Biliary Atresia - Clinical Tree

Introduction

Biliary atresia is a uniquely perinatal disease that 30 years ago would have been universally fatal. With the development of the palliative Kasai portoenterostomy (Morio Kasai, 1922–2008), along with advances in pediatric liver transplantation (first performed by Thomas Starzl, 1926–2017), survival into adulthood and long-term quality of life are excellent. Biliary atresia is the main indication for liver transplantation in pediatrics.

Biliary atresia is a rapidly progressive, obliterative, fibrosing cholangiopathy affecting the intrahepatic and rebreak: extra-hepatic bile ducts. It occurs throughout the world and affects all ethnicities; however, there are differences in the incidence of biliary atresia according to geographic location, with the incidence in Europe being about 1 in 17,000 to 20,000.

Although biliary atresia is usually an isolated developmental defect, there are other development anomalies in up to 15% of cases that require thorough evaluation before transplant ( Table 34.1 ). This is known as biliary atresia splenic malformation syndrome (BASM).

Table 34.1

Developmental anomalies associated with biliary atresia requiring evaluation before transplantation

Developmental Anomaly	Frequency (%)	Implications
Preduodenal portal vein	75	Alternative course of the portal vein
Polysplenia	90	May have splenunculi or asplenia
Situs inversus	50	Positioning of the graft
Malrotation	50	Risk of bowel infarction Consideration of roux loop position
Interrupted inferior vena cava	30	Azygous veins—may be dilated
Cardiac anomalies	30	Detailed cardiology and anesthetic review
Intrapulmonary shunting	5	Risk of hepatopulmonary syndrome in long-term survivors
Pancreatic anomalies	2-5	Alternative anatomy

The exact cause of biliary atresia remains unknown, but it is thought that a number of pathological processes may result in the same clinical phenotype of biliary atresia. A postulated pathogenesis includes viral infection, genetic polymorphisms, ciliopathy, autoimmune and alloimmune mediation, and toxins. There is no recurrence of the disease following transplantation.

Kasai Portoenterostomy

The Kasai portoenterostomy is a palliative operation aiming to reestablish bile flow. It is usually carried out using a transverse laparotomy incision following immediately after diagnostic operative cholangiography. The entire extrahepatic biliary tree is excised by transecting the bile duct remnant of the porta hepatis at the level of the liver capsule and exposing the remaining ductules. A jejunal Roux loop is anastomosed to the exposed cut surface to enable bile to enter the bowel.

A successful Kasai procedure is defined by the clearance of jaundice within 6 months, which in expert centers occurs in up to 60% of cases. If the Kasai procedure is not successful at establishing bile flow, liver transplantation will be required. Factors influencing successful bile flow include the following:

Age at Kasai—the success rates are lower when the Kasai procedure is performed at more than 6 weeks after birth.
Signs of chronic liver disease at the time of the Kasai procedure include ascites and intraabdominal varices.
Prematurity may perhaps be attributed to diagnostic difficulties or a more severe phenotype.
Concomitant cytomegalovirus (CMV) infection confers a worse prognosis.
Prophylactic antibiotics are used to reduce the risk of cholangitis within the first 3 months after birth.

However, the Kasai procedure is a palliative operation, because even with the clearance of jaundice, the intrahepatic bile ducts remain diseased, and chronic liver disease develops. Lifelong hepatology specialist follow-up will be required to manage the chronic liver disease and identify complications that will require liver transplantation; most patients with biliary atresia will require liver transplantation at some time. In patients who clear their jaundice and have their native liver at 2 years of age, up to 50% will survive to adulthood with their native livers but may need transplantation as adults. There is, however, a 6% risk of pre-transplantation mortality because of complications of chronic liver disease.

Liver Transplantation

Liver transplantation for biliary atresia is an excellent therapeutic option, with up to a 95% 5-year survival. It is curative for the liver disease. Survival rates and quality of life following transplantation are good.

However, children may clinically deteriorate while on the waiting list, despite adequate and complete medical management. The Eurotransplant registry suggests that those who require listing at a very early age (< 6 months) with advanced liver disease, as demonstrated by a high pediatric end-stage liver disease (PELD) score in 25% of cases, died while awaiting transplantation. This information aids in the prioritizing of patients. However, the PELD score does not accurately differentiate the severity of the liver disease in biliary atresia compared with other liver diseases.

It is important to provide support for families while awaiting transplantation, because patients may have a significant period of time on the liver transplantation waiting list.

Indications

Primary Transplantation

This is necessary if at presentation the child already has signs of advanced liver disease (e.g., hepatosplenomegaly, ascites, intraabdominal varices), because in this setting a Kasai procedure is unlikely to be successful and could potentially cause decompensation of liver function. This is more likely if the child presents late (> 10 weeks). However, if the child presents late but does not have advanced liver disease, the Kasai procedure may still be successful and mitigate the need for early transplantation.

Unsuccessful Kasai Procedure

If bile flow is not established following the Kasai portoenterostomy, liver disease progresses rapidly, and these children usually need a liver transplantation within the first 2 years of life ( Fig. 34.1 ). Bilirubin levels continuing to be elevated at 1 and 3 months following the Kasai procedure, as well as abnormal hepatic vascular flow, and have been shown to be predictive of the need for early transplantation; this should aid clinicians in identifying patients who would benefit from listing early after the Kasai procedure.

Fig. 34.1, A child with biliary atresia with a failed Kasai procedure. Shown is jaundice, a distended abdomen attributed to ascites, with protrusion of the umbilicus, and prominent abdominal veins. The abdomen is distended by ascites; the child’s arms and legs show cachexia because of her severe liver disease, despite receiving supplemental nasogastric tube feeding.

Success after surgery can best be judged by the restoration of bile flow and clearance of jaundice. At 3 months post Kasai, there is a clear difference in 2-year transplant-free survival between children with total serum bilirubin less than 2 mg/dL and those with total bilirubin more than 6 mg/dL (84% vs. 16%; P < .001). If the jaundice persists, the transplant-free survival at 3 years is only 20%. Therefore, it is prudent to evaluate for transplantation early to avoid the development of complications.

Recurrent Life-Threatening Cholangitis

A small number of children develop severe cholangitis, which is life threatening and requires intensive care support. In these cases, liver function and bilirubin levels may be normal; however, prevention of further episodes of life-threatening sepsis is by liver transplantation.

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