进行性家族性肝内胆汁淤积症3型临床病理特征分析  

Clinical and pathological features of progressive familial intrahepatic cholestasis type 3

作　　者：翁宇航 熊清芳 刘杜先 张胥磊[1] 杨永峰 WENG Yuhang;XIONG Qingfang;LIU Duxian;ZHANG Xulei;YANG Yongfeng(Department of Hepatology,Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine&Nanjing Second Hospital,Nanjing 210003,China)

机构地区：[1]南京中医药大学附属南京医院(南京市第二医院)肝病科,南京210003

出　　处：《临床肝胆病杂志》2022年第1期154-159,共6页Journal of Clinical Hepatology

基　　金：国家自然科学基金(81970454)。

摘　　要：目的探讨进行性家族性肝内胆汁淤积症3型(PFIC3)患者临床与病理学特征。方法回顾分析了2017年1月—2019年12月南京市第二医院就诊的1326例不明原因肝病患者临床资料,通过临床、病理表现及基因测序确诊PFIC3患者8例(其中1例因禁忌证未行肝组织穿刺)。分析患者临床、检验、影像、病理结果,并对ABCB4相关疾病的病理文献进行回顾,总结PFIC3临床及病理特征。结果8例PFIC3患者,其中男5例,女3例,中位年龄29.5岁。50%(4/8)表现为慢性胆汁淤积,50%(4/8)表现胆汁性肝硬化,肝硬化中75%(3/4)合并门静脉高压表现。生化检查中,75%(6/8)表现为ALP升高,100%(8/8)表现GGT升高。影像检查中,50%(4/8)表现为胆囊炎,25%(2/8)表现为胆囊结石,25%(2/8)患者胆管扩张,75%(6/8)患者脾脏肿大,25%(2/8)表现为肝硬化。肝穿刺病理中,所有患者均表现为胆管损伤和/或胆管减少,其中57.1%(4/7)表现为胆管缺失。多耐药蛋白3(MDR3)免疫组化染色42.9%(3/7)正常表达,57.1%(4/7)表达减少。根据文献回顾,其中包含胆管描述或MDR3免疫组化的文献17篇。7例低磷脂相关性胆石症中,胆管正常占71.4%(5/7),胆管减少占14.3%(1/7),胆管缺失占14.3%(1/7);6例妊娠期肝内胆汁淤积症中,胆管正常占16.7%(1/6),胆管减少占50%(3/6),胆管缺失占33.3%(2/6);8例PFIC3中,胆管减少占25%(2/8),胆管缺失占75%(6/8);21例PFIC3患者MDR3表达正常占9.5%(2/21),表达减少占23.8%(5/21),表达缺失占66.7%(14/21)。结论PFIC3以胆汁淤积、胆石症、肝纤维化为主要表现。病理表现为胆管损伤,严重者可伴胆管减少或缺失,且损伤程度与疾病严重程度相关。MDR3免疫组化可表现为正常、减少或表达缺失,正常表达患者仍不能排除诊断,必要时行基因检测确诊。Objective To investigate the clinical and pathological features of progressive familial intrahepatic cholestasis type 3(PFIC3).Methods A retrospective analysis was performed for 1326 patients with unexplained liver disease who attended Nanjing Second Hospital from January 2017 to December 2019,among whom 8 patients were diagnosed with PFIC3 based on clinical/pathological manifestation and gene sequencing results(1 patient did not undergo liver biopsy due to contraindication).Clinical,laboratory,imaging,and pathological findings were analyzed and a literature review was performed for the pathology of ABCB4-related diseases to summarize the clinical and pathological features of PFIC-3.Results Among the 8 patients with PFIC3,there were 5 male patients and 3 female patients,with a median age of 29.5 years.Of all 8 patients,4(50%)manifested as chronic cholestasis and 4(50%)manifested as biliary cirrhosis,among whom 3(75%)had the manifestation of portal hypertension.As for biochemical examination,75%(6/8)had an increase in alkaline phosphatase,and 100%(8/8)had an increase in gamma-glutamyl transpeptidase.As for imaging examination,50%(4/8)had cholecystitis,25%(2/8)had gallstones,25%(2/8)had bile duct dilatation,75%(6/8)had splenomegaly,and 25%(2/8)had liver cirrhosis.As for liver biopsy,all 7 patients manifested as bile duct injury and/or reduction,and 57.1%(5/7)had absence of the bile duct.Multidrug resistance P-glycoprotein 3(MDR3)immunohistochemical staining showed normal expression in 42.9%(3/7)of the patients and reduced expression in 57.1%(4/7)of the patients.Literature review obtained 17 articles with a description of the bile duct or MDR3 immunohistochemistry.Among the 7 patients with low phospholipid-associated cholelithiasis,71.4%(5/7)had normal bile duct,14.3%(1/7)had bile duct reduction,and 14.3%(1/7)had absence of the bile duct;among the 6 patients with intrahepatic cholestasis of pregnancy,16.7%(1/6)had normal bile duct,50%(3/6)had bile duct reduction,and 33.3%(2/6)had absence of the bile duct;among the 8

关 键 词：胆汁淤积 肝内 P糖蛋白类 病理状态 体征和症状 

分 类 号：R575[医药卫生—消化系统]