Early-onset chronic liver disease (CLD) and its subsequent clinical progression have systemic impact. Its trajectory coincides with critical periods of brain development. In this study, we will test the hypothesis that early-onset CLD is associated with neurodevelopmental and psychiatric symptoms and delineate their neurobiological underpinnings through multimodal neuroimaging.

This study will recruit 100 patients with biliary atresia and 50 patients with other types of early-onset CLD, aged between 6 and 30 years, under the primary care of Paediatric Liver Services at King’s College Hospital, London, UK. Cognitive performance and autism-related behaviours will be evaluated with neurodevelopmental assessments. Participants and their parents will complete questionnaires addressing neurodevelopmental and psychiatric outcomes in everyday life, and quality of life. Multimodal neuroimaging will be conducted using electroencephalography (EEG); eye-tracking; structural, functional and diffusion MRI; and magnetic resonance spectroscopy (MRS). Clinical information will be collected from patients’ medical records and bio samples. Data of 222 neurotypical controls and 307 neurodivergent controls without CLD will be pooled from the Longitudinal European Autism Project with a similar study protocol. Neurodevelopmental and psychiatric outcomes will be compared with normative values and between groups. Associations with clinical risk factors will be explored using multivariable regression. Neuroimaging markers will be compared between groups and associations with neurodevelopmental outcomes and clinical risk factors will be tested using multivariable regression. Individual deviation from normal brain development will be quantified using Bayesian modelling and will be associated with neurodevelopmental outcomes.

This study was approved by the National Health Service Health Research Authority’s ethical committee (REC reference: 22/PR/1587). Findings from this study will be published in peer-reviewed journals, presented at national and international conferences and shared with patients and their families for widespread dissemination of the results.