Use of corticosteroids after hepatoportoenterostomy for bile drainage in infants with biliary atresia: the START randomized clinical trial.

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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00294684.

Assessment of the effectiveness of biofeedback in children with dyssynergic defecation and recalcitrant constipation/encopresis: does home biofeedback improve long-term outcomes.

The purpose of this study was to determine whether biofeedback benefits children with dyssynergic defecation and constipation/encopresis, and whether home biofeedback improves long-term outcomes. Thirty-six patients with chronic constipation who had failed at least 6 months of conventional treatment and demonstrated dyssynergic defecation at anorectal manometry were randomized to biofeedback in the laboratory alone (group 1, n=24) or in the laboratory and at home (group 2, n=12) and followed up at 2, 4, and a mean of 44 months. Thirty patients were available for long-term follow-up. Bowel movements increased in all from a mean of 1.4/week to 5.1, 5.8, and 5.1 per week at 2 months, 4 months, and long-term, respectively (p < or = 0.001). Soiling decreased in all from a mean of 5.5/week to 0.6, 0.1, and 1 per week at 2 months, 4 months, and long-term, respectively (p < or = 0.001). Laxative use decreased from a mean of 4.1 days/week to 0.6, 0.3, and 0.7 per week at 2 months, 4 months, and long-term, respectively (p < or = 0.001). Twenty-seven of 30 parents ranked their satisfaction a mean of 2.2 (range 1-excellent to 3-good). There were no significant differences in outcomes between the laboratory alone group and the laboratory plus home group. Biofeedback is beneficial for some children with chronic constipation and dyssynergic defecation. Supplemental home biofeedback does not improve long-term outcomes.