primary prophylaxis for variceal bleed in biliary atresia

Conditions: Portal Hypertension, Biliary Atresia

Summary: biliary atresia is the commonest etiology of neonatal cholestasis and is the most common indication for pediatric liver transplantation world-wide. kasai-portoenterostomy (kpe) is the operative procedure of choice which helps in restoration of biliary flow and preventing rapid progression of fibrosis. only 50-60% of infants have a successful surgery in terms of normalization of bilirubin (\<2 mg/dl) after 3 months. remaining 40-50% have rapid progression of pht and eventual decompensation. additionally, around 50-70% of infants with successful kpe have 1 or more episodes of cholangitis, and the severe ones if left untreated lead to progressive portal hypertension. moreover in indian setting a significant number of infants with biliary atresia reach late when the kpe is not feasible, and this group develops very rapid pht and decompensation. hence, overall around 70-80% of infants and children develop pht within 5 years of age. variceal bleed has been shown to be an important determinant of survival in infants with high bilirubin. usage of beta-blockers in adult cirrhotics has been shown to reduce the progression of varices and incidence of variceal bleed. although many pediatric hepatology centers worldwide use beta-blockers, there has been no controlled trial specifically to address this issue in children with biliary atresia. so, we planned this study to evaluate the efficacy of beta-blockers as primary prophylaxis for prevention of variceal bleed in biliary atresia children.

(a) aim and objectives: aim: to study the effect of beta-blockers for primary prophylaxis of variceal bleed in infants and children with biliary atresia. primary objective: bleeding free survival over 18 months fu secondary objectives: (i) progression, persistence or regression of esophageal and gastric varices, and portal hypertensive gastropathy over 3, 6, 12 and 18 months fu (ii) overall survival at 18 months fu (b) methodology: this will be an open label randomized controlled study where infants and children with biliary atresia from 6 months to 5 years fulfilling inclusion and exclusion criteria will be enrolled to receive propanolol or placebo for a duration of 18 months or till the occurrence of variceal bleed. i. study design: open label randomized controlled study with stratified randomization. ii. intervention: beta-blocker (propanolol) versus placebo. iii. study period: 1.5 years iv. study population: infants and children from 6 months to 5 years of age with biliary atresia fulfilling the inclusion and exclusion criteria. (c) expected outcome of the project: beta-blockers reduce the incidence of variceal bleed in infants and children with biliary atresia.

Eligibility criteria:
inclusion criteria: infants and children with biliary atresia from 6 months to 5 years of age fulfilling either of the following conditions: i. with unsuccessful kasai portoenterostomy procedure with a bilirubin \>2 mg/dl, or ii. who did not underwent kasai portoenterostomy, or iii. with successful kasai portoenterostomy procedure with a bilirubin \<2 mg/dl, but with features of portal hypertension i.e. clinical splenomegaly and/or thrombocytopenia (platelets \< 1,00,000/mm3). exclusion criteria: i. history suggestive of hyper-reactive airway disease. ii. congestive heart failure iii. any degree of heart block (i,, ii, iii) iv. infants and children already on beta-blockers in last 4 weeks. v. portal vein atresia or thrombosis. vi. history of variceal bleed. vii. infants and children on prophylactic or therapeutic endotherapy (band ligation or sclerotherapy). viii. potential liver transplant within 1 month.

Keywords: variceal bleed primary prophylaxis biliary atresia