The use of ultrasonography in the diagnosis of biliary atresia

Preoperative upper abdominal ultrasonograms of babies with biliary atresia were reviewed in order to determine the efficacy of this technique in the differential diagnosis of biliary atresia and neonatal hepatitis. In 4 patients with neonatal hepatitis and 8 normal controls, ultrasonograms showed echoes of the gallbladder. In 14 patients with biliary atresia, echoes of the gallbladder were not apparent. It is concluded that preoperative ultrasonograms provide an efficient diagnostic method for differentiating biliary atresia from neonatal hepatitis.Offprint requests to: T. Okasora     

The infant with possible biliary atresia: Evaluation by ultrasound and nuclear medicine

Twenty-eight infants with jaundice were evaluated with ultrasound and radionuclide scans. Comparison of these studies with pathologic, surgical and clinical examinations demonstrated good correlation between ultrasonic and radionuclide studies. Ultrasound is an important preliminary study in the workup of such patients. Combined imaging provides the most information in a patient with suspected biliary atresia.     

Neonatal cholestasis: differentiation of biliary atresia from neonatal hepatitis in a developing country

Aim:  To study the accuracy of various clinical and investigational parameters to differentiate biliary atresia (BA) from neonatal hepatitis (NH).
Methods:  It was a prospective study, conducted in a tertiary care hospital. A total 101 infants with neonatal cholestasis (NCS) were included in this study. Following a baseline hepatobiliary scintigraphic study (HBS), it was repeated after giving UDCA (40 mg/kg/day for 48–72 h). The sensitivity and specificity of clinical and investigational parameters were calculated with peroperative cholangiogram as gold standard.
Results:  The mean age was 2.8 ± 1.7 months and 82 were male. Of these, 35 were diagnosed to have BA and 66 had NH (idiopathic 25, sepsis/UTI 20, galactosaemia 11, TORCH 2 and others 8). Persistently clay stool was found to have modest accuracy (79%) and the accuracy of HBS improved significantly following UDCA therapy (91% from 77%, p < 0.01) whereas liver biopsy was 100% accurate in differentiating BA from NH. The outcome of BA cases with ductal plate malformation (DPM) was worse.
Conclusion:  One-third of all NCS in India is due to BA and among the intrahepatic causes acquired infection and galactosaemia are common. Liver biopsy is the best method to differentiate NH from BA.     

Definitive exclusion of biliary atresia in infants with cholestatic jaundice: the role of percutaneous cholecysto-cholangiography

Definitive exclusion of biliary atresia in the infant with cholestatic jaundice usually requires operative cholangiography. This approach suffers from the disadvantage that sick infants are subjected to a time-consuming and potentially negative surgical exploration. The purpose of this study was to determine if percutaneous cholecystocholangiography (PCC) prevents unnecessary laparotomy in infants whose cholestasis is caused by diseases other than biliary atresia. This study is a 10 year retrospective review of all infants with persistent direct hyperbilirubinemia and inconclusive biliary nuclear scans who underwent further evaluation for suspected biliary atresia. A gallbladder ultrasound (US) was obtained in all patients. When the gallbladder was visualized, further imaging by PCC was done under intravenous sedation; otherwise, the standard operative cholangiogram (OCG) was performed, with liver biopsy as indicated. The primary outcome was the diagnostic accuracy of PCC, especially with respect to preventing a laparotomy. There were 35 infants with suspected biliary atresia, with a mean age of 8 weeks (range 1-14 weeks). Nine infants whose gallbladder was visualized by ultrasound underwent PCC that definitively excluded biliary atresia. Of this group, the most frequent diagnosis (five patients) was total parenteral nutrition-associated cholestasis. The other 26 infants with absent or decompressed gallbladder had laparotomy and OCG, which identified biliary atresia in 16 patients (61%). Laparotomy was avoided in all 9 patients who underwent PCC, thus reducing the negative laparotomy rate by 47%. There were no complications associated with PCC. Several alternative techniques to operative cholangiogram have been described for the definitive exclusion of biliary atresia, but many of these have distinct drawbacks. Advances in interventional radiology techniques have permitted safe percutaneous contrast evaluation of the biliary tree. Identification of a normal gall bladder on sonogram is highly predictive of the absence of biliary atresia. Further confirmation can be accurately obtained by a combination of PCC and percutaneous liver biopsy.     

Serial ultrasonic examination to differentiate biliary atresia from neonatal hepatitis — special reference to changes in size of the gallbladder

We performed serial ultrasonic examinations to differentiate biliary atresia from neonatal hepatitis. The subjects studied were 144 children (100 normal neonates and infants, 31 patients with neonatal hepatitis and 13 patients with biliary atresia). They were examined by ultrasound before, during and after feeding. In 97 out of 100 normal children and all patients with neonatal hepatitis, the gallbladder was identified, and the change in size following oral feeding was observed. In four children with severe neonatal hepatitis which could not be differentiated from biliary atresia by clinical and laboratory data, we readily identified the gallbladder and observed the change in the size following oral feeding. In 8 of 13 patients with biliary atresia, we identified a small gallbladder whose size was not affected by oral feeding. In the other patients the gallbladder was not identified before, during or after oral feeding. On the basis of these results, we consider that serial ultrasonic examination with oral feeding aids in a differential diagnosis of biliary atresia and neonatal hepatits.     

Hepatic technetium-99m-mebrofenin iminodiacetate scans and serum γ-glutamyl transpeptidase levels interpreted in series to differentiate between extrahepatic biliary atresia and neonatal hepatitis

Hepatic technetium-99m-mebrofenin iminodiacetate (99mTc-mebrofenin IDA) scans and serum gamma-glutamyl transpeptidase (GGTP) have high sensitivity for extrahepatic biliary atresia (EHBA). This study was based on the hypothesis that the interpretation of results of 99mTc-mebrofenin IDA scans and serum GGTP levels in series would result in a reduction of the false positivity observed with these tests individually. The aetiology of neonatal cholestasis in 132 study patients was: 25% (33/132) EHBA, 45.5% (60/132) neonatal hepatitis (NH) with an identifiable cause and 19.7% (26/132) idiopathic NH. Of the various clinical, biochemical and imaging parameters that were significantly different between patient groups, sensitivity for EHBA was: serum GGTP > or = 150 IU l(-1) (100%), 99mTc-mebrofenin IDA scans (100%), pale stools (82.8%) and total serum bilirubin > or = 12 mg dl(-1) (66%). However, specificity ranged from 48.5 to 79%. Of the 63 patients who had non-excreting IDA scans, operative cholangiograms could be avoided on the basis of a specific aetiological diagnosis of NH, made concurrently, in only 9 infants. The rest (54) underwent operative cholangiograms; 21 (39%) of these had patent biliary trees and therefore underwent the procedure unnecessarily. If serum GGTP (< 150 IU l(-1)) had been used as a screen after IDA scanning in these 54 patients, operative cholangiograms could have been avoided in another 12 patients and thereafter only 9/42 (21%) of the operative cholangiograms would have been considered unnecessary. Conclusion: A diagnostic algorithm is proposed wherein serum GGTP level (at a cut-off level that maintains 100% sensitivity for EHBA) is used in series with non-excreting 99mTc-mebrofenin IDA scans (for patients with no specific aetiological label). This strategy reduces the false positivity of individual tests.     

A disturbance of the gastric myoelectric activity in post-operative patients with biliary atresia

Background Abnormalities in gastrointestinal motility have been reported in adult patients with advanced liver disease. However, there have so far been no reports on the gastric myoelectric activity in post-operative patients with biliary atresia (BA).Aim The purpose of this study was to evaluate the gastric myoelectric activity in post-operative patients with BA in relation to liver fibrosis.Patients and methods Twenty-one post-operative patients with BA, consisting of 6 boys and 15 girls with a mean age of 8.0 years and 6 healthy children (control group) were included in the study. The gastric myoelectric activity was measured by electrogastrography (EGG). The patients with BA were divided into two groups according to the serum hyaluronic acid (HA) level as a marker of liver fibrosis: the fibrotic group (FG, n=11), HA>50 ng/ml and the non-fibrotic group (NF, n=10), HA 50 ng/ml. All recorded data were spectrally analyzed and any parameters related to changes in the dominant peak frequency (DPF) and its power were investigated. Furthermore, the gastrointestinal symptom scores (GSS) were calculated in patients with dyspeptic symptoms according to the degree of advanced liver fibrosis.Results The results showed that 1) the postprandial DPF in the FG tended to be higher than that in the NFG (p=0.051), 2) the postprandial variability index of the DPF in the FG and NFG were significantly higher than those in the controls (p<0.05), and 3) the preprandial percentage of normal waves (PNW) in the FG tended to be lower than that in the controls (p=0.089). The postprandial PNWs in the FG and NFG were significantly lower than those in the controls (p<0.05). Especially, the postprandial PNW in the FG was significantly lower than that in the NFG (p<0.05). 4) The power ratio in the FG and NFG were significantly lower than those in the controls (p<0.05), and 5) the GSSs in the FG were significantly higher than those in the NFG (p<0.05).Conclusions The gastric myoelectric activity appeared to be disturbed in BA patients associated with portal hypertension and neurohormonal changes due to liver fibrosis.     

The expression of interleukin-33 in the serum and liver tissue of the patients with biliary atresia

目的 研究胆道闭锁(BA)血清及肝脏组织中白介素-33(IL-33)的表达及意义.方法 选取18例BA与12例无黄疸症状且肝功能正常的胆总管囊肿(CC)患儿血清和肝脏标本进行对比研究.应用酶联免疫吸附试验检测血清中IL-33的表达水平.荧光定量RT-PCR技术和免疫印迹技术分别检测肝脏组织中IL-33 mRNA及蛋白表达水平.结果 BA组血清中IL-33的表达(791.0±22.22)pg/ml明显高于CC组的(607.1±20.68) pg/ml(P＜0.0001);并与γ-谷氨酰转移酶呈正相关(r=0.629,P=0.005).BA组肝组织中IL-33 mRNA表达0.0420±0.0061明显高于CC组的0.0220±0.0027(P=0.0181).BA组肝组织中IL-33蛋白表达0.4683±0.0188亦明显高于CC组的0.3433±0.0293(P=0.0137).结论 IL-33在BA组血清及肝组织中表达均明显升高,可能在BA炎症发生及发展过程中发挥重要作用,值得进一步研究.     

肝功能检查在婴儿肝炎综合征和先天性胆道闭锁的鉴别诊断中的价值

目的：该文采用受试者工作特征曲线（ROC曲线）对肝功能检查中常用的7项血清学指标进行分析,探讨常用的肝功能检查在婴儿肝炎综合征（infantile hepatitis syndrome,IHS）和先天性胆道闭锁（biliary atresia,BA）中的鉴别诊断价值。方法：分别检测IHS组（n=103）和BA组（n=60）的丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、γ-谷氨酰基转移酶（γ-GT）、碱性磷酸酶（ALP）、血清总胆红素（TB）、结合胆红素（CB）和血清白蛋白（ALB）等7个生化指标,应用ROC曲线进行分析,评价上述各指标的敏感性和特异性,阳性预测值和阴性预测值,并得到最佳临界值。对γ-GT,TB 和CB采用联合试验,提高诊断效率。结果：与IHS组相比,BA组的ALT、AST、γ-GT、TB 和CB水平显著升高（PCB>TB>AST;CB的阴性预测值最高,TB次之。CB的阴性似然比最低;CB的Youden指数最高,γ-GT和TB次之。γ-GT、TB及CB经平行试验,敏感性和阴性预测值均提高至100%;经系列试验,特异性提高至90.4%,阳性预测值提高至87.5%。结论：γ-GT、TB和CB水平对BA有一定诊断价值,平行试验阳性者更需积极做影像学检查。［中国当代儿科杂志,2009,11（12）：953-956］     

胆道闭锁患儿血清sICAM-1与IL-18的变化及临床意义

目的　研究可溶性细胞间粘附分子 1(sICAM 1)、白细胞介素 18(IL 18)在胆道闭锁(BA)发病机制中的作用及临床意义。方法　胆道闭锁患儿 2 1例 ,男 8例 ,女 13例 ;年龄 2个月～ 12岁 ,所有患儿诊断均经手术后病理切片证实。正常对照 12例为健康体检儿童 ,年龄 1个月～ 10岁。采用ELISA法动态测定胆道闭锁患儿手术前、后血清sICAM 1、IL 18水平。结果　胆道闭锁患儿血清sICAM 1、IL 18水平明显高于健康对照组 ,且两者呈正相关。Kasai手术后两者水平比术前无明显下降 ,且黄疸越重 ,水平越高。结论　sICAM 1、IL 18参与胆道闭锁的进行性损伤的病理过程 ,手术后两者增高表明外科手术不能完全阻止BA的炎症 ,持续增高提示预后不良     

CD4+T细胞因子在胆道闭锁患儿肝脏组织中的表达及其意义

目的 检测T淋巴细胞中的11种CD4+T细胞因子在胆道闭锁(biliary atresia,BA)患儿肝脏组织中的表达,以探讨其在胆道闭锁发病机制中的意义.方法 在病理的基础上,采用流式微球技术对29例BA及9例对照组患儿肝脏组织CD4+T细胞表达的11种细胞因子(IL-12p70、IFN-γ、IL-2、IL-10、IL-8、IL-6、IL-4、IL-5、IL-1β、TNF-α和TNF-β)同时进行定量检测,并对其代表因子IFN-γ进行免疫组化定位分析.结果 CD4+T细胞表达的11种细胞因子中,BA组患儿肝脏组织中IL-1β、IL-2、IL-6、IL-8、IFN-γ、TNF-α以及Th1细胞因子总量(IL-1β、IL-2、IL-8、IL-12p70、IFN-γ、TNF-α、TNF-β)与促炎因子总量(IL-1β、IL-2、IL-6、IL-8、IL-12p70、IFN-γ、TNF-α、TNF-β)分别为2920.69、1 106.01、152.22、12 614.22、834.18、161.29、19 504.55、19653.06,数值明显高于对照组的1 096.00、243.68、5.98、965.17、147.28、30.56、2 617.93、2 623.91,差异具有统计学意义(P＜0.05).结论 由CD4+Th1细胞及其细胞因子所介导的针对胆道上皮细胞的免疫炎症性疾病可能是造成胆道闭锁的主要原因之一.     

胆道闭锁肝内iNOS及其调控因子异常表达与进行性肝损伤的相关性

目的 研究胆道闭锁(BA)患儿肝内诱导型一氧化氮合酶(iNOS)及其上下游调控因子表达情况,并探讨其与BA进行性肝损伤发生的关系.方法 应用免疫组织化学染色法对2002年10月至2007年3月在本院行Kasai手术的38例BA患儿与16例对照儿童肝组织iNOS表达情况进行研究;应用ELASA法对BA患儿和对照组外周血总一氧化氮(NO)代谢产物浓度进行测定;应用TUNEL法对BA患儿和对照组肝内胆管上皮凋亡指数进行测定;应用免疫印记法对BA患儿和对照组肝组织NF-κB表达进行半定量分析.结果 iNOS在BA患儿肝组织异常高表达,强度为0.30±0.08,而在对照组肝组织不表达.BA患儿外周血总NO代谢产物浓度为(90.40±12.46)mol/L,明显高于对照组的(63.67±5.78)μmol/L,且BA组总NO代谢产物浓度与血清ALT水平[(152.76±29.59)U/L]呈强正相关(r=0.97).BA组肝内胆管上皮凋亡指数(54.00±11.67)%远高于正常对照组(20.72±5.63)%,且与肝组织iNOS表达强度呈强正相关(r=0.99).NF-κB出在BA患儿肝组织中的表达(0.74±0.06)明显高于正常对照组(0.22±0.03),且与iNOS表达强度呈强正相关(r=0.97).结论 iNOS异常高表达在BA患儿进行性肝损伤中发挥重要作用,该作用是由iNOS及其上下游调控因子NF-κB、NO共同作用所实现.     

The relationship between procollagen-III-peptide and the severity of esophageal varices in children with biliary atresia after Kasai operation

Biliary atresia (BA) is a common cause of infantile cholestasis. Disease progression leads to intra hepaticfibrosis, and thus to the development of PH and EV. Our objective has been to study the relationship between procollagen-III-peptide (PIIIP) and the severity of EV in children with BA after Kasai operation. Children below 15 years of age (n=29) with BA after a Kasai operation were evaluated for EV by endoscopy. Healthy (n=26) children of the same age and sex distribution who participated in the hepatitis B vaccination program served as the controls. Serum PIIIP was determined by radioimmunoassay. The BA patients were classified on the basis of severity of EV (Paquet's classification) into three groups: group 1 (n=15) had grade 0, group 2 (n=8) grade 1–2, and group 3 (n=6) grade 3–4 EV. In group 3, serum PIIIP (2.9 ± 1.3 IU/ml) was significantly higher than in group 2 (1.5 ± 0.4 IU/ml) (P < 0.05). Serum PIIIP levels were increased in group 2 compared with group 1 (1.2 ± 0.4 IU/ml) and in group 1 compared with the control group (1.2 ± 0.2 IU/ml), but this difference was not significant. PIIIP levels increased with severity of the EV in the BA patients. Hence, high PIIIP levels may serve as a non invastive indicator of EV developing in postoperative BA patients. Accepted: 8 January 2001     

热休克蛋白47的表达与胆道闭锁肝纤维化及预后的相关性研究

目的 研究热休克蛋白47的表达与胆道闭锁患儿肝脏纤维化程度及预后的相关性.方法 选择30例胆道闭锁、10例胆汁淤积症和10例胆总管囊肿患儿入组,分别取肝脏组织以及外周血,通过RT-PCR、Western-blot、ELISA以及病理切片来评估不同水平HSP47的表达情况及其与肝脏纤维化相关性.结果 三组HSP47在mRNA水平(0.915±0.730比0.066±0.037比0.314±0.150,P＜0.05)、蛋白水平(3.061 81±0.504 763比1.358 018±0.373 174比1.23649±0.350 173,P＜0.05)以及血清水平(63.38±17.11比57.87±14.83比45.78±11.23,P＜0.05)的表达胆道闭锁组均比胆汁淤积组以及胆总管囊肿组高,差异有统计学意义,且不同水平表达具有一致性(mRNA比蛋白水平:r=0.836,P＜0.05;蛋白水平比血清水平:r=0.989,P＜0.01;mRNA比血清水平:r=0.883,P＜0.05).胆道闭锁血清HSP47的表达与肝脏组织光镜下纤维化程度呈正相关关系(r=0.669,P＜0.01).结论 肝脏组织HSP47的表达与血清HSP47的表达水平具有一致性,能够评估肝脏纤维化程度;血清HSP47的高表达可能作为胆道闭锁预后不良的一个监测指标.     

声触诊弹性成像联合谷氨酰转肽酶检测在胆道闭锁诊断中的应用研究

目的 探讨声触诊弹性成像(sound touch elastography,STE)联合血清谷氨酰转肽酶(gam-ma-glutamyl transpeptidase,GGT)检测对小婴儿胆道闭锁(biliary atresia,BA)的诊断价值.方法 运用STE技术对196例临床初诊为胆汁淤积性黄疸的新生儿和小婴儿进...     

血清γ-谷氨酰转肽酶联合直接胆红素诊断婴儿胆道闭锁的价值

目的 探讨血清γ-谷氨酰转肽酶（GGT）联合直接胆红素（DB）对胆道闭锁的诊断价值。方法 选取2010年7月至2018年12月住院治疗的胆汁淤积症患儿667例为研究对象,根据术中胆管造影结果和随访情况,将患儿分为胆道闭锁组（n=234）和胆汁淤积组（n=433）。比较两组的发病年龄、性别,以及血清总胆红素（TB）、DB、丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、总胆汁酸（TBA）、GGT水平。将有统计学意义的指标纳入受试者工作特征曲线（ROC）分析,计算ROC曲线下面积（AUC）和最佳诊断界值。结果 胆道闭锁组患儿发病年龄早于胆汁淤积组（P < 0.001）。两组患儿性别、ALT及AST水平比较差异无统计学意义（P > 0.05）。胆道闭锁组TB、DB、TBA、GGT水平显著高于胆汁淤积组（P < 0.05）。GGT联合DB诊断胆道闭锁的AUC最大,为0.892（95% CI：0.868~0.916）。当GGT取值为324.0 U/L,DB取值为115.1 μmol/L时,GGT与DB联合诊断胆道闭锁的敏感度和特异度分别为79.8%、83.2%。结论 GGT联合DB诊断胆道闭锁的敏感度和特异度较高,可作为诊断胆道闭锁的有效指标之一。     

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.     

Cholangitis associated with cystic dilatation of the intrahepatic bile ducts after antireflux valve construction in biliary atresia

 An intussusception-type antireflux valve (ARV) has been introduced to prevent postoperative ascending cholangitis in the management of biliary atresia (BA). We investigated the characteristics of cholangitis in the management of BA using the ARV in 38 patients who had undergone an operation at our institution; 29 underwent ARV construction at the same time as portenterostomy (PEO) or hepaticojejunostomy. One patient underwent ARV construction for refractory cholangitis with cystic dilatation of the intrahepatic bile ducts (CDIB) long after the PEO. Five of 29 patients who had ARV construction developed CDIB complicated by severe, refractory cholangitis. One or two episodes of mild cholangitis were observed in 5 (20.8%) of 24 patients who did not show CDIB. An ARV created for postoperative recurrent cholangitis associated with CDIB was ineffective. Preoperative cholangitis associated with a type I choledochal cyst and CDIB was observed in 1 patient. In conclusion, the ARV was effective in preventing refractory cholangitis without CDIB, but ineffective in preventing cholangitis with CDIB. Our findings suggest that CDIB resulting from the ongoing process of BA could be a potential target of bacterial infection through other routes than bilioenteric reflux. Accepted: 14 April 2000