Spectrum of congenital anomalies associated with biliary atresia

Several congenital anomalies have been reported in association with biliary atresia. We have analysed the type and frequency of anomalies observed over a 10-year period in consecutive patients operated for extrahepatic biliary atresia at our institution. Of the 107 infants who underwent a laparotomy and surgical correction of biliary atresia, 9 (8.4%) showed significant associated anomalies. Among them, 5 (55.5%) had splenic malformations, 6 (66.6%) had digestive anomalies in the form of malrotation, Meckel's diverticulum and jejunal atresia. One patient had the classical polysplenia syndrome. Our follow-up period was limited (i.e. 5 months) during which time 3 of the 9 (33.3%) patients with associated anomalies became jaundice-free. A higher incidence of malformations found in association with biliary atresia supports the congenital theory and a more thorough search for these anomalies is recommended.     

Implication of early‐onset biliary atresia and extrahepatic congenital anomalies

Background: The aim of the present study was to determine the rate of early‐onset biliary atresia (BA) and its implications, for embryonic‐type BA in Taiwan, a high‐prevalence area for BA. The relationship between the timing of disease onset and congenital extrahepatic anomalies was also identified. Methods: Medical records of 130 infants born in Taiwan with biliary atresia between January 1996 and December 2005 were reviewed retrospectively. The gold standard for the diagnosis of biliary atresia was intraoperative cholangiography. As well as medical records review, abdominal imaging and echocardiograms were performed to determine other structural anomalies. Early‐onset BA was defined as acholic stool and cholestatic jaundice observed before 2 weeks of age. Results: On review of onset of acholic stool and cholestatic jaundice before 2 weeks of age, 31 patients (23.8%) were defined as having early‐onset BA. Twenty patients (15.4%) had major congenital extrahepatic anomalies. One (0.7%) had biliary atresia splenic malformation syndrome (BASM). Both early‐onset and late‐onset BA may be associated with other structural anomalies. Patients with early‐onset BA had a higher probability of having major extrahepatic anomaly (9/31 vs 11/99, P= 0.046). Situs anomalies accompanying major gastrointestinal (GI) tract anomalies occurred only in early‐onset BA patients. Conclusions: After comprehensively investigating the timing of onset and associated congenital extrahepatic anomalies in BA patients in Taiwan, only one BASM with double spleen was detected. A total of 23.8% of patients had early‐onset BA, and this group of patients is prone to extrahepatic anomalies. Situs anomalies accompanying major GI tract anomaly may be indicative of embryonic‐type early‐onset BA.     

Clinical and pathological characteristics of cystic lesions of extrahepatic bile duct in neonates

Aim: To investigate the differences in clinical and pathological manifestations between biliary atresia with extrahepatic biliary cyst and choledochal cyst in neonates. Methods: Symptoms and clinical signs in 5 neonates with biliary atresia with extrahepatic biliary cyst (4 of type I and 1 of type III) and 17 neonates with choledochal cyst were recorded. The levels of serum alkaline phosphatase, bilirubin, direct bilirubin, transaminase, gamma-glutamyl transpeptidase were analysed. Width and length of gallbladder and choledochal cyst were measured on B-mode ultrasound before surgery. Intrahepatic or extrahepatic biliary ducts were visualized with intraoperative cholangiography. The pathologic features in specimens of the liver were studied with light- and electron transmission microscopy. Results: All malformations occurred more commonly in girls, and obstructive jaundice was the main manifestation in both groups. Laboratory tests showed similar results for all patients in this study. With regard to pathological features, no significant difference was seen in either light microscopy or transmission electron microscopy, but it was shown with ultrasound that the length and width of the cysts and the gallbladder in neonates with biliary atresia were all shorter than the measurements in patients with choledochal cyst. The intrahepatic bile ducts could not be visualized on intraoperative cholangiography in type III biliary atresia. Deformation of the biliary ducts within the liver and stricture of the portal bile duct were the predominant features in type I biliary atresia, while the bile duct within the liver was normal or dilated in neonates with choledochal cyst.

Conclusions: Cystic lesions of the extrahepatic bile duct might be a common manifestation of biliary atresia and choledochal cyst. Intraoperative cholangiography is a precise and effective technique in the differential diagnosis of those lesions and helps decide on the most rational method of treatment.     

Differentiation between extrahepatic and intrahepatic cholestasis by discriminant analysis

Discriminant analysis was used to differentiate between extrahepatic biliary atresia and intrahepatic cholestasis. Among the ten laboratory variables tested, three (gamma-glutamyl transpeptidase, alkaline phosphatase and total serum bilirubin) were useful in the differential diagnosis. gamma-Glutamyl transpeptidase contributed most to the discrimination (85%). From a population study of 28 babies with extrahepatic biliary atresia and 24 infants with intrahepatic cholestasis, the procedure achieved a diagnostic accuracy and specificity of 92.9% and an efficiency of 92.3%. The jackknife procedure has also confirmed that the mathematical model was robust for discriminant analysis and therefore it may be valid for screening infants with cholestasis for early surgical intervention. Discriminant analysis is a useful adjunct for differentiation between intrahepatic cholestasis and extrahepatic biliary atresia.     

Intrahepatic biliary tract abnormalities in children with corrected extrahepatic biliary atresia

Three children with surgically corrected extrahepatic biliary atresia developed recurrent cholangitis associated with bile lakes that failed to drain via the hepatoportoenterostomy. Surgical or percutaneous drainage of these cysts was followed by both resolution of the infection and spontaneous internal drainage. We postulate that the ongoing inflammatory process resulted in intrahepatic biliary obstruction, which caused cholangitis and bile cysts. Successful treatment required not only antibiotics but drainage of the bile lakes. Development of bile cysts is a new cause of recurrent cholangitis seen in extrahepatic biliary atresia.     

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)     

Congenital structural abnormalities in biliary atresia: evidence for etiopathogenic heterogeneity and therapeutic implications.

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 less than 0.01).     

Biliary atresia syndrome and splenic malformation. A case report

Biliary atresia is a severe neonatal malformation in which the entire extrahepatic biliary tract or part of it is absent and replaced by fibrosclerotic tissue. Having been described for the first time by Thomson in 1891, biliary atresia has an incidence of 1:10,000-15,000 live neonates with a slight predominance in the female sex; it is associated with other malformations in 25% of cases. In 1993 Davenport et al. identified a subgroup of patients with biliary atresia who presented a splenic malformation. This condition was known as biliary atresia and splenic malformation syndrome (BASM). The cases of biliary atresia and BASM are still not clear and a number of etiopathogenetic hypotheses have been put forward. The treatment is surgical and includes a first stage of hepatic-porto-enteroanastomosis using a defunctionalised Roux loop (Kasal), followed by the definitive operation comprising liver transplant. We report the case of a boy who was brought to our attention with jaundice, polypnea and hepatosplenomegalia; instrumental tests allowed the diagnosis of biliary atresia, median liver, stomach and spleen on the right, polysplenia, atresia of the intrahepatic tract of the inferior vena cava, presence of a superior vena cava to the left that drained into the upper left portion of the common atrium. Moreover, the cardiac apex was present on the right, extensive DIA of the common atrium type, extensive DIV and right aortic arch.     

Neonatal hepatitis and extrahepatic biliary atresia associated with cytomegalovirus infection in twins.

Prenatally acquired cytomegalovirus infection in twins was temporally associated with a discordant development of neonatal hepatitis and extrahepatic biliary atresia. This case presents evidence suggesting an association between perinatal cytomegalovirus infection and selected extrahepatic biliary atresia and neonatal hepatitis. Congenital cytomegalovirus infections and cytomegalovirus hepatitis are also discussed.     

Lack of correlation between infection with reovirus 3 and extrahepatic biliary atresia or neonatal hepatitis

Infection with reovirus 3 (Reo-3) has been suggested as the cause of extrahepatic biliary atresia and idiopathic neonatal hepatitis, but confirmation has been lacking. Therefore we have searched for a specific anti-Reo-3 antibody response in the sera of patients with biliary atresia or neonatal hepatitis and for Reo-3 antigens in their hepatobiliary tissues. Sera from 23 infants with extrahepatic biliary atresia, 12 with neonatal hepatitis, 30 age-matched control patients with other liver diseases, and 55 control patients without liver disease were tested by an enzyme-linked immunosorbent assay for total (IgA, IgG, and IgM) anti-Reo-3 antibodies; sera of infants younger than 6 months of age were tested also for IgM anti-Reo-3 antibodies alone. There was no difference between either total or IgM anti-Reo-3 antibody levels in infants with extrahepatic biliary atresia or neonatal hepatitis and levels in control infants. Reo-3 antigens were not detected in the hepatobiliary tissues of 19 infants (18 with biliary atresia, one with neonatal hepatitis) by an immunoperoxidase method that readily demonstrated Reo-3 in control infected HEp-G2 cells. Our data do not support a relationship between neonatal liver diseases and infection with Reo-3.     

Significance of the anomalous arrangement of the pancreaticobiliary duct in the etiology of biliary atresia.

BACKGROUND/PURPOSE: The anomalous arrangement of the pancreaticobiliary duct (AAPBD) is one theory used to explain the etiology of biliary atresia. We investigated whether AAPBD could be involved and evaluated its significance for the etiology of biliary atresia. MATERIALS AND METHODS: Of 43 patients with biliary atresia, the area between the common bile duct and the duodenum could be visualized by operative cholangiogram in 5 patients with an uncorrectable type of biliary atresia. Three of the 5 showed an anomalous arrangement of the pancreaticobiliary duct. In these 3 patients, the type of anomalous arrangement of the pancreaticobiliary duct and the length of the common channel were studied by operative cholangiogram. Histological findings of the gallbladder and the common bile duct were examined in addition to the measurement of the serum amylase levels. RESULTS: All 3 patients showed AAPBD with the P-C type of pancreaticobiliary junction. The length of the common channel ranged from 7 mm to 12 mm. Two of the 3 cases did not show an elevated serum amylase level. Epithelial hyperplasia of the gallbladder was observed in one patient, while the other two showed no hyperplasia. Inflammatory changes in the mucosa of the gallbladder and the common bile duct were not remarkable in these 3 patients. CONCLUSIONS: From these results it seems that AAPBD in biliary atresia might not be an etiological factor for atresia of the extrahepatic bile duct, but might be an associated anomaly in biliary atresia. Other factors should be examined to clarify the etiological factor leading to lumenal obstruction of the extrahepatic bile duct.     

Morphologic Studies of the Liver and Bile Ducts in Biliary Atresia

We studied 233 patients with biliary atresia seen between 1953 and 1985. Specimens of the extrahepatic bile ducts and liver which were taken at the time of corrective operation were examined histologically. We noted the presence of inflammation in the extrahepatic bile ducts, which confirmed in retrospect the necessity for early operation. The results of these studies are discussed in connection with the pathogenesis, pathophysiology and clinical features of this disease.     

Time course of the intrahepatic lesion of extrahepatic biliary atresia: a morphometric study

The time course of the intrahepatic lesions of untreated extrahepatic biliary atresia was evaluated by morphometric analysis of 49 specimens from 27 patients. The data show an early phase of rapid bile ductular proliferation, with peak in this material at 205 days, followed by rapid duct regression to approximately 400 days, and slower progressive intrahepatic duct loss thereafter. The ratio of ducts to connective tissue in portal tracts follows a similar course. Connective tissue in portal tracts rises on a slower course and continues to increase after maximum duct regression is reached, so the ratio of parenchyma to fibrous septa falls over the later course of the process. Although duct and connective tissue proliferation in hepatic portal tracts is associated in many liver diseases, the data of this study demonstrate dissociability of the relationships, with the fibrosis in the later stages of the intrahepatic process in extrahepatic biliary atresia apparently neither responsive to nor inducing biliary ductular proliferation.     

Time Course of the Intrahepatic Lesion of Extrahepatic Biliary Atresia: A Morphometric Study

The time course of the intrahepatic lesions of untreated extrahepatic biliary atresia was evaluated by morphometric analysis of 49 specimens from 27 patients. The data show an early phase of rapid bile ductular proliferation, with peak in this material at 205 days, followed by rapid duct regression to approximately 400 days, and slower progressive intrahepatic duct loss thereafter. The ratio of ducts to connective tissue in portal tracts follows a similar course. Connective tissue in portal tracts rises on a slower course and continues to increase after maximum duct regression is reached, so the ratio of parenchyma to fibrous septa falls over the later course of the process. Although duct and connective tissue proliferation in hepatic portal tracts is associated in many liver diseases, the data of this study demonstrate dissociability of the relationships, with the fibrosis in the later stages of the intrahepatic process in extrahepatic biliary atresia apparently neither responsive to nor inducing biliary ductular proliferation.     

Preferentially longer survival of males than of females with untreated extrahepatic biliary atresia: correlations with time course of intrahepatic lesions and suggestion of possible ethnic influences

Males with untreated or unsuccessfully treated extrahepatic biliary atresia show statistically significantly longer survival than females. Females show a greater degree of intrahepatic biliary ductular proliferation than males in the early phase of the process (to age approximately 200 days) and greater duct regression and more rapid connective tissue proliferation than males from approximately 200 to 400 days. Females also show greater frequency of statistically significant hepatomegaly than males over the first year. The black and Hispanic patients in this series tended to show a less marked degree of bile ductule proliferation in the early phase of the process than other patients, but the numbers of such patients available for study were not enough for statistical significance. This point, and its possible clinical correlates, will require further analysis, as will possible biochemical explanations for the differences between males and females in the time course of the intrahepatic lesions of 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.     

Spontaneous perforation of the extrahepatic biliary tract in infancy and childhood

Spontaneous perforation of the extrahepatic biliary tract in infancy and early childhood is a poorly understood and infrequently reported disorder of unknown etiology. The reported experience with 77 operative cases is reviwed. The onset is generally insidious, but may be acute in 25% of cases. The major symptoms are abdominal distention and jaundice. The younger the patient at the time of onset, the more likely is jaundice to be found. Drainage-type operations were most commonly used in the early reported cases while more recently anastomosis/bypass procedures have predominated due to the relatively frequent occurrence of distal biliary tract obstruction. This disorder appears to be a part of the biliary atresia — neonatal hepatitis — choledochal cyst complex which occurs in the neonatal period and early infancy and appears to be acquired rather than congenital. Because of the theoretical potential for late malignancy, lifelong follow-up with periodic evaluation of the intra- and extrahepatic biliary tracts is recommended. The advisability of liver transplantation (and accompanying immunosuppression) as the primary surgical treatment for biliary atresia may be questioned.     

Biliary atresia.

Although biliary atresia is characterized by luminal obstruction of the extrahepatic bile ducts, the etiology and the pathophysiology of the liver are still controversial. The prognosis of biliary atresia has been improved after the introduction of Kasai's hepatic portoenterostomy, but there are still many problems to be solved in the treatment of this disease. Successful results of hepatic portoenterostomy depend on early diagnosis and operation, adequate operative technique, prevention of postoperative cholangitis, and precise postoperative management. However, we are on the verge of a new era in the therapy of biliary atresia combining portoenterostomy with liver transplantation.     

Post-operative abdominal CT scanning in extrahepatic biliary atresia

A retrospective review of the abdominal CT scans of 26 children with extrahepatic biliary atresia was performed, and the results were correlated with available surgical and pathologic data. Associated congenital anomalies or acquired abnormalities were identified in these patients. Congenital anomalies included polysplenia, venous anomalies and bowel stenosis. Acquired abnormalities developed secondary to cirrhosis, portal hypertension, intrahepatic biliary duct dilatation, and hepatic ischemia. Despite frequent episodes of ascending cholangitis in these children, no hepatic abscesses were identified by CT or by pathologic examination. In conclusion, abdominal CT scanning of children with extrahepatic biliary atresia can define congenital and acquired abnormalities and provide important anatomic data for the surgeons before liver transplantation.     

Extrahepatische Gallenwegserkrankungen im S?uglingsalter

Biliary atresia and choledochal cysts are diseases of the extrahepatic biliary system in infants. Both conditions can also affect the intrahepatic bile ducts. The pathophysiology is characterized by chronic inflammation and surgical therapy is a central component in management in both diseases and impacts the prognosis. Replacement of an abnormal biliary tract by a small bowel loop can provide definitive treatment of either choledochal cysts or biliary atresia. In biliary atresia with hepatic portoenterostomy (Kasai operation) biliary cirrhosis is a more frequent outcome of surgery than for choledochal cysts. Therefore, liver transplantation is a cornerstone of therapy for these patients. Timely diagnosis and management in specialized centers are important for outcome. This article reviews new aspects of the pathophysiology, therapy, and prognosis of biliary atresia and choledochal cysts.