A Randomized, Double-Blinded, Placebo-Controlled Trial of Corticosteroid Therapy Following Portoenterostomy in Infants with Biliary Atresia (START)

General Description

Biliary atresia is a condition in which the common hepatic bile duct becomes blocked, preventing bile drainage from the liver. Biliary atresia occurs in infants and requires portoenterostomy, a surgical procedure, in order to re-establish bile flow from the liver to the small intestine. Despite the surgical intervention, about half of the children will need a liver transplant before the age of five. The aim of the START study was to determine whether corticosteroid treatment after portoenterostomy would improve bile drainage and reduce the need for liver transplantation, compared to surgery alone.

The START study participants were recruited from the PROBE study and randomized into either the corticosteroid or placebo group within 72 hours after the portoenterostomy procedure. Participants were given their assigned treatments daily over the course of 13 weeks. After the treatment period, participants underwent follow-up testing and assessments until age 24 months.

Objectives

The objective of the START study was to determine the efficacy of corticosteroids on the outcome of infants with biliary atresia.

Outcome Measure

Primary Outcome Measures:
Participants were tested 6 months after portoenterostomy. The percentage of patients with a native liver and serum total bilirubin below 1.5 mg/dL was compared between the two groups.

Secondary Outcome Measures:
Participants were tested and monitored until age 2 for serum total bilirubin concentration; survival with native liver; growth; serum biomarkers or sufficiency of fat-soluble vitamins; and presence of ascites.

Criteria

Inclusion Criteria:
Participants of the study were age 6 months or younger; weighed at least 4.4 pounds (2000g); and underwent a portoenterostomy operation within 72 hours prior to enrollment.

Exclusion Criteria:
Individuals were excluded from the study if they had immunodeficiency, diabetes mellitus, or significant systemic hypertension; unconjugated bilirubin below the minimum levels for the infant’s age; a condition that prevented the use of corticosteroids; diagnosed bacteremia or other tissue infection; diagnosed congenital infection or disease with herpes simplex virus, toxoplasmosis, or cytomegalovirus inclusion disease of the liver; received the live attenuated rotavirus vaccine within 5 days prior to administration of study drug; or the infant’s mother tested positive for HIV, HBsAg, or Hepatitis C.

Outcome

The study found that corticosteroid usage after portoenterostomy did not improve the clinical outcome of infants with biliary atresia. Results showed that there were no significant statistical differences in bile drainage, serum total bilirubin levels, or survival with the native liver between the two groups at any point during the study. However, those in the corticosteroid group developed serious adverse events earlier than their placebo comparators. Due to the findings, corticosteroid therapy is not a recommended treatment for infants with biliary atresia following portoenterostomy.