Definition:
A disease of newborns marked by fibrous obliteration of the extrahepatic biliary ducts. While the name implies that it is a congenital absence of the ducts, it is actually believed to be a progressive obliteration of the bile ducts near birth or during the first few weeks of life. Jaundice may be present at birth, but usually appears at 1-2 weeks of age. Biliary atresia occurs in 1 in 10,000 to 1 in 20,000 live births with a slight female predominance. There is not believed to to be a racial predilection in the United States.

Associated problems:
Biliary atresia may be associated with polysplenia syndrome. Polysplenia syndrome is: absent IVC (azygous drainage); bilobed, symmetric liver; preduodenal portal vein; abdominal heterotaxia; malrotation; bilobed lungs; cardiac defects. 10-20% of patients with biliary atresia have polysplenia syndrome.

Prognosis:
Without treatment, biliary atresia leads to cholestasis, and cirrhosis. Death typically occurs before 2 years of age. The prognosis is improved with early operation: Generally the patients undergo a Portoenterostomy (Kasai Procedure) as an infant. The surgery is successful in establishing bile flow in 70% of patients. Those that resolve their jaundice within the first 6 months of life are closely monitored for progression and liver failure. When the liver stops functioning adequately, they are referred for liver transplantation. In the 30% patients who do not resolve their jaundice after Kasai procedure, an early referral for liver transplant is made.

Etiology:
The cause of biliary atresia remains unknown. Several theories exist, including: failure of recanalization of the bile ducts, vascular insufficiency, genetic factors, environmental teratogenesis, perinatal viral infection. The cluster of anomalies seen in polysplenia syndrome supports the hypothesis of defective early embryogenesis. Only one set of twins reported. We have taken care of a set of identical twins (one with, and one without biliary atresia, but both with congenital nephrotic syndrome).

Schrieber reported on a common pathway in 1993 [Schrieber et al (J Pediatr Gastro Nutr 16:111, 1993)] which included an initial injury (toxic, viral, etc) lead to upregulation of biliary epithelium, with expression of new antigens. T-cells then mediated an inflammatory response resulting in fibrosclerotic reaction.

Pathology:
Not true atresia – (not a failure to form). It is believed to be a progressive inflammatory disease. Patients have varying degrees of inflammatory infiltrates, scarring. Ductules are present in first month. Initially liver is enlarged and cholestatic (green with unexcreted bile). Later it becomes hard and shrunken. In contrast to neonatal hepatitis, the liver architecture is initially preserved. The histopathology on needle biopsy may overlap with neonatal hepatitis in 5-10% of cases with periportal fibrosis and bridging microscopically. Cirrhosis is seen later.

Classification by the Japanese Society of Pediatric Surgery:

• Type 1: atresia of CBD +/- cyst in porta hepatitis
• Type 2: atresia of CHD
• Type 3: atresia of right and left hepatic ducts

Classification:

• (70%) Extrahepatic ducts replaced by fibrotic cords GB fibrotic, “white bile”
• (20%) Residual patency of the GB, cystic duct and CBD with obliteration of the hepatic ducts
• (10%) proximal hilar cysts, distal obliterated ducts

Who gets workup for Biliary Atresia?

• Any infant with > 20% conjugated bilirubin warrants investigation
• Jaundice > 2 weeks warrants investigation with fraction of bilirubin, etc.

Differential Dx (other causes) of newborn jaundice included:

• Unconjugated hyperbilirubinemia (Noncholestatic Jaundice):
  Overproduction of bilirubin, sepsis, Rh/ABO incompatibility, hematoma (birth trauma), drugs (e.g., vitamin K), polycythemia, Maternal-fetal or twin-to-twin transfusion, delayed clamping of umbilical cord, erythrocyte defects (e.g., congenital spherocytosis), erythrocyte enzyme defects (e.g., glucose-6-phosphate dehydrogenase, other hemoglobinopathies, physiological jaundice, impaired transport of bilirubin, hypoxia, acidosis, drugs (e.g., sulfonamides, aminosalicylic acid [ASA])
• Acquired cholestatic jaundice:
  Hepatocellular cholestatic jaundice, neonatal hepatitis, ductal cholestatic jaundice, biliary hypoplasia, paucity of intrahepatic bile ducts, choledochal cyst, inherited cholestatic jaundice, Familial cholestatic syndromes (e.g., benign recurrent cholestasis, metabolic cholestasis, galactosemia, hereditary fructose intolerance, hereditary tyrosinemia, neonatal iron storage disease, cystic fibrosis, alpha1-antitrypsin deficiency, glycogen storage disease, inborn errors of bile acid metabolism ,other storage diseases, Niemann-Pick disease, Gaucher’s disease, “noncholestatic” syndromes, Dubin-Johnson syndrome, Rotor’s syndrome

Typical Workup:

• Ultrasound (rule out choledochal cyst, presence of gallbladder is irrelevant)
• Phenobarbital 5days followed by HIDA
• Labs (Hepatitis, LFT’s, alpha1 AT, CF DNA)
• Percutaneous liver biopsy (if diagnosis is unlikely) or open biopsy with Cholangiogram if highly suspicious.

NOTE: The diagnostic evaluation to exclude EVERY possibility could take weeks and should not be done

Symptoms:

• Progressive jaundice
• Normal growth 1st month
• Acholic (colorless) stool
• 40% of infants with biliary atresia passed normal meconium at birth
• 60% continue to have “yellowish” stools

Labs Results:

• Serum bilirubin usually 6-12 mg/dl, 50-80% conjugated; Transaminases (ALT, AST) are 2 to 3x’s normal value. Alkaline phosphatase and gamma GGT levels elevated. TORCH titers are negative, hepatitis titers are negative. Normal alpha -1-antitrypsin studies.

Ultrasound:

• Gallbladder may be shrunken, but presence does not exclude biliary atresia. Also, ultrasound visualization of a common bile duct does not mean the bile duct is patent. Patients often have a fibrotic cord where the bile duct should be. Ultrasound evidence of polysplenia syndrome is highly suggestive of biliary atresia in the setting of acholic stools. Dilatation of bile ducts or presence of choledochal cysts also helps rule out biliary atresia.
• Nuclear Imaging (HIDA scan, or similar study) in biliary atresia will show hepatocyte uptake normal (if study done early in disease) with no excretion of the tracer into the bowel. Absence of gut excretion is not diagnostic – False negatives = 67% of children with hepatitis syndromes in one study. Pretreatment for 4 or 5 days with Phenobarbital may decrease false positive tests.

Diagnosis: Operative Cholangiogram and Open Liver Biopsy

• Most accurate diagnosis through intra-operative cholangiogram
• Wedge and/or tru-cut needle biopsy is also obtained if diagnosis unclear.

Kasai Procedure (hepatic portoenterostomy)

• Dissection of fibrotic biliary tree into the liver and creation of a conduit for bile drainage into the GI tract (Roux en Y jejunostomy, or cholecystoportoenterostomy)

Complications:
Treatment of cessation of Bile Flow: Often associated with cholangitis: Antibiotics,methylprednisolone (controversial),choleretic, Reoperation is an option, but less common now with higher liver transplant survival.

Portal Hypertension

• Indicates progressive disease even if no jaundice
• Varicies in 40-80% of children by 5 years
• Inflammation may contribute
• Fibrosis may continue despite a successful Kasai procedure
• Partial Splenic Embolization may delay transplant
• Routine esophagoscopy and treatment of varicies delays transplant
• Systemic shunts are only used as a bridge to transplant and are much less common now. Esophageal banding of varices may prevent recurrent bleeds. Transplantation is preferred to shunting once the bleeding has been controlled.

Cholangitis

• Most frequent complication
• 40-100% of infants after Kasai
• Most frequent in first 2 years
• Must have both bacterial contamination and stasis

Biliary Atresia Prognosis and Kasai Results:

Impact of age at Kasai operation on short- and long-term outcomes of type III biliary atresia at a single institution.  Nio, Sasaki, Wada, Kazama, Nishi, Tanaka.  J of Ped Surg (2010) 45 2361-2363.

This study spans years 1953-2009 and only includes type III Biliary Atresia.   Groups refer to age at operation.  Y axis is Native Liver Survival without transplant.  Groups 1&2 = age < 60 days,  group 3 is age 60-90 days,  Group 4 is 91-120 days, Group 5 is age 121-150 days, Group  6 is age > 151 days

NLSR = Native Liver Survival Rate (without transplant).  The actual survival would be expected to be higher in the current era with successful liver transplant.

• Impact of age at Kasai operation on short- and long-term outcomes of type III biliary atresia at a single institution.  Nio, Sasaki, Wada, Kazama, Nishi, Tanaka.  J of Ped Surg (2010) 45 2361-2363
• Bile flow in 50-85% of infants Better bile flow in patients undergoing surgery at younger age (less than 6-8 weeks of age), but this may be due to a better prognosis for congenital forms of biliary atresia. Some centers have reported no difference in results based on timing of surgery if done at less than 4 months of age.
• Success is defined as an infant becoming nonicteric (no jaundice) by 3 months post-op
• Bilirubin < 1.0 by less than 2 months is best.
• 10 year survival 30-55%
• 50% of these survivors, however, are jaundiced with portal hypertension.
• 50% have normal or near normal liver fxn
• Combined with liver transplant, children have an 80-90% long term survival

Role of early liver transplantation:

• Late diagnosis (> 6 months?)
• Failure to drain bile after Kasai
• Decompensated liver disease after Kasai

Reference(s):

Nio, M., et al., Impact of age at Kasai operation on short- and long-term outcomes of type III biliary atresia at a single institution. J Pediatr Surg, 2010. 45(12): p. 2361-3.

JOHNSON, K.N., C.S. KOONTZ, and R.R. RICKETTS, Role of Hepatic Portocholecystostomy (‘Gallbladder Kasai’™) in Treating Infants with Biliary Atresia. THE AMERICAN SURGEON, 2010. 76(August): p. 883.

Azarow et al, Biliary Atresia: Should All Patients undergo a portoenterostomy? J Pediatr Surg, 1997  32:  p. 168-

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