66例胆道闭锁Kasai术后近期疗效分析

目的探讨胆道闭锁Kasai术后的近期疗效及影响生存的因素。方法对2007～2009年本院收治的66例胆道闭锁行Kasai手术的患儿进行回顾性分析。男55例,女11例。手术时年龄30～180d,其中〈60d29例;60—90d20例;〉90d17例。术后3～5d内先后静脉滴注甲基强的松龙20mg、15mg、10mg、5mg,每剂量连用3d后递减,疗程结束后口服强的松每日5mg;熊去氧胆酸每日15mg／kg,口服抗菌素1年。每月检测血总胆红素1次,随访胆管炎是否发作,将是否生存及存活时间、年龄、术后总胆红素水平、胆管炎发作例次等数据录入计算机,进行Kaplan-meier生存分析、Cox regression分析及χ^2检验。结果66例均获随访,随访时间2～24个月。存活46例,死亡20例。Kaplan-meier生存分析显示2年生存率为67．3％,中位生存时间为17．9个月;Coxregressin分析提示血总胆红素为影响生存的因素;Kaplan-meier生存分析显示,术后长期血总胆红素〈34．2μmol／L者2年内生存率最高（P〈0．05）,全组胆汁排出率85％,黄疸完全消退率62％,手术年龄〈60d者术后黄疸消退率为86％,较其他年龄组高（P〈0．05）,胆管炎发生率为30．3％（20／66）。结论影响胆道闭锁Kasai术后近期疗效的主要因素在于术后血总胆红素水平,保持术后血总胆红素〈34．2μmol/L者预后较好。     

胆道闭锁肝纤维化与自体肝生存关系的研究进展

胆道闭锁是婴儿期最严重的肝胆系统疾病之一。肝门-空肠吻合术(Kasai手术)是治疗胆道闭锁的主要手段,但术后自体肝长期生存效果不佳,大部分患儿需要通过肝移植来挽救生命。肝纤维化是影响胆道闭锁患儿自体肝生存的重要因素之一,其发生机制复杂,涉及多种信号通路及细胞因子的调控。Kasai手术后胆汁引流不畅、胆管炎发作都会导致肝纤维化进展,进而发生肝硬化。在完善早期诊断、早期手术、通畅引流胆汁及控制胆管炎的同时,还应积极应对患儿肝纤维化的持续进展,以期达到自体肝的长期生存。     

胆道闭锁Kasai手术后胆管炎病因的研究进展

胆道闭锁Kasai术后胆管炎影响了患儿自体肝的生存状况,尤其是Kasai术后1年内反复发生的胆管炎,更易形成难治性胆管炎,严重影响了胆道闭锁Kasai手术的治疗效果。目前Kasai术后胆管炎病因尚不清楚,多数学者认为并非单一因素所致,与胆汁引流量下降、术后类固醇激素使用、肠道菌群移位、自身免疫损伤等因素密切相关。本文综述了胆道闭锁Kasai术后胆管炎发生的相关因素,为将来胆道闭锁的进一步治疗及Kasai术后胆管炎并发症的防治提供参考。     

胆道闭锁Kasai术后近中期疗效及部分影响因素分析

目的 探讨胆道闭锁Kasai术后的近中期疗效及其影响因素.方法 回顾性分析2005年10月至2010年9月在本院行Kasai手术并获得随访的152例胆道闭锁患儿,男68例,女84例,手术时的中位日龄为75 d(31～528 d),平均(82.36±45.17)d,定期门诊复诊并电话随访,平均随访时间(20.11±16.11)个月(2～62个月),对其诊疗过程及随访情况进行分析,对黄疸消退情况、生存率及影响因素采用Kaplan-Meier生存分析、Cox regression分析及x2检验.结果 Kasai术后黄疸消退率为50％(74/149),Ⅰ、Ⅱ、Ⅲ型患儿的黄疸消退率分别为67％、67％、47％,差异无统计学意义(P=0.306);≤60 d、60～≤90d、91～120 d手术组患儿的黄疸消退率分别为54％、53％、46％,≥120 d手术组患儿的黄疸消退率明显降低(25％),但差异无统计学意义(P=0.310);胆管炎发生率57％(85/149),有无胆管炎发作的黄疸消退率分别为31％、75％,差异有统计学意义(P＜0.01).Kaplan-Meier生存分析Kasai术后2、4年的自体肝存活率分别为56％、49％,有胆管炎组和无胆管炎组的2年自体肝存活率分别为43％、77％,差异有统计学意义(P＜0.01).结论 Kasai手术是目前我国治疗胆道闭锁的首要方法,手术年龄和分型与Kasai术后的近中期效果无明显相关,胆管炎是影响Kasai术后效果的重要因素.     

胆道闭锁Kasai手术后自体肝生存时间小于2年的危险因素分析

目的探讨胆道闭锁(biliary atresia,BA)Kasai手术后自体肝生存(native liver survival,NLS)时间小于2年的危险因素。方法回顾性分析山西省儿童医院2009年1月至2017年6月行Kasai手术的BA患者临床资料及随访资料。根据术后NLS时间是否小于2年分为死亡组(n=78)和生存组(n=46)。将BA分型、性别、巨细胞病毒(cytomegalovirus,CMV)感染、手术年龄、术后使用抗生素方案、术后使用激素方案、是否合并早期胆管炎及术后黄疸是否消退作为自变量,采用Kaplan-Meier法绘制生存曲线并进行Log-rank检验,采用Cox比例风险模型(逐步前进法)筛选BA患者Kasai手术后NLS时间小于2年的危险因素。结果共纳入124例BA患者,其中生存组46例,死亡组78例,2年NLS率为37.1%。单因素分析结果显示合并早期胆管炎及术后黄疸消退是影响BA患者术后2年NLS率的因素(P<0.05)。Cox比例风险模型分析结果显示术后3个月内黄疸未消退为BA患者Kasai手术后NLS时间小于2年的独立危险因素,术后3个月内黄疸未消退组患者NLS时间小于2年的风险是黄疸消退患者的5.65(95%CI:2.45~13.04)倍。结论BA患者Kasai手术后3个月内黄疸未消退是NLS时间小于2年的危险因素。     

78例胆道闭锁患儿诊疗与近期随访分析

目的 回顾性分析本院78例胆道闭锁患儿的诊疗经验,探讨胆道闭锁患儿的近期预后及影响近期预后的因素.方法 2003年1月至2008年12月本院共收治胆道闭锁患儿78例,对其诊疗过程及随访情况进行分析,影响预后的因素采用卡方检验、秩和检验等进行分析,P＜0.05为差异有统计学意义.结果 黄疸平均发生日龄为（13.00±18.36）d,其中48例行Kasai手术,平均手术日龄为（84.50±34.48）d.中位随访时间为（12.82±11.65）个月.Kasai术后黄疸消退率为45.83%,手术时间＜60d、60～90d、＞90 d的患儿黄疽消退率分别为60.00%、56.67%和15.38%,差异有统计学意义.Ⅰ、Ⅱ型胆道闭锁患儿术后黄疸消退率为66.67%,Ⅲ型胆道闭锁术后黄疸消退率为41.03%,差异无统计学意义.Kasai术后有无胆管炎发生者黄疸消退率分别为40.91%、50.00%,差异无统计学意义.病毒感染、先天性畸形及术前应用中药退黄治疗对预后无显著影响.结论 提高胆道闭锁的疗效是小儿外科的一大难题,手术日龄是决定Kasai手术短期预后的关键因素.     

手术年龄对胆道闭锁Kasai手术后预后影响的研究

目的 探讨胆道闭锁患儿接受Kasai手术时的年龄对预后的影响。方法回顾性分析2001年1月-2005年2月我院85例行Kasai手术的胆道闭锁患儿病例资料。按手术年龄分为〈60d组32例,60-90d组40例,〉90d组13例。至2007年2月,获随访且术后存活时间超过2年的患儿27例。结果〈60d组中,56．25％的患儿术后1个月血清胆红素较术前下降三分之一：40．63％的患儿术后3个月血清胆红素降至正常;46．88％的患儿术后6个月血清胆红素降至正常。60．90d组中．术后1个月血清胆红素下降三分之一、术后3个月及6个月降至正常率分别为65％、37．5％和50％。〉90d组患儿中则分别为46．15％、23．08％和23．08％。术后1个月、3个月血清胆红素下降率3组差异无统计学意义;〉90d组患儿术后6个月黄疽消退率较其他两组降低,P〈0．05。获随访的27例存活2年以上患儿中．〈60d组、60～90d组和〉90d组分别为15例、9例和3例,各占60％、32．14％和30％,P〈O．05。结论胆道闭锁患儿早期手术（出生后1～3个月）血清胆红素下降快,黄疸消退率及2年以上存活率均明显高于晚期手术者;2年无黄疸生存预示长期生存和生活质量提高。     

Kasai术后近期胆管炎相关危险因素分析

目的 探讨Kasai术后近期胆管炎发生的可能相关因素.方法 回顾2002年9月～2005年11月于我院行Kasai术的胆道闭锁患儿资料.肝炎病毒筛查阴性,生存1年以上者123例.平均随访时间(20.54±8.57)个月(13～41个月).分析术后胆管炎与患儿手术年龄、是否合并巨细胞病毒感染、术中胆汁引流量、黄疸消退时间等因素的相关性.结果 平均手术年龄(70.48±11.23)d(32～126 d),术后1年内胆管炎发生率52.85%(65/123).手术年龄是胆管炎发作的危险因素(Odds Radio=1.921,P＜0.01),胆管炎首次发作时间与手术年龄负相关(Spearman's rho=-0.3646,P=0.037＜0.05).约三分之一患儿1年内发作≥3次(23/65),但次数多少与手术年龄及首次发作时间不相关(P＞0.05).巨细胞病毒活动性感染与否(P=0.1523＞0.15)和术中胆流量多少(P=0.399＞0.15)不是影响胆管炎发作的危险因素.术后6个月总黄疸消退率58.62%,黄疸消退受术后胆管炎发作次数影响(Odds Radio=3.7668,P＜0.01),并与术中胆流量情况相关(Odds Radio=0.3280,P=0.011＜0.05).20例胆管炎病例常规血培养,仅1例1次大肠埃希菌阳性.结论 Kasai术年龄与胆管炎发作相关.巨细胞病毒活动性感染并不是胆管炎发生的危险因素.手术近期胆管炎发作的次数影响术后黄疸的消退,并可能影响整个疾病的预后.     

胆道闭锁Kasai手术后综合管理

胆道闭锁(biliary atresia,BA)是婴儿期肝内外胆管进行性炎症及肝纤维化的疾病,其病因及疾病进展机制尚不清楚.Kasai手术(Kasai portoenterostomy,KPE)是治疗胆道闭锁的首选术式,成功的Kasai手术能够重建胆汁引流,但Kasai手术后长期自体肝生存(native liver s...     

腹腔镜与开放Kasai手术治疗Ⅲ型胆道闭锁中期疗效的对比

目的比较腹腔镜与开放Kasai手术治疗先天性胆道闭锁的中期疗效。方法回顾性分析2010年9月至2011年9月在本院行Kasai手术并获得随访的103例Ⅲ型胆道闭锁患儿,根据手术方式分为腹腔镜辅助Kasai手术组(LP组)和开腹Kasai手术组(OP组)。通过术后12~30个月肝生化ALT和TBil中位数的秩和检验,比较两组Kasai术后中期肝功能情况;应用Kaplan-Meier生存分析比较两组中期生存率;比较两组对二期自体肝移植手术及术后生存情况的影响。结果 103例Ⅲ型胆道闭锁患儿中,LP组55例,OP组48例;两组年龄分布、性别比例、术前肝功能(TBil、ALT、AST)中位数等均无统计学差异。术后12个月、18个月、24个月、30个月两组肝功能(TBil,ALT)恢复情况无统计学差异。Kasai术后LP组和OP组的自体肝生存率,1年生存率分别为78.2%和75%,2年生存率分别为66.9%和55.8%,3年生存率分别为66.9%和55.8%。Kasai术后实施肝移植11例(LP组4例,OP组7例),1例移植术后死亡。结论胆道闭锁患儿实施腹腔镜Kasai手术与开放Kasai手术后中期效果无明显差异。     

A multicenter study of the outcome of biliary atresia in the United States, 1997 to 2000

OBJECTIVE: To determine the prognostic factors and optimal approaches to the diagnosis and management of biliary atresia, the leading indication for liver transplantation in children. STUDY DESIGN: A retrospective study was performed of all children who underwent hepatoportoenterostomy (HPE) for biliary atresia between 1997 and 2000 at 9 centers in the United States. Outcome at age 24 months was correlated with demographic and clinical parameters. RESULTS: A total of 104 children underwent HPE; 25% had congenital anomalies, and outcome was worse in those with biliary atresia splenic malformation syndrome. Diagnostic and clinical approaches varied, although specific approaches did not appear to correlate with outcome. The average age at referral was 53 days, and the average age at HPE was 61 days. At age 24 months, 58 children were alive with their native liver, 42 had undergone liver transplantation (37 alive, 5 dead), and 4 had died without undergoing transplantation. Kaplan-Meier analysis of survival without liver transplantation revealed markedly improved survival in children with total bilirubin level<2 mg/dL at 3 months after HPE (84% vs 16%; P<.0001). CONCLUSIONS: Outcome in the study centers was equivalent to that reported in other countries. Total bilirubin in early follow-up after HPE was highly predictive of outcome. Efforts to improve bile flow after HPE may lead to improved outcome in children with biliary atresia.     

Biliary atresia: perspective on transplantation

In North America, long-term, jaundice-free survival following Kasai's operation for biliary atresia is 25%–35%; thus, the majority of patients require liver transplantation for salvage. The timing of organ replacement is crucial. Patients without bile drainage because of either surgical election or operative failure should be referred immediately. Patients with ongoing but inadequate biliary drainage should be referred at a time that coincides with a plateau of the growth curve or if cholangitis is recalcitrant. Portal hypertension itself is not an indication for transplantation irrespective of its manifestations. Ascites, however, when primarily due to hypoalbuminemia, is a solid indication for transplantation. Other tests of liver function are generally unreliable. Factors found to be unimportant or of questionable adverse impact on transplant outcome include previous operation, coexisting infection limited to the liver, nonpatent portal vein, and/or abnormal liver function tests. The only factor that was found to significantly influence outcome was patient size and age. Thus, bile drainage after Kasai portoenterostomy, by permitting growth, improves the chances for a favorable outcome. Transplant 1-year survival is from 60% to 88%. Liver replacement is not without complications, namely technical errors, infection, and rejection. Nonetheless, in a majority of cases hepatic transplantation provides the only opportunity for high-quality long-term survival. Offprint requests to: R. J. Hall     

先天性胆道闭锁肝内毛细胆管超微结构与临床预后关系探讨

目的 探讨先天性胆道闭锁（ＣＢＡ）肝脏毛细胆管超微结构与临床预后的关系。方法 用ＰｈｉｌｉｐｓＣＭ１０透射电镜观察肝内毛细胆管超微结构,比较肝组织电镜切片中发育良好与发育不良的毛细胆管数目并与临床预后作比较。结果 ２７例ＣＢＡ患儿中,肝内毛细胆管发育良好为主１３例,其中１２例术后生存,生存率为９２．３１％;毛细胆管发育不良为主的１４例中,仅有４例生存,生存率为２８．５７％,两组生存率有显著性差异（     

IMMUNE RESPONSES IN PATIENTS WITH OBSTRUCTIVE JAUNDICE OF INFANCY

ABSTRACT. To investigate possible involvement of immune responses in the pathogenesis of obstructive jaundice in infancy we measured antibody to liver specific lipoprotein (LSP) by radio immunoassay and immune complexes by their ability to bind Clq in sera from 16 patients with extrahepatic biliary atresia and 16 with neonatal hepatitis and 13 age matched controls. Anti-LSP was present in 6 of 16 with preoperative biliary atresia and 6 of 16 with hepatitis. Mean percentage Clq bound was higher in hepatitis (22 SD 15 %) than preoperative biliary atresia (11.1 SD 2.3 %). Nine of 16 hepatitis patients had elevated Clq binding as compared with 1 of 16 with biliary atresia. The highest value for anti-LSP and Clq binding were found in sera from patients with histologically severe hepatitis and hepotitis associated with specific viral or bacterial causes. Anti-LSP was significantly raised 5 months post-operatively in all of 6 patients with biliary atresia and poor biliary drainage but only 2 of 5 survivors. Elevated Clq binding was detected in 6 of 7 with poor drainage and 1 of 7 survivors at the same stage. Anti-LSP and Clq binding fell in 4 patients with neonatal hepatitis on recovery. These findings suggest that immunological mechanisms, possibly involving antibody to hepatocyte membrane components and immune complexes, may be involved in the pathogenesis of progressive liver disease in biliary atresia.     

Contemporary surgery of biliary atresia

The etiology of biliary atresia is not due to a congenital malformation but rather to a continuing process beginning in utero that affects not only the extrahepatic biliary ducts but also the intrahepatic parenchyma. Over the last decade, the outlook for patients who were previously felt to be uncorrectable has been significantly improved by Kasai's operation. Successful biliary reconstruction depends on early diagnosis and treatment (before three months of age). The essentials of hepatic portoenterostomy consist of excision of the entire extrahepatic duct structure with anastomosis of an intestinal conduit to the area of the transected duct at the liver hilus. After operation, many patients experience complications, including cholangitis, portal hypotension, and vitamin deficiencies. Despite these difficulties, growth and development continue on a relatively normal course, and long-term survival has been accomplished in many children. For those in whom biliary drainage is not achieved or with significant parenchymal damage, liver transplantation should be considered as part of ongoing care.     

Prediction of survival in extrahepatic biliary atresia by hepatic duplex sonography

BACKGROUND: The clinical course of biliary atresia patients is extremely variable. To optimize conservative treatment and correctly schedule liver transplantation, noninvasive investigations that are predictive of individual survival and that can be performed regularly are needed. In this study, the prognostic value of Doppler sonography was investigated in these patients. METHODS: Thirty biliary atresia patients (age range, 1 month to 15.2 years; mean, 4.0 years) and 38 control subjects underwent standardized Doppler sonography of liver and spleen. Biochemical tests of liver function and of fibrogenesis were performed in parallel. Individual clinical outcome was registered 1 and 2 years later. RESULTS: In control subjects, maximum portal flow velocity (Vmax) was more than 16 cm/sec, and the hepatic vein flow pattern was triphasic. Among children with biliary atresia, those with diminished portal Vmax, a flattened hepatic vein flow curve, or a hepatic artery resistance index of 0.8 or more had significantly lower indices of hepatic protein synthesis (albumin, cholinesterase), higher bilirubin levels, and higher concentrations of markers of connective tissue turnover (procollagen peptides, laminin P1) than did those with normal Doppler sonography measurements. The rate of survival without transplantation during the following 2 years was significantly lower in children with abnormal Doppler findings. From portal and hepatic vein flow measurements, patient survival 2 years later could be predicted with an accuracy of 93%. CONCLUSIONS: In children with extrahepatic biliary atresia, Doppler sonography of the hepatic blood flow is a noninvasive indicator of disease severity. Moreover, it allows a highly accurate prediction of patient survival for the following 2 years.