Digital pathology and spatial omics in steatohepatitis: Clinical applications and discovery potentials

Abstract

Steatohepatitis with diverse etiologies is the most common histological manifestation in patients with liver disease. However, there are currently no specific histopathological features pathognomonic for metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), or MASLD with increased alcohol intake (MetALD). Digitizing traditional pathology slides has created an emerging field of digital pathology (DP), allowing for easier access, storage, sharing, and analysis of whole-slide images (WSI). Artificial intelligence (AI) algorithms have been developed for WSI to enhance the accuracy and speed of the histological interpretation of steatohepatitis and are currently employed in biomarker development. Spatial biology is a novel field that enables investigators to map gene and protein expression within a specific region of interest (ROI) on liver histological sections, examine disease heterogeneity within tissues, and understand the relationship between molecular changes and distinct tissue morphology. Here, we review the utility of DP (using linear and nonlinear microscopy) augmented with AI analysis to improve the accuracy of histological interpretation. We will also discuss the spatial omics landscape with special emphasis on the strength and limitations of established spatial transcriptomics and proteomics technologies and their application in steatohepatitis. We then highlight the power of multimodal integration of DP augmented by machine learning algorithms with spatial biology. The review concludes with a discussion of the current gaps in knowledge, the limitations and premises of these tools and technologies, and the areas of future research.