Banff移植肝病理学诊断标准及其进展

郭晖; 王政禄; 丛文铭; 陈知水

doi:10.3969/j.issn.1674-7445.2021.05.003

Banff移植肝病理学诊断标准及其进展

doi: 10.3969/j.issn.1674-7445.2021.05.003

430030 武汉，华中科技大学同济医学院附属同济医院器官移植研究所器官移植教育部重点实验室国家卫生健康委员会器官移植重点实验室中国医学科学院器官移植重点实验室（郭晖、陈知水）；天津市第一中心医院中国医学科学院移植医学重点实验室天津市器官移植重点实验室南开大学移植医学研究院（王政禄）；上海东方肝胆外科医院（丛文铭）

基金项目:

中国医学科学院中央级公益性科研院所基本科研业务费专项资金资助 2019PT320014

详细信息

作者简介:
郭晖，研究方向为移植病理学基础与临床应用研究，Email：zcguo@tjh.tjmu.edu.cn

通讯作者:
陈知水，研究方向为肝移植临床与基础研究，E-mail: zschen@tjh.tjmu.edu.cn

中图分类号: R617, R36
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出版历程
- 收稿日期: 2021-07-09
- 网络出版日期: 2021-09-15
- 刊出日期: 2021-09-15

Banff classification and progress on liver allograft pathology

Organ Transplantation Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation of Ministry of Education, Key Laboratory of Organ Transplantation of National Health Commission of China, Key Laboratory of Organ Transplantation of Chinese Academy of Medical Sciences, Wuhan 430030, China

More Information

Corresponding author: Chen Zhishui, E-mail: zschen@tjh.tjmu.edu.cn

摘要

摘要: 移植肝活组织检查(活检)病理学不仅在供肝病理学评估，而且在移植术后并发症的诊断和鉴别诊断中是不可缺少的。移植肝并发症的病理学诊断相关研究随着临床肝移植的扩展而日益深入，国际上逐渐制订了Banff移植肝活检病理学诊断标准，我国移植肝活检的病理学研究也逐步开展，并逐渐形成了适合我国肝移植临床实际的移植肝活检病理学诊断标准。本文对Banff移植肝活检病理学研究的历史和移植肝并发症的主要病变进行综述，旨在为我国更好地开展移植肝活检病理学诊断，协助临床进行肝移植术后并发症的明确诊断和针对性治疗，进一步提高移植肝和受者的良好存活提供参考依据。
- 移植病理学 /
- 肝移植 /
- 活组织检查 /
- 病理学诊断标准 /
- 抗体介导的排斥反应(AMR) /
- T细胞介导的排斥反应(TCMR) /
- 慢性移植物血管病 /
- 药物性肝损伤
Abstract: The pathology of liver allograft biopsy is not only essential for the evaluation of liver donor, but also for the diagnosis and differential diagnosis of posttransplantation complications. With the development of liver transplantation in clinical practice, relevant studies of the pathological diagnosis of liver allograft complications have been deepened. Banff classification on liver allograft pathology have been gradually established within the international community. In China, pathological studies related to liver allograft pathology have been steadily carried out, and the pathological diagnostic basis of liver allograft pathology suitable for the clinical practice of liver transplantation in China has been gradually formed. This article reviews the history of Banff liver allograft pathology and major pathological lesions of liver allograft complications, aiming to provide reference for implementing pathological diagnosis of liver allograft pathology in China, assisting clinical diagnosis and targeted treatment of complications after liver transplantation, and further improving the survival of liver allograft and recipients.
- Allograft pathology /
- Liver transplantation /
- Biopsy /
- Diagnostic classification of pathology /
- Antibody-mediated rejection (AMR) /
- T cell-mediated rejection (TCMR) /
- Chronic allograft vasculopathy /
- Drug induced liver injury

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图 1 供肝大泡性脂肪变性和局灶性缺血性坏死的病理学表现

注：A图示供肝活检组织冷冻切片(油红O，×400)，肝细胞内脂滴呈大颗粒红染阳性；B图示供肝活检快速石蜡切片中大多数肝细胞(＞70%)明显大泡性脂肪变性(HE，×200)；C图示供肝楔形活检组织内肝小叶腺泡Ⅲ区肝细胞缺血性坏死及部分区域两个肝小叶内坏死区域融合，蓝线内坏死肝细胞比例 > 20%(HE，×100)。

Figure 1. Pathological findings of macrovesicular steatosis and focal ischemic necrosis of the donor liver

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图 2 移植肝急性TCMR的病理学表现

注：A图示移植肝门管区内炎症细胞浸润，门管区内淋巴细胞浸润(星号所示)即小叶间胆管炎(箭头所示)(HE，×200)；B图示门管区内小叶间胆管炎，可见小叶间胆管上皮内多个淋巴细胞浸润(箭头所示)(HE，×1 000)。

Figure 2. Pathological findings of acute TCMR in liver allograft

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图 3 移植肝中央静脉炎型急性排斥反应的病理学表现

注：A图示中央静脉内皮炎表现(箭头所示)(HE，×400)；B图示中央静脉周围肝细胞出血坏死(箭头所示)(HE，×200)。

Figure 3. Pathological findings of acute rejection of central venulitis in liver allograft

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图 4 移植肝急性AMR的病理学表现

注：A图示部分肝窦内皮呈C4d阳性(箭头所示)(免疫酶组化，×200)；B图示门管区内毛细血管内皮C4d阳性(箭头所示)(免疫酶组化，×200)。

Figure 4. Pathological findings of acute AMR in liver allograft

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图 5 移植肝慢性排斥反应的病理学表现

注：A图示移植肝小叶间胆管萎缩及消失改变(HE，×400)；B图示移植肝活检组织内CK19免疫组化染色(免疫酶组化，×400)，可见小叶间胆管萎缩(箭头所示)；C图示移植肝动脉的慢性排斥反应动脉血管病，图示肝动脉分支内膜泡沫细胞增生填塞及管腔狭窄(箭头所示)(HE，×400)。

Figure 5. Pathological findings of chronic rejection in liver allograft

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图 6 移植肝胆管并发症的病理学表现

注：A图示移植肝活检组织门管区内轻微水肿，小叶间胆管周围及其上皮层内中性粒细胞浸润(HE，×400)；B图示移植肝小叶中央区域内的毛细胆管明显扩张及胆汁淤积(HE，×400)。

Figure 6. Pathological findings of biliary complications in liver allograft

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图 7 移植肝复发性乙型病毒性肝炎的病理学表现

注：A图示移植肝活检组织内HBsAg免疫组化染色在肝细胞呈弥漫性阳性(免疫酶组化，×200)；B图示肝细胞胞浆内呈HBsAg阳性的病毒颗粒(箭头所示)(免疫酶组化，×1 000)。

Figure 7. Pathological findings of recurrent hepatitis B in liver allograft

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图 8 移植肝复发性自身免疫性肝炎病理学表现

注：图示移植肝活检组织内门管区周边典型的界板性炎症表现，同时可见局部的炎症向周围邻近肝组织扩展(HE，×200)。

Figure 8. Pathological findings of recurrent autoimmune hepatitis in liver allograft

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图 9 肝移植后GVHD所致皮疹的皮肤活检的病理学表现

注：A图示活检皮肤组织内鳞状上皮基底部有淋巴细胞及中性粒细胞浸润，基底细胞凋亡坏死呈“木乃伊细胞”(箭头所示)(HE，×400)；B图示皮肤活检真皮组织内的微血管周围淋巴细胞围管状浸润(HE，×200)。

Figure 9. Pathological findings of skin biopsy of skin rash caused by GVHD after liver transplsntation

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表 1 Banff标准中移植肝排斥反应的RAI评分

Table 1. RAI scoring of rejection of liver allograft in Banff classification

计分(分)	门管区炎症	胆管炎症	血管炎症
1	仅少数的门管区内可见淋巴细胞等炎症细胞浸润，门管区范围无明显扩大	少数小叶间胆管上皮内炎症细胞浸润和胆管上皮轻度损伤改变(包括细胞核增大、核/浆比增加)	少数小叶间血管(小叶间动脉或小叶间静脉)和(或)中央静脉的血管炎表现
2	多数或全部门管区内均出现混合性炎症细胞浸润(包括淋巴细胞、浆细胞、少数中性粒细胞和嗜酸性粒细胞等)，门管区扩大。如果出现多量嗜酸性粒细胞浸润伴门管区水肿和微血管内皮细胞肿大改变，应注意急性AMR因素	多数胆管上皮内炎症细胞浸润，较多胆管出现损伤改变包括胞核多形性、极像紊乱和胞浆空泡变	多数或全部小叶间血管和(或)中央静脉的血管炎表现，少数中央静脉周围肝细胞脱失
3	多数或全部门管区出现混合性炎症细胞浸润，门管区因水肿和大量炎症细胞浸润范围扩大，部分门管区内炎症细胞扩展进入周围肝组织内	在2的基础上出现多数或全部胆管退化或灶性胆管腔破坏崩解	在2的基础上，出现中重度中央静脉炎及其周围炎并延伸至周围肝实质和中央静脉周围多数肝细胞坏死

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表 2 移植肝慢性排斥反应的病理学诊断标准

Table 2. Pathological diagnostic criteria for chronic rejection of liver allograft

主要病变部位	早期的慢性排斥反应 (至少符合两条)	晚期的慢性排斥反应 (至少符合两条)
小胆管(< 60 μm)	多数门管区内小叶间胆管出现损伤， < 50%门管区出现小叶间胆管消失	≥50%门管区出现小叶间胆管消失，其余门管区内小叶间胆管出现损伤退化
小叶间动脉	< 25%门管区出现小叶间动脉消失	≥25%门管区出现小叶间动脉消失
终末肝静脉和Ⅲ区肝细胞	终末肝静脉周围单个核细胞浸润，腺泡Ⅲ区肝细胞坏死和炎症细胞浸润，轻度纤维化	终末肝静脉程度不等的炎症细胞浸润，局灶性静脉闭塞，中到重度(桥样)纤维化
肝动脉主干分支	动脉内膜炎、局灶性泡沫细胞沉积，无管腔狭窄或闭塞	内膜泡沫细胞沉积及纤维组织增生导致管腔狭窄甚至闭塞
胆管主干分支	炎症损伤和灶性泡沫细胞沉积	管壁纤维化
其他	“过渡性”肝炎和多灶性肝细胞坏死	肝窦泡沫细胞沉积、胆汁淤积

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