Connectome-based mapping of gray matter abnormalities in hepatic encephalopathy.

Objective: Hepatic encephalopathy (HE) is linked to widespread gray matter abnormalities, but it remains unclear whether these changes follow the organizing principles of large-scale brain networks. This study examined the spatial distribution of gray matter abnormalities in HE and their relationships with brain network hubs, neighborhood connectivity, and disease epicenters. Methods: In this cross-sectional study, 45 patients with HE and 45 healthy controls underwent high-resolution T1-weighted MRI. Cortical thickness was extracted from 308 cortical regions using the Desikan-Killiany atlas, and volumes were measured from 14 subcortical structures. Group differences were analyzed controlling for age, sex, and total intracranial volume. Connectome-based analyses were based on normative functional and structural connectomes from the Human Connectome Project and assessed hub-related vulnerability, network-neighborhood effects, disease epicenters, and individual-level network patterns. Results: Patients with HE showed widespread gray matter abnormalities in the prefrontal, motor, temporal, and limbic cortices, as well as basal ganglia and thalamus, without significant alignment with normative functional or structural hubs. Structural neighborhood abnormalities were positively correlated with cortical changes ( Conclusion: These findings suggest that gray matter abnormalities in HE are non-randomly organized, constrained by structural connectivity, and associated with prefrontal-centered disease epicenter networks, providing connectome-based insights into gray matter abnormalities in HE.