Management of adult survivors of biliary atresia

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Abbreviations

BA

biliary atresia

HCC

hepatocellular carcinoma

HPS

hepatopulmonary syndrome

Biliary atresia (BA) is a fibroinflammatory, obliterative disorder of bile ducts whose underlying cause is not yet adequately understood. It presents with jaundice during the early weeks of life, with an incidence of 0.5 to 0.75 cases per 10,000 live births in North America and Europe, and 1.1 per 10,000 in Japan.1 BA was uniformly fatal before an effective therapeutic approach was devised, which now enables the majority of affected children to survive. Initial treatment is with the Kasai portoenterostomy in the newborn period (Fig. 1), with subsequent liver transplantation if indicated for deteriorating liver function or other intractable complications.

Figure 1.

Anatomy of the Kasai portoenterostomy.

Widespread application of this approach to treatment has led to increasing numbers of affected children entering adulthood and seeking ongoing care from adult hepatologists (Fig. 2). Many of these patients undergo liver transplantation as children, but this review will focus on the clinical status and management priorities for the minority of affected patients who survive to adulthood with their native liver.

Figure 2.

Survival in 271 infants who underwent the Kasai portoenterostomy operation for biliary atresia between 1968 and 1982. In the dataset represented above, patients were not censored at the time of liver transplant. From Lykavieris et al.2

Severity of Liver Disease in Adults With BA and Their Native Liver

Between 23% and 44% of children with BA survive to 20 years of age with their native liver.2, 3, 4, 5 The likelihood of achieving long‐term, transplant‐free survival is increased by earlier age of Kasai portoenterostomy in infancy, absence of major extrahepatic congenital anomalies, and presence of atresia that only affects the more proximal common hepatic ducts (with patent common bile duct).3 Interestingly, in one series of adults with BA, risk factors for the development of new‐onset deterioration in liver function after 20 years of age still included variables related to their initial disease course and management in infancy (age at Kasai, time to clearance of jaundice after Kasai, and early episodes of bacterial cholangitis).6

The clinical status of adults with BA and their native liver can be characterized as follows:2, 3, 4

• Cirrhosis is present in 49% to 79%.

• Portal hypertension is present in 46% to 97%.

  • ○ Esophageal and/or gastric varices in approximately 35%.

  • ○ Gastrointestinal bleeding episodes during adult follow‐up in 4% to 17%.

  • ○ Although BA is classically associated with biliary cirrhosis, noncirrhotic portal hypertension has also been reported in adults with BA.7

• Bacterial cholangitis occurs in 21% to 37% during adulthood.

  • ○ Increased risk with obstruction at the Kasai portoenterostomy.

  • ○ May occur in association with evidence of sclerosing cholangitis on imaging, found in 60% in one adult case series.7

  • ○ Intrahepatic ductal gallstones are reported in 6% to 22% of adult survivors of BA, sometimes asymptomatic but often in association with recurrent cholangitis.

• Other complications have been rarely reported in adults with BA, including:

  • ○ Hepatopulmonary syndrome (HPS). Although reports of HPS in adults are scarce, systematic study of its incidence has not been undertaken.

  • ○ Hepatic malignancies. Children with BA are at risk of hepatocellular carcinoma, with an incidence of 0.8% to 1.3%.8 Rare cases of cholangiocarcinoma have also been reported. The risk of malignancy is expected to persist and increase through adulthood.

Associated Extrahepatic Anomalies

Major extrahepatic anomalies are found in approximately 16% of patients with BA.9 Of the numerous defects that have been described, many will have ongoing importance during adult life (Table 1).

Table 1.

Congenital Anomalies Commonly Associated With BA

Cardiac	Atrial isomerism
	Aortic arch abnormalities, coarctation
	Atrial or ventricular septal defects
	Pulmonary artery or valve stenosis
	Tetralogy of Fallot
Vascular	Interrupted inferior vena cava
	Preduodenal portal vein
	Absence of portal vein
	Hepatic artery anomalies
Laterality defects	Situs inversus
Gastrointestinal	Esophageal atresia
	Malrotation
	Atresia of duodenum or jejunum
	Anorectal anomalies
	Annular pancreas
Spleen	Polysplenia
	Asplenia
Genitourinary	Cystic kidneys
	Hydronephrosis

Growth, pubertal development, and onset of menarche generally occur within normal limits, although they may be delayed in those with severe disease. The normal accrual of bone mineral density during childhood may be impaired by chronic cholestatic liver disease.

Pregnancy

Numerous successful pregnancies have been reported in women with BA and their native liver. Overall, there appears to be no excess incidence of fetal abnormalities, although isolated cases have been reported. Most women with BA have a transient elevation of liver enzymes during their pregnancy. Maternal complications include variceal bleeding (up to 20%) and hepatic decompensation requiring urgent liver transplantation either during pregnancy or in the postpartum period.10

Quality of Life

Health‐related quality of life in adult BA survivors has rarely been studied by utilizing validated questionnaires. One report compared patients in the United Kingdom and Japan with previously published normative data using the Short Form 36 (Rand Corporation, Santa Monica, CA) and revealed deficits in general health perception, role limitations due to either physical or emotional problems, and social functioning.11 Other case series show the vast majority of patients to be successful in obtaining employment or in attending higher education institutions. Detailed studies of the neurodevelopmental status of adult BA survivors have not been undertaken; however, in the available published experience, only occasional patients suffer significant neurodevelopmental delays requiring special arrangements for care.

Recommendations for Management of Adults With BA and Their Native Liver

As with all patients with cirrhotic or progressive liver disease, management is multi‐faceted and complex. Selected areas to highlight include the following:

1. Monitor for signs of deterioration of liver function at regular intervals whose frequency is dictated by the severity of the underlying liver disease in each individual patient. Liver transplantation should be considered for patients with deterioration of synthetic function or with treatment‐refractory or progressive complications (see below).

2. Treat suspected bacterial cholangitis promptly with intravenous broad‐spectrum antibiotics. Seek risk factors for recurrent cholangitis, including strictures in the intrahepatic bile ducts or at the Kasai portoenterostomy and the presence of obstructive intraductal gallstones. Optimal approaches to the management of these biliary complications have not been defined. Accessing and dilating strictures at the Kasai site is a major challenge, remembering that the original surgery was not a choledocho‐jejunal anastomosis but instead involves suturing of the intestine over a raw cut surface of liver at the porta hepatis. Strictures and stones have been reported to recur after operative intervention. Long‐term prophylactic antibiotics are commonly prescribed in infancy to prevent recurrent cholangitis, but the balance of risks and benefits in older patients with BA has not yet been defined.

3. Screen for complications of cirrhosis and provide appropriate management according to published guidelines (e.g., American Association for the Study of Liver Diseases Clinical Practice Guidelines), including the following:

   1. Esophageal varices

   2. Hepatic malignancies

   3. HPS

   4. Encephalopathy

4. Whenever possible, undertake prepregnancy evaluation of liver disease severity, presence of varices, and status of other associated anomalies (e.g., congenital heart disease). Monitor hepatic status closely throughout pregnancy, and be prepared for significant deterioration and need for urgent listing for transplantation.

5. Ensure that associated extrahepatic anomalies are identified and plans for their ongoing management are in place, in collaboration with appropriate subspecialists where necessary.