肝移植受者急性移植物抗宿主病治愈后临床免疫耐受一例报道

Clinical immune tolerance after healing of acute graft-versus-host disease following liver transplantation： one case report

目的总结一例肝移植受者发生急性移植物抗宿主病（aGVHD）治愈后达到临床免疫耐受的诊疗经验。方法受者为男性，46岁，因原发性肝癌切除术后局部复发行原位肝移植术，供肝来自于脑死亡继发心脏死亡后器官捐献供者。受者采用巴利昔单抗诱导治疗，维持期采用他克莫司＋麦考酚钠肠溶片＋小剂量激素方案。术后早期陆续出现不典型症状，术后20 d，颈部及前胸出现大片红色斑疹，皮肤组织病理学检查结果：不除外aGVHD。供、受者HLA配型6个位点相合，嵌合体检测发现供者来源CD3阳性。结果停用免疫抑制药物，应用巴利昔单抗和甲泼尼龙冲击治疗，并快速减量，加强抗感染等，皮疹情况逐渐好转，但血象三系水平持续降低，应用集落刺激因子等无缓解，再次出现发热，移植后46 d再次出现皮疹。采用改良的激素方案，甲泼尼龙，2 mg·kg^－1·d^－1，持续用4 d，并缓慢减量，后受者血象三系水平恢复，停用皮质激素。术后21 d撤除免疫抑制药物，281 d停用皮质激素，之后随访期间受者肝功能完全正常。结论结合临床表现、病理学检查、HLA配型及嵌合体检测，可早期发现、诊断肝移植后aGVHD，治疗上可以使用缓慢减量的皮质激素方案并巴利昔单抗等。受者aGVHD治愈后短期达到临床免疫耐受状态可能与HLA配型相合度高及微嵌合体等因素有关，尚需进一步研究。

ObjectiveA successful salvage treatment of acute graft-versus-host disease （GVHD） after liver transplantation（OLT） with prognosis of immune tolerance was reported and the treatment experience was summed up.MethodsA 46-year-old man with hepatic carcinoma recurrence after resection underwent OLT from an ABO-identical male donor after cardiac death due to brain death. Post-transplant immunosuppression regimens consisted of induction with anti-interleukin-2 receptor monoclonal antibody （basiliximab） followed by maintenance with tacrolimus, mycophenolate mofetil and low dose of steroids. On the postoperative day （POD） 20, the patient developed skin rashes on his limbs and trunk, and skin biopsy showed histological features consistent with acute GHVD. Donor-recipient dominant HLA was matched at 6 loci, with donor CD3＋ T-cell chimerism positive.ResultsImmunosuppressants were withdrawn. Basiliximab combined with high dose of steroids was used, and the dosage was quickly reduced. Anti-infection treatment was strengthened. The skin rash recovered quickly, while the hemogram was significantly decreased, which was insensitive to colony stimulating factor. The fever came back with the skin rash on the POD 46. The modified hormone regimen was used, low dose of steroids with slowly reduction, and the patient recovered with the normal hepatic function.ConclusionWith the untypical clinical presentation, pathological examination, HLA-matching and chimerisms, aGVHD could be early detected and diagnosed, with a therapy of low dose of steroids with slow reduction combined with basiliximab. Recipient achieved immune tolerance, which may result from the high match of HLA and chimerisms.