Efficient sampling of liver tissue for histological analysis of rodent MASLD/MASH models.

Mouse and rat models of MASLD/MASH can provide valuable information about the effects of potential new treatments on liver histopathology. Liver samples for histology must therefore be representative of the entire organ, but it is also important that they can be collected efficiently. In rodent toxicity studies, it is recommended to collect samples for histopathology from the left lateral liver lobe (LLL), the right medial lobe (RML), and the caudate lobe (CL). Samples collected from multiple lobes provide a representative overview of the entire liver, but at the same time, increase the workload in the histology laboratory. The aim of the present study was to explore whether the number of histology samples per animal could be reduced and still provide the same information about treatment effects on quantitative histology endpoints. This was examined in different mouse and rat MASH models, where fibrosis (marker: picrosirius red), stellate-cell activation (marker: smooth muscle actin), and inflammation (marker: CD45) were quantified by image analysis of the three recommended liver lobes. Results determined in a single lobe, as well as combined analysis of the LLL and RML, revealed the same relative treatment effects as analysis of all three lobes combined. Results from single lobes tended to have slightly higher variation than results based on the analysis of three lobes, with the CL being the most variable. In conclusion, sampling of the LLL and/or the RML provides information about treatment effects comparable to sampling of three lobes and allows for efficient processing of histology samples in the laboratory.