Figure 103-49. A: Normal scan using p-isopropyl acetanilidoiminodiacetic acid (PIPIDA) as the hepatobiliary scanning agent. At 45

minutes, isotope is clearly visible in the liver (L) and the intestine (I). B: Scan after phenobarbital administration in infant with

biliary atresia. Even after 8 hours, isotope is apparent only in the liver and the urinary bladder (UB). C: Patient with cholestatic

jaundice. At 65 minutes, isotope is visible in the liver (L) and the intestine (I). Hepatocyte uptake is variable but usually decreased

or normal, whereas excretion into the gut is predictably present with cholestatic jaundice or hepatocellular disease.

Clinical Presentation and Diagnosis

The cardinal sign of biliary atresia is progressive neonatal jaundice during the first few weeks of life.

Dark urine and acholic stools are expected findings. Progressive hyperbilirubinemia produces clinical

jaundice around 2 to 4 weeks of age. The physical examination is generally unremarkable except for

jaundice and possibly mild hepatomegaly. Alagille syndrome, which presents with neonatal jaundice,

can usually be distinguished from biliary atresia on physical examination. Children with Alagille

syndrome have biliary hypoplasia and distinctly abnormal facies, growth retardation, vertebral defects,

and pulmonic stenosis.

A characteristic laboratory finding is conjugated hyperbilirubinemia consistent with obstructive

jaundice. A direct fraction of bilirubin greater than 50%, or greater than 2 mg/dL, in an infant requires

prompt investigation. Mild elevation of hepatic transaminases is commonly seen. The alkaline

phosphatase is significantly elevated, often in the range of 500 to 1,000 IU/L. There are no specific

biochemical markers for biliary atresia, as these serum profiles can be seen in other causes of neonatal

cholestasis. Late findings in biliary atresia include failure to thrive, feeding intolerance, stigmata of

portal hypertension, and fat-soluble vitamin deficiency.

Table 103-13 is a partial list of the causes of neonatal cholestatic syndromes. Neonatal physiologic

jaundice is commonly encountered. This condition is self-limited once the glucuronyl transferase system

matures, allowing the hepatocytes to conjugate bilirubin efficiently. Because of the numerous causes of

neonatal jaundice and the relative infrequency of biliary atresia, a delay in diagnosis is common. Given

the age-sensitive nature of biliary atresia and the improved outcome in younger infants, the diagnostic

workup should be expedient.

ETIOLOGY

Table 103-13 Causes and Associations of Neonatal Cholestasis

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Figure 103-50. The essential features of the portoenterostomy for biliary atresia include appropriate mobilization (A) and

transection (B) of the fibrous biliary tract remnant. C: Creation of a Roux-Y jejunal conduit with biliary enteric anastomosis

completes the procedure.

Radioisotope Scanning. Pertechnetate 99 m–iminodiacetic acid (99mTc-IDA) analogues are widely used

for hepatobiliary imaging and provide the basis for a sensitive and specific test for biliary atresia. The

sensitivity of this diagnostic examination for biliary atresia can be 100%, with a specificity of 94%.172

To improve sensitivity, infants are administered oral phenobarbital (5 mg/kg daily) to induce hepatic

microsomal enzymes and increase hepatocyte processing of 99mTc-IDA. Both hepatic uptake of

radionuclide and excretion into the gastrointestinal tract are evaluated over a timed interval. Infants

with primary hepatocellular disorders characteristically have impaired hepatocyte uptake of

radionuclide, whereas normal infants and infants with biliary atresia have prompt uptake. Normal

infants excrete the isotope rapidly into the gut through the biliary tract. In biliary atresia, there is no

excretion into the gut because of the obliteration of the extrahepatic bile ducts (Fig. 103-49). The

hepatobiliary scanning is a rapid test that can be performed simultaneously with other diagnostic

examinations, for example, ultrasound. This test reliably identifies infants with choledochal cyst as well.

Other Diagnostic Tests. Several other diagnostic tests are of interest in the workup of an infant with

conjugated hyperbilirubinemia in whom obstructive jaundice is suspected. MRI cholangiography is

emerging as a sensitive, specific examination for the identification of extrahepatic anatomy. The

important management principle is that prompt operative exploration, liver biopsy, and

cholangiography should be performed in any infant in whom biliary atresia is suspected. An aggressive

approach is warranted in that unnecessary delay in definitive drainage may lead to a less favorable

outcome.

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Ultrasound. A standard examination of the jaundiced infant is a comprehensive abdominal ultrasound,

with particular attention given to the liver and the biliary tract. The most common ultrasonographic

finding in biliary atresia is a diminutive or absent gallbladder without associated intrahepatic duct

dilatation. Biliary tract obstruction from a choledochal cyst also can be reliably identified by ultrasound.

Other rare causes of extrahepatic biliary duct obstruction are associated with proximal duct dilatation.

Figure 103-51. Several types of conduits have been used for biliary drainage following portoenterostomy. There are relatively few

data to help in selecting from among them, and current trends emphasize simplicity. These are the three most commonly used

conduits. The primary importance of this issue is that the reoperative surgeon must be familiar with the anatomic variations.

Liver Biopsy. Because the histologic findings in biliary atresia are not specific, about 20% to 25% of

infants who undergo percutaneous liver biopsy remain undiagnosed. Liver biopsy is often performed in

conjunction with the workup of conjugated hyperbilirubinemia following hepatobiliary scanning and

ultrasonography, but in the setting of biliary atresia, it has limited utility. The histologic examination of

a percutaneous liver biopsy is probably most helpful in diagnosing nonoperative causes of neonatal

jaundice, thus avoiding anesthesia and operative exploration.

Alpha1-Antitrypsin Deficiency. Alpha1

-antitrypsin deficiency is perhaps the single most important

medical condition that may be difficult or impossible to differentiate from biliary atresia. All jaundiced

infants should have plasma alpha1

-antitrypsin levels determined before operative exploration for

suspected biliary atresia. Infants with alpha1

-antitrypsin deficiency do not benefit from operative

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exploration or portoenterostomy.

Treatment

Infants with biliary atresia require surgical therapy as the initial management intervention. Medical

therapy is directed to the postoperative management of the chronic liver disease. The use of sequential

surgical treatment, using portoenterostomy in infancy and orthotopic liver transplantation for children

with progressive hepatic failure, provides improvement in overall survival.173,174 Limited organ

availability and a higher rate of perioperative complications limit primary liver transplantation for most

infants with biliary atresia younger than 1 year. In the rare instance of unrecognized biliary atresia in

an older child with established hepatic dysfunction, primary orthotopic liver transplantation may be a

reasonable option.

Portoenterostomy. The recommended initial procedure for the treatment of biliary atresia is

portoenterostomy. Before the development of portoenterostomy in Japan by Morio Kasai during the

late 1950s, all infants with biliary atresia died of chronic liver disease and cirrhosis. Current

management dictates that operative exploration and portoenterostomy be performed promptly. Early

intervention by portoenterostomy to provide biliary drainage has been proposed to arrest or reverse the

parenchymal liver injury, but the point at which the liver injury becomes irreversible remains unknown.

From a clinical standpoint, most long-term success with portoenterostomy alone appears to be achieved

in infants younger than 2 to 3 months, whereas infants older than 3 to 4 months appear to have a less

favorable prognosis. Portoenterostomy for this “late” group has been reported successfully in

approximately one-third of infants, however, and should be considered a potential alternative in the

absence of available liver transplant donors.175

The initial approach to the infant with suspected biliary atresia is to perform an operative

cholangiogram. If the diagnosis is confirmed, a portoenterostomy is constructed (Fig. 103-50). To

maximize the potential for effective biliary drainage with portoenterostomy, several technical caveats

are worthy of mention. An open liver biopsy is routinely performed to document the state of

parenchymal injury. The cholangiogram is generally attempted through the gallbladder. In the 10% to

15% instance of a patent distal biliary tree, treatment still requires portoenterostomy. A nonpatent,

fibrous cord rather than a normal common bile duct is found in the hepatoduodenal ligament. This cord

is dissected free proximally to the level of the porta hepatis between the portal vein bifurcation. The

fibrous remnant is sharply transected at this level to preserve any patent bile ducts. A short, 15- to 25-

cm retrocolic, jejunal Roux-Y limb is constructed. There has been no clear advantage with longer or

modified conduits with intussusception-type antireflux valves in the prevention of cholangitis.176,177

Previously, some surgeons preferred to exteriorize the biliary conduit (Fig. 103-51). With an

exteriorized biliary conduit, postoperative bile flow is directly visible. The diverting stoma must be

closed, however, and there is potential to develop parastomal variceal hemorrhage from progressive

portal hypertension. In addition, fluid and electrolyte losses from the biliostomy can be significant, and

there are no reported survival differences between patients with exteriorized and closed biliary conduits

following portoenterostomy. Because many of these infants may ultimately require liver

transplantation, there is a trend toward using a simple, closed biliary conduit with portoenterostomy.

Therefore, the use of a stoma to divert the bile flow in the Roux limb has been largely abandoned.

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Figure 103-52. Classification of choledochal cyst.

Results and Complications. Following portoenterostomy, bile flow occurs in about 66% to 75% of all

infants when operated on at less than 60 days of age; however, establishment of bile flow may take

weeks to months. The probability of bile flow appears related to age at the time of operation.

Cholangitis is a constant concern and an important postoperative problem after portoenterostomy.

The clinical signs include fever, leukocytosis, and decreased bile flow in the absence of other systemic

illness. All patients are at risk for the development of postoperative cholangitis, but reported

postoperative rates of cholangitis are 40% to 50%. Cholangitis following portoenterostomy is

characterized by a systemic inflammatory response and may be associated with progressive liver injury.

Treatment is generally intravenous fluid resuscitation and broad-spectrum antibiotics. Occasionally,

steroids or other antiinflammatory agents may be helpful, whereas reoperation or endoscopic revision

of the portoenterostomy usually is not.178 In an effort to determine the optimal treatment of infants

with biliary atresia, a group of investigators have formed the Biliary Atresia Research Consortium

(BARC).179 The primary objectives of the consortium are to establish a clinical database and tissue

repository. A retrospective BARC study of 104 children with biliary atresia treated in the United States

demonstrated that at 2 years of age, 58 patients were alive with their native liver and 42 had undergone

liver transplantation.180 Data from the United Kingdom demonstrated improved measurable outcomes in

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children with biliary atresia treated with Kasai portoenterostomy by regionalization of care to three

centers in the UK health care system.181

Figure 103-53. An anomalous, extramural junction between the distal common bile duct and the pancreatic duct is characteristic

of type I choledochal cyst. A: Schematic depiction of this anatomy. B: Operative cholangiogram from a patient with a long

extramural common channel. It has been suggested that the long common channel may allow reflux of pancreatic secretions into

the common bile duct resulting in inflammation and proteinase-mediated injury to the common duct, possibly contributing to the

development of the cyst itself. CBD + PD, common bile duct and pancreatic duct; Duod, duodenum; PD, pancreatic duct.

Nearly all patients with biliary atresia have residual liver injury. Hepatic synthetic failure, portal

hypertension with esophageal variceal bleeding, hypersplenism, and fat-soluble vitamin deficiencies can

be problematic. Most institutions report 5-year survival rates between 30% and 50% for

portoenterostomy alone. About 25% to 35% of patients undergoing a portoenterostomy survive more

than 10 years without liver transplantation. The remaining two-thirds of children with biliary atresia

ultimately require liver transplantation for survival. Although the failure rate for portoenterostomy is

high, the possibility of long-term success is notable. In addition, the limited availability of infant donor

organs and the technical limitations of liver transplantation in infants younger than 1 year make

portoenterostomy an accepted initial treatment of biliary atresia in most centers.

Hepatic Transplantation. Hepatic transplantation is discussed in detail elsewhere in this text. For

biliary atresia, transplantation offers a means of long-term survival in children with failed

portoenterostomies. The current 5-year survival of children with biliary atresia who undergo liver

transplantation ranges from 75% to 94.4%.182,183 In addition, with the use of reduced-size cadaveric

donor livers as well as living-related donor livers, the mortality rate for infants on transplant waiting

lists may be decreasing. Indications for liver transplantation in biliary atresia include progressive

hepatic failure despite portoenterostomy, growth retardation, and complications of portal hypertension.

It is important to consider the consequences of life-long immunosuppression in these children, including

the risks of infection and treatment-related malignancy.

Congenital Choledochal Cystic Disease of the Biliary Tract

Anatomy

The anatomic description and classification scheme for choledochal cystic disease initially proposed by

Alonso-Lej et al. in 1959 and modified by Todani et al. are illustrated in Figure 103-52.184,185 The most

frequently encountered are type I cysts, accounting for approximately 85% to 90% of the lesions in

most series. Type I cysts are characterized by fusiform dilatation of the entire common bile duct with

only mild dilatation of the common hepatic duct; the intrahepatic ducts are normal. Variations are

common, and biliary atresia is occasionally seen in association with choledochal cystic disease.

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Type I cysts are generally quite large and often cause displacement of neighboring viscera. The

fusiform dilatation usually begins at the origin of the common bile duct, generally sparing the common

hepatic ducts. The distal common bile duct is diminutive and typically is distorted mechanically by the

large cyst, leading to the common clinical presentation of obstructive jaundice. The junction of the

distal common bile duct and the pancreatic duct is not within the normal intramural duodenum but

rather is extrinsic and proximal to the duodenal wall and the sphincter of Oddi (Fig. 103-53). It remains

unknown whether the configuration of a long, extramural common channel allows greater pancreatic

secretion reflux into the common bile duct.

Microscopic examination of the choledochal cyst wall reveals that the normal biliary epithelium is

absent or replaced by abnormal and occasionally dysplastic columnar epithelium. The cyst wall has

normal smooth muscle with variable degrees of inflammation and fibrosis. The exception to this

common histologic characteristic is the type III cyst, which is generally lined by normal duodenal

mucosa. Choledochal cysts tend to have less inflammation in infancy and early childhood. In contrast,

there is well-established inflammation involving the cyst and surrounding structures in the

hepatoduodenal ligament in adolescents and adults.

Figure 103-54. Typical 99MTc-N-substituted-2,6-dimethylphenyl carbamoylmethyl iminodiacetic acid (HIDA) scan from a child

with a type I choledochal cyst. Images were made in 5 minutes (A), 30 minutes (B), and 3 hours (C), after isotope injection. The

isotope is retained within the choledochal cyst more than 24 hours, and the pattern of hepatocyte uptake is normal.

Pathophysiology

The mechanism for the development of cystic lesions of the biliary tract is unclear. Choledochal cysts

have been identified accurately by prenatal ultrasound, and it appears likely that these lesions represent

abnormalities in the developing biliary tract. Several hypotheses for the development of choledochal

cyst have been proposed. Whether the cystic dilatations result from abnormal recanalization of the

primitive bile duct cords or from inflammation caused by reflux of pancreatic secretions into the

common bile duct remains unknown. The pathophysiology of choledochal cyst is that of obstructive

jaundice. The obstruction may be primarily the result of mechanical outflow obstruction of a diminutive

distal common bile duct with a dilated choledochal cyst. Alternatively, a large inflammatory cyst can

cause obstruction of the biliary tract and of neighboring viscera by extrinsic compression. When

discovered during infancy, obstructive jaundice is usually the initial clinical finding. The liver injury is

typically reversible, and progression to biliary cirrhosis is rare. The exception to this situation is type V

disease, which is associated with a high incidence of hepatic fibrosis.

Other initial clinical situations include cholelithiasis and acute bacterial cholangitis secondary to

diminished bile drainage. Children with type III cysts may have acute pancreatitis. Infrequently,

extrinsic compression of the portal vein by a large choledochal cyst may produce symptoms and signs of

portal hypertension. Abdominal pain and tenderness following minor injury may lead to an incidental

diagnosis of choledochal cyst on imaging studies.

Carcinoma of the biliary tract occurs in about 3% to 5% of patients with choledochal cyst. The

number of reported cases remains small in the literature, but the incidence for biliary tract neoplasm is

about 1,000 times that of the normal population.186 Patients with choledochal cyst are at increased risk

for the development of biliary tract carcinoma in adolescence or early adulthood. The dysplastic cyst

epithelium may be susceptible to malignant change from chronic inflammation. Interestingly, there

appears to be an increased risk of malignancy to develop anywhere in the biliary tract, gallbladder, or

pancreas, and not just the choledochal cyst itself.187 Therefore, current treatment emphasizes complete

cyst excision or the cyst epithelium while providing adequate biliary drainage to prevent stasis and

chronic inflammation. Infants and children treated for choledochal cyst should have long-term follow-up

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for complications and potential malignancy.

Clinical Presentation and Diagnosis

Choledochal cysts present most commonly in infancy and early childhood with symptoms of obstructive

jaundice. In older children and adults, the classic clinical triad of episodic abdominal pain, a palpable

right upper-quadrant mass, and jaundice occurs in fewer than 50% of patients. Adults occasionally

present with hepatomegaly or evidence of portal hypertension. The diagnosis in infants and most

children can be confirmed by ultrasound examination and 99mTc-IDA imaging studies (Figs. 103-54 and

103-55). In older children, both MRI cholangiography and endoscopic retrograde

cholangiopancreatography (ERCP) are highly sensitive and specific in confirming diagnosis. These

lesions also are diagnosed incidentally during radiologic imaging studies for other reasons. Partial

duodenal obstruction may lead to an upper gastrointestinal series that shows extrinsic compression from

a large type I cyst or an intraluminal filling defect from a type III cyst. CT imaging of the abdomen

following blunt trauma may lead to the diagnosis of biliary tract dilatation. Liver biopsy is not specific

in choledochal cyst and has little diagnostic role other than to document the extent of liver injury.

Figure 103-55. Ultrasound image of a type I choledochal cyst (arrow; longitudinal image). The gallbladder (GB) is also shown.

Treatment

Type I Cysts. Initial operative strategy for a type I choledochal cyst is exploration and cholangiography,

usually through the gallbladder, but occasionally contrast injection must be made directly into the

common bile duct. Cholecystectomy is routinely performed. Historically, internal drainage procedures

without cyst excision were widely used. These procedures have been associated with a higher rate of

failure because of stricture, stone formation, pancreatitis, and cholangitis. In addition, there is the

potential for the development of biliary tract carcinoma in the retained cyst. Therefore, internal

drainage procedures without cyst excision have been abandoned. Current consensus for the surgical

management of type I choledochal cyst is performance of primary cyst excision with Roux-Y

hepaticojejunostomy reconstruction (Fig. 103-56). Primary cyst excision is accomplished routinely in

infants and children.188 For adults with severe inflammation and fibrosis, dissection may present

problems resulting from inflammation and adhesion of the cyst wall to the hepatoduodenal ligament. A

safer approach in this situation may be intramural cyst dissection and removal of the cyst wall

epithelium, leaving the posteromedial outer cyst wall adjacent to the portal vein and hepatic artery

intact.

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