肝移植术后抗体介导的排斥反应与胆道狭窄的关系及诊疗策略分析
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昆明医科大学附属甘美医院/昆明市第一人民医院 肝胆胰外科,云南省器官移植临床医学中心,云南 昆明 650011

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莽源祎,昆明医科大学附属甘美医院/昆明市第一人民医院主治医师,主要从事肝胆胰外科及肝移植方面的研究。

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云南省科技厅科技计划基金资助项目(202201AY070001-198,202302AA310018);“春城计划”高层次人才创业创新团队专项基金资助项目(2022SCP002-C-11)。


Analysis of the relationship between antibody-mediated rejection and biliary strictures following liver transplantation and its diagnosis and treatment strategies
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Department of Hepato-biliary-pancreatic Surgery, the Calmette Affiliated Hospital of Kunming Medical University/the First people Hospoital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming 650011, China

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    摘要:

    背景与目的 肝移植术后抗体介导的排斥反应(AMR)相对少见,但AMR是移植后移植物失功能的重要危险因素。本研究探讨肝脏移植术后AMR的发生情况,以及AMR与胆道狭窄的关系及诊疗策略。方法 回顾性分析2016年1月—2023年10月在昆明市第一人民医院接受的脑死亡捐献肝移植的203例患者的临床资料。结果 203例肝移植患者中,发生肝移植术后急性排斥反应20例,其中AMR 7例、T细胞介导的急性排斥反应(TCMR)13例;发生胆道狭窄18例。发生急性排斥的患者中,6例(30.0%)发生胆道狭窄,未发生急性排斥患者中,12例(6.6%)发生胆道狭窄,前者胆道狭窄的发生率明显高于后者(P=0.002)。AMR患者中5例(71.4%)发生胆道狭窄,其中诊断急性AMR时3例患者合并胆道狭窄并处理,2例患者在AMR治疗好转后1年随访过程中出现胆道狭窄;TCMR患者中仅1例(7.7%)于术后3年发生胆道狭窄,AMR患者胆道狭窄的发生率明显高于TCMR患者(P=0.007)。7例AMR患者中,1例在移植术后2个月出现肝功能异常,在1周内快速出现肝功能恶化,经激素冲击治疗无效后因肝功能衰竭并颅内出血死亡;其余6例在处理胆道狭窄(发生胆道狭窄的患者)并针对AMR治疗后,肝功能均恢复正常。结论 肝移植术后AMR增加胆道狭窄风险,对于急性AMR合并胆道狭窄的患者,除通畅胆道引流治疗外应尽快考虑AMR诊断和对应治疗。

    Abstract:

    Background and Aims Antibody-mediated rejection (AMR) is relatively uncommon after liver transplantation, but it poses a significant risk factor for graft function loss. This study investigated the occurrence of AMR after liver transplantation, its relationship with biliary strictures, and the associated diagnostic and therapeutic strategies.Methods The clinical data from 203 patients who underwent brain death donation liver transplantation at the First People's Hospital of Kunming from January 2016 to October 2023 were retrospectively analyzed.Results Among the 203 liver transplant recipients, 20 cases developed acute rejection after transplantation, including 7 cases of AMR and 13 cases of T-cell-mediated acute rejection (TCMR). Additionally, 18 cases had biliary strictures. Among patients with acute rejection, 6 cases (30.0%) developed biliary strictures, while among those without acute rejection, 12 cases (6.6%) developed biliary strictures, indicating a significantly higher incidence in the former group (P=0.002). In the AMR group, 5 cases (71.4%) developed biliary strictures, of whom 3 cases had concomitant biliary strictures at the time of acute AMR diagnosis and were treated accordingly, while 2 cases developed biliary strictures during the one-year follow-up after AMR treatment. Only 1 TCMR patient (7.7%) developed biliary stricture 3 years after operation, the incidence of biliary strictures in AMR patients was significantly higher than in TCMR patients (P=0.007). Among the 7 AMR patients, one experienced rapid deterioration of liver function within two months after transplantation, leading to death despite steroid pulse therapy. The remaining 6 patients, after managing biliary strictures and receiving AMR-specific treatment, showed normalization of liver function.Conclusion AMR after liver transplantation increases the risk of biliary strictures. For patients with acute AMR and concurrent biliary strictures, prompt consideration of AMR diagnosis and corresponding treatment is essential, in addition to ensuring biliary drainage.

    表 3 7例AMR患者诊疗详情Table 3 Details of diagnosis and treatment in the 7 AMR patients
    表 1 肝移植术后急性排斥反应与胆道狭窄的关系分析[n(%)]Table 1 Analysis of the relationship between acute rejection after liver transplantation and biliary strictures [n (%)]
    图1 急性AMR血管内皮炎,移植肝活检提示血管内皮肿胀、坏死、脱落,血窦、门管区大量红细胞外溢小血管周围多个炎细胞浸润(箭头所示),H评分2~3(HE×100)Fig.1 Acute AMR vascular endothelialitis, and the biopsy of the transplanted liver reveal vascular endothelial swelling, necrosis, detachment, and numerous inflammatory cells infiltrate around small vessels with extravasation of red blood cells in the sinusoidal and portal vein areas (as indicated by arrows), and an H-score of 2-3 (HE×100)
    图2 AMR治疗前、后的免疫荧光染色(黄色标记C4d,绿色标记CD34以显示血管内皮)可见急性AMR显著的C4d沉积和血管内皮破坏,经治疗后病检仍可见C4d沉积,但血管内皮结构可见Fig.2 Immunofluorescence staining before and after AMR treatment (C4d marked in yellow, CD34 marked in green to visualize endothelial cells) reveals significant C4d deposition and endothelial damage in acute AMR, and pathological examination still shows C4d deposition after treatment, but improvements are observed in the endothelial structure
    图3 胆道造影诊断胆道狭窄 A:ERCP造影;B:PTCD造影Fig.3 Cholangiography for diagnosis of biliary strictures A: ERCP image; B: PTCD image
    图4 胆道支架治疗胆道狭窄 A:ERCP诊断胆道狭窄后行金属覆膜支架置入;B:PTCD造影诊断胆道狭窄后行塑料支架置入Fig.4 Biliary stent insertion in treatment of biliary strictures A: Metal-coated stent implantation after ERCP diagnosis of biliary strictures; B: Plastic stent implantation after PTCD angiography for diagnosis of biliary strictures
    表 2 排斥反应类型与胆道狭窄之间的关系分析[n(%)]Table 2 Analysis of the relationship between types of rejection reaction and biliary strictures [n (%)]
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莽源祎,杨彦,高杨,马俊,陈国煜,张升宁,王新超.肝移植术后抗体介导的排斥反应与胆道狭窄的关系及诊疗策略分析[J].中国普通外科杂志,2024,33(1):9-17.
DOI:10.7659/j. issn.1005-6947.2024.01.002

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  • 收稿日期:2023-11-29
  • 最后修改日期:2024-01-20
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  • 在线发布日期: 2024-02-05