Proteomics Insight into the Pathogenic Evolution of Chronic Hepatitis B across Distinct Clinical Stages

Chronic hepatitis B (CHB) is clinically classified into different clinical stages during which dynamic interactions occur among the virus, host immune system, and hepatic tissue. The lack of systematic proteomic analysis of liver tissue and functional change characteristics across different stages of CHB has prevented the provision of novel critical clues for precise staging interventions in HBV infection. In this study, we performed the first comprehensive proteome comparison of liver tissue across four clinical phases of CHB: the immune-tolerant (IT) phase, immune-active (IA), inactive carrier (IC), and hepatitis B e antigen (HBeAg)-negative hepatitis (ENEG) phases. The four stages of CHB liver exhibited a dynamic cascade of "metabolic stress-mitochondrial damage-immune imbalance-fibrosis", wherein mitochondrial dysfunction represents the core pathological mechanism of CHB. Furthermore, correlations between changes in immune cell subpopulations and clinical features across the four infection stages suggest therapeutic potential in targeting alterations in immune cells, offering novel perspectives for precise stage-targeted interventions and mechanistic insights into CHB.