New dimension in viral hepatitis research.

Area of Science:

• Hepatology and immunology
• Genomics and transcriptomics
• Infectious diseases

Background:

• Chronic hepatitis B (HBV) is a major cause of liver cancer, affecting millions globally.
• Hepatitis delta virus (HDV) coinfection accelerates disease progression in HBV patients.
• Understanding liver immune responses is crucial for achieving an HBV functional cure.

Purpose of the Study:

• To investigate spatial gene expression patterns in liver tissues of patients with HBV infection.
• To explore the utility of digital spatial profiling (DSP) in analyzing HBV and coinfections.
• To identify distinct transcriptomic signatures associated with viral burden and immune features.

Main Methods:

• Utilized GeoMx nanostring digital spatial profiling (DSP) technology on liver tissue samples.
• Analyzed gene expression in specific regions of interest (ROIs) from three patients (HBV, HBV/HDV, HBV/HIV).
• Mapped precise gene expression for targeted analysis of immune responses and viral load.

Main Results:

• Identified spatially distinct transcriptomic signatures related to immune cell infiltration and viral burden.
• Revealed a component of underinvestigated immune cells within the liver microenvironment.
• Demonstrated the feasibility of spatial transcriptomics for analyzing HBV infection dynamics.

Conclusions:

• Spatial transcriptomics, particularly DSP, is a viable approach for studying HBV infection.
• The study identified unique transcriptomic profiles linked to viral presence and immune activity.
• Further multiomics integration is needed to overcome diagnostic challenges and advance HBV therapy.