肝移植受者移植后淋巴组织增生性疾病的单中心诊疗经验

目的  总结肝移植受者移植后淋巴组织增生性疾病（PTLD）的发病情况和诊疗经验。方法  回顾性分析734例肝移植受者的临床资料，收集肝移植受者中PTLD的发病情况、临床症状、实验室数据及影像学资料；分析PTLD受者的病理学结果与治疗方式；分析PTLD受者的预后情况。结果  肝移植受者PTLD发生率为2.2%（16/734）, 中位术后发病时间为8（3, 46）个月。PTLD的临床表现主要为发热、淋巴结肿大，部分出现贫血、肝脾肿大、肝功能异常和消化系统症状等。16例PTLD受者中，1例他克莫司血药浓度异常升高；6例转氨酶升高；14例爱泼斯坦-巴尔病毒（EBV）DNA载量升高；5例巨细胞病毒（CMV）DNA载量升高。13例受者正电子发射计算机体层显像仪（PET/CT）检查提示相关肿大淋巴结¹⁸F-氟代脱氧葡萄糖代谢增高；2例受者颈部及腹部CT检查提示相应区域多发淋巴结肿大；1例受者仅超声提示淋巴结肿大。16例PTLD受者均行病理学检查, 其中13例受者原位杂交结果提示EBV编码的小RNA（EBER）阳性。降低免疫抑制剂水平是PTLD受者的基础治疗方案，根据不同病理类型的PTLD可联合利妥昔单抗靶向治疗及化学药物治疗；针对肿大淋巴结，给予手术及放射治疗。1例受者因PTLD治疗致移植肝衰竭死亡。结论  肝移植术后免疫抑制剂的使用可增加PTLD的患病风险，PTLD在儿童肝移植受者中发生率高于成人，尽早诊断和合理治疗可极大地改善PTLD受者的预后。

Diagnosis and treatment of posttransplant lymphoproliferative diseases in liver transplant recipients: a single-center experience

Objective To summarize the incidence, diagnosis and treatment experience of posttransplant lymphoproliferative diseases (PTLD) in the liver transplant recipients. Methods Clinical data of 734 liver transplant recipients were retrospectively analyzed. The incidence, clinical symptoms, laboratory and imaging data of PTLD in liver transplant recipients were collected. The pathological results and treatment methods of PTLD recipients were analyzed. The prognosis of PTLD recipients was evaluated. Results The incidence of PTLD in liver transplant recipients was 2.2% (16/734). The median time of onset after operation was 8(3, 46) months. The main clinical manifestations of PTLD were fever and lymph nodes enlargement. Some patients developed anemia, hepatosplenomegaly, abnormal liver function and digestive system symptoms, etc. Among 16 PTLD recipients, 1 case showed abnormal increase in blood concentration of tacrolimus, 6 cases of elevated transaminase levels, 14 cases of increased Epstein-Barr virus (EBV) DNA load and 5 cases of increased cytomegalovirus (CMV) DNA load. Positron emission tomography and computed tomography (PET/CT) showed hypermetabolism of 18F-flurodeoxyglucose in the enlarged lymph nodes of 13 recipients. CT scan of the neck and abdomen indicated multiple lymph node enlargement in the corresponding area of 2 recipients. Lymph nodes enlargement of 1 recipient showed on ultrasound only. All 16 PTLD recipients received pathological examination. In situ hybridization showed that EBV-encoded small RNA (EBER) was positive in 13 recipients. Reducing the immunosuppressant level was the basal treatment plan for PTLD recipients, and it can be combined with rituximab-targeted therapy and chemotherapy according to different pathological types of PTLD. Surgery and radiotherapy were used for enlarged lymph nodes. One recipient died of transplant liver failure due to PTLD treatment. Conclusions Administration of immunosuppressants after liver transplantation can increase the risk of PTLD. The incidence of PTLD is higher in pediatric liver transplant recipients than in adults. Early diagnosis and reasonable treatment can significantly improve the prognosis of PTLD recipients.