New research indicates that early-onset liver disease in childhood adversely affects the developing brain

Research from King’s College London and funded by NIHR Maudsley BRC and Mowatlabs has found that a significant proportion of children with Biliary Atresia (BA), a rare and serious early-onset liver condition, may face significant challenges in communication, motor skills and social interaction.

These challenges can be seen from as early as toddlerhood, suggesting that liver disease impacts the developing brain. Published in The Journal of Paediatrics, this is the first study to comprehensively profile the general, cognitive and social development of toddlers and children with BA and underscores the urgent need for early developmental screening in children with BA. It also opens new avenues for understanding how early-onset organ disease can affect brain development, potentially informing care strategies for other paediatric conditions.

It revealed that 47 per cent of children aged under 12 with BA required additional developmental support, according to parental reports. The research also found that nearly 30 per cent of the cohort met research criteria for autism, a rate far exceeding the national average in children in England.

The study collected data using three approaches, from 2020-2024:

• A survey to parents of children under 12 with BA, under the care of King’s College Hospital, one of the world’s leading centres for the care of infants and children born with biliary atresia.  47 percent of parents reported they needed additional support.
• A comparison of general development (motor, language, cognition) in 50 children under five years of age with BA to children with a low and high likelihood of neurodevelopmental difficulties
• In the same 50 children with BA, a further examination to see if key medical factors, such as age of diagnosis, the success level of the initial intervention surgery , and whether the child had a liver transplant, was related to later developmental outcomes.

Dr Megan Earl, Research Associate, IoPPN, King’s College London, and the first author, said: “Even before the age of two, a sizeable number of these children show brain developmental delays. The finding that a higher than expected number infants with Bilary Artersia also have autistic rates suggests an impact on social communication, a novel finding for this cohort.

Early intervention

The study highlights the importance of early diagnosis and timely surgical intervention. Children with BA undergo an intervention surgery at the time of diagnosis to restore bile flow and clear their jaundice, and this study highlighted that the children who underwent this surgery earlier, and who cleared their jaundice quicker, had better general neurodevelopmental outcomes. However, these improvements did not extend to the social behaviours associated with autism, suggesting there may be different mechanisms underlying general and more specific differences in brain development.

Grainne McAlonan, Director, NIHR Maudsley Biomedical Research Centre, and Professor of Translational Neuroscience at King's College London, and an author of the paper, said:

“Our results should encourage us to remember the developing brain in the context of physical illness in children. They encourage a whole person approach to assessing need and managing young children with early onset liver disease. Given these findings, we advocate for the inclusion of children with BA in further research and consider their access to early developmental intervention programmes, like those already in place for preterm infants, children with cerebral palsy, and those with autism.

As a psychiatrist I have also learned so much working with the paediatric liver team lead by Dr Marianne Samyn and Professor Anil Dhawan. Their holistic approach to the children and young people under their care is a model to emulate.”

Exploring the brain-liver connection

The study proposes several possible mechanisms linking early liver disease to neurodevelopmental outcomes which may be investigated in future research:

• High levels of toxicity due to the increased bilirubin (a yellow substance found naturally in the blood that causes jaundice), a known risk factor for brain injury in new borns.
• Gut-brain axis (a complex network connecting the brain and gut) disruption as altered bile acid composition and gut microbiome imbalance in BA may influence neurodevelopment.
• Perinatal inflammation in early life is implicated in both BA and autism spectrum conditions.

Whilst this study offers critical insights, the authors acknowledge several limitations including a small, but modest, sample size due to COVID-19 pandemic disruptions, and the use of a single autism observation tool instead of the combination with a matching parental interview that provides a more comprehensive diagnostic picture. It does not address how these neurodevelopmental differences change over time, something which requires on-going follow-up.

General and autism-related neurodevelopmental difficulties in Biliary Atresia (2025) The Journal of Pediatrics.; Earl, MA, Samyn, MB, Blackmore, CA, Brace, MA, Day, JB, Javed AA, Begum-Ali, JC, Johnson MHC, Jones, EJHC, Dhawan, AB, McAlonan, GMA.