Biliary Atresia (BA)

Biliary atresia (BA), a rare liver disease starting from birth, occurs due to a blockage in the ducts that carry bile from the liver to the gallbladder. The disease presents soon after birth and can lead to various complications related to bile flow and liver damage. The incidence ranges from five to 32 cases per 100,000 newborns per year, with higher rates occurring in Asia and the Pacific regions. Biliary atresia is the most common reason for liver transplantation in children.

The underlying causes of BA are not completely understood. For some patients, biliary atresia may occur because the bile ducts did not form properly during fetal development and in others, inflammation around the time of birth leads to the destruction of bile ducts. As a result of the disease, bile acids are not able to adequately drain from the liver, resulting in signs and symptoms shortly after birth, including jaundice, dark urine, and enlarged liver. The rapid progression of BA necessitates surgical intervention within the first months of life.

Pediatric patients with biliary atresia undergo a Kasai procedure (also known as hepatoportoenterostomy or HPE), an operation to help bile drain from the liver into the gut, bypassing the blocked bile ducts. The Kasai procedure is not a cure for biliary atresia. Over time, bile can still build up in the liver and can lead to severe liver damage. As a result, despite the Kasai procedure, approximately half of children with biliary atresia will require a liver transplantation within two years of diagnosis. There remains a substantial unmet medical need for therapeutic interventions as invasive surgery is often unsuccessful. There are currently no approved therapies to treat biliary atresia.

Biliary Atresia (BA)

BA is a rare liver disorder in which there is a blockage or absence of large bile ducts that leads to bile accumulation in the liver and ultimately results in progressive cholestasis and liver damage. BA occurs in infants and is estimated to affect one in every 10,000 to 15,000 live births in the United States. BA is the most common reason for liver transplantation in children.

The underlying causes of BA are not completely understood. For some patients, BA may occur because the bile ducts did not form properly during fetal development and in others, inflammation around the time of birth leads to destruction of bile ducts. As a result of BA, bile acids are not able to adequately drain from the liver, resulting in an array of signs and symptoms shortly after birth, including jaundice, dark urine and enlarged liver. The rapid progression of BA necessitates surgical intervention within the first months of life.

There remains a substantial unmet medical need for therapeutic interventions, as invasive surgery is often unsuccessful. The standard of care for BA is the Kasai procedure, a surgery in which a segment of the small intestine is used to attach the small intestine directly to the liver where bile is expected to drain and is most successful if conducted in the first eight weeks of life. The success rate of the Kasai procedure is approximately 30% to 40%. The remaining patients are at risk of progressive liver disease requiring liver transplantation. We believe ASBT inhibition has therapeutic potential in this patient population.