Comments,
story ideas
Click here to
e-mail the Record
|
|
|
Comments,
story ideas Click here to e-mail the Record |
|
|
|
|
||||||
|
|
||||||||||||||||||||||||||||
|
 |
|
Early diagnosis of biliary atresia focus of study
By Kimberly Leydig In the first effort of its kind, researchers around the world are collaborating to develop new strategies to quickly and definitively detect infants with biliary atresia -- the most severe and rapidly progressive digestive disease of infancy and the most frequent cause for liver transplantation. The University is one of the primary institutions involved in the multicenter consortium, which is supported by a five-year, $10 million grant from the National Institutes of Health.
"The most exciting aspect of this work is that if the underlying mechanisms that cause progression can be understood, targeted treatment strategies could be designed to prevent disease progression," said Ross W. Shepherd, M.B.B.S., professor of pediatrics, clinical director of the Pediatric Liver Program and principal investigator for the St. Louis site. It is not known if underlying molecular defects or environmental factors, such as viruses during pregnancy or the ingestion of toxins by the mother, induce biliary atresia, an abnormal formation of bile ducts that causes progressive liver damage and death in untreated cases. Furthermore, diagnosis of the disease is difficult. At 2 to 3 weeks of age, babies may appear jaundiced and pass pale stools and dark urine. The liver also becomes enlarged by 1 month of age, but this symptom often goes unnoticed. Shepherd stresses that early diagnosis is critical. Early detection of biliary atresia allows physicians to intervene with an operation called the Kasai procedure, which can improve long-term outcomes for some patients. Before the widespread application of the Kasai procedure, which was developed by a Japanese surgeon in the 1960s, almost all infants with biliary atresia died by 2 years of age. However, outcomes from the Kasai procedure are far from optimal: About 30 percent of infants still get progressive liver disease and will need a liver transplant before their first birthday, with another 30 percent to 50 percent requiring transplants at later ages -- making the disease the most common reason for liver transplants in children worldwide. Unfortunately, little new knowledge about the causes, timely diagnosis or improved therapy has emerged over the past 40 years, largely because systematic research has been limited since biliary atresia is relatively uncommon. On average, St. Louis Children’s Hospital diagnoses six to 10 patients with the disease every year, and in the United States there are about 250-400 new cases yearly. The University is coordinating clinical contributions from several collaborating sites in the United States and one in Australia. The St. Louis Clinical Center also will be initiating a research program that emphasizes studying mechanisms of liver damage and identifying patterns of cellular gene expression within liver tissue of patients. Now, researchers will be able to access an electronic database that logs collected clinical data and tissue specimens from the participating medical centers. By studying a larger sample of specimens, the team aims to determine whether the extent of hepatic fibrosis and the expression of specific genes that promote fibrosis are predictive of disease progression. Shepherd explained that if better methods of predicting which infants will progress to end-stage liver disease can be developed, scientists can provide a potential window of opportunity to halt the progress of liver injury. Genetics may unlock the mystery. Researchers surmise that the advent of new genomic technology will provide an unprecedented opportunity to discover genetic markers for biliary atresia and to improve diagnosis and management strategies of the disease. "The plans put forward by all the participating institutions are really exciting," Shepherd said. "There is no doubt that over the next five years we will learn a great deal more about this mysterious disease than we have over the past four decades." |
|
|||||||||||||||||||||||||
|
|
