胆道闭锁15例

目的探讨胆道闭锁(BA)的临床特点、治疗与预后的关系。方法回顾性分析经中国医科大学附属盛京医院小儿外科近2 a来诊治的15例BA患儿的临床症状、体征、实验室检查结果,诊断、治疗经过及预后,并结合文献报道,对其发病原因、治疗经验、疾病转归及预后进行综合分析。结果男9例,女6例;年龄28~90 d。胆总管闭锁型(Ⅰ型)、肝管闭锁型(Ⅱ型)各3例,肝门区胆管闭锁型(Ⅲ型)8例,胆总管闭锁并先天性肠旋转不良1例。11例生后即出现黄疸,4例出生1周内逐渐发生黄疸。大便进行性变浅或表现为陶土样便13例,2例生后2 d即排陶土样便。15例胆红素水平均有升高,且排泄性肝胆超声均表现为胆囊收缩不良。并巨细胞病毒感染14例,感染率为93%。患儿均行手术治疗,术后病理结果均表现为胆汁淤积性肝硬化。10例患儿术后6~28 d出院,5例患儿术后2 d家属放弃治疗出院。目前随访患儿共12例,随访时间1个月~1.5 a,生长发育均良好,9例有黄疸,10例有黄绿色便排出,2例排陶土样便,4例Ⅰ型和3例Ⅱ型的BA患儿胆红素水平术后可降至正常水平,2例Ⅲ型BA患儿胆红素在术后1个月左右降至正常水平,但反复发生毛细胆管炎。结论BA的病因与病毒感染...     

Vitamin D Metabolism in Pre-Operative Extrahepatic Biliary Atresia

ABSTRACT. In order to clarify the pathogenesis of rickets in preoperative patients with extrahepatic biliary atresia, we evaluated baseline serum 25-OHD and 1,25(OH)₂D levels and correlated serum 25-OHD levels with increase in age and season of birth in 16 preoperative patients. Further, parenteral vitamin D₂ tolerance tests were performed in 5 cases. Serum 25-OHD and 1,25(OH)₂D levels were significantly lower than those in 15 normal controls. There was a negative correlation between the serum 25-OHD levels and increase in age. The patients born during the winter had lower serum 25-OHD concentrations than those born in summer. The mean value of increased 25-OHD levels after the parenteral vitamin D₂ tolerance tests did not differ from that of 6 controls. Since there was no impairment of vitamin D 25-hydroxylation, the reduction in serum 25-OHD may therefore be mainly due to disturbed intestinal vitamin D absorption. It was also concluded that season of birth and increase in age are pathogenic factors in the etiology of rickets in preoperative patients with extrahepatic biliary atresia.     

Does ”Cystic” Biliary Atresia Represent a Distinct Clinical and Etiological Subgroup? A Series of Three Cases

We describe a unique series of 3 cases of biliary atresia (BA) associated with a choledochal cyst. All 3 children presented with jaundice at birth and had no other abnormalities. Although these children had a fetal form of BA, their presentation and outcome differed from those of biliary atresia splenic malformation syndrome (BASM), the well-described form of early onset BA. Unlike those with BASM, these children had no other associated malformations, had a normal birth weight, and did not yet require a liver transplant. We believe that the present series of patients and their associated pathology may represent a distinct phenotype with a common, prenatally acquired etiology that is different from other fetal forms of BA, such as BASM, and from patients who present with the classic perinatal form of BA.     

The Screening of Patients with Extrahepatic Biliary Atresia by Measuring Total Bile Acids Absoredin Dried Blood Spots

The efficency was assessed of the screening for extrahepatic biliary atresia by measuring total bile acids absorbed in dried blood spots at around 5 days of age. When the cut-off level was 54.0 μmol/l, the sensitivity, the specificty and the efficiency of the screening test were 87.9%, 93.9% and 93.9% respectively. The case-finding rate was 0.009% in this type of screening which was three times as many as an early case-finding rate by population screening. These results suggest that teh efficiency of this screening is acceptable.     

Bile duct ligation in neonatal rats: Is it a valid experimental model for biliary atresia studies?

Abstract:  BA is the most important disease requiring liver transplantation in children. Common BDL in rats is a classic experimental model to study biliary obstruction. The response of the neonatal animal to BDL has yet to be completely understood and few reports have focused on the behavioral differences of the liver between neonatal and adult animals. Ninety newborn Wistar rats aged six days, weighing 8.0–13.9 g, and 90 adult Wistar rats weighing 199.7–357.0 g, were submitted to BDL. After surgery, they were randomly divided and killed on the 3rd, 5th, 7th, 14th, 21st and 28th day post-BDL. Hepatic biopsies were obtained and the following were measured: (i) semiquantification of the bile ductule proliferation and inflammatory infiltrate by HE stain, (ii) quantification of portal and periportal fibrosis with the Sirius-red stain. Although the initial response of ductule proliferation and inflammatory infiltrate were less intense in the newborn animal, the portal and periportal fibrosis were higher when compared with adult animals (p < 0.0491). These findings may contribute to the understanding of the pathophysiology of BA.     

Congenital Structural Abnormalities in Biliary Atresia: Evidence for Etiopathogenic Heterogeneity and Therapeutic Implications

ABSTRACT. The clinical, surgical, laboratory and histological data of 237 children with extrahepatic biliary atresia were reviewed. Forty-seven patients (20%) had associated congenital anomalies, and of these, 28 had cardiovascular, 22 digestive and 19 splenic malformations. Of the 19 patients with splenic malformations, 13 showed the polysplenia syndrome and two had asplenia. Chromosome studies were performed in eight children, six having associated anomalies, and two of them showed karyotype abnormalities (46,XX,del 18 p- and 49,XXXXY). These observations indicated that biliary atresia could be subdivided into four distinct etiopathogenic subgroups, three involving a congenital form that could arise through a malformation, a disruption or a chromosome abnormality, and the remaining to agents active in the perinatal period (the acquired form). The surgical outcome in 171 patients operated on by an experienced surgeon was not influenced by the presence of anomalies but by the timing of surgery. Seventy-one percent of 24 patients operated on by 8 weeks of age were jaundice-free as opposed to only 34% of those who had later surgery ( p <0.01)     

婴儿巨细胞病毒感染与胆道闭锁的关系

目的　探讨巨细胞病毒 (CMV)感染与胆道闭锁的关系 ,了解婴儿CMV肝炎并胆道闭锁的临床特点。方法　对确诊为CMV感染并胆道闭锁 1 6例患儿的临床资料进行回顾性分析 ,并与同期诊断为单纯CMV肝炎 2 9例患儿进行比较。结果　CMV感染并胆道闭锁患儿血清CMV IgM抗体和外周血多形核白细胞中CMV pp65抗原均阳性 9例 ,IgM阳性 1例 ,仅pp65阳性3例 ,IgM和pp65均阴性 3例 (但其肝组织CMV pp65阳性 )。 1 5例肝组织标本中CMV pp65阳性 1 4例。CMV感染并胆道闭锁患儿各项指标明显重于有黄疸的单纯CMV肝炎 (P均 <0 .0 5) ,肝组织病理检查 1 5例显示胆小管增生伴肝纤维化 ,继发性胆汁性肝硬化 2例。结论　CMV感染可同时累及肝细胞和胆管上皮细胞 ,导致胆管闭锁。对以胆汁淤积为主要表现且已明确为CMV感染患儿应警惕是否并胆道闭锁 ,避免丧失手术治疗机会。     

Microdissection Study of the Myentric Plexus in Acardia, Ataxia-telangiectasia, Cystic Fibrosis, Extrahepatic Biliary Atresia, Pediatric Aids and Werdnig-Hoffmann Disease

Microdissection-point count morphometric study of the myenteric (Auerbach) plexus or esophagus, small intestine, and colon was done for infants and children with acardia (2), ataxia-telangiectasia (5), cystic fibrosis of the pancreas (CFP) (25), extrahepatic biliary atresia (EBA) (17), pediatric AIDS (10), and Werdnig-Hoffmann disease (WHD) (8). Values for fractional area of neural tissue in the plane of the plexus were compared to those of control patients in same age range as those in each disease category by t-test. Statistically abnormal values included low values for small intestine and colon in Werdnig-Hoffmann disease, high values for small intestine and colon in biliary atresia, and high value for colon but a low value for small intestine in cystic fibrosis. Values for all three loci were within the normal range for ataxia telangiectasia and pediatric AIDS. The mechanisms of the low value for small and large intestines in WHD, which causes chronic constipation as a result of skeletal muscle weakness, and of the high values for colon in CFP and EBA, both causing malabsorption with bulky stools, are unclear. The value for small intestine in acardia was normal for term but lower than expected for fetal bowel of the same size, possibly because of reduced neural crest inflow to the fetal bowel.     

茵栀黄注射液在胆道闭锁患儿手术前后的辅助治疗效果

目的 了解茵栀黄注射液在胆道闭锁（BA）患儿手术前后的辅助治疗效果。方法 将32例BA患儿按照手术前后是否辅以茵栀黄注射液治疗分为试验组（18例）和对照组（14例），患儿均经手术及病理切片证实诊断。采用ELISA测定患儿血清总胆红素、直接胆红素、ALT、AST水平，结合胆汁排出率和随访获得的黄疸消退率及胆管炎发生率综合评定茵栀黄辅助治疗效果。结果 试验组患儿上述生化指标在入院时均高于对照组（Pa〈0．05），术后2周再次测定时则明显低于对照组（Pa〈0．05）。随访持续使用茵栀黄达3个月以上黄疸消退率优于对照组，而发生胆管炎的比例明显降低。结论 茵栀黄可显著降低BA患儿血清转氨酶及胆红素水平，提高患儿术后黄疸消退率，降低胆管炎发生。     

Biliary Atresia and Cytomegalovirus Infection: A DNA Study

The cause of extrahepatic biliary atresia (EHBA) is undetermined in most instances, but an infectious agent is widely suspected. Cytomegalovirus (CMV) infection has been associated with intrahepatic bile duct destruction and paucity, raising the question of its role in EHBA. We identified 12 children in the past 5 years with biliary atresia and examined the bile duct biopsy. These showed acute/chronic inflammation and epithelial degeneration. CMV inclusions were not identified. We used in situ hybridization and the polymerase chain reaction (PCR) for CMV-DNA on formalin-fixed, paraffin-embedded tissue. All samples showed the presence of amplifiable DNA using β-globin primers. No biopsy tissue showed CMV DNA using specific probes and primers. The absence of demonstrable CMV DNA by in situ hybridization and PCR in EHBA biopsies implies that it is unlikely that this virus has any major role in the pathogenesis of this condition. Received October 29, 1997; accepted March 27, 1998.     

Biliary atresia in Turkish children

AIM: To evaluate surgical success, survival rate and relationship of outcome parameters with time at diagnosis and operation of extrahepatic biliary atresia (EHBA) patients in Izmir, Turkey. METHODS: Clinical and laboratory data were reviewed from case reports of 27 EHBA patients. Twenty-five patients were operated on using Kasai procedure and two cases received liver transplants without portoenterostomy due to decompansated liver cirrhosis on diagnosis. Post operational success was defined as clearance of jaundice (bilirubine level <2 mg/dL). Patients were studied in two groups: I (jaundice free and/or compensated liver disease with liver transplant if needed after 3 years of age) and II (progressive liver disease with death or liver transplant if needed before 3 years of age). Kasai success, age at diagnosis and operation, survival and correlation of outcome with age, preoperative liver functions were evaluated. Eight patients received liver transplants. RESULTS: Median age at diagnosis was 63.5 days (21-212) and portoenterostomy was performed at median age of 67.5 days (25-220). Kasai operation was successful in two cases (8%) and the operation was performed at 35 and 42 days. Age at diagnosis (P = 0.13) and operation (P = 0.2) was not different between the two groups. Group I and II consisted of seven (28%) and 18 (72%) infants. Pre-existing ascites, serum alanine aminotransferase (ALT) and globulin levels were significantly higher in group II patients (P = 0.008, P = 0.04, P = 0.017, respectively). CONCLUSIONS: The results of the present study indicate that general practitioners should pay close attention to the evaluation of infants with prolonged jaundice in Turkey. Because of frequent late diagnosis presenting with cirrhosis at admission and also because of the low organ donation rates in Turkey, living related liver transplantation is an option and is currently undergoing detailed ethical consideration.     

99mTc-EHIDA肝胆显像在先天性胆道闭锁诊断中的价值

目的评价99mTc—EHIDA肝胆显像在先天性胆道闭锁(BA)诊断中的临床价值。方法对45例有持续性黄疸的患儿,进行99mTc—EHIDA肝胆显像检查.并经手术病理和临床随访结果证实。结果最终诊断为BA的加例患儿中.99mTc—EHIDA肝胆显像全部检出;非BA组25例中15例为真阴性,10例为假阳性,灵敏度、特异度和准确性分别为100%、60%和77.8%。结论99mTc—EHIDA肝胆显像是一种无创、安全、有效的检查方法,对于BA的诊断,有较高的临床价值。     

HEPATIC HETEROTOPIAS IN THE JEJUNUM: A Case Study over Time Showing Progressive Degenerative Changes

Multiple foci of heterotopic liver in the jejunum were sequentially discovered in an infant boy at the ages of 1 day, 2 months, and 4 months. This is the second reported case of jejunal heterotopic liver, a rare entity in any site. Progressive histological changes indicative of biliary duct obstruction were observed in the hepatic heterotopias, which demonstrated no connections to the main body of the liver or biliary tree.     

EXCRETION OF BILE ACIDS IN EXTRAHEPATIC BILIARY ATRESIA AND INTRAHEPATIC CHOLESTASIS OF INFANCY

This series included 24 infants, 16 boys and 8 girls, who were admitted to hospital with the diagnosis of obstructive jaundice. Five of the infants were subsequently found to have extra-hepatic biliary atresia (BA) and the other 19 infants intrahepatic cholestasis of infancy (IHC). The infants were investigated given special attention to: the quantitative urinary excretion of cholic and chenodeoxycholic acids, the isotope excretion after intramuscular injection of cholic acid-24–¹⁴C, the nature of labelled urinary bile acids, the half-life and the pool size of cholic acid. At the first examination of the infants after admission the urinary excretion of cholic and chenodeoxycholic acids varied greatly between the patients. However, on comparing the values obtained in the two groups, it was found that there was virtually no difference between the mean daily values of cholic and chenodeoxycholic acids in urine, and the ratio cholic to chenodeoxycholic acid between the BA group and the IHC group. After the injection of isotopic cholic acid most of the isotope was recovered in the urine in all cases. In the infants with BA the faecal excretion of the isotope was low, being less than 3 per cent of the injected isotope. Out of the 19 infants with IHC the recovery of the injected isotope in faeces was also less than 3% in 11 infants. In 8 infants with IHC the faecal isotope excretion was significantly high to exclude extrahepatic biliary atresia. The first 24 hour urine specimen contained small amounts of unconjugated labelled cholic acid in all cases whereas in no case did the patients excrete unconjugated labelled cholic acid 48 hours after the injection of the isotope. No transformation of cholic acid was observed. There was no difference between the BA group and IHC group with regard to the percentage labelled glycine conjugates of total excreted urinary conjugates. Neither was there any difference between the two groups with regard to half-life and pool size of cholic acid. There was no difference with respect to the bile acid metabolism between infants with congenital CMV infection, decreased serum concentrations of alfal-antitrypsin and the other patients.     

胆道闭锁患儿血浆胰岛素样生长因子-1的变化及临床意义

目的 了解胆道闭锁(BA)患儿血浆胰岛素样生长因子-1( IGF-1)水平的变化及其临床意义.方法 选择20例BA患儿(BA组).年龄1～3个月.于确诊后取空腹静脉血2mL,采用ELISA法检测其血浆IGF-1水平.采用全自动生化分析仪进行肝功能检测,指标包括ALT、总胆红素(TB)、结合胆红素(DB)、γ-谷氨酰转移酶(y-GT)、前清蛋白(PA)及清蛋白.另选择20例健康婴儿作为健康对照组,其性别、年龄均与BA组相匹配.结果 与健康对照组比较,BA组患儿血ALT、TB、DB及y-GT水平均显著升高(P.＝0.00),分别为(160.05-50.79)U·L-1vs(46.15±9.84)U·L-1、( 260.30±128.65)μmol·L-1 vs(16.00 ±3.46) μmol·L-1、( 191.75±85.69) μmol·L-1 vs (6.63±1.84) μnol·L-、(485.95±214.79)U·L-1 vs(44.65±13.04)U·L-1;BA组IGF-1及PA水平分别为(31.96±5.37) μg· L-1和(77.35 ±14.59) mg·L-1,显著低于健康对照组[ (54.90±8.78) μg·L-1和(126.34±11.97) ng·L-1].1GF-1与ALT、TB、DB及γ-GT之间呈高度负相关(Pa＜0.01),而与PA清蛋白呈正相关(Pa＜0.01).结论 BA患儿肝细胞合成IGF-1功能下降,IGF-1水平降低是蛋白合成低下的主要原因之一,也是反映肝细胞受损的指标.检测IGF-1水平变化对判断BA患儿肝细胞功能及营养状况具有一定意义.     

Biliary complications of living related pediatric liver transplant patients

Patients who undergo living related left lateral segment liver transplants have been reported to have a high incidence of biliary complications and some studies suggest that most patients will ultimately need operative revision. We reviewed our experience with living related transplantation in pediatric recipients to examine the occurrence of biliary complications and the utility of percutaneous biliary procedures in their management. Over a 10-yr period, 48 living donor transplants were performed in 47 patients. Sixteen patients (33%) had biliary complications. Complications included 10 leaks (20%) and eight strictures (17%). Although leaks were treated predominantly with operation, other biliary complications were treated almost exclusively non-operatively. Self limited leaks that lead to biloma accumulation were most often treated via percutaneous catheter drainage and all strictures were treated using percutaneous transhepatic biliary cholangioplasty and stenting. Sixty-seven percent of biliary complications underwent non-operative biliary intervention. Most strictures were focal anastomotic strictures and were successfully treated with cholangioplasty although multiple interventions were necessary and patients required stenting for an average of 13 months. Three of eight strictures were diffuse in nature and these included the only patient who required retransplantation. Graft survival with respect to biliary complications was 94%; 1 yr, 5 yr and overall patient survival for those with biliary complications was 88, 88 and 81%, and for the entire living related group was 84, 81 and 77%, respectively. Although biliary complications are frequent in pediatric living related transplantation, they are not associated with decreased patient survival. Excepting significant bile leaks, the majority can be treated non-operatively via biliary cholangioplasty and stenting. Strictures are especially amenable to this technique which, in our experience, has been successful at decreasing or postponing the need for retransplantation.     

Mortality of biliary atresia in children not undergoing liver transplantation in the Netherlands

In order to further improve the outcome of BA, we characterized the mortality of BA patients who did not undergo OLT in the Netherlands, and compared our results with international data. For this purpose, we analyzed the causes of mortality of non-transplanted BA patients before the age of five yr, using the NeSBAR database. To evaluate trends in mortality, we compared the cohort 1987-1996 (n=99) with 1997-2008 (n=111). We compared clinical condition at OLT assessment with available international data, using the PELD-score. Mortality of non-transplanted BA children was 26% (26/99) in 1987-1996 and 16% (18/111) in 1997-2008 (p=0.09). Sepsis was the prevailing direct cause of death (30%; 13/44). PELD-scores at the time of assessment were higher in non-transplanted BA patients (median 20.5; range 13-40) compared with international data (mean/median between 11.7 and 13.3). Based on our national data, we conclude that pretransplant mortality of BA patients is still considerable, and that sepsis is a predominant contributor. Our results strongly indicate that the prognosis of patients with BA in the Netherlands can be improved by earlier listing of patients for OLT and by improving pretransplant care.