The Biesecker Pediatric Liver Center at The Children’s Hospital of Philadelphia is actively involved in research studies on liver fibrosis and cirrhosis. Characterized by the excessive production and decreased degradation of abnormal extracellular matrix, liver fibrosis and cirrhosis are a major cause of morbidity and mortality in biliary atresia.
Although adequate bile drainage can be achieved in many patients through a Kasai hepatoportoenterostomy, fibrosis generally progresses and is notable for being among the most rapidly progressive forms of liver fibrosis known. The etiology of biliary atresia and the mechanism for the unusually rapid fibrosis are not well understood.
Most of the fibrogenic cells in the liver are a-smooth muscle actin-expressing myofibroblasts and most are derived from the transdifferentiation of hepatic stellate cells. It has recently been recognized, however, that other cells, including fibroblasts and bone marrow-derived stem cells, may also contribute. In particular, portal fibroblasts are believed to play a significant role in early biliary fibrosis.
Through the use of isolated cells in culture, animal model systems and banked human tissue, researchers in the Biesecker Pediatric Liver Center at CHOP are studying the major populations of fibrogenic cells in biliary atresia and are identifying the factors (some specific to this disease) that induce these cells to secrete abnormal and excess matrix. Investigators hope that by understanding the process of fibrogenesis in biliary atresia, they will be able to develop rational therapies.