Elsevier

Seminars in Neonatology

Volume 8, Issue 5, October 2003, Pages 383-391
Seminars in Neonatology

Biliary atresia

https://doi.org/10.1016/S1084-2756(03)00065-4Get rights and content

Abstract

Biliary atresia (BA) is a congenital obliterative cholangiopathy of unknown aetiology, affecting both the intra- and extrahepatic bile ducts. Although relatively rare, BA must be excluded in any infant with conjugated hyperbilirubinaemia since the prognosis is improved by early diagnosis and prompt surgery. At least two phenotypes of BA are currently recognized; the syndromic variety is associated with other congenital anomalies and a poorer outcome. The results of treatment have steadily improved and, with a combination of timely expert surgery (Kasai portoenterostomy) and liver transplantation in specialist centres, good quality long-term survival is now possible in more than 90% of affected patients. A better understanding of the aetiology of BA and the pathogenesis of hepatic fibrosis is needed in order to develop new therapeutic strategies.

Section snippets

Incidence

BA is rare. Reliable incidence figures are available from France (one in 19 500 live births), the UK and Eire (one in 16 700 live births), Georgia in the USA and Sweden (one in 14 000 live births).1, 2, 3, 4The highest recorded incidence is in French Polynesia.1No significant seasonal variation or clustering was found in the French study. In most large series, there is a slight female preponderance.

Aetiology and pathogenesis

Despite intensive interest and investigation, the cause of BA remains unknown. Two different forms are described.5In syndromic BA (also known as the embryonic type), there are associated congenital anomalies such as an interrupted inferior vena cava, preduodenal portal vein, intestinal malrotation, situs inversus, cardiac defects and polysplenia. In this variety, which accounts for about 10–20% of all cases, BA is likely to be due to a developmental insult occurring during differentiation of

Pathology

BA is a cholangiopathic disease affecting both the intra- and extrahepatic bile ducts. The lumen of the extrahepatic biliary tree is obliterated by inflammatory tissue to a variable extent. There are three main types of obliteration, of which type 3 (occlusion at the level of the porta hepatis) is the most common, occurring in almost 90% of cases. Atresia of the common bile duct (type 1) or common hepatic duct (type 2) with patent proximal ducts is much less common but carries a better

Clinical features and diagnosis

Although BA may occur in premature infants, birth weight and gestation are usually normal. Presenting features include conjugated hyperbilirubinaemia, dark urine and pale stools. Malabsorption of fat-soluble vitamin K may lead to coagulopathy and bleeding (which can be intracranial). On examination, the liver is usually enlarged and there may be splenomegaly.

Early diagnosis and prompt surgery improve the outcome of infants with BA. Neonatal jaundice that persists beyond two weeks of age demands

Screening tests

Only 0.04–0.2% of newborns have conjugated hyperbilirubinaemia due to cholestatic hepatobiliary disease. In an attempt to achieve earlier diagnosis of BA, various screening tests have been explored but none has satisfied criteria for widespread use. The use of tandem mass spectrometry to measure conjugated bile acids in dried blood spots from newborn infants has proved disappointing.27Gamma-glutamyl transpeptidase (GGT) is a hepatic enzyme which may be found in amniotic fluid from the second

Surgery

The diagnosis of BA is confirmed at laparotomy(Fig. 1). A cholangiogram is performed if there is doubt about ductal patency. The obliterated extrahepatic biliary tract is separated from the underlying portal vein and adjacent hepatic artery, and then transected high in the porta hepatis where patent microscopic biliary ductules may be present.30Biliary continuity is restored using a Roux loop of jejunum, which is anastomosed to the transected tissue (portoenterostomy). Infants tolerate the

Results of portoenterostomy

The results of surgery have steadily improved during the last 30 years. The age at which surgery is carried out is the single most widely quoted prognostic variable. Resolution of jaundice is more likely if surgery is performed at less than eight weeks of age, but this age correlation is not linear. Results are considerably worse if the infant is older than 100 days at the time of portoenterostomy32, 33because the obliterative cholangiopathy and hepatic fibrosis are more advanced. However, the

Long-term complications

In addition to the risk of progressive liver disease, numerous other complications may occur afterportoenterostomy for BA. These include:

  • bacterial cholangitis;

  • portal hypertension;

  • metabolic and nutritional sequelae;

  • intrahepatic cysts;

  • hepatopulmonary syndrome;

  • hepatic malignancy.

Prognostic markers

From the preceding account, it is apparent that the Kasai procedure revolutionized the treatment of BA, but numerous complications may still jeopardize long-term outcome. Can long-term prognosis after portoenterostomy be determined at an early stage? Rapid resolution of jaundice and complete normalization of biochemical liver function are associated with a good long-term outcome but this scenario is uncommon. Conventional biochemical liver function tests are neither specific nor particularly

Conclusions

BA is a rare, complex disorder and demands expert multidisciplinary management. Despite progressive improvement in the results of treatment, the condition is extremely distressing for parents and families who not only face the anxieties of newborn surgery with an uncertain outcome, but also the possibility of eventual liver transplantation and its attendant risks. Parental education and support is essential, and charities such as the Children's Liver Disease Foundation (//www.childliverdisease.org

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