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Challenges in MASH discovery

Because MASH is deeply systemic (affecting glucose metabolism, immune response, and lipid synthesis), single-target drugs are rarely sufficient. Also, many traditional models fail to mirror the full spectrum of the human disease, leading to high failure rates in clinical trials.

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A ourely diet induced model was developed to mirrorthe human condition. High fat, high carb diet fed zebrafish develops a progressive steatosis followed by lobular inflammation, ballooning and fibrosis.  Morphometric methods were used for the first level of screening

 

Morphometric Traits: Extracts specific metrics such as collagen fiber width, fiber length, and reticular network density.


 Nuclear Morphology: Calculates quantitative features like nuclear elongation, vacuolation, and texture homogeneity, tracking cellular senescence along the liver zonation

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Spatial Morphology Measurements 

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Histology Scoring

1 - Steatosis
2 - Ballooning
3 - Lobular Inflammation
4 - Fibrosis
5 - Cirrhosis

Solutuions for Pre-clinical studies in MASH

Histology grading with AI assisted workflows were employed to generate a high degree of precision in screening.

 

​Key Quantifiable Histological Readouts
•    Steatosis: Explicitly measures the total fat area fraction and fat droplet distribution.
•    Lobular Inflammation: Maps out and measures inflammation density across specific zones.
•    Hepatocellular Ballooning: Quantifies cellular injury, swelling, and nuclear deformation.
•    Fibrosis Architecture: Measures collagen architectural traits (e.g., septa and nodule formations) crucial for tracking anti-fibrotic drug efficacy

 

AI-assisted workflows demonstrated outright superiority over manual reads for identifying complex MASH features (specifically hepatocellular ballooning and precise zone inflammation) and determining correct trial eligibility.

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