ABCB11基因突变导致的进行性家族性肝内胆汁淤积症的临床病理观察  

Progressive familial intrahepatic cholestasis caused by ABCB11 gene mutation:a clinicopathological study

作　　者：冯佳燕 陈莲 马阳阳 赵菁 FENG Jia-yan;CHEN Lian;MA Yang-yang;ZHAO Jing(Department of Pathology,Children＇s Hospital of Fudan University,Shanghai 201102,China)

机构地区：[1]复旦大学附属儿科医院病理科,上海201102

出　　处：《临床与实验病理学杂志》2018年第7期729-733,共5页Chinese Journal of Clinical and Experimental Pathology

摘　　要：目的探讨ABCB11基因突变导致的进行性家族性肝内胆汁淤积症(progressive familial intrahepatic cholestasis,PFIC)的临床特点、组织学形态、免疫表型及其鉴别诊断。方法分析8例ABCB11基因突变导致PFIC的临床资料、基因检测、病理学形态和免疫表型,并复习相关文献。结果基因检测显示8例均有ABCB11基因突变,1岁内起病,以持续性黄疸为主要表现,不伴肝外异常症状,血清GGT水平均较低或正常。7例肝活检组织HE染色镜下均可见弥漫的肝细胞气球样变及多核巨肝细胞形成,同时伴明显的肝细胞内胆汁淤积及较轻的肝小叶内炎症,汇管区纤维化及炎症程度不等。1例巨肝细胞病变程度轻且无明显的炎症,所有病例均未发现真性胆小管增生。7例肝活检组织中BSEP蛋白表达缺失或减少,1例表达无明显减少。结论肝组织的病理特征及BSEP蛋白的免疫组化检测是明确诊断ABCB11基因突变导致PFIC的重要手段,结合临床表现可对该病进行早期筛查,提高基因检测及临床诊疗的针对性。Purpose To analyze the clinicopathological characteristics of progressive familial intrahepatic cholestasis （PFIC） caused by ABCBll gene mutation and to discuss the differential diagnosis. Methods The clinical, histopathological profiles and genetic test results in 8 pediatric cases of PFIC caused by ABCB11 gene mutation was reviewed. Results Genetic detection showed that 8 cases had ABCBll gene mutate. All patients were onset within the age of 1 year. The patients presented with persistent jaundice and low or normal levels of serum GGT, without extrahepatic abnormal symptoms. Histologically, 7 cases of liver biopsy samples showed visible diffuse hepatocellular ballooning, multinueleated giant and cholestasis hepatic cells with a mild intrahepatic inflammation as well as mild to moderate fibrosis and inflammation in portal. Macro-hepatocytes lesions were mild and no significant inflammatory changes could seen in one case. No real bile duct hyperplasia was found in all cases. By immunohistochemistry, the liver biopsy showed that BSEP protein expression was absent or decreased in 7 ca- ses, BSEP protein expressed normal in 1 case. Conclusion The pathological morphology and BSEP protein detection in liver tissue were one of the most important means to definitive diagnose PFIC by ABCBll gene mutation although it cannot be used. Nonetheless, the disease can be early screening in combination with clinical manifestation, as well as improving pertinence of genetic tests and clinical diagnosis and treatment.

关 键 词：进行性家族性肝内胆汁淤积症 ABCB11基因 GGT BSEP 病理学 免疫组织化学 

分 类 号：R735.7[医药卫生—肿瘤]