血清半乳糖凝集素-3水平判断胆道闭锁患儿术后预后的意义

目的 探讨半乳糖凝集素-3(Gal-3)、透明质酸(HA)与胆道闭锁(BA)患儿术后肝损害、肝纤维化的关系.方法 选择行Kasai术术后BA患儿为BA组(n=35),同期体检健康儿童为健康对照组(n=10).BA组根据胆红素水平分为黄疸组(n=11)和无黄疸组(n=24),根据胃镜下食管静脉曲张情况分为门静脉高压(PH)组(n=27)和非PH组(n=8).应用自动生化仪检测2组肝功能,采用ELISA检测2组血清Gal-3水平,采用放射免疫法检测2组血清HA水平.结果 BA组肝损害、肝纤维化程度较健康对照组重,血清Gal-3、HA水平均较健康对照组显著升高(Pa＜0.05);黄疸组肝损害、肝纤维化程度较无黄疸组重,血清Gal-3、HA水平均较无黄疸组显著升高(Pa＜0.05);无黄疸组血清Gal-3水平较健康对照组显著升高(P ＜0.05);PH组血清Gal-3水平较非PH组显著升高(P＜0.05);血清Gal-3水平与总胆红素、ALT、γ-谷氨酸转肽酶水平呈正相关(Pa＜0.05),与HA水平亦星正相关(P＜0.05).结论 血清Gal-3水平与BA术后患儿肝损害程度和肝纤维化程度密切相关,可作为BA术后判断患儿预后的重要生化指标.     

PDCD5在胆道闭锁患儿胆管组织中的表达及意义

目的研究促凋亡基因PDCD5在胆道闭锁及胆总管囊肿患儿胆管组织中的表达规律,探讨促凋亡基因PDCD5在胆道闭锁发病机制中的作用。方法分别取18例胆道闭锁（Biliary Atresia,BA）和11例胆总管囊肿（Choledochal cyst,CC）患儿的胆管组织,应用蛋白质印迹（westong blot）与荧光实时定量（quantitative real—time PCR,qRT-PCR）的方法分别检测PDCD5在胆道闭锁与胆总管囊肿患儿胆管组织中的表达,并进行定位和定量分析与比较。结果PDCD5在CC组胆管组织中的CT值为（6．7292±1．169）,高于BA组的相应CT值（4．0125±1．0735）,P〈0．05。应用2-△△CT计算出CC与BA中PDCD5基因表达量的比值为1：6．57。PDCD5在BA组胆管组织中mRNA转录水平明显高于对照组;Western blot结果显示,PDCD5在BA组胆管组织中蛋白表达量明显高于CC组。结论PDCD5在胆道闭锁患儿胆管组织中的蛋白和基因表达水平均增强。PDCD5可能参与胆道闭锁胆管上皮细胞凋亡,从而参与胆道闭锁的炎性反应,在胆道闭锁的发病机制中发挥重要作用。     

胆道闭锁术后真菌感染

目的 探讨胆道闭锁手术后真菌感染发生的原因、危害性和诊治方法。方法 对近14年来本科行Kasai手术的131例胆道闭锁患儿的临床资料进行分析。比较手术前、后浅层和深部组织发生真菌感染情况，统计术后真菌性胆管炎发生率。结果 35例发生皮肤真菌感染或口腔鹅口疮。60例胆道造瘘患儿，从造瘘口收集物进行检查，19例为细菌感染，14例发生胆道真菌感染，其胆道排出物可见真菌。另5例发生细菌和真菌混合感染。1例发生真菌性脑脓肿，并致死亡。结论 阻塞性黄疸手术后应用大量激素和广谱抗生素，可能是术后易发生真菌感染的原因。深层真菌感染可引起严重并发症，甚至死亡。胆管炎不仅可由细菌引起，也有可能是真菌感染所致。     

胆道闭锁Kasai术后生存分析

目的 探讨胆道闭锁患儿Kasai术后各因素对生存期的影响。方法 对51例胆道闭锁Kasai术后患儿进行回顾性分析,观察生存时间,以Kaplarr—Meier法描述生存曲线,收集可能影响预后的若干因素,运用Cox比例风险模型,进行统计分析。结果 术后胆汁引流量和是否长期随诊,积极治疗影响生存时间。全组3个月、6个月、12个月的累积生存率分别为69．15％、56．33％、32．50％,中位生存期为8个月;手术日龄越大,中位生存期越短。结论 Cox多因素分析认为：术后胆汁引流量和是否长期随访、积极治疗是影响生存时间的相关因素。手术日龄不同,生存曲线有较大变化。     

胆道闭锁患儿亲体肝移植术后急性肺损伤风险因素分析

目的 分析胆道闭锁患儿亲体肝移植术后急性肺损伤的风险因素.方法 收集天津市第一中心医院2012年5月至2016年3月实施的112例胆道闭锁患儿亲体肝移植术临床资料,回顾性分析临床因素对患儿术后急性肺损伤的影响.结果 112例胆道闭锁患儿亲体肝移植患儿术后23例发生急性肺损伤,发生率为20.5％.单因素logistic回归分析显示肺部并发症组与对照组间年龄(P=0.010)、术前白蛋白(P=0.012)、术前总胆红素(P=0.001)、术前血清肌酐(P＜0.001)、术后1周内总胆红素峰值(P=0.035)差异有统计学意义(P＜0.05).多因素logistic回归分析显示,术前白蛋白(P=0.010,OR=0.830,可信区间为0.720～0.957)、术前总胆红素(P=0.001,OR=1.010,可信区间为1.004～1.016)及术前血清肌酐(P=0.001,OR=1.237,可信区间为1.104～1.387)是术后急性肺损伤发生的高危因素.结论 急性肺损伤是胆道闭锁患儿亲体肝移植术后的严重并发症,术前血清白蛋白、总胆红素及肌酐水平是患儿急性肺损伤发生的高危风险因素.     

小儿胆道闭锁与肝移植

小儿胆道闭锁是小儿外科有代表性的常见病之一。自然死亡率为 10 0 % ,很少存活过 2周岁。葛西手术打破了 10 0 %死亡的铁门 ,然而晚期效果仍很不满意。肝移植如果能 10 0 %成功 ,则患儿可获得 10 0 %的正常寿命与生活质量。《实用儿科临床杂志》组织这 5篇文章 ,正是为了攀登这个目标而铺路。专家们分别从几个方面介绍了胆道闭锁与小儿肝移植的现代观点与技术。对我们开展此项工作将有很大的帮助。欲求小儿胆道闭锁疗效的提高 ,我认为当前应从以下三方面入手 :　　一、扭转对胆道闭锁的“放弃”态度目前因为许多家长认为其疗效很不满意 ,医…     

胆道闭锁患儿生长发育及营养支持研究进展

胆道闭锁患儿普遍存在营养问题,且常常合并生长障碍和神经发育迟缓。越来越多的证据表明,营养不良不仅是胆道闭锁患儿生长障碍和神经发育迟缓的危险因素,也是其患病和死亡的危险因素,因此早期进行营养干预对改善预后极其重要。该文综述了胆道闭锁患儿营养不良与生长障碍以及神经发育迟缓的关系,并探讨营养支持的时机及方法。     

腹部磁共振在胆道闭锁患儿Kasai术后随访中应用的相关研究

目的 探讨腹部磁共振(MR)检查在胆道闭锁患儿Kasai术后随访中应用的可行性.方法 收集2015年12月至2016年4月于首都医科大学附属北京儿童医院普外科门诊复查,资料完整、自肝生存的胆道闭锁Kasai术后14例,行腹部MR检查.观察MR检查结果所示肝、脾形态学改变;通过公式计算患儿标准肝体积值,与腹部MR检查测量3次所得的患儿平均肝体积值比较,获得平均肝体积值、肝体积比值、肝体积差值,同理获得平均脾体积值、脾体积比值、脾体积差值,及脾/肝体积比值;并收集同期患儿血清AST、血小板计数(PLT),通过公式计算AST与血小板比值(APRI),结合肝硬度测量(LSM)与上述指标进行相关性分析;对患儿合并的腹腔内畸形进行进一步观察.结果 腹部MR观察到,患儿的肝表现为不同程度的肝各叶比例失调(6/14),伴有结节状改变(1/14)等.脾的形态改变主要表现为脾不同程度的增大(14/14).此外腹部MR检查还观察到一些继发于门静脉高压的表现如腹水(2/14),侧枝循环形成(1/14)等.本组脾/肝体积比值、脾体积比值、脾体积差值与LSM值呈线性正相关(r值分别为0.684、0.633和0.579,P值分别为0.007、0.015和0.030),脾/肝体积比值、平均脾体积、脾体积比值、脾体积差值与APRI值呈线性正相关(r值分别为0.764、0.646、0.659和0.796,P值分别为0.001、0.013、0.010和0.001);平均肝体积、肝体积比值、肝体积差值均与LSM值、APRI值无线性相关关系.胆道闭锁患儿合并的腹腔内畸形,脾畸形(4/14),全内脏转位(1/14)亦可通过腹部MR检查进一步观察.结论 通过腹部MR检查可以观察到胆道闭锁患儿Kasai术后肝、脾形态学改变,对肝纤维化水平进行定性评估;通过测量肝、脾体积,可对患儿肝纤维化情况进行定量评估,尤其是脾/肝体积比值,与目前常用的评估肝纤维化的指标LSM值、APRI值呈线性正相关;对胆道闭锁患儿的腹腔内合并畸形进行进一步观察.腹部MR检查可以用于胆道闭锁患儿Kasai术后的随访中.     

胆道闭锁患儿Kasai术后早期胆管炎相关危险因素分析

目的 探讨影响胆道闭锁患儿(biliary atresia,BA)经典Kasai术后早期胆管炎发生的相关因素.方法 对本组中35例BA患儿的临床资料应用二项分类logistic同归分析方法作回顾性分析.结果 胆道闭锁患儿术后近期胆管炎发生与术后胆汁引流效果、术后辅以激素治疗及术中预留胆支长度有显著相关性,而与患儿性别、手术日龄、术前总胆红素及肝功能、手术前后辅以熊去氧胆酸和苯巴比妥利胆退黄治疗、术中设置防反流瓣及术后抗感染力度等因素无关.结论 胆道闭锁患儿Kasai术后胆汁引流效果好,辅以激素治疗,同时术中预留胆支长度充分的BA患儿,其术后不易发生早期胆管炎;反之,患儿发生早期胆管炎风险增加.

Abstract：

Objective To evaluate the factors affecting the early post-operative cholangeitis after classical Kasai operation for biliary atresia (BA) in children. Methods The clinical data of thirty-five BA children from pediatric surgery department of Nanjing Childrens Hospital was retrospectively analyzed using binary logistic regression analysis. Results The occurrence of early cholangitis after classical Kasai operation was found to correlate with post-op biliary drainage effect, hormone therapy and the length of Roux-loop in operation. No correlation could be established between early cholangeitis and sex,age, total bilirubin and pre-op liver function, ursodeoxycholic and luminal therapy, the installation of anti-refluxing valve in operation and the dosage of antibiotics. Conclusions Good biliary drainage,hormone therapy and sufficient length of Roux-loop were associated with decreased risk of early cholangitis.     

先天性胆道闭锁患儿的维生素D代谢及佝偻病防治

将我院２３例手术确诊为先天性胆道闭锁（ＣＢＡ）患儿随机分成两组，观察组术后２￣３天肌注ＶｉｔＤ３３０万单位（１５例），未肌注ＶｉｔＤ３（８例）为对照组。结果两组患儿术前、后血清２５－ＯＨＤ的升高值，Ｃａ的升高值，ＡＫＰ的下降值均有显著性差异（Ｐ均〈０．０５）。观察组血清２５ＯＨＤ升高值与血Ｃａ的升高值呈正相关，与术前血ＡＬＴ呈负相关。结果提示术后肌注ＶｉｔＤ３３０万单位对这类患儿佝偻病防治有效，Ｃ     

Elevation of serum stem-cell factor in postoperative biliary atresia

BACKGROUND: Biliary atresia (BA) is one of the most common causes of neonatal cholestasis. Stem-cell factor (SCF) has been implicated in the development of fibrosis in various diseases. The objective of the present study was to examine the significant role of SCF in BA. METHODS: Fifty-seven pediatric patients with BA after Kasai operation and 30 healthy children were recruited. The mean ages of BA patients and controls were 6.1 +/- 0.6 years and 6.1 +/- 0.7 years, respectively. The patients were categorized into two groups according to their serum levels of total bilirubin (TBil < 2 mg/dL, no jaundice vs TBil > or = 2 mg/dL, persistent jaundice) and alanine aminotransferase (ALT < 100 vs ALT > or = 100 U/L). The serum SCF levels were determined on commercially available enzyme-linked immunosorbent assay. RESULTS: The mean serum SCF level of the BA children was higher than that of normal controls (748.3 +/- 17.9 pg/mL vs 582.2 +/- 17.3 pg/mL; P < 0.001). Subsequent analysis demonstrated that the BA patients with serum ALT > or = 100 U/L had significantly greater levels of serum SCF compared to those with serum ALT < 100 U/L (796.5 +/- 22.6 pg/mL vs 694.7 +/- 25.0 pg/mL, respectively; P = 0.002). In addition, serum SCF levels were significantly elevated in the patients with portal hypertension (PH) compared with those without PH (810.0 +/- 18.8 pg/mL vs 634.1 +/- 20.1 pg/mL, P < 0.001). CONCLUSION: The current study showed that BA patients had higher serum SCF levels compared with controls. The significant elevation in SCF levels is associated with the presence of PH and the degree of hepatic injury. These findings suggest that SCF may play a part in the pathogenesis of hepatic fibrosis in BA patients after Kasai procedure.     

Current concept about postoperative cholangitis in biliary atresia

Background  Postoperative cholangitis characterized by fever and acholic stool and positive blood culture is a common and serious complication following Kasai’s operation for biliary atresia. The aim of this review was to describe the pathogenesis, clinical manifestations, medical treatment and outcome of postoperative cholangitis. Data sources  Articles on biliary atresia retrieved from Pubmed and MEDLINE in the recent 10 years were reviewed. Results  The pathogenesis of postoperative cholangitis is still controversial. Recent methods for the diagnosis of postoperative cholangitis include urinary sulfated bile acids (USBA) and magnetic resonance cholangiopancreaticography (MRCP). High-dose steroids and oral antibiotics have been used to reduce the incidence of postoperative cholangitis, and recurrent cholangitis leads to a lower survival rate. Conclusions  Cholangitis is one of the most important determinants of long-term survival after the Kasai’s procedure. The knowledge on postoperative cholangitis has been increasing in the past 10 years, showing a lower incidence of the disease and better therapeutic results.     

钙黏蛋白-11在胆道闭锁患儿肝组织中的表达及意义

目的分析钙黏蛋白-11(cadherin-11,CDH11)在胆道闭锁(biliary atresia,BA)患儿肝组织内的表达及意义。方法选取2014年11月至2016年12月就诊的BA和胆总管囊肿(CC)患儿作为研究对象。分析患儿肝脏CDH11与肝纤维化标志基因和血清肝功能指标的相关性。结果 BA组50例,女25例、男25例,中位年龄59.5(46.8～71.8)天;CC组8例,女5例、男3例,中位年龄70.0(49.0～125.3)天。BA组患儿肝脏中CDH11 mRNA表达水平显著高于CC组,差异有统计学意义(P<0.01)。BA肝内CDH11 mRNA表达水平与转化生长因子β1(TGFB1)、转化生长因子β2(TGFB2)、角蛋白19(KRT19)、肌动蛋白α2(ACTA2)、Ⅰ型胶原α1链(COL1A1)和Ⅳ型胶原α1链(COL4A1) mRNA表达水平呈显著正相关(r=0.36～0.73,P均<0.01)。与轻度肝纤维化BA患儿相比,CDH11表达水平在重度肝纤维化BA患儿肝内显著升高(P<0.01)。BA肝内CDH11 mRNA表达水平与血清γ-谷氨酰...     

Hyaluronic acid: Additional biochemical marker in the diagnosis of biliary atresia

BACKGROUND: The purpose of the present paper was to evaluate the value of biochemical markers, including conventional liver function tests, gamma-glutamyl transferase (GGT), and hyaluronic acid (HA), in the diagnosis of neonatal cholestasis. METHODS: Infants with neonatal jaundice were consecutively enrolled during 1 year period. The patients were diagnosed as having biliary atresia (BA) if there was either bile ductular proliferation in the portal tracts, atretic common bile duct/gallbladder, or evidence of bile duct obstruction demonstrated by liver pathology or intraoperative cholangiography, respectively. Serum HA was measured using an enzyme-linked immunosorbent assay-based test. RESULTS: A total of 25 patients diagnosed as having BA (n = 10), neonatal hepatitis (NH; n = 9), choledochal cyst (n = 3) and parenteral nutrition-induced cholestasis (n = 3), were studied. The age at diagnosis was not significantly different between groups. Only GGT and HA were significantly elevated in the patients with BA when compared to NH (P = 0.02, P = 0.03, respectively). In BA, the median value of serum HA was 514 ng/mL (range 19-4476 ng/mL), compared to 50 ng/mL (range 19-315 ng/mL) in NH. Additionally, the serum HA level was much higher in children with choledochal cyst. CONCLUSION: HA could be considered as a complementary biochemical marker for evaluating infants with prolonged jaundice.     

Evaluation of catch-up growth after liver transplantation in children with biliary atresia

Orthotopic liver transplantation (Tx) has improved survival in infants with extrahepatic biliary atresia (BA) when portoenteroanastomosis fails. Symptoms leading to Tx include liver failure, poor quality of life and growth failure. The objective of the study was to determine catch-up growth in children with BA. Medical records and growth data of 36 patients (24 girls) who received a Tx due to BA were analyzed. Thirty-two patients completed 3 yr and 15 patients 7 yr of follow-up after Tx. At Tx, the median age was 2.7 yr (range 0.7-12.6) and mean height Z score (+/-s.d.) was -1.56 (+/-1.3). Patients were divided in two groups according to age at Tx: group I (n = 10), younger than 1.0 yr, and group II (n = 26) older than 1.0 yr. Median age (range) at Tx in group I was 0.8 yr (0.7-1.0) and in group II it was 3.35 yr (1.25-12.6). Thirteen patients (nine in group I) were receptors of living related donors. We evaluated linear growth, liver and renal function, immunosuppressive regimen and allograft rejection episodes. We did not find any significant differences in allograft or renal function, immunosuppressive therapy and number of acute rejection episodes or height Z score at Tx, second and third year post-Tx between both groups. The mean height Z score at Tx in group I was -1.61 and in group II -1.54; at the second year, group I -0.66 and group II -1.08; at the third year, group I -0.17 and group II -0.85; and at the seventh year (total group) -0.3. However, the height gain at the third year was better in group I than in group II (p < 0.01, t-test). Height Z score at the third year improved more than 1 SDS in seven out of eight patients in group I and in only nine out of 24 in group II (odds ratio 11.6). We also found a correlation between height gain at the third year and age at Tx (r-0.65) and between height gain at the third year and height Z score at Tx (r-0.54) (Pearson, p < 0.05). Children with BA who are transplanted before 12 months of age presented better catch-up growth without change survival and morbidity. Orthotopic liver Tx improves survival and also enables height gain in these children.     

Retinal neurodevelopmental assessment with electroretinogram in patients with biliary atresia

BACKGROUND: To evaluate the effect of n-3 polyunsaturated fatty acid (PUFA) deficiency on the development of retinal function in children with biliary atresia (BA), we examined serum fatty acid levels and performed electororetinogram (ERG) in patients with BA. METHODS: The study group was composed of one male and four female BA patients (8-14 years) with serum bilirubin levels ranging from 0.40 to 1.48 mg/dL. All of the subjects were born as full-term infants. The fatty acid composition of total lipids in serum was analyzed by gas chromatography before the Kasai operation, approximately 10 months after the Kasai operation, and at the time of the ERG study. The ERG was recorded using corneal contact lens electrodes. RESULTS: Two of the five patients showed decreased levels of arachidonic acid and docosahexaenoic acid (DHA) before and after the operation, but no abnormal findings on ERG were detected in these patients. The other three patients had decreased levels of alpha-linolenic acid or DHA after the operation, but again, no abnormalities were found on ERG. CONCLUSION: These results suggest that insufficiencies of DHA and other n-3 PUFA in full-term infants might not have an influence on later ERG results.     

Magnetic compression anastomosis for postoperative biliary atresia

We report a case of successful magnetic compression anastomosis (MCA) for obstructed cyst‐jejunostomy in a young woman who had undergone surgery for type 1 biliary atresia (BA) on day 78 of life. A 16‐year‐old girl was admitted with obstructive jaundice. Jaundice resolved with percutaneous trans‐hepatic cholangiodrainage (PTCD) but contrast medium injected from the PTCD tube did not flow through the anastomosis. Magnets were placed on each side of the anastomosis, in the cyst and the jejunum, to compress the partition. On postoperative day (POD) 6, the anastomosis was recanalized and the PTCD tube placed trans‐anastomotically until POD 245. The patient remained free from jaundice after removal of the PTCD tube. MCA can be a useful and less invasive procedure for treating biliary tract anastomotic obstruction in patients with BA.     

Clinical significance of plasma endothelin levels in patients with biliary atresia

Biliary atresia (BA) is the end-result of a destructive inflammatory process that affects intra- and extrahepatic bile ducts, leading to fibrosis and obliteration of the biliary tracts with the development of biliary cirrhosis and portal hypertension (PH). Endothelins (ET) are 21-amino-acid peptides of endothelial origin with potent vasoconstrictor activity that bind to various cells of the liver. Nothing is presently known about plasma ET levels in BA. The aim of this study was to determine the clinical significance of plasma ET levels in patients with BA after hepatic portoenterostomy (Kasai's procedure) and to correlate these with liver function tests (LFT) and PH. We measured plasma concentrations of ET in 19 patients with BA (5 boys and 14 girls; mean age 11.6 ± 5.5 years) after portoenterostomy and 10 age-matched controls. Patients were grouped according to outcome based on LFT: group A consisted of 9 patients with an ‘‘unfavorable outcome” and Group B 10 patients with a “favorable outcome”. The plasma ET levels were measured using a highly sensitive and specific enzyme immunometeric assay (EIA). No patient had ascites or hepatorenal syndrome. Plasma ET levels were significantly higher in patients with BA than in controls (3.42 ± 0.42 vs 1.75 ± 0.39 pg/ml, respectively; P < 0.01) and in patients in group A than in group B. (3.75 ± 0.25 vs 3.06 ± 0.23 pg/ml, respectively; P < 0.01). In group A, plasma ET levels were higher in patients with PH (n = 4) than in those without PH (n = 5) (3.99 ± 0.06 vs 3.64 ± 0.22 pg/ml, respectively; P < 0.05). We conclude that plasma ET levels are high in patients with BA, especially those with severe biliary cirrhosis, and that ET may partially contribute to development of PH in BA. The results of the present study also suggest that plasma ET concentrations may be a useful marker in the follow-up of patients with BA. Accepted: 12 September 1997