肝移植术后慢性排斥反应的临床与病理分析

Clinical and pathological analysis of chronic rejection following orthotopic liver transplantation

目的探讨原位肝移植术后慢性排斥反应的病理组织学特点、临床表现以及诊治经验。方法回顾性分析2004年1月至2006年12月收治的516例原位肝移植患者的临床病理资料；对肝移植术后发生慢性排斥反应患者的病理组织学改变、临床表现、诊治方案加以分析。结果516例肝移植患者中，发生慢性排斥反应12例（2．3％，12／516），其中早期慢性排斥反应7例，晚期慢性排斥反应5例。其主要组织学特征是移植肝组织内的胆管严重减少或缺失和累及中等动脉的闭塞性动脉炎；其中早期慢性排斥反应可表现为小叶间胆管的细胞变性和其数量进行性减少以及形成小叶中央坏死性炎症。12例慢性排斥反应患者中，7例早期慢性排斥反应患者经激素冲击治疗和调整免疫抑制药物后病情得到控制（包括2例接受抗CD3抗体治疗，2例接受抗胸腺细胞球蛋白治疗）且近期疗效满意；5例晚期慢性排斥反应患者肝功能迁延不愈最终至肝功能衰竭而行再次肝移植，其中2例伴术后严重腹腔内感染而死亡，1例死于术后多脏器功能衰竭，另外2例再移植病例获临床治愈。本组慢性排斥反应发生的时间为术后4—26个月；与慢性排斥相关的病死率为25．0％（3／12）。结论肝移植术后发生慢性排斥反应的患者缺乏典型的症状和体征，其病理改变可以有重叠和复合存在；移植肝连续穿刺活检和再次移植术后病理仍是目前诊断慢性排斥反应的“金标准”。如能及时发现早期慢性排斥反应并积极进行合理的治疗，病情则具有潜在的可逆性；晚期阶段慢性排斥反应所致的移植肝功能衰竭需要再次肝移植治疗。

Objective To investigate the clinical manifestation and pathological features of chronic rejection（CR） and the management of CR after othotopic liver transplantation （OLT）. Methods From January 2004 to December 2006, there were 516 patients who had undergone OLT. All the clinical and pathological data were collected and retrospectively studied. Clinical manifestation, histopathological feature, diagnosis and anti-rejection treatment of CR were summarized and analyzed. Results The incidence of CR was 2. 3% （12/516） ,including 7 cases with early phases of CR and 5 cases with late phases of CR. The main pathological changes of CR were the vanishing bile duct syndrome and obliterative arteriopathy;and the early stage of CR were the damage of inter lobular bile duct, necrotic inflammation in central lobule, and inflammatory cells infiltation in portal area. Among 12 patients with CR,7 cases with early CR were reversed by methylprednisolone（MP） pulse treatment and adjusting immunosuppressant dose, including 2 cases of whom were prescribed OKT3 treatment and 2 cases treated by ATG, and 5 cases with late CR underwent liver retransplantation（re-LT）. Two patients died from infection, 1 case died from multiple organ failure in perioperative period after re-LT, another 2 cases were cured by re-LT, and the CR related mortality was 25.0% （3/12）. Conclusions Chronic rejection following OLT is lack of typical clinical manifestation and pathological features, and the pathological changes can overlap and coexist. Post-transplant liver biopsy and graft specimen after re-LT is still ＂gold standard＂ to CR diagnosis. Some of early CRs can be reversed by early diagnosis and early treatment; for late CR recipient, re-LT should be considered.