No benefit from post-HPE corticosteroid therapy in infants with biliary atresia

WASHINGTON — Infants with biliary atresia did not experience improved bile drainage or transplant-free survival from a high dose of corticosteroids administered after hepatoportoenterostomy in a study presented at The Liver Meeting.

In the multicenter, double blind START trial, researchers randomly assigned 140 infant patients with biliary atresia who underwent hepatoportoenterostomy (HPE) to either placebo (n=70) or 4 mg/kg IV methylprednisolone daily for 2 weeks, followed by 2 mg/kg oral prednisolone for 2 weeks, with a tapering dosage over the subsequent 9 weeks (n=70). All patients began receiving treatment or placebo within 72 hours of HPE, and underwent postoperative treatment with antibiotics, ursodeoxycholic acid, fat-soluble vitamins and standardized nutrition.

The primary endpoint was the proportion of patients with improved bile drainage, defined as total serum bilirubin levels less than 1.5 mg/dL with their native liver, 6 months after HPE.

Patients who received corticosteroids did not have significantly better bile drainage than placebo recipients, with 58.6% in the treated group achieving the primary endpoint at 6 months compared with 48.6% in the placebo group (adjusted RR=1.14; 95% CI, 0.83-1.57). Similar results were observed when patients were assessed at age 2 years (49.4% in the treated group vs. 39.8%; adjusted HR=0.8; 95% CI, 0.5-1.2). Transplant-free survival also occurred at similar rates in the two groups at 2 years (58.7% vs. 59.4%; aHR=1; 95% CI, 0.6-1.8).

Investigators observed no significant differences between treated and placebo patients in incidence of serious adverse events (81.4% of treated patients vs. 80% in placebo patients; P=1), weight (P=.16) and height (P=.28) or the incidence of infectious adverse events (P=.4). Patients receiving corticosteroids, however, had a significantly shorter time to incidence of serious adverse events than placebo recipients (P=.0079).

The two groups also had similar serum bilirubin levels at all time points, and similar rates of early treatment discontinuation (P=.72), ascites at 12 months (P=.41) and 24 months (P=.29) and inadequate response to immunization (P=.43).

“High-dose steroid therapy after HPE did not improve bile drainage or result in greater transplant-free survival at 2 years of age,” researcher Jorge A. Bezerra, MD, Cincinnati Children’s Hospital Medical Center, said. “Administration of high-dose therapy was associated with earlier onset of SAEs, raising concerns for safety. Therefore, the addition of high-dose steroids as an adjuvant treatment after HPE cannot be recommended.”

Disclosure: Bezerra reports no relevant financial disclosures.

For more information:

Bezerra JA. #111: Presidential Plenary: Translational Advances in Hepatology: High-dose Corticosteroid Therapy Following Portoenterostomy in Infants with Biliary Atresia Does Not Improve Outcome: The Multicenter, Randomized, Double-Blind, Placebo-Controlled START Trial. Presented at: The Liver Meeting 2013; Nov. 1-5, Washington.