eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology
Biliary Atresia
Updated: Apr 28, 2009
Introduction
Background
Biliary atresia is characterized by obliteration or discontinuity of the extrahepatic biliary system, resulting in obstruction to bile flow.1 The disorder represents the most common surgically treatable cause of cholestasis encountered during the newborn period. If not surgically corrected, secondary biliary cirrhosis invariably results. Patients with biliary atresia can be subdivided into 2 distinct groups: those with isolated biliary atresia (postnatal form), which accounts for 65-90% of cases, and patients with associated situs inversus or polysplenia/asplenia with or without other congenital anomalies (fetal/embryonic form), comprising 10-35% of cases.Biliary atresia.
The pathology of the extrahepatic biliary system widely varies in these patients, and the following classification is based on the predominant site of atresia:
- Type I involves obliteration of the common duct; the proximal ducts are patent
- Type II is characterized by atresia of the hepatic duct, with cystic structures found in the porta hepatis
- Type III (>90% of patients) involves atresia of the right and left hepatic ducts to the level of the porta hepatis. These variants should not be confused with intrahepatic biliary hypoplasia, which comprises a group of distinct and surgically noncorrectable disorders.
Pathophysiology
Although histopathologic features of biliary atresia have been extensively studied in surgical specimens from excised extrahepatic biliary systems of infants undergoing portoenterostomy, the pathogenesis of this disorder remains poorly understood. Early studies postulated a congenital malformation of the biliary ductular system. Problems of hepatobiliary ontogenesis are suggested by the fetal/embryonic form of atresia that is associated with other congenital anomalies. However, the more common neonatal type is characterized by a progressive inflammatory lesion, which suggests a role for infectious and/or toxic agents causing bile duct obliteration.
In type III, the most prevalent histopathological variant, the fibrous remnant demonstrates complete obliteration of at least a portion of the extrahepatic biliary system. Ducts within the liver, extending to the porta hepatis, are initially patent during the first few weeks of life but may progressively be destroyed. The same agent or agents that damaged the extrahepatic ducts may be causative, and the effects of retained toxins in bile are contributing factors.
Identification of active and progressive inflammation and destruction of the biliary system suggests that extrahepatic biliary atresia likely represents an acquired lesion. However, no single etiologic factor has been identified. Infectious agents seem to be the most plausible candidates, particularly in the isolated (neonatal) form of atresia. Several studies have identified elevated antibody titers to reovirus type 3 in patients with biliary atresia when compared with controls. Other viruses, including rotavirus and cytomegalovirus (CMV), have also been implicated.
Frequency
United States
Individual studies suggest an overall incidence in the United States of 1 per 10,000-15,000 live births.
International
The incidence of biliary atresia is highest in Asian populations, and it may be more common in Chinese infants compared with Japanese infants.
Mortality/Morbidity
Prior to the development of liver transplantation as a therapeutic option for children with end-stage liver disease, the long-term survival rate for infants with biliary atresia following portoenterostomy was 47-60% at 5 years and 25-35% at 10 years. In one third of all patients, bile flow is inadequate following surgery, and these children succumb to complications of biliary cirrhosis in the first few years of life unless liver transplantation is performed. Following portoenterostomy, complications include cholangitis (50%) and portal hypertension (>60%).
Hepatocellular carcinoma may be a risk for patients with cirrhosis and no clinical evidence of portal hypertension. Progressive fibrosis and biliary cirrhosis develop in children who do not drain bile. Thus, as discussed below (see Prognosis), liver transplantation may be the only option for long-term survival in most patients.2
Race
Incidence of biliary atresia is highest in Asian populations. The disorder also occurs in black infants, with an incidence approximately 2 times higher than that observed among white infants.
Sex
Extrahepatic biliary atresia is more common in females than in males.
Age
Biliary atresia is a disorder unique to the neonatal period. Two presentations are described in this chapter (see Background). The fetal/perinatal form is evident within the first 2 weeks of life; the postnatal type presents in infants aged 2-8 weeks.
Clinical
History
Regardless of etiology, the clinical presentation of neonatal cholestasis is remarkably similar in most infants.
- Typical symptoms include variable degrees of jaundice, dark urine, and light stools.
- In the case of biliary atresia, most infants are full-term, although a higher incidence of low birthweight may be observed.
- In most cases, acholic stools are not noted at birth but develop over the first few weeks of life. Appetite, growth, and weight gain may be normal.
Physical
Physical findings do not identify all cases of biliary atresia. No findings are pathognomonic for the disorder.
- Infants with biliary atresia are typically full term and may manifest normal growth and weight gain during the first few weeks of life.
- Hepatomegaly may be present early, and the liver is often firm or hard to palpation. Splenomegaly is common, and an enlarging spleen suggests progressive cirrhosis with portal hypertension.
- Direct hyperbilirubinemia is always an abnormal finding and may be present from birth in the fetal/embryonic form. Consider biliary atresia in all neonates with direct hyperbilirubinemia.
- In the more common postnatal form, physiologic jaundice frequently merges into conjugated hyperbilirubinemia. The clinician must be aware that physiologic unconjugated hyperbilirubinemia rarely persists beyond 2 weeks. Infants with prolonged physiologic jaundice must be evaluated for other causes.
- In patients with the fetal/neonatal form (polysplenia/asplenia syndrome), a midline liver may be palpated in the epigastrium .
- The presence of cardiac murmurs suggests the presence of associated cardiac anomalies.
- A high index of suspicion is key to making a diagnosis because surgical treatment by age 2 months has clearly been shown to improve the likelihood of establishing bile flow and to prevent the development of irreversible biliary cirrhosis.
Causes
The disorder is rarely seen in infants who are stillborn or in premature infants, which supports a late gestational etiology. By contrast, infants with idiopathic neonatal hepatitis, which is the major differential diagnosis, are often preterm, small for gestational age, or both.
- Infectious agents
- No single agent has been identified as causative for biliary atresia, although the role of infecting organisms has been the most extensively studied.
- Fischler et al reported cytomegalovirus (CMV) infection in almost 25% of affected infants in one study based on immunoglobulin M (IgM) serology.3 Interestingly, an even higher frequency of CMV infection has been found by Chang et al in cases of idiopathic neonatal hepatitis, lending support to the concept that both disorders are ends of the same pathological spectrum, originally described by Landing as infantile obstructive cholangiopathy.4
- Investigations of reovirus type 3 have yielded conflicting results. Wilson et al noted in one study that the virus damages the bile ducts and hepatocytes in mice,5 whereas another study by Steele et al failed to demonstrate evidence of infection in infants with cholestasis.6
- Other studies have examined the role of rotavirus groups A, B, and C and the common hepatitis viruses A, B, and C; however, no clear associations have been found.
- Genetic factors
- The existence of the fetal/perinatal form of biliary atresia, frequently associated with other GI and cardiac anomalies, suggests the possibility of a disorder in ontogenesis. Studies have identified specific genetic mutations in mice with visceral heterotaxy and cardiac anomalies, defects similar to those found in conjunction with the fetal/perinatal form of biliary atresia.
- Various genetic abnormalities, including deletion of the mouse c-jun gene (a proto-oncogene transcription factor) and mutations of homeobox transcription factor genes, are associated with hepatic and splenic defects; however, a direct link to biliary atresia has not been described.
- Other causes
- Disorders of bile acid synthesis are part of the differential diagnosis of biliary atresia. In fact, bile acids almost certainly contribute to ongoing hepatocellular and bile ductular damage in infants with the disorder. Although associated defects in bile acid metabolism may hasten progression of liver disease, no primary role for bile acids in the development of biliary atresia has been identified.
- Several investigators have studied the potential effects of other etiological agents, including teratogens and immunological factors. Again, no clear correlations with biliary atresia have been demonstrated.
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| References |
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References
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Further Reading
Keywords
biliary atresia, extrahepatic biliary atresia, cholestasis, jaundice, obliteration of the extrahepatic biliary system, discontinuity of the extrahepatic biliary system, obstruction of bile flow, bile obstruction, biliary obstruction, secondary biliary cirrhosis, isolated biliary atresia, postnatal biliary atresia, situs inversus, polysplenia, asplenia, liver transplantation, end-stage liver disease, cholangitis, portal hypertension, hepatocellular carcinoma, hepatomegaly, splenomegaly, diagnosis, treatment
