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Developmental anomalies / cysts

Extrahepatic biliary atresia


Editorial Board Member: Monika Vyas, M.D.
Deputy Editor-in-Chief: Aaron R. Huber, D.O.
Manju Ambelil, M.D.

Last author update: 22 June 2023
Last staff update: 5 July 2023

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PubMed Search: Extrahepatic biliary atresia

Manju Ambelil, M.D.
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Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2
Cite this page: Ambelil M. Extrahepatic biliary atresia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/liverextrahepaticbiliaryatresia.html. Accessed April 25th, 2024.
Definition / general
  • Biliary atresia or obliterative cholangiopathy is a multifactorial fibrosing and destructive disease that involves both extrahepatic and intrahepatic bile ducts
  • Common cause of pathologic infant jaundice that presents in the initial few weeks of life
Essential features
  • Clinically presents as cholestatic jaundice of infants with normal gestational age
  • Radiologic evidence of absent or atretic gallbladder
  • Obstructive pattern of injury featuring extensive bile ductular reaction, portal edema, mixed portal inflammation, bile plugs in ductules, portal fibrosis and lobular cholestasis
Terminology
  • Extrahepatic biliary atresia
ICD coding
  • ICD-10: Q44.2 - atresia of bile ducts
Epidemiology
  • More frequently seen in Asian countries; incidence ranges from 1 in 5,000 - 10,000 (Taiwan and Japan) (J Autoimmun 2016;73:1)
  • 1 in 15,000 - 20,000 in Europe and North America (J Pediatr 2017;187:253)
  • Most are term infants with normal birth weight
Sites
  • Both extra and intrahepatic bile ducts are affected
  • Based on the level of injury, it is further divided into 3 types (Ann Surg 2011;254:577)
    • Type 1 (~5% of cases)
      • Atretic common bile duct
      • Patent right and left hepatic ducts and common hepatic duct
      • Gallbladder often has bile
    • Type 2 (~2% of cases)
      • Atresia within common hepatic duct
      • Gallbladder is empty
    • Type 3 (> 90% of cases)
      • Atresia of porta hepatis area (proximal portions of extrahepatic biliary tract)
      • Gallbladder atretic
Pathophysiology
  • Inflammatory destruction of extrahepatic biliary system in genetically susceptible individuals
Etiology
  • Exact etiology is not known
  • Suggested mechanisms include (Pediatr Transplant 2005;9:646)
    • Genetic defects in morphogenesis and development
      • Associated anomalies seen in 20% of cases
      • Most common is polysplenia or asplenia (biliary atresia splenic malformation syndrome)
      • Other associated malformations include absent inferior vena cava, cardiac anomalies, situs inversus, intestinal malrotation, duodenal atresia and anomaly of the portal vein
    • Cystic biliary atresia
      • Comprises 5 - 10% of patients and is identified on antenatal ultrasound in ~50% of cases
    • Defective prenatal hepatic circulation
    • Viral infections
      • Cytomegalovirus (CMV)
      • Rubella
      • Rotavirus
    • Intrauterine or perinatal toxin exposure
    • Immunologic dysfunction
Clinical features
  • Persistent neonatal jaundice (Lancet 2009;374:1704)
  • Dark urine, pale stools and failure to thrive
  • Clinical phenotypes include
    • Fetal / embryonal or prenatal form
      • 10 - 35% of cases
      • Symptoms start shortly after birth
      • Associated with extrahepatic developmental anomalies
    • Perinatal or acquired form
      • 65 - 80% of cases
      • Jaundiced after a few weeks of birth
      • No associated congenital anomalies
Diagnosis
  • Ultrasound
  • Hepatobiliary iminodiacetic acid (HIDA) scan (Trop Gastroenterol 2012;33:62)
  • Percutaneous liver biopsy
    • Shows histologic evidence of biliary obstruction
  • Intraoperative cholangiography (Pediatr Surg Int 2006;22:140)
    • Confirmatory procedure before surgical intervention
  • Limited diagnostic role for endoscopic retrograde cholangiopancreatography
Laboratory
Radiology description
  • Absent or atretic gallbladder on ultrasound
  • HIDA scan findings include good hepatic intake with reduced / failure to excrete into intestine
    • Specificity of this finding is low as absent excretion can be seen in other pediatric cholestatic liver disease
  • Reference: Trop Gastroenterol 2012;33:62
Prognostic factors
  • With Kasai portoenterostomy (KPE), ~35% of patients with a native liver survive > 10 years (J Pediatr Gastroenterol Nutr 2019;69:416)
  • Recurrent episodes of ascending cholangitis and sepsis in those who do not respond to Kasai portoenterostomy
    • Progression to cirrhosis with portal hypertension and required orthotopic liver transplantation
  • Patient survival after transplantation is ~85% at 10 years
Case reports
Treatment
  • Kasai portoenterostomy
  • Liver transplantation
Gross description
  • Dark green and nodular explanted liver
Gross images

Contributed by Qian Wang, M.D., Ph.D.

Nodular liver



Images hosted on other servers:

Rock hard, dark green liver

Microscopic (histologic) description
  • Histologic findings vary in the course of disease
    • Nonspecific findings in early biopsies
      • Variable cholestasis
      • Extramedullary hematopoiesis
      • Little bile ductular proliferation
  • Portal tracts (Am J Surg Pathol 2016;40:1601, Clin Gastroenterol Hepatol 2011;9:357)
    • Portal edema
    • Bile ductular proliferation
    • Bile plugs / ductular cholestasis
    • Mixed portal inflammation
    • Prominent hepatic arteriole
    • Portal and periportal fibrosis
      • Progress to bridging and cirrhosis in later stages of disease
  • Hepatic lobules
    • Cholestasis
    • Minimal inflammation
    • With or without hepatocyte giant cell transformation
    • With or without extramedullary hematopoiesis
  • Hilar plate
    • Fibrosis
    • Small sized or obstructed bile ducts
    • Variable periductal inflammation
Microscopic (histologic) images

Contributed by Manju Ambelil, M.D., Jialing Huang, M.D., Ph.D. and Albina Joldoshova, M.D.
Ductular reaction and portal inflammation

Ductular reaction and portal inflammation

Ductular reaction

Ductular reaction

Explanted liver

Explanted liver

Hilar plate

Hilar plate

Prominent hepatic artery

Prominent hepatic artery

Trichrome

Trichrome

Positive stains
  • CK7, CK19: positive expression in bile ductular proliferation
  • CD56 / NCAM: proliferating ductules in most cases of extrahepatic biliary atresia are positive
Molecular / cytogenetics description
  • Mutations leading to laterality defects like CFIC and ZIC3 are identified in ~10% of biliary atresia patients (J Hepatobiliary Pancreat Sci 2013;20:459)
  • JAG1 gene has also been associated with the pathogenesis of biliary atresia
Sample pathology report
  • Liver, needle core biopsy:
    • Bile ductular reaction with lobular cholestasis (see comment)
    • Comment: Portal tracts expanded with edema, extensive bile ductular reaction and rare ductules with bile plugs. The lobules show cholestasis with minimal inflammation and rare hepatocyte giant cell transformation. The findings are compatible with biliary atresia. Other possibilities include large duct obstruction, total parenteral nutrition associated cholestasis and alpha-1 antitrypsin deficiency.
Differential diagnosis
  • Choledochal cyst:
    • Thick fibrous wall without much inflammation
    • Minimal bile ductular reaction
    • Imaging findings are helpful
      • No area of atresia
      • Normal appearing gallbladder
  • Alpha-1 antitrypsin deficiency:
    • Decreased serum alpha-1 antitrypsin level
    • PASD positive cytoplasmic globules may not be seen in infants < 3 months old
  • Total parenteral nutrition associated cholestasis:
    • Clinical history of total parenteral nutrition
  • Neonatal hepatitis:
    • Notable giant cell transformation with mild cholestasis
    • Focal or mild bile ductular reaction
  • Alagille syndrome:
    • Ductular reaction is typically absent but rare examples present with ductular reaction in early infancy
    • Paucity of intrahepatic bile ducts
    • Characteristic clinical manifestations of Alagille syndrome
  • CMV infection:
    • Presence of viral inclusions
    • Serum PCR for CMV viremia
  • Progressive familial intrahepatic cholestasis type 3 (PFIC3):
    • Age at onset varies from infancy to 20 years
    • Elevated gamma glutamyl transferase, unlike PFIC1 and PFIC2
    • Histologic findings are similar to biliary atresia including expanded portal tracts with extensive bile ductular reaction
    • Mutations in ABCB4 gene which codes for MDR3
Board review style question #1


A 6 week old term female infant presented with jaundice and dark urine. Liver function tests revealed conjugated hyperbilirubinemia and elevated gamma glutamyl transferase levels. No gallbladder was visualized on ultrasound abdomen examination. Liver biopsy image is shown above. What is the diagnosis?

  1. Biliary atresia
  2. Choledochal cyst
  3. Neonatal hepatitis
  4. Paucity of bile ducts
Board review style answer #1
A. Biliary atresia. The patient is presenting with jaundice, cholestatic pattern of liver function test, nonvisualization of gallbladder by imaging and biopsy finding of bile ductular reaction with bile plug. This is likely due to biliary atresia. Answer B is incorrect because in a choledochal cyst, usually the gallbladder appears normal by imaging. Bile ductular reaction in choledochal cysts is usually mild. Answer C is incorrect because of the absence of prominent giant cell transformation and bile ductular reaction is usually mild. Answer D is incorrect because ductular reaction is typically absent in paucity of bile ducts.

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Reference: Extrahepatic biliary atresia
Board review style question #2
Which of the following therapies is offered first for infants diagnosed with biliary atresia?

  1. Kasai portoenterostomy
  2. Liver transplant
  3. Steroids
  4. Ursodeoxycholic acid
Board review style answer #2
A. Kasai portoenterostomy establishes bile flow in the majority of infants. Kasai portoenterostomy is not curative but establishes bile flow in the majority of infants and is an important bridge to liver transplantation. Answer B is incorrect because a liver transplant is not the first therapy option offered; it is done as an initial option in those not responsive or who fail Kasai portoenterostomy. Answer C is incorrect because medical management with steroids is not a standard treatment option for biliary atresia. Answer D is incorrect because medical management with ursodeoxycholic acid is not a standard treatment option for biliary atresia.

Comment Here

Reference: Extrahepatic biliary atresia
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