Infants who received corticosteroids following bile duct surgery to treat a rare liver disease known as biliary atresia experienced no clinical benefit of the medicine and could suffer harm, according to results of a National Institutes of Health-funded clinical trial published May 3 by the Journal of the American Medical Association (JAMA).
Ronald Sokol, MD, professor of pediatrics at the University of Colorado School of Medicine and Children’s Hospital Colorado, is the senior author of the JAMA article.
“The results show no benefit of the steroids and that infants who received steroids after bile duct surgery suffered surgical complications, infections, and GI bleeding sooner than the placebo group. These findings were unexpected and we hope that doctors who care for these infants thoroughly consider the risks and benefits of using corticosteroids in these very vulnerable children,” said Sokol, chair of the steering committee of the Childhood Liver Disease Research and Education Network (ChiLDREN).
Biliary atresia affects about one out of every 5,000 to 18,000 infants and eventually 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.
Biliary atresia is an inflammatory process leading to blockage of the large bile ducts. The bile becomes trapped, and causes damage to the liver. The damage leads 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 as well. Worldwide, it is the most common reason for pediatric liver transplantation.
The Steroids in Biliary Atresia Randomized Trial (START) is a multicenter clinical study to determine whether giving high-dose steroids to infants with biliary atresia after bile duct surgery is better than surgery alone to maintain bile flow and preserve the children’s livers.
Before this trial, some studies suggested that using steroids post-surgery reduced inflammation and scarring, promoting bile flow. These studies became the foundation for widespread use of steroids following bile duct surgery in the United States and in other countries. These studies were largely uncontrolled and had limited ability to assess side effects or potential harm of using these drugs in young babies.
START, the largest clinical trial ever conducted in biliary atresia, was conducted at 14 ChiLDREN clinical centers, including at the Pediatric Liver Center at Children’s Hospital Colorado. One-hundred-forty infants with biliary atresia (mean age 10 weeks) were enrolled between September 2005 and February 2011; follow-up ended in January 2013. Half the participants were randomly assigned to receive steroids for 13 weeks. The other half received placebo. The drugs or placebo were started within 72 hours of surgery. In the absence of 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 bile duct surgery. Fifty-eight percent of infants in the steroids group achieved the study’s primary goal compared to 48.6 percent of infants in the placebo group. Further analysis revealed 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. However, 37 percent of those in the steroids group experienced their first complication within 30 days of bile duct surgery, whereas the rate was 19 percent in the placebo group.