A Randomized, Double-Blinded, Placebo-Controlled Trial of Corticosteroid Therapy Following Portoenterostomy

This is a multi-center randomized, double-blinded, placebo-controlled trial to prospectively
determine the efficacy of corticosteroids on the outcome of infants with biliary atresia.
The trial will be conducted by the NIDDK-funded network of ten clinical centers comprising
the Biliary Atresia Clinical Research Consortium (BARC), whose goal is to study the
etiology, pathogenesis, diagnosis, and treatment of infants with biliary atresia. For the
trial, our overall hypothesis is that therapy with corticosteroids following
portoenterostomy (including gall bladder Kasai procedure) will improve bile drainage and
long-term outcome in infants with biliary atresia. This hypothesis will be tested through
the following specific aims and hypotheses:

Aim 1: To determine whether corticosteroid therapy decreases serum bilirubin concentration
after portoenterostomy.

Aim 2: To determine whether corticosteroid treatment after portoenterostomy will improve
outcome as defined by survival without transplantation at 24 months of age.

Aim 3: To determine whether corticosteroid treatment after portoenterostomy will improve
growth of infants with biliary atresia.

Aim 4: To determine whether corticosteroid treatment improves biochemical indicators of each
of the fat-soluble vitamins after supplementation with standard doses.

Aim 5: To determine whether corticosteroid treatment after portoenterostomy will decrease
the incidence of persistent ascites or ascites that requires medical treatment.

The significance of the proposed trial is that it will determine whether corticosteroids are
an effective medical treatment to improve bile drainage and long-term outcome, and whether
its use reduces the need for liver transplantation in infants with biliary atresia.

Subjects will be recruited from patients enrolled in the BARC prospective observational
database study who undergo portoenterostomy or portochelecystostomy (gall bladder Kasai) for
biliary atresia.

The Primary outcome measure is the percentage of patients with serum total bilirubin <1.5
mg/dL and with native liver at 6 months after portoenterostomy.

Secondary outcome measures are:

1. Serum total bilirubin concentration (and also at 3 months after portoenterostomy)

2. Survival with native liver at 24 months of age

3. Growth

1. Weight for age Z-score (in patients without ascites)

2. Height for age Z score

4. Serum biomarkers of sufficiency of fat-soluble vitamins

1. Vitamin A: molar ratio of serum retinol/retinol binding protein

2. Vitamin D: serum level of 25-hydroxy vitamin D

3. Vitamin E: ratio of serum vitamin E/total lipids

4. Vitamin K: International Normalized Ratio (INR)

5. Presence of ascites

All measurements will be made at 12 and 24 months of age (unless noted otherwise):