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摘要: 胆汁淤积性肝病（CLD）是指各种病因引起的胆汁代谢异常、流出受阻、胆管损伤等肝脏疾病，主要病因包括：药物、毒物、免疫、遗传、梗阻、感染、肿瘤等。胆汁淤积是CLD共有的病理改变，而不同病因淤胆的部位、组织病理及超微结构等改变，具有相对特异性。依据病因，重点阐述自身免疫性胆管炎、遗传代谢性肝病、大胆管病变的病理学特征，引申鉴别其他CLD，以期提高对CLD病理学的认识，助力精准诊疗。Abstract: Cholestatic liver disease （CLD） is a group of liver diseases caused by various reasons， such as abnormal bile metabolism， blocked outflow， and bile duct injury， and the major causes of CLD include drugs， poisons， immunity， genetics， obstruction， infection， and tumor. Cholestasis is a common pathological change in CLD； however， the site， histopathology， and ultrastructure of cholestasis due to different etiologies are relatively specific. According to the etiology， this article elaborates on the pathological characteristics of CLD such as autoimmune cholangitis， inherited metabolic liver disease， and large bile duct disease and introduces the differential diagnosis of other types of CLD， in order to improve the understanding of CLD pathology and facilitate accurate diagnosis and treatment.
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Key words:
- Cholestasi /
- Biopsy /
- Pathology /
- Diagnosis
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图 1 巨细胞变肝细胞（HE染色）
注： a，×100；b，×200。较多巨细胞变肝细胞，胞体巨大，多核，胞质内可见淤胆性色素颗粒，汇管区小胆管损伤及轻微扩张，间质可见中性粒细胞等炎性细胞浸润。
Figure 1. Hepatocyte with giant-cell transformation（HE staining）
图 2 PBC典型的病理学特征
注： a，小胆管损伤伴淋巴细胞、浆细胞包围浸润及上皮样细胞肉芽肿，偶见多核巨细胞（HE染色，×100）；b，旺炽型胆管炎，胆管上皮细胞嗜酸性化，核固缩，排列不整齐，管壁及管周较多淋巴细胞、浆细胞聚集浸润，散在少许嗜酸性粒细胞（HE染色，×200）；c，CK7标记未见小胆管缺失，可见轻微细胆管反应（免疫组化，×100）。
Figure 2. Typical pathological features of PBC
图 3 PSC典型的病理学特征
注： a，肝硬化，汇管区轻度炎症，小胆管轻度扩张，管周纤维化（HE染色，×20）；b，汇管区轻度炎症，小胆管基底膜增厚，周围“洋葱皮样”纤维化，小动脉扩大，管壁轻微增厚，门静脉分支扩张及管周纤维化，汇管区周围肝细胞气球样变性（HE染色，×100）；c，免疫组化CK7显示肝细胞胆管化（IHC染色，×100）；d，小胆管基底膜增厚（D-PAS染色，×100）。
Figure 3. Typical histopathological features of PSC
图 4 肝豆状核变性的组织病理学及超微结构特征
注： a，肝细胞水肿、脂肪变性、气球样变性，部分胞质呈淡红色颗粒状，腺泡1区少许糖原核肝细胞。汇管区轻度炎症（HE染色，×100）；b，肝细胞胞质内较多红色铜颗粒沉积（罗丹宁铜染色，×100）；c，肝细胞胞质内线粒体形态不规则，内外膜分类，可见内嵴扩张空泡及圆形高电子致密颗粒。肝细胞胞质内也可见脂滴、含高电子致密度的淤胆性色素颗粒沉积（TEM，×12 000）。
Figure 4. Histopathological and ultrastructural characteristics of WD
图 5 CHF典型的组织病理学特征
注： a，CHF“地图样”纤维化，胆管板畸形，胆汁淤积（HE染色，×40）；b，汇管区胆管板畸形，门静脉狭窄、闭塞，肝细胞轻度水肿（HE染色，×100）；c，畸形的胆管板内陷于汇管区纤维组织中，门静脉分支狭窄、闭塞（HE染色，×200）；d，胆管板畸形，形态不规则，管腔扩张，可见胆栓，间质少许淋巴细胞、浆细胞浸润（HE染色，×200）。
Figure 5. Typical histopathological features of CHF
图 6 EPP的组织病理学及超微结构特征
注： a，肝细胞及毛细胆管内两种颜色的淤胆颗粒及胆栓，一种“巧克力”色，另一种淡黄色（HE染色，×100）；b，偏振光显微镜可见红色双折光中的“Maltese十字”或星状暗区（HE染色，偏振光，×200）；c，毛细胆管内可见原卟啉结晶（箭头），呈丝状弧形排列，毛细胆管腔面微绒毛减少，紧密连接延长（TEM，×15 000）；d，Kupffer细胞胞质溶酶体内充满丝状原卟啉结晶（箭头），窦周间隙可见胶原纤维束沉积（TEM，×15 000）。
Figure 6. Histopathological and ultrastructural characteristics of EPP
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