CINCINNATI -- Unexpected discovery of a new molecular signature for a destructive and often lethal pediatric liver disease may lead to a new therapeutic target for the hard-to-treat condition.
In a study that included human livers and a mouse model of biliary atresia, researchers report in the November Journal of Clinical Investigation that not all children with biliary atresia share the same disease process. Some patients have a second molecular conductor of disease called Th2 (T helper cell 2) immune system.
Biliary atresia is disease that destroys the bile ducts in and near the liver in the first few months of life. Driven by an overly aggressive immune system response after birth, the condition is the most common cause of severe pediatric liver disease. The ducts, which normally carry bile from the liver and gall bladder to the intestines, become blocked over time. Even with treatment, which can include surgery, children often need a liver transplant within two years of birth.
Despite the need for better therapies, progress has been hampered by a limited knowledge of biological processes driving the disease, according to Jorge Bezerra, MD, principal study investigator and a researcher/physician in the division of Gastroenterology, Hepatology and Nutrition at Cincinnati Children's Hospital Medical Center.
"Our findings add a new dimension to the understanding of biliary atresia," Bezerra said. "They provide a potential target for new therapies and have implications for clinical trials. Now, depending on the molecular signature of a child's disease, we can develop new strategies to also target the Th2 immune system with anti-inflammatory agents."
Bezerra said physicians have learned in clinical trials that not all children with biliary atresia respond in similar fashion to the same treatment protocols. The current study may help explain why.
Until now, only molecular signals from the Th1 cytokines
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Cincinnati Children's Hospital Medical Center