IMPORTANCE Biliary atresia is the most common cause of end-stage liver disease in children. Controversy exists as to whether use of steroids after hepatoportoenterostomy improves clinical outcome. OBJECTIVE To determine whether the addition of high-dose corticosteroids after hepatoportoenterostomy is superior to surgery alone in improving biliary drainage and survival with the native liver. DESIGN, SETTING, AND PATIENTS The multicenter, double-blind Steroids in Biliary Atresia Randomized Trial (START) was conducted in 140 infants (mean age, 2.3 months) between September 2005 and February 2011 in the United States; follow-up ended in January 2013. INTERVENTIONS Participants were randomized to receive intravenous methylprednisolone (4 mg/kg/d for 2 weeks) and oral prednisolone (2 mg/kg/d for 2 weeks) followed by a tapering protocol for 9 weeks (n = 70) or placebo (n = 70) initiated within 72 hours of hepatoportoenterostomy. MAIN OUTCOMES AND MEASURES The primary end point (powered to detect a 25% absolute treatment difference) was the percentage of participants with a serum total bilirubin level of less than 1.5 mg/dL with his/her native liver at 6 months posthepatoportoenterostomy. Secondary outcomes included survival with native liver at 24 months of age and serious adverse events. RESULTS The proportion of participants with improved bile drainage was not statistically significantly improved by steroids at 6 months posthepatoportoenterostomy (58.6% [41/70] of steroids group vs 48.6% [34/70] of placebo group; adjusted relative risk, 1.14 [95% CI, 0.83 to 1.57]; P = .43). The adjusted absolute risk difference was 8.7% (95% CI, −10.4% to 27.7%). Transplant-free survival was 58.7% in the steroids group vs 59.4% in the placebo group (adjusted hazard ratio, 1.0 [95% CI, 0.6 to 1.8]; P = .99) at 24 months of age. The percentage of participants with serious adverse events was 81.4% [57/70] of the steroids group and 80.0% [56/70] of the placebo group (P > .99); however, participants receiving steroids had an earlier time of onset of their first serious adverse event by 30 days posthepatoportoenterostomy (37.2% [95% CI, 26.9% to 50.0%] of steroids group vs 19.0% [95% CI, 11.5% to 30.4%] of placebo group; P= .008). CONCLUSIONS AND RELEVANCE Among infants with biliary atresia who have undergone hepatoportoenterostomy, high-dose steroid therapy following surgery did not result in statistically significant treatment differences in bile drainage at 6 months, although a small clinical benefit could not be excluded. Steroid treatment was associated with earlier onset of serious adverse events in children with biliary atresia.

SUMMARY Live pentavalent human–bovine reassortant rotavirus vaccine is recommended in the United States for routine immunization of infants. We describe three infants, two with failure to thrive, who had dehydration and diarrhea within 1 month after their first or second rotavirus immunization and subsequently received a diagnosis of severe combined immunodeficiency. Rotavirus was detected, by means of reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay, in stool specimens obtained from all three infants, and gene-sequence analysis revealed the presence of vaccine rotavirus. These infections raise concerns regarding the safety of rotavirus vaccine in severely immunocompromised patients.

To evaluate the efficacy of non-transplant surgery for pediatric cholestasis, 58 clinically diagnosed children, including 20 Alagille syndrome (ALGS), 16 Familial Intrahepatic Cholestasis-1 (FIC1), 18 Bile Salt Export Pump (BSEP) disease, & 4 others with low γ-glutamyl transpeptidase disease (levels <100 U/L), were identified across 14 Childhood Liver Disease Research Network (ChiLDReN) centers. Data were collected retrospectively from individuals who collectively had 39 partial external biliary diversions (PEBD), 11 ileal exclusions (IE) and 7 gallbladder-to-colon diversion (GBC). Serum total bilirubin decreased after PEBD in FIC1 (8.1±4.0 vs. 2.9±4.1 mg/dL, preop vs. 12–24 months postop respectively, p=0.02) but not in ALGS or BSEP. Total serum cholesterol decreased after PEBD in ALGS patients (695±465 vs. 457±319 mg/dL; preop vs. 12–24 months postop respectively; p=0.0001). Alanine aminotransferase levels increased in ALGS after PEBD (182±70 vs. 260±73 IU/L, preop vs. 24 mos. p=0.03) but not in FIC1 or BSEP. ALGS, FIC1, and BSEP patients experienced less severely scored pruritus after PEBD (ALGS: 100% vs. 9% severe, FIC1: 64% vs. 10%; BSEP: 50% vs. 20%, preop vs. >24 mos. postop respectively, p<0.001). ALGS patients experienced a trend toward greater freedom from xanthomata after PEBD. There was a trend toward decreased pruritus in FIC1 after IE and GBC. Vitamin K supplementation increased in ALGS after PEBD (33% vs. 77%, p=0.03. Overall, there were 15 major complications after surgery. 12 patients (3 ALGS, 3 FIC1, 6 BSEP) subsequently underwent liver transplantation. Conclusion This is the first multi-center analysis of non-transplant surgical approaches to intrahepatic cholestasis. Approaches vary, are well tolerated, and generally although not uniformly result in improvement of pruritus and cholestasis.