Immune response- and viral control-related pathways in the progression of chronic hepatitis B

•This work performed the pairwise comparisons of the hepatic transcriptomes of CHB under different phases.•Relative to immune tolerant phase, TGF-beta receptor signaling in EMT pathway was changed in immune clearance phase.•Nuclear receptor transcription and adenylate cyclase activating pathways were altered in inactive carrier state.•The host genes related to DNA strand elongation showed difference between immune clearance and inactive carrier states.

BackgroundChronic hepatitis B (CHB) is a complicated and dynamic course, and is associated with advanced liver disease. Host immune response against viral infection plays a pivotal role in the progression of CHB. However, it is still uncharted that how the hepatic transcriptomes in patients with CHB are correlated with the clinical phases.ObjectiveThis study aimed to identify the specific sub-networks across various phases of CHB and infer potential pathways for phenotypic outcome prediction.MethodsIn this study, we performed the pairwise comparisons of the hepatic transcriptomes of CHB patients under different phases, and constructed the differential co-expression networks (DCNs). We firstly identified the critical genes from each DCN according to the adjacency matrix of the network. Then, the specific sub-networks were digged by iteratively affiliating genes that can increase the classification accuracy, using a snow-ball sampling strategy. Permutation test was implemented to determine the statistical significance of these sub-networks. Finally, each sub-network was given a most significant functional pathway.ResultsWe constructed 3 DCNs by pairwise comparing the hepatic transcriptomes among three CHB phases, and systemically tracked 1, 1 and 2 specific sub-networks and pathways, respectively. Relative to immune tolerant phase, TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) pathway was significantly changed in the immune clearance phase, and nuclear receptor transcription pathway and adenylate cyclase activating pathway were altered in inactive carrier state. The host genes related to DNA strand elongation showed significant difference between the immune clearance phase and inactive carrier state.ConclusionsBy pairwise comparing the hepatic transcriptomes of CHB patients under a network view, several immune- and viral control-related pathways were identified in this study. These results might serve as a foundation for characterizing the host transcriptomes responded to CHB infection, and hold clues for the development of potential targets for disease control.