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Spatial profiling of chronic liver disease: a pilot spatial case series
Shota Sasagawa1, Atsushi Ono2, Koji Arihiro3
1Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
Scientific Reports
|April 20, 2026
Summary
Chronic liver disease tissues share a common spatial organization, with specific immune, metabolic, and viral programs varying by cause, such as alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatohepatitis (MASH). This spatial architecture offers new insights into liver disease progression.
Area of Science:
- Hepatology
- Molecular Biology
- Genomics
Background:
- The spatial organization of chronic liver disease (CLD) across different causes is not fully understood.
- Investigating CLD spatial architecture can reveal disease mechanisms and therapeutic targets.
Purpose of the Study:
- To explore the spatial transcriptomic landscape of alcohol-associated liver disease (ALD), metabolic dysfunction-associated steatohepatitis (MASH), and chronic hepatitis C (HCV).
- To identify shared and distinct spatial features and cell-cell communication patterns in CLD.
Main Methods:
- Sequencing-based spatial transcriptomics applied to human liver tissues.
- Viral-aware workflow for in situ detection of viral RNA.
- Histology-guided niche annotation and cell-cell communication analysis.
Main Results:
- Viral RNA in HCV cases localized to immune-enriched areas and pathways involved in cell-cycle and immune checkpoints.
- Histology-guided segmentation aligned with transcriptomic clusters in ALD and MASH.
- Recurrent functional compartments and immune-mesenchymal signaling hubs were identified across etiologies.
Conclusions:
- Chronic liver disease tissues exhibit a shared pseudolobular functional architecture.
- Etiology-specific programs (immune, metabolic, viral) are superimposed on this architecture.
- Spatial transcriptomics provides a powerful tool for dissecting CLD heterogeneity.
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