Approach
Biliary atresia is a potentially serious disease requiring prompt early diagnosis, ideally before 6-8 weeks of age. Data suggest that direct or conjugated bilirubin is elevated during the first week of life in neonates with biliary atresia.[50][51] Jaundice in an infant greater than 2 weeks of age necessitates examination of fractionated bilirubin.
There are many causes of neonatal jaundice and diagnosis relies on the exclusion of other differentials.
History
History and examination findings alone are not sufficient to make the diagnosis, but a child typically presents with onset of jaundice between birth and 6-8 weeks of age. Biliary atresia is very unlikely if a child is older than 8 weeks old at the onset of jaundice. There may not be any associated abnormalities. Parents may notice jaundice, urine that stains the nappy yellow, or pale-coloured stools.
Examination
Affected infants often look healthy and have normal growth and development at the time of presentation to the paediatrician. Jaundice is the only absolute physical finding. Acholic (pale) stools support the possibility of biliary obstruction, and yellow-staining urine in the nappy is common. Hepatomegaly is common, but not essential for diagnosis. Ascites will only be present in advanced cases when liver damage has occurred.
Investigations
Biliary atresia is one cause of prolonged neonatal jaundice. Investigations focus on identifying treatable causes first and are ideally done within the first 5 days of initial presentation.
The first tier of investigations includes:
Direct or conjugated bilirubin level of >17.1 micromoles/L (1 mg/dL) is considered abnormal.[51] A direct bilirubin to total bilirubin ratio exceeding 20% is no longer recommended as a diagnostic test.[51]
Review of the newborn screen to exclude thyroid dysfunction, galactosaemia, cystic fibrosis, and rare metabolic disorders. It may be necessary to repeat one or more of these tests if the diagnosis is still suspected (e.g., urinary succinylacetone for tyrosinaemia).
Liver function tests and a clotting screen (prothrombin time/INR and partial thromboplastin time). A high level of gamma-glutamyl transferase supports biliary disease. Clotting disorders are a serious complication and more common if presenting late.
Full blood count will help ascertain the overall health of the child. Low white blood cell (WBC) count and platelets may be seen with advanced liver disease, or a raised WBC count may support an alternative infectious cause.
Imaging studies
Abdominal ultrasound is indicated if biliary atresia remains a possible diagnosis. A choledochal cyst can be visualised, and the triangular cord sign is highly suggestive of the condition but rarely seen. Ultrasound may also identify laterality defects that could be consistent with a biliary atresia diagnosis, such as polysplenia or pre-duodenal portal vein.
Subsequent investigations
If no abnormality is detected and cholestasis persists, further evaluation is required. The next steps will depend upon many factors including the age of the infant and other associated clinical signs that may suggest an alternative diagnosis.
Hepatobiliary scintigraphy may have a role in some cases. Failure of excretion is not diagnostic, and further investigation is warranted, either liver biopsy or cholangiogram.[52] Hepatobiliary scintigraphy is generally not useful if stools are acholic.
Needle biopsy of the liver can be performed to assess for signs of biliary obstruction (portal expansion, ductular proliferation and bile plugs), bile duct paucity, or giant cell hepatitis.
A cholangiogram demonstrating a lack of patency is the diagnostic standard for biliary atresia.[53] It is performed intraoperatively in patients in whom biliary atresia is likely e.g., when liver biopsy shows characteristic features of obstruction.
Tests to exclude other differentials
May be undertaken initial investigations or after exclusion of biliary atresia, depending on the clinical presentation.
Chest x-ray (CXR). Alagille syndrome has characteristic features (e.g., butterfly or haemivertebrae) that may be seen on CXR. If Alagille syndrome is suspected, an echocardiogram and eye examination are also useful. Dextrocardia may be identified in biliary atresia splenic malformation syndrome.
Infection screen. The most common infections causing jaundice are toxoplasmosis, herpes, rubella, syphilis, adenovirus, enterovirus, and cytomegalovirus. Bacterial sepsis or a urinary tract infection may also be responsible. Less commonly, parvovirus B19, paramyxovirus, HIV, listeriosis, and tuberculosis have also been reported to cause jaundice. A combination of serology, blood cultures, and urinary antigen tests is needed to exclude these as differentials.
Serum amino acids to exclude type 1 tyrosinaemia.
Alpha-1 antitrypsin levels and protease inhibitor typing to exclude alpha-1 antitrypsin deficiency, which can present in a similar fashion to biliary atresia.
Random cortisol level to exclude adrenal insufficiency.
Urinary organic acids, specifically to look for organic acidaemias, peroxisomal diseases, and mitochondrial diseases.
Urinary bile acids to look for bile acid defects.
Lactate/pyruvate. An abnormal ratio may indicate a mitochondrial disorder.
Genetic testing may be indicated to identify other genetic aetiologies, depending on clinical presentation.
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