Biliary Atresia

Descriptive text is not available for this imageBASICS

DESCRIPTION

Biliary atresia (BA) is a disease of early infancy characterized by inflammation, fibrosis, obstruction, and obstruction of the extrahepatic biliary tree, followed by rapidly progressive liver injury and end-stage liver disease in the 1st year of life.

EPIDEMIOLOGY

  • BA occurs with variable geographical frequency ranging from 1:8,000 to 18,000 live births.
  • BA has a slight female predominance (1.25:1), especially in patients with splenic malformations.
  • BA has rare familial recurrence.
  • BA accounts for the most frequent indication for pediatric liver transplantations worldwide.

ETIOLOGY

Etiology is not completely defined, but many different pathogenic mechanisms have been proposed, including the following:

  • Viral infection: cytomegalovirus, human papilloma virus, human herpes virus 6, Epstein-Barr virus, reovirus, and rotavirus implicated, but identification of individual viruses in affected tissues has been inconsistent in different populations.
  • Immune dysregulation
  • Defective embryogenesis: might be genetically driven
  • Abnormal fetal or prenatal circulation
  • Environmental toxins: Biliatresone, a phytosterol, selectively destroys extrahepatic bile ducts in zebrafish larvae in a dose- and time-dependent manner.

RISK FACTORS

Genetics

Although gene mutations causally linked to BA in humans have not been identified, gene sequence variants as susceptibility factors continue to be investigated, but the biologic relevance of identified single nucleotide polymorphisms (SNPs) remain unknown.

PATHOPHYSIOLOGY

  • Biliary obstruction begins at, or near, the time of birth and progresses throughout early infancy, leading to damage and ultimately scarring of liver parenchyma.
  • There are four clinical phenotypes of BA:
    • ~80% of patients have the perinatal form or nonsyndromic BA. A subgroup of these patients might have single or multiple nonhepatic malformations (e.g., cardiovascular anomalies, intestinal malrotation).
    • Approximately 10% of patients have the embryonic form. Splenic abnormalities (asplenia, polysplenia, double spleen), in addition to interrupted inferior vena cava, midline liver, situs inversus, preduodenal portal vein, and intestinal malrotation, have been reported. Infants with this biliary atresia splenic malformation (BASM) syndrome have a higher association with maternal diabetes and a worse outcome following hepatoportoenterostomy (HPE).
    • <8% have a cystic variant.
    • The fourth phenotype is cytomegalovirus-associated BA.

There's more to see -- the rest of this topic is available only to subscribers.