Two forms of biliary atresia have been recognized. The embryonic or fetal type is often associated with congenital malformations suggesting the insult occurs prenatally. The more common perinatal type usually presents at 4-8 weeks of life. Because the disease occurs so early in the perinatal period, a genetic factor being causal or contributory must be considered. Previous data has been conflicting; there are case reports of biliary atresia occurring in families and HLA identical twins that are discordant for biliary atresia. In one study, HLA-B 12 was found more commonly then expected in children with biliary atresia. HLA-Cw4/7 has also been increased in children with biliary atresia and in adults with primary sclerosing cholangitis. However, all these studies suffer from the small number of subjects and single-center studies. The etiologic mechanism(s) for biliary atresia remain enigmatic. By analyzing HLA types in a large cohort of children with biliary atresia and neonatal hepatitis, determination of any genetic predisposition to these disorders should be accelerated. Biliary atresia remains the leading indication for pediatric liver transplantation in the United States. Recently, the Pediatric Liver Disease Severity Score (PELD) was proposed to improve organ allocation for children in need of liver transplants. The major limitation of the PELD score is that it has not been prospectively validated. However, the PELD score is based on only a few variables that can be objectively assessed and are reproducible. No individual center has sufficient patients with biliary atresia or neonatal hepatitis to ascertain whether the PELD score can predict outcomes prospectively. This proposal brings together a unique consortium of investigators and resources within the State of California with a plan for a participating Clinical Center in the Biliary Atresia Clinical Research Consortium. Our research plan describes the establishment of a large multicomponent Clinical Center patient database that would contribute to the proposed multicenter Biliary Atresia Clinical Research Consortium. These include tertiary care referral specialty clinics at a large university medical center and an HMO patient population. We propose to identify patients with biliary atresia and neonatal hepatitis from these sources, to allow participation in the Consortium. Secondly, we propose two research protocols that would use the Biliary Atresia Clinical Research Consortium to explore a possible etiologic relationship between HLA type and biliary atresia and allow a prospective evaluation of the PELD score.
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