Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics

Area of Science:

• Hepatology
• Immunology
• Genomics

Background:

• Chronic hepatitis B (CHB) intrahepatic processes, particularly with hepatitis delta virus (HDV) or HIV co-infection, require deeper understanding.
• Spatial transcriptomics offers novel insights into complex intrahepatic biology for personalized treatment strategies.

Purpose of the Study:

• To evaluate spatial transcriptomics for characterizing the intrahepatic transcriptional landscape, cellular composition, and biological pathways in liver biopsies.
• To investigate HBV, HDV, and HIV co-infections using this advanced methodology.

Main Methods:

• Utilized NanoString GeoMx digital spatial profiling on FFPE liver biopsies from treatment-naïve patients.
• Quantified gene expression using the GeoMx Human Whole Transcriptome Atlas and deconvoluted cell type proportions.
• Applied weighted gene correlation network analysis to evaluate transcriptomic signatures.

Main Results:

• Identified spatially discrete transcriptomic signatures and distinct biological pathways linked to HBV infection and immune responses.
• Observed shared features like 'cytotoxicity' and 'B cell receptor signalling' across patients.
• HDV/HBV co-infection showed upregulated apoptosis and immune cell recruitment genes; HIV/HBV co-infection revealed interferon response regulation genes. γδT cells were abundant in HDV/HBV samples. Hepatocyte function differences suggest metabolic disruption in HDV/HBV co-infection.

Conclusions:

• This proof-of-principle study demonstrates the utility of spatial transcriptomics in dissecting complex intrahepatic immune landscapes.
• The platform highlights relevant host pathways contributing to disease pathogenesis in viral hepatitis co-infections.