胆道闭锁Kasai术后肝移植患儿不同自体肝生存的临床与病理分析

Clinicopathological analysis with different native liver survivals for biliary atresia after Kasai

目的分析和比较胆道闭锁(Biliary Atresia,BA)Kasai术后肝移植患儿不同自体肝生存情况,结合手术时病理及肝功能指标,初步探讨自体肝生存时间较长患儿的肝脏病理特点。方法将43例Kasai术后行肝移植的BA患儿按Kasai术与肝移植术间隔时间分为3组:G1组(n=17),间隔时间<6个月;G2组(n=18),间隔时间6个月至2年;G3组(n=8),间隔时间>2年。分析各组患儿临床资料包括Kasai手术时年龄、术后胆管炎发生情况、肝移植术前肝功能生化指标,同时对实施Kasai手术时及肝移植手术时的肝组织进行HE、Masson及免疫组化(CK19)染色,观察肝脏纤维化程度、胆管增生程度、淤胆情况以及炎性细胞浸润情况。结果 (1)三组Kasai手术时平均日龄分别为66.65 d、58.39 d、49.63 d,差异有统计学意义(F=3.757,P=0.032);三组患儿术后出现胆管炎的比例分别为12/17(70.6%)、14/18(77.8%)、4/8(50.0%),经统计学分析差异无意义(χ~2=2.035,P>0.05);三组出现频发胆管炎的例数分别为7/10(41.2%)、12/18(66.7%)、1/8(12.5%),经统计学分析差异有意义(χ~2=6.679,P=0.032);肝移植手术前三组患儿肝功能指标显示G3组AST、ALT、TBI、DBI、GGT、TBA均低于前两组,但差异无统计学意义(P>0.05)。(2)Kasai手术时肝纤维化分级为3(2～3),胆管增生分级为2(1～2.5),胆栓分级为1(1～2.5),汇管区炎细胞浸润程度分级为3(1.5～3);移植时肝脏病理显示三组肝纤维化程度分级分别为4(4～4)、4(4～4)、4(2～4),经统计学分析差异有意义(χ~2=5.978,P=0.047);胆管增生程度分级分别为3(3～3)、2(1～3)、0(0～2),经统计学分析差异有意义(χ~2=19.577,P<0.001);胆栓分级分别为3(2.5～3)、1(1～3)、1(1～3),经统计学分析差异有意义(χ~2=13.998,P<0.001);炎细胞浸润程度分级分别为2(1～2)、1.5(1～2)、1(1～1),差异具有统计学意义(χ~2=6.221,P=0.044)。(3)Kasai手术日龄越早,术后胆管炎发作次数越少的BA患儿,其肝纤维化进展速度缓慢,胆管增生、淤胆及炎细胞浸润程度轻,自体肝生存时间较长。结论 (1)BA患儿行Kasai手术的日龄及术后胆管炎发作的频次,是影响术后肝脏病理及自体肝生存时间的重要因素。(2)对于自体肝生存时间长的BA患儿,Kasai手术解除了胆道梗阻,降低了炎细胞浸润程度,有助于延缓肝纤维化进程。

Objective To compare the survival conditions of different native livers in biliary atrcsia （BA） patients after Kasai operation and explore the pathological characteristics of liver in children with a longer survival time with hepatic pathology and biochemistry. Methods A total of 43 BA patients undergoing Kasai and liver transplantation （LT） were divided into 3 groups according to interval time between Kasai and LT： group 1 （ n = 17 ）, interval time 〈 6 months ; group 2 （ n = 18）, from 6 months to 2 years ; group 3 （ n = 8 ）, 〉 2 years. A retrospective study was conducted for clinical data of each group including age at Kasai, occur- rence of cholangitis and biochemical values pre-LT. Meanwhile, pathological examinations of liver pathology during Kasai and LT included hematoxylin-eosin （HE）, Masson and immunohistochemical （CK19） staining for evaluating grade of liver fibrosis, extension of bile duct, cholestasis and infiltration of inflammatory cells. Results In three groups, the average ages at Kasai were 66.65, 58.39, 49.63 days （P 〈 0.05 ） ; number of cases with cholangitis 12/17 （70.6%）, 14/18 （77.8%）, 4/8 （50%） （ P 〉 0.05 ） and with frequent cholangitis 7/10 （41.2%）, 12/18 （66.7%）, 1/8 （ 12.5% ） （ P 〈 0.05 ） post-Kasai ; biochemical values pre- LT showed that the levels of AST, ALT, TBI, DBI and GGT in group 3 were lower than other groups and the differences not statistically significant. The grade of hepatic fibrosis was 3 （2 - 3 ） , bile duct proliferation 2 （ 1 - 2.5 ）, portal bile plug 1 （ 1 - 2.5 ） and infiltration of inflammatory cells 3 （ 1.5 - 3 ） during Kasai ; Pa- thology during LT showed that the grades of hepatic fibrosis 4 （4 -4 ）, 4 （4 -4 ）, 4 （2 -4 ） （P 〈 0.05 ）, ＇. Jle duct proliferation 3 （3 - 3）,2 （ 1 - 3 ）, 0 （0 - 2 ） （P 〈 0. 001 ）, bile plug 3 （2.5 - 3 ）, 1 （ 1 - 3 ）, 1 （ 1 - 3 ） （ P 〈 0. 001 ） and infiltration of inflammatory cells 2 （ 1 - 2 ）, 1.5 （ 1 - 2 ）, 1 （ 1 - 1 ） （ P 〈 0.05 ）. The differ- ences were statistically significant. Clinicopathological data showed earlier operations of BA patients and less occurring frequency of cholangitis, slower progress of hepatic fibrosis and milder proliferation of bile duct, cho- lestasis and inflammatory cell infiltration and longer survival time of native liver. Conclusion Age of Kasai and frequency of cholangitis are essential for the changes of native liver pathology and survival time of BA patients. For those with a longer native liver survival time, Kasai operation may resolve cholestasis and decrease inflammation infiltration so as to delay the progress of liver fibrosis.