Biliary Atresia

Biliary atresia, also known as extrahepatic ductopenia and progressive obliterative cholangiopathy, is a childhood disease of the liver characterised by abnormally narrow, blocked, or absent bile ducts. This condition can be congenital or acquired. The incidence of biliary atresia in the United States is one in 10,000 to 15,000 live births, with a higher frequency of one in 5,000 in East Asia.

Signs and Symptoms

Initially, the symptoms of biliary atresia are similar to those of neonatal jaundice, which is typically harmless. However, infants with biliary atresia will experience progressive conjugated jaundice, pale white stools, and dark urine. There may be a degree of fat and fat-soluble vitamin malabsorption, leading to poor growth and a tendency to bleed due to Vitamin K deficiency.

If untreated, the condition progresses to cirrhosis and portal hypertension, eventually causing liver failure. Unlike other forms of jaundice, biliary atresia-related cholestasis does not usually result in kernicterus because the liver can still conjugate bilirubin.

Causes

The exact cause of biliary atresia remains unclear, and multiple factors may be involved. Maternal rotavirus infection during pregnancy has been implicated, as well as other viral infections such as COVID-19 and congenital cytomegalovirus. Autoimmune processes may also contribute, although the evidence is not definitive.

Genetic factors are significant, with associations found between biliary atresia and genes such as ADD3 and GPC1. In Egyptian infants, a deficiency in glutathione S transferase M1 (GST M1) has been linked to aflatoxin-induced cholangiopathy, known as Kotb disease.

Pathophysiology

There are three main types of extra-hepatic biliary atresia:

1. Type I: Atresia is restricted to the common bile duct.
2. Type II: Atresia of the common hepatic duct.
3. Type III: Atresia involves the most proximal part of the bile ducts, accounting for over 95% of cases.

In approximately 10% of cases, other anomalies may be associated, such as heart lesions, polysplenia, situs inversus, and absent venae cavae. Progressive cirrhosis leads to portal hypertension, esophagogastric varix bleeding, hypersplenism, hepatorenal syndrome, and hepatopulmonary syndrome.

Diagnosis

Diagnosis involves a combination of history, physical examination, blood tests, liver biopsy, and ultrasound scans. Prolonged jaundice and abnormal liver function tests prompt further investigation. Imaging such as radio-isotope liver scans can be used, but confirmation typically occurs during exploratory surgery.

Differential Diagnoses

The differential diagnoses for biliary atresia include:

• Alagille syndrome
• Alpha-1-antitrypsin deficiency
• Byler disease
• Caroli disease
• Choledochal cyst
• Cholestasis
• Congenital infections (e.g., cytomegalovirus, herpes simplex virus, rubella, syphilis, toxoplasmosis)
• Cystic fibrosis
• Galactosaemia
• Idiopathic neonatal hepatitis
• Lipid storage disorders
• Neonatal hemochromatosis
• Total parenteral nutrition-associated cholestasis

Treatment

Most infants with biliary atresia undergo the Kasai procedure, or hepatoportoenterostomy, to restore bile flow and reduce jaundice. While not curative, this procedure can relieve jaundice and halt liver fibrosis, allowing normal growth and development. Approximately 50-55% of infants achieve normal bilirubin levels, and 40-50% retain their liver function for up to 10 years or more.

Liver transplantation is an option for those whose liver function does not improve post-Kasai operation.

Corticosteroid treatment post-Kasai can enhance bile flow and clear jaundice, but its long-term impact on survival is unclear. The ideal dosing and duration of steroid treatment remain controversial.

Epidemiology

Biliary atresia affects females slightly more than males and is more common in Asians and African Americans than in Caucasians. It is usually an isolated occurrence within families, with no known links to medications or vaccinations during pregnancy. Diabetes in pregnancy, especially in the first trimester, may increase the risk of congenital abnormalities, including biliary atresia.

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Self-assessment MCQs (single best answer)

What is the incidence of biliary atresia in the United States?

Which of the following is NOT a symptom of biliary atresia?

Which viral infection has been implicated in the maternal cause of biliary atresia?

Which gene has been associated with biliary atresia?

What percentage of biliary atresia cases involve Type III atresia?

Which of the following is NOT typically included in the differential diagnosis for biliary atresia?

What is the primary surgical treatment for biliary atresia?

What is the main objective of the Kasai procedure?

Biliary atresia is more common in which ethnic group?

What is a common complication if biliary atresia is left untreated?