A discovery by a researcher at Cincinnati Children's Hospital Medical Center, published in The Lancet, may lead to new treatments for a deadly liver disease of infancy -- dramatically reducing the number of liver transplants in children.
Jorge Bezerra, MD, and a team of researchers at Cincinnati Children's have revealed a genetic underpinning to biliary atresia, the most common reason for liver transplant in children.
Biliary atresia occurs in infants and usually becomes evident two to eight weeks after birth. Its cause has been unknown. Symptoms include unexplained jaundice, dark urine, clay-colored stools and weight loss. The disease destroys bile ducts in the liver, trapping bile, rapidly causing damage to liver cells and severe scarring.
Biliary atresia accounts for up to 50 percent of children who undergo liver transplantation. Although a surgical procedure is successful in many infants, three of every four children who have biliary atresia need a liver transplant before the age of 20. The total annual cost, including transplant care, of treating all infants with biliary atresia is estimated to be $65 million.
For his study, Dr. Bezerra, a physician/researcher in the division of Gastroenterology, Hepatology and Nutrition at Cincinnati Children's, obtained biopsies of livers of 14 infants with biliary atresia.
Using gene chip technology, he and the Cincinnati Children's research team discovered that in the early phases of biliary atresia, inflammatory genes are activated and immunoglobulin genes are suppressed, pointing to a potential role of cytokines (proteins that control inflammation) secreted by disease-fighting blood cells in the origin and development of the disease.
The team also obtained biopsies of six infants with cholestasis, an arrest in the flow of bile due to blocked bile ducts not due to biliary atresia. In 65 percent of infants with biliary atresia, the cytokine gamma-interferon was produced. It was not produced, however, in any of the infants with cholestasis.
"This means that infants with biliary atresia may be very prone to drive an inflammatory response against themselves," says Dr. Bezerra. "These inflammatory cells see the biliary system as a foreign target."
In addition to continuing patient-based studies, Dr. Bezerra is working with a mouse model of biliary atresia to understand the molecular process more fully and determine the exact pathways causing the disease. He hopes to develop a novel therapeutic to target disease progression in the future.
Cincinnati Children's has a longstanding reputation as a national leader in pediatric liver care. The Pediatric Liver Care Center at Cincinnati Children's integrates all aspects of liver care and is led by physicians known throughout the world for their expertise in pediatric liver disease. The Center is recognized as a Center of Excellence in the management of complex liver disease by many insurance organizations because of quality of care and cost effectiveness. The Pediatric Liver Care Center's research efforts include basic science, clinical and translational research.
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