Microscopic messengers: roles and prospects of extracellular vesicles in hepatitis B and C

Extracellular vesicles (EVs) are important mediators of intercellular communication in hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. EVs released from infected hepatocytes can carry viral nucleic acids, proteins, and regulatory non-coding RNAs to immune and nonimmune cells, thereby influencing viral dissemination, immune regulation, and disease progression. In particular, EV-associated cargos modulate antiviral immunity by affecting interferon signaling, natural killer cell function, cytokine production, immune checkpoint pathways, and T-cell exhaustion. These effects may promote viral persistence and immune evasion, although some EV populations can also enhance innate antiviral responses, indicating context-dependent dual roles. EVs also contribute to fibrosis and hepatocarcinogenesis by regulating hepatic stellate cell activation, inflammatory signaling, and tumor microenvironment remodeling. In addition, EV-derived RNAs and proteins show potential as noninvasive biomarkers and therapeutic targets. This review summarizes current evidence on EVs in HBV and HCV infection, with emphasis on immune regulation, viral persistence, disease progression, and translational prospects, while also discussing key challenges such as EV heterogeneity and co-isolation with viral particles.