BILACO Trial to Identify Neurocognitive Risk Factors in Pediatric Biliary Atresia

Biliary atresia represents the most severe form of cholestatic liver disease in children, characterized by progressive destruction of the bile ducts. This condition leads to high morbidity and mortality, with affected children experiencing devastating pruritus, chronic fatigue, severe failure to thrive, progressive hepatic failure, and profound impaired neurodevelopment. The precise etiology remains largely unknown, complicating targeted therapeutic strategies. More than half of these children ultimately require a new liver from a living or deceased donor during childhood. However, the correct timing of this life-saving transplantation is extremely difficult due to a critical lack of consensus-based clinical assessment tools. Despite its relatively low incidence, the societal and individual cost of this disease is tremendous, both from a clinical burden and a human suffering perspective. Key knowledge gaps persist regarding protocolized neurodevelopmental tests, genetic profiling, precise malnutrition evaluation, biochemical markers, brain MRI-scans, body composition, immunological function, and determining the optimal time for transplantation in cholestatic children.

The BILACO trial is designed as a prospective, observational study aiming to comprehensively investigate risk factors related to brain, heart, gut, and immunological function in a well-defined Danish cohort of children suffering from severe cholestasis due to biliary atresia. The primary study cohort comprises 75 children aged 0-18 years. To provide robust comparative data, two distinct control groups have been established: 30 aged and gender-matched healthy children and 20 children diagnosed with Tetralogy of Fallot. All participants will undergo extensive and advanced evaluations, including detailed liver function assessment, comprehensive genetic profiling, thorough nutrition and immunological status assessments, advanced neuro-imaging techniques, and rigorous neurocognitive evaluations. These multi-modal assessments are scheduled at critical developmental milestones: at the time of diagnosis, at 2 years of age, during the pre-school period, pre-teenage years, and teenage years. Furthermore, in cases where a liver transplantation becomes necessary, additional neuro-cognitive tests will be performed to capture post-surgical impacts.