目的

探讨肝移植术后急性移植物抗宿主病（aGVHD）的诊治经验。

方法

回顾性分析2000年1月至2022年1月第九〇〇医院诊治的4例肝移植术后aGVHD 患者临床资料。患者均签署知情同意书，符合医学伦理学规定。其中男3例，女1例；年龄分别为67、59、50、51岁。4例病例均采用经典原位肝移植术，术中常规放置胆汁引流管和胃肠营养管，免疫抑制剂方案：甲基泼尼松龙+他克莫司+吗替麦考酚酯。总结分析肝移植术后aGVHD的诊治经过和经验教训。

结果

肝移植术后aGVHD发生率为0.6%（4/650），发病时间为术后12.0～21.0 d，中位时间16.5 d。肝移植术后aGVHD临床特点：（1）发病时间肝移植术后2～4周；（2）典型临床表现为发热、皮疹、腹泻以及全血细胞减少；（3）皮肤组织活检典型的病理表现，表皮网篮型角化过度+，胶样小体角化不良+，基底层空泡样变性+++，空泡型界面皮炎++，表皮内裂隙形成；真皮色素失禁+，浅层血管周围炎症+；炎症细胞组成：淋巴细胞+，单核细胞+。治疗方案采用类固醇激素冲击疗法，后递减至20 mg口服维持；注意调整免疫抑制剂的用量；预防感染和消化道出血。4例发病期间移植肝功能正常，1例经治疗后临床症状改善，骨髓象恢复正常，aGVHD缓解率为1/4。4例患者于发病后7.0～41.0 d内死亡，中位生存时间17.8 d；死亡率达4/4，死于消化道出血1例、脑出血1例、多器官功能衰竭2例。

结论

肝移植术后aGVHD发病率低，但死亡率极高，诊断依据典型的临床表现和病理学检查。目前仍无统一有效的治疗方案，激素冲击、减低或停止免疫抑制剂用量、预防感染可能是有效的治疗手段。

Objective

To investigate the diagnosis and treatment experience of acute graftversus-host disease （aGVHD） after liver transplantation.

Methods

Clinical data of 4 patients with aGVHD after liver transplantation admitted to the 900^th Hospital from January 2000 to January 2022 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them，3 patients were male and 1 female，aged 67，59，50 and 51 years，respectively. Classical orthotopic liver transplantation was performed in 4 cases. Bile drainage tube and gastroenteric nutritional tube were routinely placed during the surgery. The immunosuppressant regimen was methylprednisolone + tacrolimus + mycophenolate mofetil. The diagnosis and treatment experience of aGVHD after liver transplantation was summarized and analyzed.

Results

The incidence of aGVHD after liver transplantation was 0.6%（4/650）. The onset time of aGVHD was 12.0-21.0 d after surgery，with a median time of 16.5 d. Clinical characteristics of aGVHD after liver transplantation were as follows:（1） The onset time was 2-4 weeks after liver transplantation；（2） Typical clinical manifestations included fever，rash，diarrhea and pancytopenia；（3） Typical pathological manifestations of skin biopsy，epidermal reticular hyperkeratosis+，dyskeratosis of colloid bodies+，vacuolar degeneration of basal layer+++，vacuolar interfacial dermatitis++，and formation of epidermal cracks；dermal pigment incontinence+，superficial perivascular inflammation+. Inflammatory cell composition: lymphocytes+ and monocytes+. Steroid hormone shock therapy was adopted，and then decreased to 20 mg oral maintenance therapy. Attention was paid to adjusting the immunosuppressant dosage. Infection and gastrointestinal bleeding were prevented.4 cases had normal transplanted liver function during the onset，1 case obtained alleviated clinical symptoms and normal myelogram after treatment. The remission rate of aGVHD was 1/4. 4 patients died within 7.0-41.0 d after onset，with a median survival time of 17.8 d. The mortality rate reached 4/4，including 1 case of gastrointestinal bleeding，1 case of cerebral hemorrhage and 2 cases of multiple organ failure.

Conclusions

The incidence rate of aGVHD is low，whereas the mortality rate is extremely high after liver transplantation. The diagnosis relies on typical clinical manifestations and pathological examination.At present，there is no unified and effective treatment regimen. Hormone shock，reducing or terminating the dosage of immunosuppressants and preventing infection may be effective treatment methods.