinical trials are underway to identify new, more specific drugs and combinations which could be useful in induction immunosuppression.
肝移植术后早期进行的免疫抑制对移植物和患者的存活起着关键作用。环孢素的引入是移植领域的一个重要里程碑，直到如今，钙调神经磷酸酶抑制剂仍是大多数诱导免疫抑制方案的基础。正在研发更具特异性、旨在预防排斥反应的新药，并且已提出多种药物联合使用，以减少个别药物的不良反应。硫唑嘌呤和新型抗代谢药物霉酚酸酯已被添加到以钙调神经磷酸酶抑制剂为基础的方案中，取得了不同程度的成功。抗体诱导已发展成为一种有效的免疫抑制形式，也是避免某些不良反应（尤其是肾毒性）的一种手段。随着更具特异性的单克隆抗体（如莫罗单抗CD3（OKT3）或白细胞介素（IL）-2受体（IL-2R）拮抗剂）的研发，多克隆制剂所带来的众多不良反应已有所减少。抗IL-2R抗体制剂巴利昔单抗和达利珠单抗因其强大且高度靶向的免疫抑制作用以及最小的不良反应，已显示出优异的早期效果。需要进一步研究以确定这些新药在肝移植情况下最适宜的剂量、给药时间和患者群体。尽管已描述了多种不同的诱导方案，但没有一种单一方案适用于所有肝移植受者。相反，某些方案具有优势，可能更适合特定亚组的患者使用。目前正在进行多项临床试验，以确定可用于诱导免疫抑制的新型、更具特异性的药物及联合用药方案。
