From the Guidelines
Biliary atresia is a destructive inflammatory process of unknown etiology that results in fibrosis and obliteration of the extrahepatic bile ducts and variable involvement of the intrahepatic ducts, and early diagnosis is critical to improve outcomes. The pathogenesis of biliary atresia involves an initial insult (likely viral, genetic, or immune-mediated) that triggers bile duct inflammation, followed by progressive fibrosis and obstruction of bile flow, as noted in 1. This process typically begins in utero or shortly after birth, with complete obstruction occurring within weeks to months.
When gathering history for suspected biliary atresia, several key points should be considered:
- Focus on the timing and progression of jaundice, as persistent jaundice beyond two weeks of life is concerning, as indicated in 1.
- Ask about stool color, as acholic (pale or clay-colored) stools suggest bile duct obstruction.
- Inquire about urine color, as dark urine indicates conjugated hyperbilirubinemia.
- Document growth parameters and feeding patterns, as failure to thrive may occur due to fat malabsorption.
- Ask about any maternal infections during pregnancy, as some viral infections have been associated with biliary atresia, as mentioned in 1.
- Family history is important to identify potential genetic syndromes associated with biliary atresia.
The Kasai portoenterostomy procedure is most successful when performed before 60 days of life, while delayed diagnosis often leads to liver failure requiring transplantation, as highlighted in 1 and 1. Therefore, it is essential to prioritize early diagnosis and timely intervention to improve outcomes for patients with biliary atresia.
From the Research
Pathogenesis of Biliary Atresia
- Biliary atresia (BA) is a rare and severe inflammatory and obliterative cholangiopathy that affects both extra- and intrahepatic bile ducts 2.
- The causes of BA remain unknown, but several mechanisms, including genetic and immune dysregulation, may lead to the obliterative cholangiopathy 2.
- Growing evidence shows that BA is not a single entity with a single etiology but a phenotype resulting from multifactorial events whose common path is obliterative cholangiopathy 3.
- The etiology of BA has been explained as resulting from genetic variants, toxins, viral infection, chronic inflammation or bile duct lesions mediated by autoimmunity, abnormalities in the development of the bile ducts, and defects in embryogenesis, abnormal fetal or prenatal circulation, and susceptibility factors 3.
Important Points to Consider for Gathering History
- BA symptoms occur shortly after birth with jaundice, pale stools, and dark urines 2.
- Early diagnosis is very important since the chances of success of the Kasai procedure decrease with time 2.
- The prognosis of BA has dramatically changed in the last decades, with BA patient survival close to 90% with sequential treatment with Kasai operation ± liver transplantation 2.
- Histopathological findings in liver biopsies include the expansion of the portal tracts, with edematous fibroplasia and bile ductular proliferation, with bile plugs in duct lumen 4.
- The immune response also activates the expression of type 2 cytokines that promote epithelial cell proliferation and extracellular matrix production by nonparenchymal cells 5.
Key Factors in BA Pathogenesis
- Genetic predisposition has been proposed as a factor for the development of BA 4.
- Viral infection initiates biliary epithelium destruction and release of antigens that trigger a Th1 immune response, leading to further injury of the bile duct, resulting in inflammation and obstructive scarring of the biliary tree 4.
- Innate immunity plays a crucial role in the pathogenesis of BA, with macrophages adopting different functional programs and influencing the surrounding cytokine environment and cell response to injury 6.