Wiesner R H, Ludwig J, Krom R A, Hay J E, van Hoek B
Division of Gastroenterology, Mayo Clinic, Rochester, MN 55905.
Mayo Clin Proc. 1993 Jan;68(1):69-79. doi: 10.1016/s0025-6196(12)60022-6.
Hepatic allograft rejection remains a major cause of morbidity related to the need for increased immunosuppression and continues to be a principal cause of late failure of the graft. Hepatic allograft rejection is defined on the basis of morphologic findings; cellular rejection is defined as portal or periportal hepatitis with nonsuppurative cholangitis or endotheliitis (or both), and ductopenic rejection is defined as loss of interlobular and septal bile ducts, typically in at least 50% of the portal tracts. The overall incidence of episodes of cellular rejection, which usually occur within the first 2 weeks after liver transplantation, varies from 50 to 100%. Ductopenic rejection occurs in approximately 8% of patients who undergo initial liver transplantation and is usually diagnosed between 6 weeks and 6 months after transplantation. Induction and maintenance immunosuppression with triple-drug (cyclosporine, prednisone, and azathioprine) therapy and other combinations that include antilymphocyte preparations, however, has decreased the incidence of both cellular and ductopenic rejection. In patients experiencing episodes of cellular rejection, high-dose intravenously administered corticosteroid therapy yields the best response and is associated with a lower incidence of ductopenic rejection than is low-dose and orally administered corticosteroid therapy. The correlation between degree of biochemical liver dysfunction and presence of histologic rejection is minimal early after transplantation. Histologic severity of rejection, however, suggests which patients will require more immunosuppression and which patients may need antilymphocyte therapy for controlling the rejection episode. With the availability of new immunosuppressive agents, distinguishing patients at high risk for rejection is important. The goals for use of new immunosuppressive agents and regimens are to improve graft and patient survival, to decrease the incidence of cellular and ductopenic rejection, and to minimize side effects and complications.
肝移植排斥反应仍然是与免疫抑制增加需求相关的发病的主要原因，并且仍然是移植物晚期失败的主要原因。肝移植排斥反应是根据形态学表现来定义的；细胞性排斥反应被定义为伴有非化脓性胆管炎或内皮炎（或两者皆有）的门脉性或门脉周围性肝炎，而胆管减少性排斥反应被定义为小叶间和间隔胆管的丧失，通常在至少50%的门脉区域出现。细胞性排斥反应发作的总体发生率通常在肝移植后的头2周内出现，为50%至100%不等。胆管减少性排斥反应发生在约8%接受初次肝移植的患者中，通常在移植后6周和6个月之间被诊断出来。然而，采用三联药物（环孢素、泼尼松和硫唑嘌呤）疗法以及包括抗淋巴细胞制剂在内的其他联合方案进行诱导和维持免疫抑制，已降低了细胞性和胆管减少性排斥反应的发生率。在经历细胞性排斥反应发作的患者中，大剂量静脉注射皮质类固醇疗法产生的反应最佳，并且与低剂量口服皮质类固醇疗法相比，胆管减少性排斥反应的发生率更低。移植后早期，肝脏生化功能障碍程度与组织学排斥反应的存在之间的相关性很小。然而，排斥反应的组织学严重程度提示哪些患者需要更多的免疫抑制，哪些患者可能需要抗淋巴细胞疗法来控制排斥反应发作。随着新的免疫抑制药物的出现，区分高排斥风险患者很重要。使用新的免疫抑制药物和方案的目标是提高移植物和患者的存活率，降低细胞性和胆管减少性排斥反应的发生率，并尽量减少副作用和并发症。
