肝移植后急性体液性排斥反应的诊断和治疗两例

Diagnosis and treatment of acute humoral rejection after liver transplantation： report of 2 cases

目的回顾并总结肝移植术后急性体液性排斥反应的诊断和治疗经验。方法总结2例肝移植术后发生急性体液性排斥反应的病例资料。例1为重症乙型肝炎患者接受血型不相容的肝移植，供者ABO血型为AB型，受者为A型；例2为自身免疫性肝病患者接受血型相同的肝移植，供、受者血型均为O型。结果移植后两例患者均应用他克莫司＋吗替麦考酚酯＋泼尼松预防排斥反应，例1采用了兔抗人淋巴细胞球蛋白诱导治疗，两例患者术后1周内移植肝功能均恢复良好，血清转氨酶和胆红素总量持续性下降。术后7d开始两例均出现肝功能的持续恶化。例1抗B型血型抗体滴度持续性升高，移植肝穿刺组织病理学证实发生急性体液性排斥反应，予以血浆置换＋硼替佐米＋静脉注射免疫球蛋白（IVIG）治疗，治疗后体液性排斥反应逆转，移植肝功能逐渐恢复正常。例2经护肝、利胆治疗后移植肝功能无明显改善，反复进行移植肝穿刺组织病理学检查，未见急性排斥反应组织学表现，出现少数肝细胞坏死和局部毛细胆管内明显胆汁淤积，检测群体反应性抗体水平，发现HLA-I类抗体为3．4％，Ⅱ类抗体为95．9％，怀疑发生急性体液性排斥反应；予以血浆置换＋硼替佐米＋IVIG治疗，治疗后移植肝功能无明显改善，于第1次肝移植后2个月行再次肝移植；移植肝切除后病理检查证实为移植肝急性体液性排斥反应。结论对于血型不相容的肝移植以及自身免疫性肝病肝移植受者，应警惕其发生急性体液性排斥反应。移植肝穿刺病理学检查、群体反应性抗体水平的检测对于明确诊断有帮助。治疗应抓紧时机，采用综合治疗的方法，治疗无效时实施再次肝移植。

Objective To analysis and summarize the diagnosis and treatment of acute humoral rejection after liver transplantation. Method The clinical data of 2 patients with humoral rejection after liver transplantation were analyzed. One patient with severe hepatitis B underwent A]30- incompatible liver transplantation and the donor blood type was AB and recipient blood type was A. Another patient with autoimmune liver disease was subjected to liver transplantation with the same blood type. Result Two patients were given tacrolimus, mycophenolate mofetil and prednisone immune suppression scheme. Anti-human lymphocyte immune globulin was used in case 1 for induction therapy. Both cases recovered well after liver transplantation in one week evaluated by the transplanted liver function, but liver function deteriorated from 7 days after transplantation. Titer of anti blood type B antibody was increased in case 1, and biopsy of transplantation liver confirmed acute humoral rejection. Plasma exchange, bortezomib plus intravenous immunoglobulin （IVIG） were used for therapy for acute humors1 rejection, and acute humors1 rejection in case 1 was reversed after treatment and graft function recovered gradually. However, the graft function was not improved after treatment in case 2, and liver graft biopsy showed no acute cellular rejection signs. Only few liver cells necrosis and cholangiole cholestasis were seen. The levels of HLA I and Ⅱ class antibody were 3. 4%and 95.9% respectively. We suspected acute humoral rejection in case 2. Plasma exchange,bortezomib plus IVIG were given, but liver graft function was not improved after treatment, and liver re-transplantation was done 2 months after first liver transplantation. Acute humoral rejection diagnosed pathologically. Conelusion We should alert the occurrence of acute humoral rejection in ABO-incompatible liver transplantation, and the patients with autoimmune liver disease due to the disorder of immune function after liver transplantation. Liver graft biopsy, and detection of the levels of panel reactive antibodies will help to diagnose the acute humoral rejection. The treatment should seize the opportunity and combine a variety of approaches. Liver re-transplantation is performed once the rejection can not be reversed