胆道闭锁肝纤维化与血清学监测

胆道闭锁（Biliary Artesia,BA）是新生儿阻塞性黄疸最常见的原因之一。其病理特征为胆管的进行性炎症和肝纤维化,发展速度快,涉及肝内外胆管,虽然通过Kasai手术（即肝门空肠吻合术）能够改善肝内外胆道的梗阻。但多数患儿仍发生进行性肝内胆管破坏和肝纤维化。最后发展为肝硬化和门静脉高压。晚期病例肝脏移植将不可避免。BA病人的预后受多种因素的影响,如Kasai手术时的年龄、病变的类型以及肝纤维化程度等。预测BA的预后以及判断肝纤维化程度。对选择肝移植的手术时机有着极其重要的意义。     

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...     

胆道闭锁术时年龄及肝脏病理与近期预后的相关性研究

目的 研究胆道闭锁患儿Kasai手术术时年龄、肝脏病理与近期预后之间的相关性.方法 对2008年7月至2011年6月收治于我院普外科的胆道闭锁患儿进行Kasai术后6个月的近期预后随访,分为优秀组、良好组和不良组.每组随机抽取20例共计60例作为样本.回顾样本病历资料获取术时年龄.获取样本病例Kasai手术术中取得并保存的肝脏病理标本,应用Masson染色评定肝纤维化程度;应用CK19免疫组化染色和图像分析技术评定胆管反应程度.统计学分析术时年龄、肝脏病理学指标和近期预后之间的相关性.结果 优秀组、良好组和不良组的平均术时年龄分别为(77.55±24.64)d、(90.30±24.13)d和(72.35±24.53)d,无术时年龄＜30d病例;优秀组、良好组和不良组的无肝硬化病例和肝硬化病例分别为11:9、11:9和16:4;优秀组、良好组、不良组平均胆管面积比例分别为(5.62±3.62)％、(8.50±4.08)％和(5.15±3.77)％.不同预后病例术时年龄、肝脏病理学指标均无统计学差异;肝硬化组较无肝硬化组术时年龄无统计学差异,肝硬化组较无肝硬化组胆管反应程度严重;术时年龄与胆管反应呈显著线性正相关.结论 胆道闭锁患儿Kasai术后6个月近期预后和术时年龄、肝纤维化程度、胆管反应程度均无明显相关性,近期预后可能受术者经验和手术技巧影响;术时年龄越大胆管反应越重,胆管反应对肝纤维化有促进作用,尽早手术对改善远期预后有帮助.     

胆道闭锁诊治新进展

胆道闭锁(Biliary Atresia,BA)是以肝内外胆管闭锁和梗阻性黄疸为特点的小儿外科常见畸形,其发病率为1/5 000～1/18 000.Kasai手术是该病一线治疗方法,但经Kasai手术治疗的BA患儿仍有约70%最终发展为肝硬化,需要接受肝移植治疗.早期诊断和治疗是提高BA预后的重要途径,因此本文对BA诊断和治疗方面的最新研究进展进行综述,以期提高BA诊断水平和改善BA治疗效果.     

胆道闭锁Kasai术后药物辅助治疗的研究进展

胆道闭锁(biliary atresia, BA)是婴儿特有的肝胆系统疾病, 肝门肠吻合术(Kasai手术)是目前首选的治疗方式。然而, Kasai术后持续进展的肝脏炎症及纤维化导致绝大多数患儿需要肝移植才能长期生存。因此, 如何改善Kasai手术的预后、推迟甚至避免肝移植的发生, 是当前研究的重点和热点。本文回顾并总结Kasai术后辅助性治疗相关文献及最新研究进展, 期望为改善BA患儿预后提供思路。     

胆道闭锁诊治新进展

胆道闭锁(Biliary Atresia,BA)是以肝内外胆管闭锁和梗阻性黄疸为特点的小儿外科常见畸形,其发病率为1/5 000～1/18 000.Kasai手术是该病一线治疗方法,但经Kasai手术治疗的BA患儿仍有约70%最终发展为肝硬化,需要接受肝移植治疗.早期诊断和治疗是提高BA预后的重要途径,因此本文对BA诊断和治疗方面的最新研究进展进行综述,以期提高BA诊断水平和改善BA治疗效果.     

胆道闭锁自体肝病理学研究3例

<正>胆道闭锁(Biliary Atresia,BA)肝移植时期出现肝纤维化严重、肝衰竭。Kasai术后胆汁引流通畅是延缓肝纤维化进程的重要因素。现在有些外科医生开始关注如何改进经典的Kasai术式,尽可能使肝内开放胆管利于胆汁引流至肝外~([1])。对于BA病理学研究有助于提高病理诊断准确率及对术后疾病预后的评估。本研究对肝脏八段胆管形态进行研究,初步观察胆管形态改变在每段中所具有的特点,为Kasai手术解剖范围提供新的思路。     

胆道闭锁患者肝门的病理解剖学研究

目的通过解剖胆道闭锁患者肝脏肝门组织,探讨Kasai术后肝门改变与肝内病理改变的差异,为改进Kasai手术提供理论依据。方法收集Kasai术后因胆汁淤积性肝硬化而行肝移植的胆道闭锁患儿13例,将其中术后胆汁引流情况较差者作为引流不良组,切取肝门及肝内组织。收集3例Kasai术后因肝门部囊肿,反复发作胆管炎而行肝移植的胆道闭锁患儿,3例术后胆汁引流较好,为引流良好组,自吻合口开始,沿左右肝管分别间隔1 cm连续取材。结果引流不良组:肝内病理改变以纤维化加重、胆管增生及血管增生为主,增生胆管直径较小,肝门淤胆程度较肝内相对重。引流良好组:靠近肝门部位胆管增生较肝内轻,并以大胆管为主。肝左叶胆管直径较大(最大750μm),具有引流功能;肝右叶胆管增生明显,胆管直径较小(最大390μm)。结论 Kasai术后胆汁引流较好的病例均呈现左叶胆管直径较大,可能提示解剖肝门广度需要增加。     

胆道闭锁Kasai术后糖皮质激素治疗的研究进展

胆道闭锁是累及肝内外胆管的一种进行性疾病,目前广泛采用的治疗策略是行肝门-空肠吻合术(Kasai手术),术后辅以包括糖皮质激素、抗生素等多种药物治疗,然而糖皮质激素在胆道闭锁的治疗中争议较多,其应用方案也多种多样,现将糖皮质激素在胆道闭锁Kasai术后的应用进展进行综述。     

胆道闭锁Kasai术后胆管炎的病因及诊治进展

胆道闭锁是威胁新生儿生命的严重先天性肝内、外胆管畸形,目前针对该疾病的治疗主要依靠Kasai手术,即肝门-空肠吻合术纠正发育不良的胆道系统,胆管炎是胆道闭锁Kasai术后最常见且较难处理的并发症,发病机制尚未完全清楚,多种因素如肠道细菌的上行感染、肝内胆管发育异常及手术损伤、肠道内容物反流等都可影响疾病的发生发展。而胆管炎的首发时间、发生次数可影响术后原生肝脏功能,对其进行及时诊治尤为重要。Kasai术后胆管炎的诊断缺乏特异性,主要依据临床表现、生化异常以及手术史,对于难治性胆管炎应考虑完善放射性同位素肝胆成像、经皮胆道造影和小肠镜检查。其防治重点在于围术期的术前护理、术式改进和术后护理以及疾病随访过程中的药物防治等。     

Biliary atresia and liver transplantation: results and thoughts for primary liver transplantation in select patients

Biliary atresia (BA) is one of the most common indications for liver transplantation in children. Despite advances in biliary atresia surgical techniques, most children will ultimately require liver transplantation. Possible pre-operative predictors of outcome after the Kasai operation are: 1. Age at operation 2. Presence of the biliary atresia splenic malformation syndrome (BASM) 3. Center specific factors 4. Liver histology and 5. Anatomic pattern of bile ducts found at surgery.Age at surgery is considered a strong predictor of success after portoenterostomy. In a recent study, age of 75 days or more at surgery was associated with less frequent resolution of jaundice and decreased transplant free survival. Similarly, the Ohi type II or III anatomy was associated with a higher risk of transplantation or death than type I. Inflammatory findings on pre-operative biopsy predicted a pooreroutcome after a Kasai procedure than obstructive changes. Nodularity of the liver at surgery as well as ascites was associated with a poorer prognosis.Primary transplantation is rarely done despite excellent outcome. Deaths on the waiting list also have improved with routine use of split and live donor transplantation. The Kasai operation has the highest failure rate in its stated objective than any other operation in pediatric surgery. Failure to achieve any improvement in jaundice occurs in over 30% of all cases, even in the best of hands, and transplantation or listing for transplantation occurs in over half the children with type II and III BA by one year of age in countries where liver transplantation is readily available.There are almost no studies in children with BA that compare the outcome after liver transplantation for BA with or without a prior Kasai procedure. It is postulated that a prospective trial in children predicted to have a poor prognosis after the Kasai procedure based on anatomic pattern, liver histology and presence of BASM, would yield improved care, spare some infants needless surgery, and quite possibly result in diminished morbidity and mortality following liver transplant.     

Surgical modifications,additions, and alternatives to Kasai hepato-portoenterostomy to improve the outcome in biliary atresia

Kasai hepato-portoenterostomy (HPE) is the most widely used surgical technique to restore bile flow in biliary atresia (BA). We aimed to review literature on HPE substitutes and additions to Kasai especially in advanced BA (ABA). A PubMed search was done for surgical procedures apart from or along with Kasai HPE for BA. Additional procedures to prevent cholangitis were also reviewed. Procedures and outcome were analysed. Alternative procedures done by the authors have also been described briefly. Results have been compiled in this review article. In ABA, with portal hypertension and liver cirrhosis, Kasai HPE is associated with poor outcome, increased morbidity, and even mortality. Most require liver transplant (LT). Some alternatives to HPE include exploration at porta hepatis to assess the bile flow yet avoid the major surgery (HPE) as a bridge to LT. Conduit diversion may help to combat cholangitis resistant to steroid therapy. Stoma formation is not preferred in cases listed for LT due to high risk of bleeding. Hepatocyte infusion, stem cell therapy, and synthetic liver are the future options to meet the challenges in BA. Various alternative procedures may become handy in the future especially in ABA.     

Biliary atresia: clinical aspects

Biliary atresia (BA) remains an enigmatic disease with a degree of etiologic heterogeneity. A number of variants can be defined clinically, and these include the syndromic group (typically BA splenic malformation), cystic BA, and cytomegalovirus (CMV) IgM +ve associated BA. The remainder, and still the largest group, may be termed isolated BA(.) There is a wide variation in incidence across the globe from 1 in 5000 in Taiwan to 1 in 20,000 live births in Northern Europe, although the reasons for such a disparity remain obscure. Management remains primarily surgical with an attempt to restore bile flow by resection of extrahepatic biliary remnants and a reconstruction portoenterostomy (the Kasai procedure), reserving liver transplantation for those where this fails or complications of chronic liver disease supervene. Clearance of jaundice to normal values has been achieved in 40%-55% of cases in large series from around the world, with an expectation of 5-year native liver survival of similar proportions.     

胆道闭锁Kasai术后肝内胆管囊性扩张的形成特点与病理研究

目的分析胆道闭锁(biliary atresia,BA)患儿Kasai术后肝内胆管囊性扩张(intrahepatic biliary cysts,IBC)的形成特点及病理学表现,探索其与预后之间的关系。方法选取2017年1月至2018年12月天津市儿童医院Kasai术后行肝移植手术的BA患儿179例(男75例,女104例),收集患儿的临床资料和影像学资料,用以判断是否存在IBC,其中36例CT检查结果提示存在肝内胆管扩张,作为IBC(+)组,143例未检测到肝内胆管扩张,作为IBC(-)组,比较两组的自体肝生存状况及肝功能指标。同时收集到上述患儿中50例患儿的肝移植时的病肝组织,其中IBC(+)组18例,IBC(-)组32例,进行HE染色,观察肝脏纤维化程度、胆管增生程度、淤胆以及胆管板畸形的发生情况。结果①IBC(+)组女患儿有27例,占75.0%(27/36),IBC(-)组女患儿有77例,占53.8%(77/143),两组中女患儿占比的差异具有统计学意义(P=0.021),两组患儿在行Kasai术时的日龄及术后胆管炎的发生率的比较中,差异无统计学意义(P>0.05);②IBC(+)组患儿的中位生存期为11.5个月,明显高于IBC(-)组患儿的9.0个月。Log-Rank检测发现,IBC(+)组术后自体肝生存状况优于IBC(-)组患儿,且差异具有统计学意义(P=0.038);③肝功能的比较结果发现IBC(+)组除胆汁酸(total bile acids,TBA)外,均低于IBC(-)组患儿,其中总胆红素(total bilirubin,TBI)、结合胆红素(direct bilirubin,DBI)水平在两组的差异具有统计学意义(P<0.05);④IBC(+)组患儿的肝纤维化程度、胆管增生程度及胆管板畸形发生率均较IBC(-)组略低,差异无统计学意义;但IBC(+)组淤胆程度明显低于IBC(-)组,差异具有统计学意义(P=0.013)。结论BA患儿Kasai术后发生IBC可能是肝脏代偿的积极表现,短期内不会导致胆汁淤积的加重,相反扩张的胆管可以减轻胆汁淤积的程度,改善肝功能及病理分级,从而延长自体肝生存时间。     

不同年龄胆道闭锁患儿手术效果分析

目的 分析胆道闭锁手术年龄与术后早期效果的关系以及较大年龄（＞90 d）患儿的Kasai手术指征.方法 2004-2010年复旦大学附属儿科医院收治胆道闭锁患儿452例,均经术中胆道造影确诊.手术采用标准的Kasai术,术后常规使用激素,对不同年龄组患儿术前肝功能、B超等资料及术后胆红素下降情况进行分析,总胆红素水平低于20 mmol/L定为黄疸完全消退.结果 将所有患儿根据年龄分为三组,手术年龄≤60 d者146例,手术年龄在60～90 d者222例,＞90 d者84例（90～10Od者33例,100～110 d 26例,110～120d 10例,120～ 130 d 8例,＞130 d 7例）.术前各年龄组总胆红素、直接胆红素、谷丙转氨酶无显著差异.术后2周,60 d以内组,胆红素下降水平最低（P＜0.05）,＜45 d患儿胆红素下降水平并未更加显著.术后3个月随访率为61.3％,各年龄组总胆红素水平无显著差异（F=0.132,P=0.970）.术后6个月随访率37.4％,90 d以上组总胆红素（58.09±58.55） mmol/L,90 d以内组总胆红素水平（27.67±30.60） mmol/L（P=0.226）.＞90d患儿,每间隔10d分成一组,各组间术后早期胆红素下降水平无差异（F=1.115,P=0.355）.＞90 d手术患儿两年自体肝生存率为36.1％.90 d以上患儿延误手术原因：39.2％因家长未重视,51.6％因误诊婴儿肝炎耽误治疗.结论 胆道闭锁患儿＞90 d并非手术绝对禁忌,多数患儿可取得较好的早期黄疸消退,部分患儿术后6个月可以有较好的肝功能恢复.     

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。     

胆汁酸代谢相关药物在胆道闭锁治疗中的应用与展望

胆道闭锁患儿胆汁酸代谢异常可损伤肝细胞及胆管上皮细胞。熊去氧胆酸作为目前胆道闭锁手术后常规用药,其疗效及使用方法仍存在争议;胆汁酸甾体类核受体激动剂(奥贝胆酸)及非甾体类核受体激动剂(LJN-452)、肠道胆汁酸重吸收相关蛋白调控药物(A4250)、肝脏内胆汁酸转运蛋白、肾脏转运蛋白相关药物的开发研究近年来发展迅速,不少药物已开始临床Ⅱ、Ⅲ期试验,将来可能对胆道闭锁肝门空肠吻合术后逐步恢复胆流的患儿有一定帮助,成为胆道闭锁肝门空肠吻合术后新辅助用药。     

The anatomy of the porta hepatis in patients with preduodenal portal vein,with special reference to portoenterostomy for biliary atresia

The aims of this study were to demonstrate the anatomic relationship between portal vein (PV) branches and hepatic ducts in the porta hepatis in individuals with preduodenal portal vein (PDPV) and to examine the validity of portoenterostomy (Kasai procedure) for patients with biliary atresia (BA) and PDPV. The porta hepatis of four subjects with PDPV without BA was dissected. Similar dissection supplemented by computer-aided three-dimensional reconstruction of the hilar structures was undertaken in a patient with BA and PDPV who underwent an unsuccessful Kasai procedure and died at 5 months of age. In three of the four subjects with PDPV alone, PV branches and extrahepatic bile ducts were abnormally arranged in the porta hepatis, some of the hepatic ducts entering the liver substance posterior, and occasionally lateral, to the main PV branches. The three-dimensional study showed that the original right main intrahepatic bile duct was located anterolateral to the portoenterostomy, which had been placed just anterior and to the right of the PV bifurcation. These findings strongly suggest that the PV may not be a reliable landmark for the Kasai procedure in patients with BA and PDPV.