肝移植术后急性移植物抗宿主病5例诊治体会

Experience in diagnosis and treatment of acute graft-versus-host disease after liver transplantation of five cases

目的分析肝移植术后急性移植物抗宿主病(acute graft-versus-host disease,a GVHD)的临床诊治关键环节,以期为该疾病的诊断和治疗提供参考经验。方法回顾性分析2000年1月至2019年12月西安交通大学第一附属医院外科重症医学科诊断的5例肝移植术后a GVHD患者的一般资料、临床特征、诊断方法和治疗策略。结果a GVHD发病率为5.88‰(5/850),5例均为男性,年龄40~64岁,平均(56.00±8.97)岁。糖尿病、肝癌、肝移植、经导管动脉化学栓塞术(transcatheter arterial chemoembolization,TACE)及较高的免疫制剂浓度等引起免疫功能受损的疾病或操作是a GVHD发生的高危因素。从移植到a GVHD出现临床表现的时间为15~32 d(中位时间21 d)。所有病例均以发热为首发表现,随后出现皮疹和三系细胞减低,3例出现腹泻,肝功能基本正常。3例患者术后继发肺部感染(痰培养为细菌和真菌)。急性起病,有免疫受损的高危因素,同时结合典型的临床表现和病理可作为诊断a GVHD的重要依据。治疗策略包括使用甲强龙冲击联合降低(2例)或停用(3例)免疫抑制剂,其中4例患者使用不同类型的淋巴细胞清除药物作为二线治疗。所有患者应用经验性广谱抗生素和抗真菌药物预防或治疗感染。隔离和营养等支持性治疗,并应用造血细胞因子治疗三系细胞减少。尽管给予上述积极的ICU集束化治疗,仍有2例(2/5,40%)因脓毒症及继发的多器官功能衰竭死亡,1例(20%)因颅内出血死亡,1例(20%)因后期继发结核死亡。只有1例(20%)治疗后病情缓解出院,规律随访1年,未出现其他并发症。结论受体术前有免疫功能受损的高危因素,肝移植术后出现不明原因发热、皮疹、三系细胞减低及胃肠道症状时应警惕a GVHD,皮肤组织活检对a GVHD的早期诊断至关重要。本中心首次提出移植术后30 d内发病、体温峰值大于38.5℃、皮疹范围大于50%、并发脓毒症及三系细胞计数恢复不良可能是影响肝移植术后a GVHD预后的重要因素。一旦诊断a GVHD,需要及时给予积极治疗。类固醇和调整免疫抑制剂仍是一线方案,感染的预防和治疗是核心。此外,清除淋巴细胞药物、恢复受体免疫功能、营养等ICU集束化治疗必不可少。术前对高危因素的认识、术后早期诊断并强化治疗是改善a GVHD预后的关键。

Objective To investigate our experience in the diagnosis and treatment of acute graft-versus-host disease(a GVHD)after liver transplantation in surgical ICU.Methods We retrospectively analyzed the general data,clinical manifestation,diagnosis,and treatment strategies of five patients with a GVHD after liver transplantation in The First Affiliated Hospital of Xi’an Jiaotong University from January 2000 to December 2019.Results The incidence rate of a GVHD was 5/850(5.88‰),and all the five patients were male and aged 40-64 years(mean age56 years).Diabetes,hepatocellular carcinoma,liver transplantation,transcatheter arterial chemoembolization(TACE),and high concentration of immune agents were the main risk factors associated with the development of aG VHD.The average time from surgery until clinical symptom of aG VHD was 15 to 32 days.In our patients with aG VHD,the most common symptom was fever(5/5),followed by skin rash(5/5),pancytopenia(5/5),diarrhea(3/5),and secondary pulmonary infection(3/5).However,liver functions were not remarkable affected.Diagnostic criteria for aG VHD in our center include acute onset,risk factors,typical clinical manifestation,and histopathology after exclusion of differential diseases.Our treatment strategies include high-dose methylprednisolone,stopping/reducing current immunosuppressive protocol,and antilymphocytic agents as secondline treatment.Empirical antibiotics and antifungal agents play a vital part in infections after transplantation.Hematopoietic cytokine was administered to treat pancytopenia.Patients also received supportive therapy,such as isolation and nutritional support,with the goal of benefiting the entire condition.Despite intensive treatment,two of five patients(40%)with aG VHD died due to sepsis and multiorgan failure.One case(20%)died of intracranial hemorrhage and one case(20%)died of tuberculosis.Only one case(20%)stayed alive after 1-year follow-up without complications.Conclusion The diagnosis of aG VHD relies on clinical suspicion and is confirmed by skin pathology.The patients with aG VHD had early onset(<30 day),high peak temperature(>38.5℃),large rash range(>50%),complication of sepsis,and poor response to hematopoietic cytokine therapy indicate poor prognosis.Intensive treatment should be started immediately after aG VHD diagnosis.In conclusion,we strongly suggest an early identification,diagnosis,and vigorous treatment strategy,which is the key to improving the prognosis of aG VHD.