胆道闭锁Kasai术后胆管病理改变的研究

Changes of bile duct pathology in children with biliary atresia after Kasai portoenterstomy

目的研究胆道闭锁Kasai术后肝内胆管结构改变，分析其与胆管炎发生的关系，为临床治疗胆管炎提供依据。方法收集2013年1月至2013年6月期间胆道闭锁Kasai术后行肝移植手术切除的肝脏标本8例，其中男6例，女2例，生后出现黄疸时间为3～20d，行Kasai手术时间为生后44－85d，术后发生胆管炎的频次为1～6次或呈现胆管炎持续状态，行肝移植时间为Kasai术后6～66个月。同时收集胆道闭锁行Kasai手术肝脏活检标本8例作为阳性对照。采用HE和免疫组化等技术分别检测汇管区小叶间胆管直径、管腔数量；汇管区小叶间胆管增生分级；汇管区胆栓分级；炎症细胞浸润分级；小叶间胆管板畸形；小叶间胆管增生与纤维组织增生的比例；分析其与临床发生胆管炎的关系。结果8例行Kasai手术肝活检标本提示汇管区胆管增生4例较重，4例较轻；小叶间胆管直径〈30μm；胆管上皮增生较轻，但胆管反应较重；胆管增生与纤维组织增生比例〈1／4；汇管区炎症细胞浸润较重。8例胆道闭锁术后肝移植切除肝脏标本提示汇管区胆管组织增生6例较重，2例较轻；小叶间胆管直径1例〉100μm，7例〈30μm；胆管上皮增生及胆管反应均较重；胆管增生与纤维组织增生比例介于1／2－3／4之间；2例汇管区炎症细胞浸润较重，6例较轻。结合临床资料分析，胆道闭锁早期行Kasai手术患儿，胆管炎发生次数相对较少，胆管增生情况相对较轻，小叶间胆管直径较大，接受肝移植时间有所延长，其肝移植切除肝脏标本显示肝脏纤维化加重，胆管大量增生，而汇管区炎细胞浸润及胆栓较轻。结论胆道闭锁患儿Kasai术后汇管区胆管增生情况，胆管增生与纤维组织增生的比率，开放胆管的直径等肝内胆管改变影响术后胆管炎的发生频次；早期行Kasai手术可以适当减轻胆管的损伤，延长Kasai术后自体肝生存时间。

Objective To explore the changes of intrahepatic bile duct structure in children with biliary atresia （BA） after Kasai portoenterstomy （KP） and analyze the relationship with cholangioitis so as to provide therapeutic rationales for cholangioitis. Methods Liver specimens after KP were collected intraoperatively in 8 （6 males,2 females） patients with liver transplantation between January 2013 and June 2013. The clinical data of patients included： occurring time of jaundice was 3-20 days and operative duration within 44-85 days, frequency of cholangioitis I-6 times or persistent status, The interval time between Kasai operation and liver transplantation were 6-66 months. Also liver biopsy specimens were collected intraoperatively in 8 patients as controls. Hematoxylin I~ eosin （HE） and immunohistochemical （IHC） staining were employed for detecting the portal area with regards to interlobular bile duct diameter, lumen number; hyperplasia degree of interlobular bile duct, interlobular bile thrombi; inflammatory cell infiltration; bile duct plate malformation; proportion of bile duct proliferation and hyperplasia of fibrous tissue to analyze the relationship with cholangioitis. Results Control group： bile duct hyperplasia was severe （n = 4） and mild （n = 4） ; bile duct diameter 〈30μm; mild hyperplasia of bile duct epithelium, bile duct reaction was more severe; the ratio of bile duct hyperplasia and fiber proliferation 〈 1/4; inflammatory cell infiltration was severe. Experimental group：bile duet hyperplasia was severe （n = 6） and mild （n= 2）; bile duct diameter 〉100μm （n = 1） and 〈30 μm （n = 7） ; bile duct epithelial hyperplasia and bile duct reaction were severe; percentage of bile duct hyperplasia and fiber hyperplasia between 1/2- 3/4; inflammation cell infiltration was severe （n = 2） and mild （n = 6）. For BA children operated earlier, the frequency of cholangioitis were less, bile duct hyperplasia was relatively mild, interlobular bile duct diameter was larger, liver transplant time delayed, their liver specimens after KP showed severe fibrosis and bile duct proliferation. While inflammatory cell infiltration and bile thrombi were milder. Conclusions Among BA children after KP, intrahepatic bile duct changes including hyperplasia of periportal bile duct, bile duct proliferation and fibrous tissue hyperplasia and open bile duct diameter may impact on the frequency of cholangioitis. Early Kasai operation is recommended to reduce bile duct injury and prolong autologous liver survival time.