What is biliary atresia?

Biliary Atresia: Definition and Management

Biliary atresia is a rare cholestatic liver disease characterized by progressive inflammation and obliteration of the extrahepatic bile ducts, leading to obstruction of bile flow, which is universally fatal without treatment, typically causing death within 1-2 years of life. 1, 2

Definition and Epidemiology

• Biliary atresia is a cholangiodestructive disease affecting the biliary tract with an incidence of approximately 1 in 10,000-20,000 infants, with higher prevalence in Asian countries 2, 3
• The condition involves obliteration or discontinuity of the extrahepatic biliary system at variable levels, forming the basis for classification into Types I, II, and III 3
• It is clinically heterogeneous with distinct variants including isolated biliary atresia, Biliary Atresia Splenic Malformation syndrome, Cat-eye syndrome, cystic biliary atresia, and CMV-associated biliary atresia 2

Etiology

• The exact cause remains unclear but may involve multiple factors including genetic predisposition, developmental abnormalities, exposure to environmental toxins, or perinatal viral infections 2, 4
• For patients with associated congenital anomalies (up to 10% of cases), the etiology likely occurs during the first trimester of gestation 3
• For isolated biliary atresia, perinatal destruction of fully-formed bile ducts, possibly by hepatotropic viruses, has been suggested 3, 4
• The disease triggers an intrahepatic fibrotic process beginning at birth and progressing to cirrhosis within months if untreated 2

Clinical Presentation

• Affected infants present with a classic triad of:
  • Conjugated jaundice
  • Pale, acholic (non-pigmented) stools
  • Dark urine 2, 3, 5
• Physical examination may reveal hepatosplenomegaly in early stages, with ascites developing later as liver disease progresses 2
• Symptoms typically appear in the first few weeks of life, requiring prompt evaluation of any infant older than 14 days with jaundice 4

Diagnosis

• Key diagnostic tests include:
  • Liver biochemistry showing elevated liver enzymes and conjugated hyperbilirubinemia
  • Ultrasonography to evaluate the biliary tract
  • Viral serology to exclude infectious causes
  • Percutaneous liver biopsy to assess histological changes
  • Hepatobiliary scintigraphy (HIDA scan) to evaluate bile flow 3, 5
• Rapid and efficient diagnosis is essential as treatment outcomes significantly depend on early intervention 2

Treatment

Initial Management: Kasai Portoenterostomy

• The American Association for the Study of Liver Diseases recommends Kasai portoenterostomy as the initial treatment of choice 1
• The procedure should be performed within the first 2 months of life by an experienced surgeon, as success rates significantly decrease when performed after 3 months of age 1
• When performed early by experienced surgeons, the Kasai procedure can result in prolonged survival in up to 70% of infants 1
• The procedure involves excision of all extrahepatic biliary remnants and biliary reconstruction using a Roux-en-Y jejunal loop as a portoenterostomy 3, 5

Post-Kasai Management

• Ursodeoxycholic acid is commonly administered post-operatively to promote bile flow, though regimens are not standardized 1
• Prophylactic antibiotics are recommended to reduce recurrent cholangitis rates and improve survival 1
• Close monitoring for complications is essential, including:
  • Cholangitis
  • Portal hypertension
  • Variceal bleeding
  • Fat-soluble vitamin deficiencies
  • Growth failure 1

Liver Transplantation

• Liver transplantation becomes necessary in cases of:
  • Failure of the Kasai procedure
  • Development of intractable portal hypertension
  • Progressive liver failure
  • Delayed diagnosis 1, 5
• Transplantation options include reduced-size deceased donor organ, living-related liver transplantation, and split liver transplantation 1
• One-year survival rates following transplantation reach 93%, with five-year survival exceeding 85% 1

Prognosis

• Without treatment, biliary atresia is universally fatal, with death usually occurring within the first 1-2 years of life 1
• If total serum bilirubin falls below 2 mg/dL within 3 months following Kasai procedure, up to 70% of patients may have prolonged transplant-free survival 1
• Approximately 25-35% of patients who undergo Kasai portoenterostomy survive more than 10 years without requiring liver transplantation 4
• About one-third of patients achieve bile drainage but develop complications of cirrhosis requiring liver transplantation before age 10 4
• The remaining one-third experience inadequate bile flow following portoenterostomy, leading to progressive fibrosis and cirrhosis 4
• Delaying transplantation until at least 6 years of age is associated with better graft and patient survival, highlighting the importance of a successful initial Kasai procedure 1

Emerging Therapeutic Approaches

• Ileal bile acid transporter (IBAT) inhibitors are being investigated as potential therapeutics to reduce hepatic bile acid concentration after Kasai portoenterostomy 6
• By interrupting the enterohepatic circulation of bile acids, IBAT inhibitors may attenuate hepatic bile acid retention and reduce the risk of early organ failure 6
• Two IBAT inhibitors in development for pediatric cholestatic liver diseases are maralixibat and odevixibat 6