胆道闭锁 Kasai 术后肝脏病理改变的研究

Changes of hepatic pathology in children with biliary atresia after Kasai portoenterstomy

目的：探讨胆道闭锁 Kasai 手术后自体肝的形态及结构改变,分析其与 Kasai 术后肝脏损伤程度及胆管炎之间的关系。方法收集2012年5月至2012年12月间胆道闭锁患儿 Kasai 术后行肝移植手术的自体肝脏标本8例为实验组,其中男7例,女1例,同时收集另外8例胆道闭锁患儿行 Kasai 手术时肝脏活检标本为阳性对照组；收集尸检新生儿肝脏标本2例作为阴性对照组,观察胆道闭锁患儿 Kasai 术后肝脏病理变化特点,并简单分析对胆管炎发生的影响。采用 HE 和免疫组化技术等检测肝脏纤维化程度、胆管及血管的增生情况、肝细胞损伤情况以及炎症细胞的浸润情况,观察 Kasai 术后肝脏的病理改变。结果实验组中生后出现黄疸时间为0~15 d,行 Kasai 手术时间为44~105 d,出现胆管炎的频次为1~6次,肝移植距离 Kasai 手术后时间5~67个月。阳性对照组中肝活检的肝脏标本外观普遍增大,淤胆严重,质地中等；HE 和免疫组化结果显示肝脏纤维化分级介于Ⅱ~Ⅳ级之间,汇管区胆栓情况介于0~Ⅰ级之间,汇管区血管增生情况介于Ⅲ~Ⅳ级之间,胆管增生介于Ⅰ~Ⅲ级之间。实验组中肝脏外观多数呈现部分段、叶萎缩情况,也有部分肝脏标本呈现肥厚改变；肝脏纤维化分级都属于Ⅳ级,汇管区胆栓情况Ⅰ~Ⅱ级之间,汇管区血管增生情况Ⅳ级,胆管增生Ⅲ~Ⅳ级之间。结合临床资料分析,患儿行 Kasai 手术时间越晚,其术后发生胆管炎次数越多,使部分患儿几乎呈现胆管炎持续状态,导致肝脏纤维化和胆管增生速度加快,从而使自体肝生存时间缩短,严重影响预后。反之自体肝生存期较长,预后较好。结论胆道闭锁 Kasai 术后肝病理形态学改变具有特征性。术后肝脏损伤受 Kasai 手术时间影响,并对胆管炎的发生有影响；进一步说明早期Kasai 手术、减少术后胆管炎发生频次是延长胆道闭锁自体肝生存时间的关键因素。

Objective To explore the characteristic changes of hepatic pathology in children with biliary atresia （BA）after Kasai portoenterstomy （KP）and analyze the relation with the degree of hepatic damage and cholangitis.Methods A retrospective study was conducted for 16 consecutive BA patients between May 2012 and December 2012.Eight （7 males,1 females）patients of one group underwent hepatic transplantation and a removal of native liver.And another 8 patients underwent Kasai procedure.And hepatic specimens were collected intra-operatively.The pathology of hepatic tissue from two groups was studied.Another 2 specimens of hepatic tissue were harvested from neonatal autopsy as negative control.Pathological examinations included hematoxylin ＆ eosin and immunohistochemical staining for evaluating grade of hepatic fibrosis,extension of bile duct,vascular proliferation,degree of hepatocellular damage and infiltration of inflammatory cells.Results There were swelling,severe cholestasis and medium texture in the control group.The grading of hepatic fibrosis was between Ⅱ-Ⅳ,portal bile plugs 0-Ⅰ,vascular proliferation Ⅲ-Ⅳ and bile duct proliferation Ⅰ-Ⅲ.Macroscopically,the liver specimens of experimental group had more atrophic areas.Grading of hepatic fibrosis was divided into level Ⅳ,portal bile plugs Ⅰ-Ⅱ,portal vascular proliferation Ⅳ and proliferation of bile duct Ⅲ-Ⅳ.Combined with clinical data,earlier Kasai operation was associated with less frequency of cholangitis.And hypertrophic area was more than atrophic area. Meanwhile,there was severe hepatic fibrosis,but bile duct proliferation was relatively mild.Late Kasai ＇s procedures had a worse prognosis.And some children showed persistent cholangitis and a short survival period.Conclusions The pathological changes after hepatic removal have characteristic manifestations.Hepatic damage and timing of KP are the risk factors of cholangitis in BA patients after KP.