Transcriptomic signatures of gray matter volume alterations in hepatic encephalopathy

It has been revealed that brain gray matter volume (GMV) abnormalities are present in patients with hepatic encephalopathy (HE). However, the GMV alterations in HE that have been uncovered are inconsistent, and their correlation with gene expression profiles is still unknown. We conducted a quantitative neuroimaging meta-analysis on seven studies, involving 142 HE individuals and 193 HCs, to identify consistent patterns of GMV alterations in HE. We then utilized the Allen Human Brain Atlas database to investigate transcriptome-neuroimaging spatial correlations, exploring gene expression profiles related with GMV changes in HE. Functional enrichment analyses were further performed to identify biological significance of the GMV-related genes. Compared with healthy controls, patients with HE exhibited decreased GMV primarily in the bilateral cerebellum, basal nuclei, insula, cingulate / paracingulate gyri (the anterior and the median), superior frontal gyrus (medial), precuneus and right inferior frontal gyrus. While the GMV of bilateral thalamus and right lingual gyrus were observed to increase in HE patients. Moreover, we revealed spatial associations between brain structural changes and transcriptional profiles of 2035 genes, which were enriched in specific biological processes in HE. Our findings improved the understanding of GMV abnormalities in HE and provided insights into the transcriptional expression patterns underlying these alterations.