Neonatal screening for biliary atresia
Authors: Jay H. Hoofnagle, Ronald J. Sokol
Journal: Hepatology (2006)

Biliary atresia is a rare disease, occurring in 1:8000 to 1:18,000 newborns. Despite its rarity, biliary atresia is the single major indication for liver transplantation in children. If untreated, biliary atresia rapidly leads to marked cholestasis, growth failure, cirrhosis, and death from end-stage liver disease within the first 2 years of life. Hepatoportoenterostomy (HPE, the "Kasai procedure") can restore bile flow and prevent or slow progression of disease in a proportion of patients. Retrospective analyses suggest that the HPE is more likely to be successful if within 60-90 days of birth, and some data suggest that the earlier it is performed, the better the outcome. In view of this, early suspicion of the presence of liver disease, rapid referral to a tertiary center, and prompt diagnosis and surgery are strongly recommended. Unfortunately, the disease is often detected late; in a recent U.S. survey, many children were identified late, 44% undergoing HPE after 60 days and 12% after 90 days of life. Even with prompt surgery, almost 50% of children undergo liver transplantation before 2 years of age and the long-term prognosis of the remaining is guarded. An estimated 70%-80% of children born with biliary atresia eventually require liver transplantation. Screening for biliary atresia is controversial. In an attempt to achieve earlier diagnosis and better outcomes of HPE in biliary atresia, several countries of the world have instituted routine screening for this disease or a national policy regarding sites of performance of the corrective surgery and transplantation. The cause of biliary atresia is not known and there are no specific, non-invasive tests for its detection. The diagnosis of biliary atresia is usually based upon persistence of jaundice and elevations in conjugated bilirubin beyond the first few weeks of life, exclusion of other causes, liver biopsy, and ultimately cholangiography and exploratory surgery. In some countries, routine screening for biliary atresia has been initiated using stool color cards showing several grades of stool color, from white to dark yellow and green. The parents are asked to return the card after checking the infant's stool color at about 4 weeks of age or bring the card at the time of a 1-month routine health care visit. The efficacy of this approach has yet to be proven, but data are emerging from several countries of the world. In the United States, newborn screening is performed routinely for several metabolic diseases, but the types of screening tests vary by state, and none recommend routine screening for biliary atresia. The reasons for not screening for biliary atresia are the absence of a convenient and accurate screening method and the lack of evidence that screening results in early detection or in improvement in outcome. To further address these issues and to survey current understanding of the etiology, natural history, outcomes and consequences of biliary atresia, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the Office of Rare Diseases of the National Institutes of Health (NIH), in collaboration with the Health Services Resource Administration (HRSA), the American Liver Foundation (ALF), and the Biliary Atresia Clinical Research Consortium (BARC), have organized a one-and-a-half day meeting on "Screening and Outcomes of Biliary Atresia" to be held in Bethesda, MD on September 11-12, 2006. The meeting will bring together investigators from the United States, Canada, United Kingdom, France, Argentina, Japan and Taiwan. The current epidemiology and clinical aspects of biliary atresia will be reviewed. Surgical and clinical outcomes will be compared among countries and specific outcome measures will be discussed. A session on pathogenesis will include talks on developmental biology, genetics, genomics, immunologic and virologic factors, and the use of gene arrays and proteomic techniques to investigate this disease. Sessions on current and innovative means of screening for biliary atresia will be followed by discussions of the needs and challenges of future research. A poster session is planned, and submission of abstracts on etiology, screening, natural history, and outcomes of biliary atresia is welcomed. A limited number of travel stipends are available and will be awarded based upon the scientific merit of a submitted abstract. A summary of the meeting will be prepared for publication. The meeting is open to all interested persons. Registration information and the full agenda is available at the NIDDK website: http://www.niddk.nih.gov/fund/other/conferences.htm#1