Infants with biliary atresia - a rare liver disease - did not benefit from corticosteroid treatment after bile duct surgery and could face more harm, according to a study funded by the National Institutes of Health. Results were published online in the Journal of the American Medical Association to coincide with the Pediatric Academic Societies annual meeting.
In biliary atresia, inflammation leads to blockage of the large bile ducts. Bile becomes trapped, causing damage to the liver and leading to scarring, loss of liver tissue and liver failure. Most infants with this serious disease require bile duct surgery and may later need a liver transplant. Worldwide, biliary atresia is the most common reason for liver transplantation in children.
The Steroids in Biliary Atresia Randomized Trial (START) set out to determine whether giving high-dose steroids to infants with biliary atresia after bile duct surgery (hepatoportoenterostomy, also known as the Kasai procedure) is better than surgery alone to maintain bile flow and preserve the children's livers.
Some previous studies suggested that using steroids after surgery reduced inflammation and scarring, promoting bile flow. Those studies became the foundation for widespread use of steroids after bile duct surgery in the United States and elsewhere. But the studies were limited in their ability to assess potential benefits and risks of using steroids in infants.
"We know that the surgery restores the flow of bile, relieves pain and delays the need for liver transplants in many infants, but we did not have data to prove that adding steroids significantly improved bile drainage in infants who had their own livers," said Averell H. Sherker, M.D., project scientist for the Childhood Liver Disease Research and Education Network (ChiLDREN) at the NIH's National Institute of Diabetes and Digestive and Kidney Diseases.
START was conducted at 14 clinical centers. The study enrolled 140 infants with biliary atresia (mean age 10 weeks) between September 2005 and February 2011 and followed them until January 2013. Half were randomly assigned to receive steroids for 13 weeks. The other half received placebo. The drugs or placebo were started within 72 hours of the Kasai procedure, in which a surgeon removes the infant's damaged bile duct and attaches it to a loop of intestine to allow bile to flow from the liver to the small intestine. Without the surgery, infants with biliary atresia are unlikely to live past age 2 without a liver transplant.
Researchers found that steroids did not significantly improve bile flow in infants 6 months after surgery. Fifty-eight percent of infants on steroids achieved improved bile drainage compared to 48.6 percent of those in the placebo group. Results also revealed that survival rates were nearly the same, with 58 percent of infants treated with steroids and about 59 percent of infants receiving placebo still living with their own livers at age 2. While members of both groups had serious adverse events, 37 percent of those on steroids experienced their first complication within 30 days of surgery, compared to 19 percent in the placebo group. These adverse events included surgical complications, infections and bleeding in the digestive tract.
"These findings were unexpected and we hope that doctors who care for these infants thoroughly consider the risks and benefits of corticosteroids in these very vulnerable children," said Jorge A. Bezerra, M.D., lead author and professor of pediatrics of Cincinnati Children's Hospital Medical Center.
Biliary atresia affects about 1 out of every 5,000 to 18,000 infants and progresses to liver failure in more than 70 percent of babies with the disease. It is more common in females, premature babies, and children of Asian or African-American heritage.
"We are grateful to the parents who enrolled their infants in START," said NIDDK Director Griffin P. Rodgers, M.D. "With their help, we learned that by reducing the use of commonly prescribed steroids we might give infants with this devastating disease a better chance for a healthier life, and researchers can continue to investigate treatment alternatives."