摘要
目的探讨肝移植术后移植物抗宿主病(graft versus host disease,GVHD)的诊断要点、治疗策略和预后。方法回顾性分析1999年05月至2024年10月陆军军医大学第一附属医院肝移植中心收治的5例诊断为肝移植术后GVHD受者的临床资料,总结并分析肝移植术后GVHD的病因、发病情况、诊断、治疗和预后。检索中国知网、万方数据库、维普数据库、中华医学期刊全文数据库、PubMed、Web of science、Google Scholar搜索引擎,中文检索词为"移植物抗宿主病+肝移植",英文检索词为"graft versus host disease+liver transplantation",检索文献的发表时间为1988年1月至2025年1月;文献纳入标准:(1)符合肝移植术后GVHD的临床或病理诊断标准;(2)受者年龄>18岁;(3)病例数≥2;排除标准:肝移植术后GVHD的发病率、病死率和临床表现等临床资料不全;对检索到的文献资料进行文献复习。结果5例受者均为男性。其中4例在本中心行肝移植,本中心肝移植术后GVHD的发病率为0.46%(4/872)。5例均在肝移植术后5~21 d(中位时间为19 d)开始出现发热、皮疹、腹泻、口腔溃疡和全血细胞减少等症状,1例出现消化道出血。2例经皮肤病理活检确诊,3例依据发热、皮疹、腹泻和骨髓抑制等临床表现诊断。1例停用免疫抑制剂、4例减少免疫抑制剂用量,4例使用大剂量糖皮质激素,4例使用静脉注射免疫球蛋白(intravenous immunoglobulin,IVIG)、3例使用芦可替尼、3例使用造血因子治疗,5例均采取保护性隔离措施、抗感染和对症支持治疗。3例使用芦可替尼治疗的受者体温恢复正常,皮疹逐渐减退,口腔溃疡逐渐愈合,全血细胞恢复正常,最终康复出院;另2例症状未好转,因严重肺部感染和多器官功能衰竭死亡。文献复习:共纳入34篇文献,肝移植术后GVHD的发病率为1.03%(279/27018),发病时间为肝移植术后7~1865 d,272例(97.49%)在1~8周。主要临床表现为发热(195例,69.89%)、皮疹(267例,95.70%)、腹泻(173例,62.01%)和骨髓抑制(214例,76.70%)。经过调整免疫抑制剂(201例,72.04%),大剂量激素(215例,77.06%)和IVIG(146例,52.33%)冲击治疗。最终83例(29.75%)痊愈出院;病死率为70.25%(196/279),死亡原因为感染、消化道出血和多器官功能衰竭等。结论肝移植术后GVHD发病率低、病死率高、预后差。主要依据典型的临床表现和组织活检病理结果诊断。早期大剂量糖皮质激素联合IVIG冲击治疗、及时减少或停用免疫抑制剂、联合芦可替尼、积极处置感染和加强对症支持治疗是治疗肝移植术后GVHD的有效手段。
Objective To explore the diagnostic key points,treatment strategies,and prognosis of graft-versus-host disease(GVHD)after liver transplantation.Methods The clinical data of 5 recipients diagnosed with GVHD after liver transplantation at the Liver Transplantation Center of the First Affiliated Hospital of Army Medical University from May 1999 to October 2024 were retrospectively analyzed.The causes,onset,diagnosis,treatment,and prognosis of GVHD after liver transplantation were summarized and analyzed.Literature was searched in CNKI,Wanfang,VIP,Chinese Medical Journal Full-text Database,PubMed,Web of Science,and Google Scholar using the Chinese keywords"移植物抗宿主病+肝移植",and the English keywords"graft versus host disease+liver transplantation".The search time ranged from January 1988 to January 2025.Inclusion criteria for the literature:(1)meeting the clinical or pathological diagnostic criteria of GVHD after liver transplantation;(2)recipient age>18 years;(3)case number≥2.Exclusion criteria:incomplete clinical data such as incidence,mortality,and clinical manifestations of GVHD after liver transplantation.The retrieved literature was reviewed.Results All 5 recipients were male.Among them,4 cases underwent liver transplantation at this center.The incidence of GVHD after liver transplantation in this center was 0.46%(4/872).All 5 cases developed symptoms such as fever,rash,diarrhea,oral ulcers,and pancytopenia on the 19th(5-21)day after liver transplantation.One case had gastrointestinal bleeding.Two cases were diagnosed by skin pathological biopsy,and three cases were diagnosed based on clinical manifestations such as fever,rash,diarrhea,and bone marrow suppression.One case discontinued immunosuppressants,and four cases reduced the dosage of immunosuppressants.Four cases were treated with high-dose glucocorticoids,four with intravenous immunoglobulin(IVIG),three with ruxolitinib,and three with hematopoietic factors.All five cases received protective isolation,anti-infection,and symptomatic supportive treatment.Among the three recipients treated with ruxolitinib,body temperature returned to normal,rash gradually faded,oral ulcers gradually healed,blood cells returned to normal,and they were eventually discharged after recovery.The remaining two cases showed no symptom improvement and died of severe lung infection and multiple organ failure.Literature review A total of 34 articles were included.The incidence of GVHD after liver transplantation was 1.03%(279/27018),and the onset time ranged from 7 to 1,865 days post-transplantation;272 cases(97.49%)occurred within 1-8 weeks.The main clinical manifestations included fever(195 cases,69.89%),rash(267 cases,95.70%),diarrhea(173 cases,62.01%),and bone marrow suppression(214 cases,76.70%).Treatment mainly involved adjustment of immunosuppressants(201 cases,72.04%),high-dose corticosteroids(215 cases,77.06%),and IVIG pulse therapy(146 cases,52.33%).In the end,83 cases(29.75%)recovered and were discharged,while the mortality rate was 70.25%(196/279),with causes of death including infection,gastrointestinal bleeding,and multiple organ failure.Conclusions GVHD after liver transplantation has a low incidence,high mortality,and poor prognosis.Diagnosis mainly relies on typical clinical manifestations and pathological results of tissue biopsy.Early administration of high-dose corticosteroids combined with IVIG pulse therapy,timely reduction or discontinuation of immunosuppressants,use of ruxolitinib,active infection management,and enhanced symptomatic and supportive care are effective strategies for treating GVHD after liver transplantation.
作者
蒋家云
王宏
廖睿
赖洁娟
刘丰豪
张城城
刘炜
欧晏娇
张雷达
Jiang Jiayun;Wang Hong;Liao Rui;Lai Jiejuan;Liu Fenghao;Zhang Chengcheng;Liu Wei;Ou Yanjiao;Zhang Leida(Department of Hepatobiliary Surgery,Southwest Hospital of Army Medical University(Third Military Medical University),Chongqing 400038,China)
出处
《中华器官移植杂志》
2025年第7期504-515,共12页
Chinese Journal of Organ Transplantation
基金
重庆市博士"直通车"科研项目(CSTB2022BSXM-JCX0004)
重庆市自然科学基金面上项目(CSTC2021JCYJ-MSXMX1018)
重庆市科卫联合医学科研项目(2022QNXM020)。
关键词
肝移植
移植物抗宿主病
诊断方法
治疗
Liver transplantation
Graft-versus-host disease
Diagnostic method
Treatment
