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肝移植急性细胞排斥反应的治疗

Author
Scott J Cotler, MD
Section Editor
Robert S Brown, Jr, MD, MPH
Deputy Editor
Anne C Travis, MD, MSc, FACG, AGAF
Translators
巩鹏, 主任医师，教授

引言

随着强效免疫抑制剂的应用，肝移植后急性细胞排斥反应的发病率有所下降，但其仍可累及15%-25%的肝移植受者[1,2]。大部分急性细胞排斥反应发生在移植后1个月内，但也可能较晚发生[3]。一项纳入970例肝移植患者的回顾性分析发现，与免疫抑制近期改变及水平降低有关的晚期急性细胞排斥反应(晚于移植后90日)的发生率为11%[4]。除免疫抑制的类型和水平外，某些移植相关特征也可能影响发生排斥反应的风险。例如，与接受尸体供肝的移植受者相比，接受活体亲缘供者器官的患者中急性细胞排斥反应的发生率可能更低[1,5]。

急性细胞排斥反应的后果不一。虽然其可能诱发激素耐药型排斥反应及移植物失功，但除了丙型肝炎病毒(hepatitis C virus, HCV)阳性患者以外，多数急性细胞排斥反应发作并不会带来长期不利影响[6](参见下文‘丙型肝炎’)。此外，在移植物没有出现生化功能障碍的情况下，计划性肝活检识别的急性细胞排斥反应通常无需加强免疫抑制即可缓解[7]。甚至有人认为，这种亚临床的免疫激活可能有利于诱导一定程度的免疫耐受性[8]。排斥反应发生的时间可能影响患者的结局。在一项大型回顾性研究中，与没有发生排斥反应的患者相比，早期急性排斥反应更有利于移植物存活，而晚期急性排斥反应会降低移植物存活率[4]。发生晚期急性细胞排斥反应的患者中28%会出现慢性细胞排斥反应，而发生移植物失功的风险为6%。

本文将总结肝移植后急性细胞排斥反应的治疗。肝移植后急性细胞排斥反应的诊断将单独讨论 (参见“肝移植：急性细胞排斥反应的诊断”)

诊断

血清氨基转移酶和碱性磷酸酶水平升高往往先于黄疸和发热这样的临床症状出现，其水平升高时通常怀疑急性细胞排斥反应的诊断。然而，生化指标对于急性细胞排斥反应的检测不敏感或没有特异性，并且与其严重程度并无相关性[9]。因此，在开始治疗排斥反应之前，应该通过肝活检证实诊断。细胞排斥反应的组织学特征包括：内皮炎、非化脓性胆管炎和汇管区混合性单个核细胞炎症[10]。 (参见“肝移植：急性细胞排斥反应的诊断”)

抗体介导的排斥反应(antibody-mediated rejection, AMR)是ABO血型相容性肝移植后移植物损伤和失功的罕见原因，并且可能与急性细胞排斥反应混淆和重叠。已提出的肝移植后AMR的特征包括：排除肝损伤的其他原因后，血清中存在供体特异性HLA同种异体抗体，活检发现微血管内皮细胞损伤，肝窦中存在线性C4d阳性染色[11,12]。

          

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Literature review current through: 2017-06 . | This topic last updated: 2015-06-30.
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