肝移植术后移植物抗宿主病6例临床分析

Clinical Analysis of 6 Cases of Graft-versus-Host Disease after Liver Transplantation

摘要: 目的：总结单中心肝移植术后移植物抗宿主病(graft-versus-host disease, GVHD)的临床经验，探讨肝移植术后GVHD发生的临床表现、诊断方法及诊疗策略。方法：回顾性收集2013年7月至2024年1月于青岛大学附属医院进行各类肝移植手术后发生GVHD患者的临床资料，包括首发症状、实验室检查、发病时间等，描述性分析肝移植术后GVHD患者的临床特点及诊疗策略。结果：通过收集1263例各类肝移植手术患者临床资料，共确诊GVHD患者6例，发生率为0.47%；其中5例患者死亡，均死于严重感染导致的多器官功能衰竭，1例经治疗后存活至今。首发症状以皮疹、腹泻、发热为主；死亡患者实验室检查示三系减少伴严重骨髓抑制。组织病理学示皮肤基底层空泡变性、淋巴细胞浸润及坏死的嗜酸性角质形成。外周血嵌合体检测示供者来源T (CD8)细胞比例大于1%；呈受者与供者混合大嵌合状态。治疗方法主要有激素冲击、降低或停用免疫抑制剂、应用高级抗生素预防感染、个体化治疗及对症治疗。结论：肝移植术后GVHD死亡率高、预后差，现阶段诊断主要依靠典型临床表现及实验室检查，治疗以激素冲击为主要手段构成的综合治疗方法。

Abstract: Objective: The present study aims to comprehensively summarize the clinical experience regarding graft-versus-host disease (GVHD) subsequent to liver transplantation within a single medical center, and to meticulously explore the clinical manifestations, diagnostic approaches, and diagnosis and treatment strategy of GVHD in the post-liver transplantation setting. Methods: Clinical data of patients who manifested GVHD after assorted liver transplantation operations in the Affiliated Hospital of Qingdao University spanning from July 2013 to January 2024 were retrospectively collated. This encompassed initial symptomatology, laboratory evaluations, onset temporalities, and other relevant aspects. A descriptive analysis was then conducted to elucidate the clinical characteristics and diagnosis and treatment strategy of patients with post-liver transplantation GVHD. Results: Upon collecting the clinical data of 1263 patients who underwent diverse liver transplantation procedures, a total of six patients were definitively diagnosed with GVHD, yielding an incidence rate of 0.47%. Among these, five patients succumbed, all attributable to multiple organ failure consequent to severe infections. One patient has survived to date following treatment. The preponderant initial symptoms comprised dermatological eruptions, diarrhea, and febrile paroxysms. Laboratory examinations of the deceased patients exhibited pancytopenia accompanied by profound bone marrow suppression. Histopathological inspection unveiled vacuolar degeneration of the epidermal basal layer, lymphocyte infiltration, and necrotic eosinophilic keratinocytes. Peripheral blood chimerism assays demonstrated that the proportion of donor-derived T (CD8) cells surpassed 1%, signifying a large mixed chimeric state between the recipient and the donor. The cardinal treatment strategies incorporated steroid pulse therapy, reduction or cessation of immunosuppressive medications, application of advanced antibiotics for infection prevention, individualized treatment modalities, and symptomatic interventions. Conclusion: GVHD after liver transplantation has a high mortality rate and poor prognosis. At present, the diagnosis mainly relies on typical clinical manifestations and laboratory tests, and the treatment is a comprehensive treatment method mainly composed of steroid shock.