原位肝移植术后耐激素性急性排斥反应的临床诊治策略

Strategies in clinical diagnosis and treatment of steroid-resistant acute rejection after orthotopic liver transplantation

目的探讨原位肝移植术后耐激素性急性排斥反应（SRAR）的诊断依据和治疗策略。方法对中山大学附属第一医院自2004年1月至2013年12月实施的1038例原位肝移植患者进行分析和总结，共有153例患者发生169次急性排斥反应（AR），其中16例对大剂量激素冲击治疗无应答，确诊为SRAR。回顾性分析此16例患者的诊断和治疗隋况。结果采用x2检验或t检验进行统计学处理，P〈0．05为差异有统计学意义。结果本组患者肝移植术后AR的发生率为14．74％（153／1038），SRAR在AR患者中的发生率为9．47％（16／169）。16例SRAR患者中，3例患者接受CD3单克隆抗体（OKT3）治疗，9例患者接受抗白细胞介素2受体单克隆抗体治疗，4例患者接受抗胸腺细胞球蛋白（ATG）治疗。16例SRAR患者中，12例患者经治疗后SRAR得以逆转，逆转率为75％，4例患者治疗无效病死，病死率为25％。结论肝移植术后SRAR发生率较低，但预后差。SRAR的诊断主要依靠临床表现、实验室检查和肝穿刺病理结果以及经用甲基强地松龙冲击治疗效果不佳或病情继续恶化的病程经过来综合判断；在治疗方面，ATG和OKT3对多数患者有明显疗效，而ATG逆转率高，不良反应相对较少，可望成为SRAR的一线治疗选择。

Objective To explore the diagnostic evidence and treatment strategies for steroid-resistant acute rejection （SRAR） after orthotopic liver transplantation. Methods A retrospective analysis was performed among 1038 patients undergoing orthotopic liver transplantation in our hospital from January 2004 to December 2013. A total of 169 acute rejection （AR） episodes occurred in 153 patients. Sixteen of the patients were diagnosed with SRAR because of no response to large-dose steroid pulse therapy. The diagnosis and treatment of the 16 patients were analyzed retrospectively. Comparison of data was made by ;（2 test or t test, and a P value of 〈0.05 was considered to be significant. Results The incidence of AR after liver transplantation was 14.74% （153/1038） in all the patients. The incidence of SRAR was 9.47% （16/169） in patients with AR. In the l 6 patients with SRAR, 3 were treated with anti-CD3 monoclonal antibody （OKT3）, 9 were treated with monoclonal antibody against IL-2 receptor, and 4 received antithymocyte globulin （ATG） therapy. After treatment, SRAR was reversed in 12 of the 16 patients and caused death of the other 4 patients, yielding a reversal rate of 75% and a mortality rate of 25%. Conclusion SRAR after liver transplantation has a low incidence rate but poorprognosis. The diagnosis of SRAR is mainly based on the clinical manifestation, laboratory test, liver biopsy, and poor response or rejection to methyl prednisolone pulse therapy. ATG and OKT3 achieve substantial outcomes in most of the patients in the treatment of SRAR. Particularly, compared with OKT3, ATG achieves a higher reversal rate and fewer adverse reactions, which is expected to become the first-line treatment of SRAR.