Primary Prophylaxis for Variceal Bleed in Biliary Atresia
Primary Prophylaxis for Variceal Bleed in Biliary Atresia
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.
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.