Pediatric Biliary Atresia Clinical Presentation

Updated: May 03, 2019
  • Author: Steven M Schwarz, MD, FAAP, FACN, AGAF; Chief Editor: Carmen Cuffari, MD  more...
  • Print
Presentation

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. [4]

  • 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.

Next:

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 it is typically 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.

Previous
Next:

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. [5] 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. [6]

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, [7] whereas another study by Steele et al failed to demonstrate evidence of infection in infants with cholestasis. [8]

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. One study, using a murine model of biliary atresia induced by rhesus rotavirus, isolated trophism for the cholangiocyte to a specific genetic region. [9]

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. In a recent murine model, insufficient SOX17 expression in the gallbladder and bile duct epithelia resulted in biliary atresia. However, confirmation of a similar abnormality in human gene expression, and its potential etiopathogenetic role in this disorder, must await further studies. [10]

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.

Previous