The single most common cause for liver transplantation in children is biliary atresia, therefore making it the most significant pediatric liver disease. Over 40% of pediatric liver transplants in the United States are performed on account of this diagnosis.
The prevalence of biliary atresia is between 10,000 – 15,000 live births. It often occurs in thriving infants who are full-term and of normal birth-weight. Particularly, biliary atresia has a slight predilection for afflicting girls more than boys, and affecting African-Americans and Asians more frequently than other ethnic groups.
Biliary atresia is an obstructive biliary tract disease. It results from a progressive sclerosing and the inflammation of the bile ducts from the point of duodenal entry to the intrahepatic bile ducts during the first three months of life. This process invariably results in biliary cirrhosis. Two clinical types have been described:
- perinatal acquired form, which is thought to occur postnatally;
- embryonic/fetal form, which is thought to result from biliary agnesis.
The latter is associated with congenital malformations such as polysplenia, dextrocardia, absence of inferior vena cava, portal vein anamolies, intestinal malrotation and/or ectopic pancreas. Both pathologic forms present similarly in terms of age and biochemical tests (i.e. bilirubin, alkaline phostphatase, or y-GT).
Several different processes have been proposed to explain this pathologic occurrence, but none have been demonstrated consistently to correlate with the disease. The various causes have been described as, to name a few:
- genetic factors, such as HLA-B8, and DR3;
- environmental/viral factors, including CMV, reovirus, rotavirus, retrovirus, HPV, HHV-6;
- immune deregulation, such as ANCA and maternal anti-Rho;
- developmental genes of the biliary tree, such as JAGGED-1 and HNF-6.
Infants with biliary atresia present during their first month of life with mild jaundice, scleral icterus, pale stools, and hepatomegaly. Given that often times these infants are otherwise thriving, the disease can be missed or misdiagnosed as ‘breast-milk jaundice.’
Since many separate causes present identically, a multi-level evaluation must be completed from the outset. Investigations to rule out anatomic anomalies, infection, metabolic causes, and genetic etiologies should be performed. Biliary scintigraphy and a confirmatory liver biopsy should be executed before the age of two months given that the success of the primary therapy for biliary atresia, the surgical reestablishment of biliary drainage via a Kasai roux-en-y portoenterostomy (KPE), depends on early intervention. The diagnosis is suspected on biochemical, nuclear scintigraphic, and histological grounds, but it is ultimately established by intra-operative cholangiogram.
Without intervention, the survival rate of biliary atresia approaches zero at 5 years of age. Only one-half of patients are alive with their native liver at 18-24 months. Moreover, approximately one-third of those receiving a KPE will remain transplant-free until the age of ten years. Patient survival with their native liver to adulthood is the exception.
Most children with a poorly functioning KPE require liver transplantation. The most common complications after KPE are cholangitis, failure to thrive and those relating to portal hypertension including ascites, variceal hemorrhage, hepatopulmonary or portopulmonary syndrome, hepatorenal syndrome, poor quality of life, and pruritis.
However, there is good news! Liver transplantation has significantly altered the natural history of biliary atresia. Multiple patient series have shown ten-year patient survival rate after liver transplant to be approximately 85-90%.