This is a rare condition characterized by a progressive inflammatory process that begins very soon after birth. The bile ducts outside the liver are usually affected first, attacked by inflammatory cells, resulting in damage and eventual disappearance. During this process, bile is trapped inside the liver and rapidly causes damage and scarring to the liver cells and cirrhosis.
The cause of biliary atresia is unknown. A viral infection has long been suspected. About 10% of cases have other associated congenital defects in the heart, blood vessels, intestine, or spleen. The disease only affects newborns and is not hereditary.
Epidemiology Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE/PREVALENCE
1/15,000 live births
About 300 new cases are diagnosed each year
AGE Birth SEX Females slightly favored
CHARACTERIZATION RADIOLOGIC ROSE BENGAL TEST
The Rose Bengal test in neonatal cholestasis: diagnostic and prognostic value.
Alvarez F, Yvart J, Odievre M.
Eur J Pediatr 1981 Sep;137(1):27-9 Abstract quote
131I Rose Bengal(131IRB) studies were performed in 73 infants with extrahepatic biliary atresia (EHBA) and in 37 with intrahepatic cholestasis of various origins.
Fecal 131IRB excretion of less than 10% ("complete' cholestasis) was observed in EHBA but also in some patients with either paucity of intrahepatic bile ducts (syndromatic type) or with alpha-1-antitrypsin deficiency. Seventy one 131IRB tests were also performed 3 to 8 weeks postoperatively in children operated on for EHBA. Fecal 131IRB excretion more than 15% was present in 27 out of 34 cases who were later completely jaundice free and in only one out of 37 cases where no bile flow restoration occurred.
These results indicate that complete cholestasis in infants can be observed in some types of intrahepatic cholestasis, as well as in EHBA, and show that a post-operative 131IRB test is a reliable means of predicting complete restoration of bile flow in EHBA.
Extrahepatic biliary atresia versus neonatal hepatitis. Review of 137 prospectively investigated infants.
Mowat AP, Psacharopoulos HT, Williams R.
Arch Dis Child 1976 Oct;51(10):763-70 Abstract quote
In a prospective regional survey of neonatal hepatitis syndrome 32 infants had extrahepatic biliary atresia (EHBA) and 103 had hepatitis. No cause for the lesion was found in infants with extrahepatic biliary atresia, but in 32 with hepatitis a specific cause was identified, 24 having genetic deficiency of the serum protein alpha1-antitrypsin. No differences were observed in parental age, mother's health in pregnancy, month of birth, birth order, or sex of the infants.
Familial idiopathic hepatitis occurred in 3 of 67 sibs of patients with idiopathic hepatitis, but the 33 sibs of EHBA patients had no liver disease. Of the infants with hepatitis, 36 were of low birthweight, less than 2.5 kg, and 23 were born prematurely. Infants with biliary atresia were all of normal birthweight and only one was born prematurely.
Consideration of clinical and biochemical abnormalities in the first 2 months of life showed no differences between the two groups except that infants with EHBA were more commonly jaundiced from birth (80%) and had more frequently acholic stools (83%). The frequency of these features in patients with hepatitis being 68% and 52%. Standard tests of liver function were not discriminatory. Percutaneous liver biopsies were diagnostic in 75% of those with EHBA and in 92% of those with hepatitis.
The I131 Rose Bengal faecal excretion was less than 10% in 26 of 28 infants with EHBA and in only 5 of 18 with hepatitis. These latter two investigations together allowed a correct preoperativer diagnosis of EHBA in all instances. Bile drainage was achieved surgically in only 3 cases. A major reason for these poor results may have been the late referral of cases for diagnosis and laparotomy, which should be performed as soon as the diagnosis is suspected and always by 70 days of age.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
In biliary atresia duct histology correlates with bile flow.
Ohi R, Shikes RH, Stellin GP, Lilly JR.
J Pediatr Surg 1984 Aug;19(4):467-70 Abstract quote
Three basic types of microscopic biliary structures at the portahepatis were distinguishable in infants with biliary atresia: bile ducts, collecting ductules of biliary glands, and biliary glands.
Correlation between the type of biliary structure and the quantity and quality of post-operative bile flow was possible in 23 instances. At 2 weeks after operation, the 11 patients in whom a bile duct was identified had a daily bile flow of 68.0 +/- 11.5 mL. Bilirubin concentration in the bile was 13.6 +/- 3.3 mg/dL and total daily bilirubin excretion was 8.77 +/- 2.74 mg. In contrast, bile flow in 12 patients having only collecting ductules and/or biliary glands in the porta hepatis was 19.1 +/- 3.9 mL and bilirubin concentration in bile was 1.7 +/- 0.3 mg/dL. Thus, total daily bilirubin excretion was 0.34 +/- 0.08 mg (P less than 0.001).
Postoperative cholangitis occurred only in patients with ducts. It is concluded that only bile ducts communicate with the intrahepatic biliary system and drain bile after hepatic portoenterostomy.
VARIANTS PAUCITY OF INTERLOBULAR HEPATIC DUCTS
Clinico-pathological studies on a transitional type between extrahepatic biliary atresia and paucity of the interlobular bile ducts.
Yamagiwa I, Obata K, Hatanaka Y, Saito H, Washio M, Iwafuchi M.
Second Department of Surgery, Yamagata University School of Medicine, Japan.
Surg Today 1993;23(4):307-14 Abstract quote
Among the neonatal and infantile cases of obstructive jaundice seen at Niigata and Yamagata University Hospitals between 1976 and 1990, extrahepatic bile ducts were visualized in 19 cases by either preoperative endoscopic retrograde cholangiopancreaticography (ERCP) or intraoperative cholangiography.
Neonatal hepatitis was diagnosed in 3 of these cases by clear images of the bile duct system extending from the common bile duct to the intrahepatic bile duct. In 7 cases, the common bile duct was able to be seen, while the common hepatic duct was only slightly visualized.
Four of these 7 cases were consistent with paucity of the interlobular bile ducts (PILBD) based on hepatic histology, while the remaining 3 showed fibrosis, bile ductular proliferation, and many bile plugs in the bile ductuli of the portal areas, concurrent with histological changes in extrahepatic biliary atresia (EHBA), not PILBD. In 9 cases, only the common bile duct was visualized while the common hepatic duct was not seen, 7 of these 9 cases being consistent with type III-a1 EHBA. In 2 cases, neither fibrosis nor proliferation of the bile ductuli was observed in the portal areas, and portal areas without any bile ductuli were also seen, in accordance with findings for PILBD.
Three cases which showed similar hepatic histological findings to EHBA despite the presence of patent extrahepatic bile ducts, and 2 cases which had obstructed extrahepatic bile ducts and hepatic histological findings similar to PILBD, were thought to be of a transitional type between EHBA and PILBD.
Hepatic portoenterostomy for biliary atresia. A comparative study of histology and prognosis after surgery.
Lawrence D, Howard ER, Tzannatos C, Mowat AP.
Arch Dis Child 1981 Jun;56(6):460-3 Abstract quote
Specimens of excised tissue from the porta hepatis in 26 infants with extrahepatic biliary atresia undergoing hepatic portoenterostomy were analysed histologically for the presence and size of biliary ductules.
No correlation could be found between the establishment of effective biliary drainage and the number or size of biliary ductules.
It is suggested that prognosis after surgery may be related to the intrahepatic lesion and age of the child at operation rather than to the histology of the extrahepatic bile duct remnants.
Ductal remnants in extrahepatic biliary atresia: A histopathologic study with clinical correlation.
Chandra RS, Altman RP.
J Pediatr 1978 Aug;93(2):196-200 Abstract quote
Atretic ducts were studied in 34 infants undergoing the portoenterostomy procedure for biliary atresia.
The specimens were grouped into three categories on the basis of the size of the lumen at the proximal margin: Type I with a lumen 150 mu or greater, Type II with single to multiple ductal structures measuring less than 150 mu, and Type III with no identifiable epithelium-lined structures in fibrous connective tissue.
A significant correlation existed between postoperative bile drainage and the duct type; bile drainage occurred in all five patients with Type I ducts, 18 of 21 patients with Type II ducts, and one of eight patients with Type III ducts. Furthermore, the duct type was the only feature that correlated with the ultimate outcome.
Ductal inflammation and hepatic histology did not correlate with postoperative bile drainage or clinical course.
A histopathological study of the remnant of extrahepatic bile duct in so-called uncorrectable biliary atresia.
Miyano T, Suruga K, Tsuchiya H, Suda K.
J Pediatr Surg 1977 Feb;12(1):19-25 Abstract quote
Histopathological study of the remnant of extrahepatic bile ducts in 40 cases of so-called uncorrectable biliary atresia, upon which we operated the last three years, has been performed.
The histological findings of the remnant were classified into three types. Only two cases were found to have type 1a ducts in the porta hepatis area, from which we can expect better prognosis postoperatively. We also found that as the patients become older, the size of the duct in the remnant becomes smaller and the hepatic fibrosis becomes more remarkable. Therefore the operation should be performed in the infant with this lesion as young as possible. As for the evaluation of operative results of hepatic portoenterostomy for this lesion, a proper evaluation can be made only in those cases in which a microscopic examination of the remnant of extrahepatic bile duct at the porta hepatis area has been adequately performed.
Concerning the pathogenesis of biliary atresia, we presume that congenital abnormalities of bile ducts are a basic factor, and additional nonspecific inflammation and bile stasis complete its pathological condition.
CHARACTERIZATION CD56 (N-CAM)
Bile ducts and ductules are positive for CD56 (N-CAM) in most cases of extrahepatic biliary atresia.
Torbenson M, Wang J, Abraham S, Maitra A, Boitnott J.
Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland 21231, USA.
Am J Surg Pathol. 2003 Nov;27(11):1454-7. Abstract quote
The diagnosis of extrahepatic biliary atresia can be challenging as the histologic features can overlap with other pediatric cholestatic liver diseases. Several previous studies have noted that biliary epithelium is positive for CD56 in the setting of extrahepatic biliary tract disease.
Thus, we explored the use of CD56 in evaluating liver biopsy specimens for extrahepatic biliary atresia. A total of 22 cases were selected and immunostained for CD56, including 14 cases of confirmed extrahepatic biliary atresia and 8 cases of other cholestatic liver diseases in which the differential diagnosis included extrahepatic biliary atresia. Bile ducts and proliferating ductules were positive for CD56 in 13 of 14 cases of extrahepatic biliary atresia. The staining intensity was generally strong with most cases showing positivity in more than two thirds of portal tracts. The one negative case was a very small biopsy (<0.3 cm), and sampling may have played a role.
In contrast, 4 of 8 cases in the control group were completely negative for CD56, with the remaining cases showing weak and focal positivity. In conclusion, bile ducts and ductules are CD56 positive in most cases of extrahepatic biliary atresia, and CD56 immunostaining can be a useful supplemental stain for diagnosing extrahepatic biliary atresia in its early, ductular proliferative phase when used in conjunction with traditional hematoxylin and eosin morphology and clinical information.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES NEONATAL HEPATITIS Giant multinucleated hepatocytes and altered reticulin structure are more prominent in hepatitis than in true biliary obstruction
Cholestasis is more severe with biliary atresian and may have proliferation of bile ductules
PROGNOSIS CHARACTERIZATION GENERAL
The treatment of biliary atresia in Europe 1969-1995.
Howard ER, Davenport M.
Department of Paediatric Surgery, King's College Hospital, London, UK.
Tohoku J Exp Med 1997 Jan;181(1):75-83 Abstract quote
European studies of biliary atresia have suggested that the aetiology is heterogeneous.
Histological studies of the liver and biliary remnants excised at portoenterostomy have failed to identify any prognostic features except for the size of bile ductules in the porta hepatis. Most of the major series have confirmed that there is a relationship between age at portoenterostomy and clearance of jaundice which has been achieved in more than 67% of infants under 10 weeks of age.
Cholangitis reduced survival and bleeding from esophageal varices has occurred in more than 19% of long-term survivors. The 5-year jaundice-free survival rate after portoenterostomy is 37% and the 10 year rate is 18%. It is predicted that these survival rates will improve.
Orthotopic transplantation now results in long-term survival in 70% of patients who fail the portoenterostomy operation and long-term survival is now achieved in a majority of children born with biliary atresia.
Biliary atresia--a 25-year survey.
Engelskirchen R, Holschneider AM, Gharib M, Vente C.
Kinderchirurgische Klinik des Kinderkrankenhauses der Stadt Koln.
Eur J Pediatr Surg 1991 Jun;1(3):154-60 Abstract quote
In the past 25 years, from 1963 to 1988, 90 children from the Department of Pediatric Surgery of the Pediatric Hospital in Cologne, Germany were treated for biliary atresia.
Of these, 47 had purely extrahepatic bile duct lesions, 21 had purely intrahepatic bile duct lesions, and 22 had both extrahepatic and intrahepatic bile duct lesions.
Forty-five of the children underwent a drainage operation, whereas the remaining 45 children underwent no surgery at all or simply a diagnostic laparotomy. Until 1966 hepato-jejunostomy with implantation of artificial bile ducts was conducted in 12 cases. Later, cholecystoduodenostomy was performed 4 times and hepatoporto-jejunostomy according to Kasai-Kimura 29 times. The latter was performed either without and enterostomy (n = 16) or with an enterostomy in the respective intestinal loop (n = 13). 27 patients survived (30%). If only the children with intrahepatic bile duct hypoplasia are considered, the survival rate was 12 out of 15 patients (80%). Eight children (27.5%) of the 29 with hepatoporto-jejunostomy are still alive today. This survival rate, compared with the survival rate of the total, is comparably large with 27.7%.
Current data from the 23 surviving patients was retrospectively gathered in our hospital or was collected from outside the establishment. It was analyzed with regard to prognosis and long-term results.
Only in 5 of the 29 cases of children with hepatoporto-jejunostomy could a lasting postoperative biliary flow be achieved. Only one of the children can be classified as completely healthy in regard to his liver.
Prognosis of extrahepatic biliary atresia.
Houwen RH, Zwierstra RP, Severijnen RS, Bouquet J, Madern G, Vos A, Bax NM, Heymans HS, Bijleveld CM.
Department of Paediatrics, University Hospital, Groningen, The Netherlands.
Arch Dis Child 1989 Feb;64(2):214-8 Abstract quote
We carried out a retrospective investigation of the 89 patients with extrahepatic biliary atresia born in The Netherlands during a 10 year period. Of these 89 patients 10 had a diagnostic laparotomy only. Eight patients had an anastomosis between the proximal bile duct and the intestine, and the remaining 71 had hepatic portoenterostomies. Bile drainage was re-established in 46 (65%).
After successful hepatic portoenterostomy the development of cholangitis was the most important determinant of long term survival; five year survival was 54% in the 19 patients who had cholangitis and 91% in the 27 who did not. In the whole group of 71 patients the five year survival was 47%. Seventeen patients were at least 5 years of age at the time of writing, three of whom had had liver transplantation.
Three patients have cirrhosis and hyperbilirubinaemia, and the other 11 have normal bilirubin concentrations and normal or slightly raised transaminase activities. To improve these results early surgical intervention in all children with extrahepatic biliary atresia is necessary, as are better methods of prophylaxis and treatment of cholangitis.
Follow-up studies of long term survivors after hepatic portoenterostomy for "noncorrectible" biliary atresia.
Kasai M, Watanabe I, Ohi R.
J Pediatr Surg 1975 Apr;10(2):173-82 Abstract quote
Fourteen patients with "noncorrectable" biliary atresia are living without jaundice for more than 2 yr after hepatic portoenterostomy or its modification. Retardation of physical growth was observed in one of them, and mental retardation in another, both of which seemed irrelevant to biliary atresia. Serial tests for liver function after operation revealed early recovery of serum bilirubin, transminase, and turbidity, and delayed improvement of alkaline phosphatase.
Postoperative needle biopsy of the liver disclosed that changes in hepatic parenchyma and ductular proliferation were rapidly improved after successful operation. Improvement of fibrosis of the liver was delayed, and it was not satisfactory in patients whose preoperative changes in the liver were severe or in whom ascending cholangitis had been a frequent complication. Histologic features of hepatic cirrhosis were observed in the liver in three cases, in two of which there had been frequent episodes of cholangitis. Only one of these showed clinical signs of portal hypertension.
Functional and morphologic cure can be achieved in "noncorrectable" biliary atresia by hepatic portoenterostomy or its modifications, although varying degree of hepatic fibrosis may remain according to severity of preoperative changes of the liver and postoperative complication of ascending cholangitis.
TREATMENT CHARACTERIZATION GENERAL KASAI PROCEDURE (PORTOENTEROSTOMY)
Biliary atresia--surgical management. A 10-year review.
Millar AJ, Davies MR, Rode H, Brown RA, Cywes S.
S Afr Med J 1986 Mar 1;69(5):288-93 Abstract quote
The surgical results in 39 children operated on for biliary atresia at Red Cross War Memorial Children's Hospital between January 1975 and January 1985 are reported.
The mean age at operation was 12.8 weeks (range 6 weeks-6 months). In the first 4 years no patient had sustained bile drainage after operation. Since 1979 16 of 32 patients (50%) have had significant bile drainage. Of these, 8 are alive and have been followed up from 6 months to 6 years after operation. Five are jaundice-free and well. The other 3 are mildly jaundiced, have evidence of ongoing liver damage, and have a poor prognosis. The deaths were due to progressive liver damage with liver failure, portal hypertension, and intercurrent infection.
Cholangitis after 'successful' porto-enterostomy was the main cause of poor prognosis and can be related to the age at referral and the presence of cirrhosis of the liver at the time of surgery; thus bile drainage does not necessarily equate with cure. Early referral of infants with conjugated hyperbilirubinaemia to a major centre is of paramount importance if we are to improve the prognosis.
Biliary atresia: review of experience with twenty-three patients.
Kourtesis GJ, Middleton AW.
Aust N Z J Surg 1983 Apr;53(2):125-8 Abstract quote
Prior to the Kasai procedure of hepatic porto-enterostomy in 1959, biliary atresia was a bleak chapter in paediatric surgery. It was only after many years, however, that the procedure became widely accepted. During the past 8 years 23 cases of biliary atresia have been treated at the Royal Alexandra Hospital for Children (RAHC).
Twenty-one had the noncorrectable type of atresia. Sustained drainage was obtained in ten patients, all of whom had the noncorrectable type anomaly. Nine are still alive, eight having survived more than one year after operation and all are free from jaundice. Cholangitis has been a problem in six of these patients and six have evidence of fibrosis or cirrhosis on subsequent liver biopsy.
Two patients have shown improvement in liver histology since operation. Sustained biliary drainage is related to age at operation, the size of biliary ductules at the porta and the subsequent development of cholangitis. Long term prognosis still remains uncertain.
The portoenterostomy procedure for biliary atresia: a five year experience.
Ann Surg 1978 Sep;188(3):351-62 Abstract quote
The portoenterostomy (Kasai) procedure in infants with biliary atresia has dramatically altered the outlook for this heretofore fatal disease.
When performed on infants under three months of age, bile drainage can be achieved in a majority of the patients. Since 1972, 37 infants have been treated with this operation at our institution. Diagnostic operative cholangiography and liver biopsy are recommended if the cause of conjugated hyperbilirubinemia is presumed to be obstructive.
When biliary atresia is encountered, identification of the atretic ducts with transection high in the porta hepatis is carried out. Thirty-two infants have had the portojejunostomy, while five, in whom the proximal hepatic ducts were atretic but the gall bladder and distal ducts were patent, underwent portocholecystostomy.
Examination of the resected fibrous duct tissue revealed a statistically significant correlation between ductal histology and postoperative outcome. Extended bile drainage has been achieved in 26 of 37 patients. Seventeen exhibit near normal growth and development four months to five years postoperatively. Seven have died with progressive liver disease despite bile drainage. Two additional patients died, jaundice free, from unrelated causes. Despite bile drainage, progressive hepatic fibrosis has been confirmed by serial biopsies in 14 patients. This finding indicates that biliary obstruction is not the sole component in the development of biliary cirrhosis.
These data suggest that extrahepatic biliary atresia is a dynamic obliterative process, which can be favorably modified in approximately 50% of the infants by early surgical treatment.
Hepatic porto-enterostomy or cholecystostomy in the treatment of extrahepatic biliary atresia. A study of 49 cases.
Odievre M, Valayer J, Razemon-Pinta M, Habib EC, Alagille D
J Pediatr 1976 May;88(5):774-9 Abstract quote
Hepatic porto-enterostomy or cholecystostomy (Kasai's procedure) was successful in restoring bile flow in 31 of 49 patients with "noncorrectable" extrahepatic biliary atresia.
However, all but one of the 31 developed acute or chronic complications such as cholangitis, bile peritonitis, or portal hypertension. During a five-year follow-up period, 26 (53%) died while 9 of the 23 survivors continue to manifest chronic or recurrent cholangitis. Thirteen of the 19 survivors who are more than one year of age have developed portal hypertension.
These complications limit the prognosis of infants with "noncorrectable" biliary malformations.
Congenital biliary atresia. Analysis of 97 cases with reference to prognosis after hepatic portoenterostomy.
Kobayashi A, Utsunomiya T, Kawai S, Ohbe Y.
Am J Dis Child 1976 Aug;130(8):830-3 Abstract quote
The prognosis of 97 patients with congenital biliary atresia treated by hepatic portoenterostomy was studied. In 37 of 97 patients (38%), good bile excretion was observed after surgery, and jaundice cleared. Sixteen of the 37 patients developed ascending cholangitis; 11, esophageal varices; and nine died.
Seven died of ascending cholangitis and two of hepatic failure. Fourteen patients had an uneventful course. In the remaining 60 patients, bile excretion was scanty, and the disease progressed to biliary cirrhosis; 52 died.
Causes of death were hepatic failure (53%), intracranial hemorrhage (16%), rupture of esophageal varices (12%), severe dehydration (9%), and postoperative complications (9%). The age at death ranged from 2 to 52 months, with an average at 16 months.
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