Abstract #4342

Imaging response to Elafibranor treatment in a rat model of non-alcoholic steatohepatitis non-invasively by oxidized-collagen molecular MRI

Veronica Clavijo Jordan ¹, Iris Yuwen Zhou¹, Nicholas Rotile¹, Noah Warner¹, Eman Aburieda Akam¹, Gunisha Arora², Smitha Krishnan², Christian Farrar¹, Alana Ross¹, Bryan Fuchs², and Peter Caravan^1,3

¹Athinoula A. Martinos Center for Biomedical Imaging, MGH, Harvard Medical School, Charlestown, MA, United States, ²Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States, ³Institute for Innovation in Imaging (i3), Charlestown, MA, United States

Elafibranor is a dual agonist of the peroxisome proliferator-activated receptor-⍺ and δ (PPAR-⍺ and δ) in Phase III clinical trials for treatment of non-alcoholic steatohepatitis (NASH). Here, we evaluated the drug’s effectiveness in a choline-deficient high fat diet (CDAHFD) NASH model by imaging oxidized collagen as a marker for fibrogenesis in the liver using a Gd-based probe and MRI. Oxidized collagen MRI of the liver showed that Elafibranor successfully reduced fibrogenesis in rats with histologically-confirmed NASH, ex-vivo total collagen quantification by hydroxyproline assay, and histology staining, also confirmed the anti-fibrotic effect of Elafibranor in the CDAHFD-induced NASH model.

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