Biliary atresia
Key points
Definition
Progressive, destructive, obliterative, inflammatory and sclerosing cholangiopathy
Affecting varying lengths of intra and extra hepatic biliary tree
In the neonate
Epidemiology
1:4-20000 in UK
1:1000 in Japan and Taiwan
Unique to neonatal period
No analogous pathological process exists in older children or adults
If left untreated, progressive liver cirrhosis leads to death by age 2 years
Commonest cause of liver transplant in children
Classification: Depends on the site of most proximal obstruction
Type 1 (12%) obstruction in common bile duct (CBD)): Cystic Biliary Atresia
Type 2 (2%) obstruction in common hepatic duct
Type 3 (85-90%) porta-hepatic obstruction
Aetiology
Congenital: Primary failure to form lumen or insufficient functional intrahepatic bile ducts as in Cystic Biliary Atresia and BASM (Biliary Atresia Splenic Malformation)
Acquired: Normally developed bile duct is damaged later, with secondary loss of luminal continuity -
Viruses linked to acquired biliary atresia (BA):
Cytomegalovirus (CMV)
Rotavirus
Reovirus
Human papilloma virus
Not hepatitis viruses
Markers in BA:
Osteopontin, basic fibroblast growth factor and hepatocyte growth factor - associated with BA progression
Raised transforming growth factor-β - improved outcomes
Presentations
Antenatal: Rarely diagnosed antenatally - 95% nil antenatal findings
Cystic biliary atresia (cyst formation within obliterated biliary tree) may be visible on 20 week USS - differentials of Choledochal malformation, duplication cyst - MRI may be helpful
Post Natal: Obstructive Jaundice in the first few weeks of life
Clinical: Jaundice, Acholic stool, dark urine
Biochemical: Conjugated hyperbilirubinemia, increased Gamma Glutamyl Transferase, Aspartate Transaminase (Other markers of progressive liver failure)
Important differentials of obstructive jaundice
Medical causes: Neonatal hepatitis, Cystic Fibrosis, Alpha 1 anti-trypsin deficiency, Alagille’s Syndrome
Surgical causes: Biliary atresia, Choledochal malformations, Inspissated bile syndrome, Spontaneous bile duct perforation
Associations
(BASM) (6%) Biliary atresia splenic malformation e.g. polysplenia, asplenia - CFC1 mutation predisposition
Structural cardiac abnormalities (e.g. isomerisms, malrotation, duodenal atresia, renal agenesis, situs inversus, preduodenal portal vein, hepatopulmonary syndrome/pulmonary hypoplasia
Absent IVC can also be seen, which is important in future if a liver transplant needs to be done
BSPGHAN guidelines investigations
Conjugated bilirubin will be abnormal from 1 hour of life
Most but not all will have raised GGT
1st stage investigations (Non-specialist centre)
Conjugated fraction
FBC, INR, Albumin, Metabolic, infection screen (TORCH toxoplasmosis, others (syphilis, hepatitis B), rubella, cytomegalovirus, herpes), HIV, thyroid finction, cystic fibrosis screen
USS after 4 hour fast to look for causes other than biliary atresia
2nd Stage (Liver unit)
MDT decision for either:
HIDA Scan (3-5 days pre scan phenobarbitone) - 99mtechnetium into the intestine from the liver proves patency of the bile duct. Can only exclude BA, not diagnose it. High false positive rate and/or Biopsy
Primary laparotomy and cholangiogram is gold standard investigation
Histology
Liver biopsy features of BA:
Portal fibrosis
Ductal bile plugs
Inflammatory cell infiltrate
Portal stromal oedema
Ductular proliferation
Biopsy cannot reliably distinguish BA from neonatal hepatitis
If taken before age 6 weeks - can be false negative
Radiology
USS Findings :
Liver: homogenous then irregular
Gallbladder: dilated, atrophic, abnormal, absent
Biliary Tree: no intra hepatic dilatation, triangular cord sign: (obliterated extra hepatic duct - >4mm thickness of echogenic anterior wall of right portal vein)
Hepatobiliary iminodiacetic acid scan (HIDA)
Negative HIDA = excretion of tracer into duodenum at 24h - shows patency of the common bile duct and ampulla. Presence of tracer in the bowel effectively rules out biliary atresia.
Positive = Gallbladder does not take up 99mTc-HIDA. However there is a high false positive rate as neonatal hepatitis may also cause this picture
Management
Earlier the intervention, the better the outcome. Ideally 100 days,
May need primary liver transplant , especially if signs of cirrhosis and/or portal hypertension
Kasai portoenterostomy (KPE)
Laparotomy - 1-2cm RUQ incision 1 finger breadth above umbilicus - inspect and palpate liver - aspirate gallbladder - if no bile, or no gallbladder, confirms diagnosis (Type 1 is obstruction in CBD, may have bile in GB)
Do cholangiogram - use 6Fr NG tube
Then enlarge incision and deliver liver - dissect porta-hepatic bile ducts away from vessels and excise, creating a raw surface on the porta-hepatic
Then raise roux loop, hoping that microscopic biliary ducts are transected
Jejunal resection 10-20 cm distal to DJ flexure.
Needs at least 20 - 40cm roux limb to prevent ascending cholangitis
Complications
Of the diagnosis: Delayed, missed or wrong diagnosis
Of the pathology: Cirrhosis, Portal Hypertension, Hepatopulmonary syndrome, malignancy
Of the Surgery: Intra-operative complications, vascular injury, Cholangitis, anastomotic stricture, failure to clear the jaundice
Outcomes of KPE
Clearance of jaundice rate (bilirubin < 20umol/L) in UK - 66%
1% Hepatocellular carcinoma rate at 2 years (KCL series Hadžić et al)
Native liver survival at 5 years - 56%
70% need transplant before adulthood
10 year survival of >90% with Split donor graft
Improved outcomes associated with increased surgeon experience and younger patient at operation
Worse outcomes associated with polysplenia and the presence of cirrhosis at the time of KPE
Severe portal hypertension and cirrhosis are only indicators for transplant
Alagille's syndrome
JAG1 (also sometimes found in BA) or NOTCH 2 mutation - autosomal dominant
Biliary hypoplasia
Stenosis and congenital paucity of intrahepatic bile ducts
Delayed HIDA scan transit in to bowel
Pulmonary stenosis
Butterfly vertebra
Standard scenario
Concern of biliary atresia - jaundiced neonate
Medical team to do BSPGHAN 1st stage investigations - medical causes
Conjugated bilrubin fraction
USS - triangular plate sign, choledochal cyst
Transfer to liver unit
MDT for HIDA scan (needs phenobarbitone) or exploratory mini laparotomy + cholangiogram (+/- biopsy)
Proceed to KPE
Post op:
Watch for cholangitis
Check jaundice clearance
Post op meds:
Ursodeoxycholic acid
Septrin
Vitamins ADEK
Prednisolone - Trial: 15% better jaundice clearance
Page edited by Prof. Ashok Daya Ram MBBS, FRCS, FRCPS, FEBPS, FRCS (Paed Surgery), Consultant Paediatric and Neonatal Surgeon, Norfolk and Norwich University Hospital, Norwich, UK. December 2024
References
Siddiqui AI, Ahmad T. Biliary Atresia. [Updated 2023 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537262/
Mack CL. The pathogenesis of biliary atresia: evidence for a virus-induced autoimmune disease. Semin Liver Dis. 2007 Aug;27(3):233-42. doi: 10.1055/s-2007-985068. PMID: 17682970; PMCID: PMC3796656.
Guideline for the Investigation of Neonatal Conjugated Jaundice Liver Steering Group, BSPGHAN Revised December 2016
Snyder E, Kashyap S, Lopez PP. Hepatobiliary Iminodiacetic Acid Scan. [Updated 2023 Jul 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539781/
Thakkar, Davenport - EPIPS podcast https://soundcloud.com/epips/epips-4-biliary-atresia-with-professor-mark-davenport
Hadžić N, Quaglia A, Portmann B, Paramalingam S, Heaton ND, Rela M, Mieli-Vergani G, Davenport M. Hepatocellular carcinoma in biliary atresia: King's College Hospital experience. J Pediatr. 2011 Oct;159(4):617-22.e1. doi: 10.1016/j.jpeds.2011.03.004. Epub 2011 Apr 13. PMID: 21489554.
Diaz-Frias J, Kondamudi NP. Alagille Syndrome. [Updated 2023 Aug 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507827/