肝脏移植术后体液性排斥反应的诊断与治疗

Diagnosis and treatment of humoral liver allograft rejection

目的寻找体液因素参与肝脏移植排斥反应的相关证据,探索临床监测和治疗体液性排斥反应的合理方案。方法通过检测肝脏移植术后肝穿组织中补体C4d、CD20(B细胞)和CD138(浆细胞)的表达情况,诊断肝损伤患者是否存在体液性排斥反应。临床结合病理诊断为排斥反应时,首先增加他克莫司(普乐可复)用量,肝功能损害严重者采用激素冲击治疗;诊断为体液性排斥反应的患者激素冲击治疗无效后,给予抗胸腺细胞球蛋白(ATG)或雷帕霉素(RPM)治疗。结果16例患者共进行25次肝脏穿刺检查,病理检查结合临床表现,10例患者诊断为体液性排斥反应15次,4例患者诊断为细胞性排斥反应6次,另外2例患者均先后诊断为急性和慢性排斥反应。体液性排斥反应激素冲击治疗有效率(29.4%,5/17)明显低于细胞性排斥反应(87.5%,7/8)。7例患者12次肝损害时诊断为耐激素性体液性排斥反应,在激素冲击治疗无效后1例给予ATG治疗,5例加用RPM,排斥反应均得以纠正,另外1例接受"O"型供肝的"AB"型患者出现2次肝功能明显异常,采取多种治疗方法无效,最终因肝功能衰竭死亡。结论体液免疫因素可能参与了部分肝脏移植急、慢性排斥反应的发生。应用ATG和RPM治疗体液性排斥反应较为有效。

Objective To explore the evidences of the hurnoral factor involved in the liver allograft rejection, and to explore better monitoring methods and therapy of the humoral liver rejection. Methods After the humoral liver rejection, liver puncture biopsies were performed. Immunohistochemical examinations of CAd, CD20＇ B lymphocytes and CD138 plasma cells were performed to judge whether humoral factor was involved in liver rejection. The dosage of tacrolimus was increased first when rejection was identified. The patients with severe liver function damage were treated with methyllprednisolone, and the steroid-insensitive cases were treated with antithymocyte globulins （ATG） and rapamycin. Results 25 biopsies were performed in 16 patients. Humoral rejection was diagnosed for 15 times in 10 patients, cellular rejection was diagnosed for 6 times in 4 patients, and the both kinds of rejection occurred in the last 2 patients. The effect of methylpredrtisolone was obviously lower in the hurmral rejection cases （29. 4%, 5/17） than that of the cellular rejection cases （7/8）. Steroid insensitive hurmral rejections were diagnosed in 12 biopsies from 7 patients receiving liver transplantation. One patient was cured with ATG and 5 patients were cured with addition of rapamydn. The case whose blond type was AB receiving a liver transplant from the donor of O blood type died of liver function failure even after an extensive treatment. Conclusions Humoral immune factors maybe involved in some acute and chronic liver allograft rejection. ATG and rapamycin are more effective for the patients with humoral liver rejection.