Harnessing exosomes for biomarker development and therapy in hepatitis virus infection

Exosomes, a specialized subclass of extracellular vesicles, have emerged as critical mediators in the pathogenesis of viral hepatitis. Hepatotropic viruses hijack host exosomal biogenesis pathways to facilitate immune evasion, promote viral dissemination, and drive chronic inflammation and hepatic fibrosis. Paradoxically, these same vesicles offer unprecedented opportunities for noninvasive disease monitoring and targeted therapeutic intervention. This narrative review synthesizes current evidence on the dual role of exosomes in hepatitis virus infection, evaluating their evolution from pathogenic vectors to clinical tools for liquid biopsy diagnostics and engineered antiviral delivery. We examined how exosomal cargo, including microRNAs, proteins, and viral nucleic acids, enables precise stratification of liver disease stages, real-time treatment monitoring, and early detection of hepatocellular carcinoma. Furthermore, we explore advanced bioengineering strategies, such as endogenous cargo loading, surface functionalization, and the targeted delivery of CRISPR/Cas9 complexes and RNA-based therapeutics, which position engineered exosomes as next-generation precision nanomedicines. Despite compelling preclinical data, clinical translation remains constrained by significant bottlenecks, including scalable good manufacturing practice (GMP) production, the lack of standardized isolation and characterization protocols, and evolving regulatory pathways. Bridging the gap between laboratory innovation and bedside application will require coordinated advancements in manufacturing technology, global standardization initiatives, and rigorous clinical validation. Successfully overcoming these hurdles could establish exosome-based platforms as transformative tools for achieving functional cures and improving long-term outcomes in patients with viral hepatitis.