From Portal Tract to Central Vein: Quantifying Zonal Steatosis and Fibrotic Bridging in Human Liver H&E Histology

Abstract

Background: Conventional liver histology evaluates steatosis, inflammation, hepatocellular injury, and fibrosis, and many studies classify the former three as percentages or stages. However, few articles analyze lesions at specific sites distributed from portal to centrilobular regions in the liver lobules. The hepatic zonation is crucial for liver physiology, which can be disrupted by metabolic dysfunction-associated steatotic liver disease.
Objective: To develop an interpretable H&E-based framework for quantifying the lobular geography of steatosis and chronic remodeling in human liver histology.
Methods: GTEx Liver whole-slide images and pathology-review metadata will be used to construct pathology-review-negative reference, steatosis, fibrosis/cirrhosis, hepatitis/inflammation, and congestion challenge groups. Portal tracts and central veins will be identified according to validated morphological rules and manual quality control. Each parenchymal tile will be assigned a normalized portal-central coordinate. The primary endpoint will be the Steatosis Zonal Bias Index (SZBI), defined as pericentral minus periportal steatosis burden. Secondary endpoints will include steatosis connectivity, Portal Inflammatory Enrichment, an H&E Fibrotic Bridge Proxy, portal-central lesion-gradient entropy, and Liver Histological Distance from Normal. External biological replication will be achieved using open tissue images from the 2026 spatial atlas of the healthy human liver, which contains mild steatosis and portal fibrosis.
Results: No inferential results are reported in this pre-results manuscript.
Conclusion: Spatially explicit liver histology may distinguish equal lesion burdens with different lobular geography and may provide a transparent bridge between routine H&E morphology and modern spatial liver biology.