Biliary atresia

Dr Catarina Jackson

George, a 3-week-old boy, is referred to the paediatric assessment unit for prolonged jaundice. He was born at term via normal vaginal delivery and mum had a normal pregnancy. After delivery he was noted to be jaundiced but his bilirubin level was below the treatment line. He was discharged home with follow up from the community midwife. He remained jaundiced after two weeks of age and was referred back to hospital after review from the community midwife. His investigations pointed towards a diagnosis of biliary atresia and he was transferred to a tertiary centre for corrective surgery.

Biliary atresia is a progressive inflammatory process, of part or all, of the extra-hepatic bile ducts leading to biliary obstruction and jaundice.

Why is it important we recognise biliary atresia?

Common cause of liver-related death in the paediatric population
Most frequent indication for liver transplantation in children
Early identification and treatment generally lead to a better outcome for the patient and family

The incidence of biliary atresia can range anywhere from 1:5,000 to 1:19,000 births. It has been noted to occur more commonly in Asian countries like Taiwan and Japan. A small number of cases are associated with other congenital abnormalities; 10-15% of all biliary atresias are associated with the splenic malformations (Biliary Atresia Splenic Malformation Syndrome, BASM).

Screening for biliary atresia?

Currently, there is no dedicated biliary atresia screening programme in the UK. However the routine assessment for any infant with prolonged jaundice should technically include this. Interestingly, a study in Taiwan showed that a simple stool colour card provided to parents at birth was successful in earlier identification of patients with biliary atresia.

Classification

This describes the macroscopic appearance of the extra hepatic ducts and is based on the level of the most proximal obstruction:

Type 1 (5%) – Atresia limited to common bile duct
Type 2 (2%) – Atresia to the common hepatic duct
Type 3 (>90%) – Discontinuity of the entire extra hepatic biliary tree

Pathogenesis

Biliary atresia is a cholangiopathy that many believe is likely evolving from birth. It is a progressive condition that ultimately results in liver cirrhosis. The exact aetiology of biliary atresia remains unknown, but several theories exist.

Genetic – There is no evidence that biliary atresia is an inherited disease per se, but it is possible that some genetic factors could play a role in its aetiology. In addition, we can imagine that during fetal development it is possible that the genes regulating the morphogenesis of these structures may be altered, leading to the disease after birth. In BASM, studies have shown a mutation in the CFC-1 gene in a small number of cases.
Infection – Several viruses have been implicated in the aetiology of biliary atresia including HPV, RSV, CMV, rotavirus and EBV. Although the possibility of pre-or perinatal infection causing an immune reaction leading to bile duct injury is entirely plausible, so far studies have struggled to evidence this.
Immunology – There is abnormal expression of Class II antigens and cytokines with an infiltration of activated CD4+ve lymphocytes and CD56+ve natural killer cells, suggestive of proinflammatory cytokine pathway.

Clinical features

The most important clinical feature is prolonged jaundice (after 14 days in term infants, 21 days in preterm infants). Other signs include pale stools and dark urine. It is good practice to remember a wide range of differential diagnoses when assessing a baby with prolonged jaundice.

Gastrointestinal	Choledochal cyst, Neonatal hepatitis, Biliary atresia
Infection	UTI, CMV, Hepatitis B, HSV
Metabolic	Galactosaemia, Tyrosinaemia, Lipid storage disease
Genetic	Alpha-1-antitrypsin deficiency, Progressive familial cholestasis, Alagille syndrome, Cystic fibrosis, Trisomy 21
Endocrine	Hypothyroidism, Hypopituitarism
Other	Breast milk jaundice

Diagnosis

Liver function tests – showing raised conjugated bilirubin and liver enzymes (especially GGT)
Ultrasound scan – may demonstrate an enlarged liver with a contracted or absent gallbladder

If intra-hepatic duct dilatation is present this indicates an alternative diagnosis to biliary atresia.

Liver biopsy – diagnostic in about 80% of cases showing cholestasis, portal tract oedema, bile duct plugging and proliferation
ERCP – May be considered if the former are inconclusive

Management

Initial Management in DGH

Referral and discussion with tertiary centre
Repeat conjugated/unconjugated bilirubin and consider starting first line investigations as per BSPGHAN guidelines
Consider IV antibiotics if patient is septic
Consider IV fluids for transfer if patient is dehydrated

Kasai Portoenterostomy

^{Image source: https://www.saintlukeskc.org/health-library/treatment-your-childs-biliary-atresia-kasai-procedure}

The Kasai procedure involves the construction of a new bile drainage system to restore bile flow. The procedure consists of initially confirming the diagnosis by inspecting the hepatobiliary system and assessing the degree of damage and presence of any other anomalies. The liver is then mobilised and the porta hepatis is dissected. The Roux Loop (anastomosis) is prepared and a portoenterostomy is created between the porta hepatis and jejunum. This then enables bile to drain directly into the jejunum.

A successful procedure is identified by jaundice clearing with normal bilirubin levels being achieved within 6 months. Most patients with a successful procedure (80%) may survive over 10 years without needing a transplant.

Complications following Kasai Procedure:

Vitamin deficiencies
Ascending cholangitis
Portal hypertension
Hepatopulmonary syndrome
End-stage liver failure

Liver Transplantation

Unfortunately, liver transplantation is often required in patients with biliary atresia and its timing depends on the success of the Kasai procedure and presence/severity of any late complications. Infants who present late (>100 days) with established cirrhosis are commonly considered for primary liver transplantation as their chances to achieve effective biliary drainage and avoid medical complications are deemed rather low.

Key learning points

Any baby with prolonged jaundice should have a full assessment in hospital including conjugated/unconjugated bilirubin
Further research into aetiology is needed but it is likely a combination of genetic, immunological and environmental factors
Kasai procedure has improved survival in biliary atresia patients, however, the sooner it is performed the better