Although biliary atresia is a rare disorder, it is the most common surgically correctable liver disorder in infancy. The most accurate estimates of national prevalence come from the United Kingdom and France, where 1 in 17,000–19,000 live-born infants are affected.1, 2 East Asian countries are most commonly affected, with a reported frequency of 1 in 5000 in Taiwan.3 Other reported estimates are 1 in 15,000 in the southeastern United Sates4 and 1 in 19,000 in the Netherlands.5 Within these regions, there appears to be a higher incidence of the disease in non-white populations (African American, French Polynesian, and Chinese) and among females (1.25:1).6, 7
Up to 20% of all cases of biliary atresia are associated with other anatomical abnormalities, suggesting that the pathologic process begins in the embryonic period. The most common congenital cluster of malformations is biliary atresia splenic malformation (BASM)syndrome, seen in approximately 10% of European and US series. BASM includes biliary atresia in association with polysplenia (90%), situs inversus (50%), and unusual vascular anomalies. In utero, there may also be an association with maternal diabetes and genetic anomalies such as trisomy 18 and 21.
In the other 80% of neonates with biliary atresia, the disorder appears to be a sporadic event with an unknown etiology, and the pathological obliterative process begins later in the perinatal period. Classic genetic inheritance is not supported by any clinical evidence as the disorder is rarely seen within families and, when seen in twins, is rarely concordant.8 Some studies have suggested time-space clustering of cases and seasonal variation, with the majority of cases occurring in the fall and winter months (December–March),9, 10 but large population-based studies from France, Sweden, and Japan have failed to identify significant seasonal or time-space clustering.9, 10, 11, and 12 After controlling for geographic and racial factors, associations have been made with advanced maternal age and increased parity, but not with smoking, maternal age, education, alcohol use, folic acid intake, gravidity, parental income, infant sex, preterm birth, infant birthweight, or plurality.5, 9, 12
Although histopathologic features of biliary atresia have been extensively studied in surgical specimens from excised extrahepatic biliary systems of infants, the pathogenesis of this disorder remains an unanswered question. Because some infants with biliary atresia are born with other congenital malformations, early studies postulated the etiology was a congenital malformation of the biliary ductal system. However, the majority of patients have isolated biliary atresia with progressive inflammatory lesions on histology occurring in the perinatal period. Therefore, it might be that biliary atresia represents a final common phenotypic pathway of neonatal liver injury caused by a diverse group of etiologies, including viral, inflammatory, immune dysregulation, or toxic exposure in genetically predisposed individuals5 (Figure 41-1).