demonstrable bowel perforation is characteristic of biliary ascites. High-fluid amylase content is seen in

pancreatic ascites, and a low protein count (<3 g/dL) is consistent with serous ascites. Elevated urea

nitrogen or creatinine in the fluid may suggest urinary ascites, particularly in a male patient. Cytology

should be performed to exclude peritoneal ascites secondary to malignancy, particularly in pubertal and

adolescent females.

If the initial fluid does not provide a diagnosis in an otherwise normal-appearing child, a

comprehensive diagnostic imaging evaluation is warranted. An echocardiogram should be obtained and

either ultrasound or CT scan imaging performed to evaluate the genitourinary system, the hepatobiliary

system, and the pancreas. A voiding cystourethrogram may also be indicated.

Treatment of neonatal or childhood ascites depends on the establishment of a specific diagnosis. In

the absence of anatomic lesion or injury, spontaneous resolution of chylous ascites occurs in 50% to

75% of cases with the temporary cessation of enteral feeding and administration of parenteral nutrition.

Persistence of chylous ascites for longer than 4 to 6 weeks is an indication for operative attempts to

ligate the cisterna chyli. Neonatal biliary ascites may result from spontaneous bile duct perforation, in

which case a diagnosis of CF must be considered. Transient bile duct obstruction typically leads to

perforation at the junction of the cystic duct with the common duct. Simple external drainage is the

treatment of choice, and complex hepatobiliary tract reconstruction in this setting is unnecessary and

potentially hazardous. Urinary ascites in a male patient requires a workup that includes a voiding

cystourethrogram to exclude posterior urethral valves. Urinary ascites resolves with the treatment of

obstructive uropathy. Pancreatic ascites is typically self-limited, and treatment by drainage procedures

is generally not required or limited for relief of persistent symptoms.

ETIOLOGY

Table 103-11 Common Causes of Childhood Ascites

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Massive neonatal ascites may cause hypoventilation secondary to impairment of diaphragmatic

excursion, and therapeutic paracentesis may be required. Childhood ascites generally responds to

adequate treatment of the underlying problem and occasionally requires medical therapy. Placement of

a peritoneovenous shunt in children for intractable ascites is rare.

Rectal Prolapse

Spontaneous rectal prolapse is relatively common in toddlers and children up to 5 years of age. A peak

incidence occurs at or near the time of toilet training. There is an association between straining during

bowel movement and rectal prolapse; it may be more commonly observed in children with CF,

myelodysplasias with sacral neuropathy, congenital anorectal malformations, Hirschsprung disease, and

colorectal polyps. However, most children presenting with rectal prolapse are normal.

A history of protrusion of mucosa or full-thickness rectum with or without bleeding is usually

described. Other lesions of childhood that have a similar appearance are prolapse of an intussusceptum

or passage of a polyp through the anus. The rectal examination is diagnostic. If the protruding intestine

is an intussusceptum, a finger can be placed adjacent to it within the rectum; this maneuver is not

possible with rectal prolapse.

Nonoperative management using manual reduction is successful in most infants and children. Sedation

may be required in some instances. Therapeutic interventions include stool softeners and parental

instruction on manual reduction. Spontaneous resolution over a few weeks is typical. For persistent

rectal prolapse in children, operative intervention is generally governed by doing the least invasive

procedure possible. Unlike adults, complex operations involving bowel resection and pelvic suspension

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are generally unnecessary in children with rectal prolapse. The most useful and commonly used

procedure is rectal submucosal injection using a sclerosant (Fig. 103-45). With the patient under general

anesthesia, injection with 5% sodium morrhuate or cow’s milk151 has been performed successfully on an

outpatient basis. About 90% of children can be treated successfully with a single four-quadrant

sclerosant technique, but on occasion further sclerosis is necessary. Submucosal dissection or

cauterization is also successful but may have a higher incidence of postoperative bleeding or stricture

formation and usually requires a short period of hospitalization. The major objective in treating

childhood rectal prolapse is to create a local extraperitoneal inflammatory process in the perirectal

space. Morbidity is low and the long-term outcome is excellent.

PEDIATRIC LIVER

Tumors of the Liver

Primary hepatic tumors are rare in children and at least 60% to 70% are malignant.152,153 Table 103-12

reviews the incidence rates and types of hepatic tumors presenting during infancy and childhood.

Pediatric hepatic tumors often manifest as asymptomatic abdominal masses discovered by parents or

pediatrician. Symptoms related to the tumor, such as pain, hemorrhage, hypertension, and precocious

puberty, are less frequent. Initial diagnostic imaging studies include plain abdominal radiographs and

ultrasound to assist in early determination as to whether the mass is cystic or solid and whether

calcifications are present. CT scan imaging and MRI remain definitive in the ability to discern anatomic

characteristics of the mass and its relationship to adjacent structures. Most children require operative

exploration for either definitive excision or incisional biopsy in lesions deemed unresectable.

Benign Tumors

Of all primary liver tumors of childhood, 30% are benign. The most common benign tumors are

hemangiomas, hemangioendotheliomas, mesenchymal hamartomas, cysts, focal nodular hyperplasia,

and hepatic adenoma. In most large series, hemangiomas constitute about 50% of the benign hepatic

tumors observed.154

Vascular Tumors. Infantile hepatic hemangiomas represent a clinically diverse spectrum of vascular

endothelial anomalies. They are characterized by a phase of proliferative growth over the first year of

life, with subsequent involution over several years. The International Society for the Study of Vascular

Anomalies classifies vascular tumors into two categories based upon the presence or absence of GLUT-1,

an erythrocyte-type glucose transporter protein expressed in the endothelium of the placenta and

hemangiomas.155 Therefore, hemangiomas are GLUT-1 positive, and other, more heterogeneous

vascular anomalies such as vascular malformations are GLUT-1 negative. Most asymptomatic infantile

hepatic hemangiomas are detected as incidental findings on diagnostic imaging studies performed for

unrelated reasons. A smaller proportion will create symptoms of enlarging abdominal mass, progressive

hepatic failure, high output cardiac failure due to shunting, thrombocytopenia, or hypothyroidism from

excess production of type III iodothyronine deiodinase.156

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Figure 103-45. Four-quadrant injection of sclerosant into the rectal submucosa for the treatment of childhood rectal prolapse.

Most benign vascular lesions of the pediatric liver do not require operative management. Operative

intervention is generally reserved for bleeding secondary to traumatic rupture symptoms not

controllable with medical management. Treatment strategies remain highly individualized based upon

the whether the lesions are focal, multifocal, or diffuse.157 In the face of multifocal or diffuse disease

associated with congestive heart failure and thrombocytopenia secondary to sequestration, medical

treatment with corticosteroid therapy may be useful. More invasive procedures such as irradiation,

selective hepatic arterial ligation, angiographic embolization, or hepatic transplantation remain useful in

selected patients with uncontrollable symptoms. Chemotherapeutic agents, including recombinant alphainterferon, low-dose vincristine, and cyclophosphamide, have been used for life-threatening vascular

lesions. Hepatic resection is generally reserved for mass lesions of unknown diagnosis, ruptured

vascular lesions with signs of active hemorrhage, or for symptomatic, locally resectable lesions.

Table 103-12 Incidence of Liver Tumors in Childhood

Hemangioendotheliomas are important vascular anomalies encountered in infants. The lesions vary in

size from 1 cm to several centimeters in diameter and may be multiple (Fig. 103-46). Symptomatic

neonates may present with an abdominal mass, hepatomegaly, and congestive heart failure. These

infants may also experience spontaneous rupture and hemoperitoneum, with tachycardia, tachypnea,

and hypovolemic shock. On examination, the infant may have other cutaneous hemangiomas visible on

the skin. Affected infants may develop thrombocytopenia secondary to platelet sequestration in the

vascular malformation (Kasabach–Merritt syndrome). CT scan imaging or MRI is diagnostic. Treatment is

directed at controlling symptoms using medical management principles as discussed previously;

however, hemangioendotheliomas tend to be more problematic than hemangiomas because of the

tendency to occur during infancy and the more extensive, symptomatic nature of the lesions.

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Figure 103-46. Selective visceral angiogram demonstrating large hepatic vascular malformation in a neonate with congestive heart

failure. This finding is consistent with a bilobar hemangioendothelioma.

Mesenchymal Hamartomas. Approximately one-third of benign hepatic tumors in children are

mesenchymal hamartomas. A mesenchymal hamartoma is often quite large and typically presents within

the first year of life as an asymptomatic, solitary abdominal mass. CT scan imaging or MRI studies are

usually diagnostic and show a solid mass that may have cystic components within the liver parenchyma.

Definitive diagnosis may require open tissue biopsy, and the therapy of choice is complete excision,

although spontaneous involution has been described. Simple enucleation may be adequate because these

tumors tend to be well circumscribed. On occasion, formal hepatic resection may be required.158

Recurrence is low after adequate resection.

Focal Nodular Hyperplasia. This tumor occurs primarily in female children and in adults and may be

associated with the use of oral contraceptives or focal hepatic injury. Focal nodular hyperplasia is

usually a well-defined, solitary mass that has characteristic findings on CT scan imaging. Open or

percutaneous biopsy may be required to differentiate the lesion from hepatic adenoma. This lesion

results from a focal inflammatory response of normal hepatic parenchyma surrounded by areas of

micronodular fibrosis and cirrhosis. Operative management is generally unnecessary unless there is a

question of diagnosis or active hemorrhage from the lesion.

Hepatic Adenoma. Adenomas are rare in infants and children and constitute less than 5% of all benign

hepatic lesions in the pediatric age group. There is an association between the use of oral

contraceptives, exogenous anabolic steroid use, and glycogen storage disease type I (von Gierke

disease). These tend to be large, solitary lesions located in the right hepatic lobe. The typical

presentation is an asymptomatic abdominal mass, although symptoms are seen more commonly than

with focal nodular hyperplasia. About 20% to 25% of patients with hepatic adenoma present with

hemoperitoneum from tumor rupture. On histologic examination, these lesions are composed of normal

hepatocytes without evidence of dysplasia. Operative therapy is usually directed at either making

definitive diagnosis or treating hemorrhage. Enucleation or local resection is adequate and recurrence

rates are low.

Hepatic Cysts. Congenital cysts of the liver may be either solitary or multiple. These cysts are thought

to result from failure of the intralobular or interlobular biliary ducts to fuse during development. They

may be lined with cuboidal, columnar, or squamous epithelium.159 The presence of multiple hepatic

cysts is associated with polycystic kidney disease, and development of progressive hepatic and renal

failure is a potential problem with this disease. The majority of children with hepatic cysts are

asymptomatic. Adjunctive diagnostic imaging, including ultrasound and CT scan imaging, may be

useful.

Asymptomatic congenital hepatic cysts do not require surgical therapy. Operative therapy is reserved

for symptomatic cysts. Resection or drainage by marsupialization or hepaticocystenterostomy may be

required. If patency to the biliary tract is present on contrast injection study of the cyst, internal

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drainage is necessary.

The differential diagnosis includes hydatid disease of the liver, which is suggested by calcification and

loculation of the cyst wall. Hydatid disease can be diagnosed using specific serologic tests, which is an

important surgical consideration prior to exploration. Patients with echinococcal cysts should be treated

with mebendazole and undergo cyst injection with hypertonic saline or other scolicidal agents into the

parent cyst before surgical excision. Careful control of the cyst contents is required during echinococcal

cyst excision or marsupialization.

Teratomas. Teratomas of the liver are exceedingly rare and have potential for harboring immature

elements capable of transforming into malignancy. Surgical resection on discovery is recommended.

Malignant Tumors

Two thirds of childhood hepatic tumors are malignant, with hepatoblastoma constituting half of the

malignancies, followed by hepatocellular carcinoma, malignant mesenchymal tumors, and sarcoma.152

Malignant hepatic tumors are fortunately rare, and effective treatment requires a multidisciplinary

approach that is best achieved in an experienced pediatric center.

Hepatoblastoma. Most hepatoblastomas are discovered in children younger than 2 years. There is a 2:1

male-to-female predominance. Hepatoblastomas usually are found as either an asymptomatic abdominal

mass or symptoms of gastrointestinal obstruction from extrinsic compression by the mass. There is an

association of hepatoblastoma in patients with Beckwith–Wiedemann syndrome and hemihypertrophy.

On examination, a firm, palpable upper abdominal mass is notable. Obstructive jaundice is unusual.

More than 90% of children with hepatoblastoma have elevated levels of alpha-fetoprotein, which is

useful serum tumor marker for postoperative surveillance. In few instances, children have initial

symptoms and signs of excess androgen secretion, including virilization and precocious puberty.

Diagnostic imaging with CT scan imaging or MRI is essential to evaluate the extent of the tumor and

evaluate for metastatic disease (Fig. 103-47).

Most children presenting with hepatoblastoma initially have unresectable disease. In the absence of

metastatic disease, however, an aggressive surgical approach is used. Cure and long-term survival with

hepatoblastoma requires complete surgical excision of the primary lesion. Therefore, localized,

resectable tumors usually are excised by formal hepatic lobectomy or extended trisegmentectomy.

Children with hepatoblastomas considered initially unresectable or with metastatic disease should

undergo percutaneous or incisional biopsy to confirm the histologic diagnosis, followed by multiagent

chemotherapy to reduce the size of the primary tumor and control metastases.160,161 Delayed resection

is appropriate if enough functional, normal hepatic parenchyma remain after resection. More than half

of the patients who initially have unresectable hepatoblastoma can be rendered disease-free with the

combination of chemotherapy and subsequent surgery. Cure rates for hepatoblastoma range from 60%

to 80% if histologically clear margins and no metastatic disease are present. All patients with

hepatoblastoma, regardless of stage, receive chemotherapy after resection. Unfortunately, cure cannot

be expected in children treated with chemotherapy and radiation therapy alone without complete

surgical resection.

Figure 103-47. Computed tomographic scan of the abdomen demonstrating an infant with hepatoblastoma of the right hepatic

lobe.

Hepatocellular Carcinoma. Hepatocellular carcinoma is significantly more common in adults but is

occasionally seen in older children and adolescents. There is a male predilection (2:1) and, except for

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the age at diagnosis, the clinical presentation is similar to that for hepatoblastoma. Children with

hepatocellular carcinoma are more likely to have jaundice and abnormal liver enzymes. The high

association of cirrhosis in adults (80%) is not seen in children with hepatocellular carcinoma; only 5% of

children develop hepatocellular carcinoma in the background of cirrhosis. An increased risk of

hepatocellular carcinoma is seen in children with Beckwith–Wiedemann syndrome, hemihypertrophy,

von Gierke disease, hepatitis B, and Fanconi syndrome. Exposure to oral contraceptives, anabolic

steroids, and some chemotherapeutic agents also has been associated with hepatocellular carcinoma.

This malignancy carries a poor prognosis with an overall survival rate of 10% to 20% despite aggressive

surgical resection and multiagent chemotherapy. A histologic variant, fibrolamellar hepatocellular

carcinoma, carries a more favorable prognosis. As with hepatoblastoma, complete surgical resection

with clear histologic margins is necessary for long-term survival and cure. In the absence of metastatic

disease, unresectable hepatoblastoma or hepatocellular carcinoma in children has been successfully

treated by orthotopic liver transplantation. Review of data from the United Network for Organ Sharing

database demonstrates good long-term survival for both hepatoblastoma (66% 10-year survival) and

hepatocellular carcinoma (58% 10-year survival) treated with liver transplantation.162

Malignant Mesenchymal Tumors. These rare hepatic malignancies occur in children 5 to 10 years of

age; initial signs are fever, pain, and an abdominal mass, which is usually quite large on diagnosis and

may have both solid and cystic components. Multidisciplinary treatment, including complete surgical

resection, multiagent chemotherapy, and radiation therapy, is required for cure. In general, the

prognosis of primary malignant mesenchymal tumors of the liver remains poor.

Sarcomas. Children may rarely have a primary sarcoma of the liver. Embryonal rhabdomyosarcoma of

the biliary tract is distinctly unusual. It may manifest with obstructive jaundice attributable to both

extrinsic and intrinsic biliary tract obstruction. Undifferentiated, embryonal sarcoma of the liver has

also been described. Angiosarcoma developing in the liver may be associated with exposure to toxins

such as arsenic. Aggressive surgical resection may be required, but long-term survival is uncommon.

Despite radical surgery, chemotherapy, and radiation therapy, the prognosis and long-term survival of

children with these malignancies remain poor, and data regarding effective drug regimens are

limited.163,164

Liver Resection

Operative principles and techniques for hepatic resection are discussed elsewhere in this book. Several

unique issues in the safe performance of hepatic resection in children should be emphasized.165

Contemporary management of hepatic resection for tumors in children requires adequate preoperative

assessment and the liberal use of intraoperative monitoring techniques. The circulating blood volume of

an infant or a child is less compared to an adult, and children are sensitive to compression of the

inferior vena cava causing decreased venous return to the right heart. Blood must be available for

transfusion and adequate intravenous access is essential. Resection can be performed through either a

subcostal incision or a right thoracoabdominal incision; in general, the ability to perform the operation

safely should not be limited by the size of the incision. In children, the right and left hepatic veins are

difficult to control near the inferior vena cava because of their short lengths, and intraparenchymal

control from an anterior approach may be safer (Fig. 103-48). Resection may be performed using total

hepatic vascular isolation by controlling the hepatic and portal inflow, the suprahepatic inferior vena

cava, and the suprarenal inferior vena cava caudal to the liver. When extrahepatic biliary duct

reconstruction is required, T-tube drainage is not routinely performed given the small diameter of the

ducts in most children.

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Figure 103-48. A: The hepatic veins in infants and children may be extremely short, making extrahepatic control impossible or

dangerous. B: Intrahepatic control of the hepatic veins via an anterior approach may be safer in infants and children.

Hepatic Infections

Hepatic infections are generally rare in the pediatric population, and their management is similar to that

used in adults. An important issue is the development of hepatic abscess in an immunocompromised

child and, in particular, the association of chronic granulomatous disease with pyogenic hepatic abscess

formation.

Pyogenic Abscess

The most common cause of pyogenic liver abscess before the advent of antibiotic therapy was

perforated appendicitis. Now the most common causative factor in the development of pyogenic hepatic

abscess in children with chronic granulomatous disease and other causes of immunosuppression.166

Chronic granulomatous disease is an inherited disorder characterized by a defect in oxidative burstmediated bacterial killing by neutrophils. These children develop skin, soft-tissue, and solid organ

abscesses. A significant number of children with pyogenic liver abscesses have chronic granulomatous

disease or other inherited/acquired immunodeficiency states. Liver abscesses are infrequently seen as a

complication of umbilical vein catheterization, omphalitis, biliary tract disease, and hepatobiliary

operations.

Patients with pyogenic liver abscess present with fever, jaundice, and leukocytosis.

Hepatosplenomegaly and a tender liver may be found on physical examination. Diagnostic imaging with

ultrasound, CT scan imaging, or MRI is useful. Common responsible organisms include staphylococcal

species, streptococcal species, and E. coli. Gram-negative organisms and anaerobic bacteria are

becoming increasingly prevalent. Treatment involves the use of broad-spectrum antibiotics. Large

abscess cavities may require image-guided percutaneous drainage to expedite resolution of sepsis.

Currently, few hepatic abscesses require open operative drainage. The outcome is dependent upon the

underlying disease process. Recovery from the abscess is predictably good following adequate antibiotic

therapy and drainage when necessary.

Amebic Abscess

Amebic abscess of the liver is uncommon in the United States, but it is endemic to areas of Central and

South America. It is caused by infection with the parasite Entamoeba histolytica. Children with amebic

dysentery develop hepatic infection as the parasite travels through the portal circulation. Patients have

a history of chronic illness, fever, and abdominal pain. Examination typically demonstrates a tender

right upper quadrant. Infection can be confirmed by a serum antibody test, and amebic abscess can be

demonstrated by ultrasound or CT scan. Spontaneous rupture of amebic abscess is reported in as many

as 10% of patients in some series.167 The treatment of choice is the antibiotic metronidazole. Surgical

resection or drainage of amebic liver abscess is typically not required for resolution.

PEDIATRIC BILIARY TRACT

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Common biliary tract problems including infectious, inflammatory, and gallstone-related problems are

managed similarly in both children and adults, and the management principles are discussed elsewhere

in this text. Two congenital problems of the biliary tract, namely, biliary atresia and congenital cystic

disease of the biliary tract (choledochal cyst), are somewhat unique to infants and children in

presentation and management and are reviewed in the following discussion.

Embryology

The fetal liver and biliary tract develop between weeks 4 and 10 of gestation, representing the fusion of

an endodermal foregut diverticulum with a mesodermal component from the septum transversum. The

hepatocytes are derived from cords of endodermal cells in the hepatic diverticulum and ultimately give

rise to the hepatic sinusoidal endothelium. The proximal hepatic diverticulum gives rise to the

extrahepatic biliary tract, including the gallbladder, cystic duct, and common bile duct. As the

intrahepatic and extrahepatic ductal systems develop, they unite to form a connected, arborizing system

of cords composed of primitive ductular epithelial cells. These epithelial cells assume tubular

configuration with ductal patency established between weeks 6 and 12 of gestation. Bile flow from the

hepatocytes and into the biliary duct system is apparent by the beginning of the second fetal trimester.

This embryologic sequence appears to take place normally in infants who develop biliary atresia. In

fact, the term biliary atresia does not reflect embryologic atresia resulting from failure of recanalization

of the biliary tree. Rather, biliary atresia is caused by an uncontrollable inflammatory process that

produces progressive obliteration of the normally developed extrahepatic biliary tract.

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Biliary Atresia

Anatomy

7 The overall incidence rate of biliary atresia is about 1 in 8,000 to 12,000 live births and is the most

common cause of chronic cholestasis in infants and children as well as the most frequent indication for

pediatric liver transplantation.168 Extrahepatic biliary atresia must be differentiated from biliary

hypoplasia. Biliary hypoplasia describes a diminutive but patent biliary system and can result from

many underlying situations such as neonatal hepatitis and alpha1

-antitrypsin deficiency. Biliary

hypoplasia involves both intrahepatic and extrahepatic ductal systems.

Microscopic Anatomy. Biliary atresia is characterized by replacement of the extrahepatic biliary tract

with dense, fibrous inflammatory tissue. In most cases, complete obliteration of the extrahepatic biliary

tract, including the gallbladder, occurs. There appears to be gradual progression of the inflammatory

process with advancing age. The common hepatic duct and common bile duct are almost uniformly

obliterated by the inflammatory process. Few or absent patent ductal remnants and an absence of portal

inflammation may be associated with a less favorable prognosis.169 Intraoperative evaluation for duct

patency by frozen section analysis has historically been used help guide the extent of proximal resection

at the porta hepatis; however, this is no longer in widespread use. The presence of bile ducts at the

porta hepatis with diameter greater than 150 μm has been reported to be associated with postoperative

bile flow in up to 90% to 95% of cases.170

Histologic features of biliary atresia reflect hepatic parenchymal injury. Neocholangiogenesis, or

biliary duct proliferation of disorganized and nonpatent ducts within the liver, is considered highly

suggestive but not specific for biliary atresia. Other findings include bile pigment deposition throughout

the liver. Characteristic early findings in biliary atresia include evidence for acute inflammation with

neutrophil predominance in the periportal regions. Older infants and children typically have chronic

inflammatory changes with considerable fibrosis. Periportal bridging fibrosis is commonly seen in

intermediate stages of the disease. Ultimately, progressive biliary atresia leads to intractable cirrhosis.

Nearly all patients with biliary atresia have histologic evidence of liver injury. The severity and extent

of liver damage may be the most important predictor of long-term outcome and survival in biliary

atresia.

Pathophysiology

Despite numerous investigations, the mechanism causing biliary atresia remains unknown. The current,

widely accepted concept is that the normally developed biliary tract undergoes inflammatory sclerosis

and subsequent obliteration. This process appears to occur during the first few weeks to months of life.

Infants who develop biliary atresia are rarely jaundiced at birth, and biliary atresia is either rare or

nonexistent in fetal autopsy studies. Clinical data are consistent with the fact that biliary atresia appears

to be a progressive, dynamic inflammatory response that is acquired during the perinatal period and

targets the extrahepatic biliary tract. Early establishment of biliary drainage via portoenterostomy

within the first 2 to 4 months of age may be associated with reversal of liver injury and subsequent

long-term survival. Conversely, infants operated on after 120 days of life typically have obliterated bile

ducts. Neonatal biliary atresia shares some clinical and morphologic features of sclerosing cholangitis in

adults. Data supporting an infectious etiologic agent and, in particular, reoviruses, rotaviruses, and

hepatitis C, have been reported and may play a role in some cases. In addition, other noninfectious

stimuli may trigger an inflammatory response directed at the neonatal extrahepatic bile duct.171 The

actual mechanism may reflect a stereotypical inflammatory response initiated by a variety of different

stimuli that is ultimately directed preferentially against the neonatal bile duct.

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