Ratziu, VladYilmaz, YusufLazas, DonFriedman, Scott L.Lackner, CarolineBehling, CynthiaCummings, Oscar W.Chen, LiPetitjean, MathieuGilgun-Sherki, YossiGorfine, TaliKadosh, ShaulEyal, EliSanyal, Arun J.2025-07-172025-07-172025Ratziu V, Yilmaz Y, Lazas D, et al. Aramchol improves hepatic fibrosis in metabolic dysfunction-associated steatohepatitis: Results of multimodality assessment using both conventional and digital pathology. Hepatology. 2025;81(3):932-946. doi:10.1097/HEP.0000000000000980https://hdl.handle.net/1805/49541Background and aims: Antifibrotic trials rely on conventional pathology despite recognized limitations. We compared single-fiber digital image analysis with conventional pathology to quantify the antifibrotic effect of Aramchol, a stearoyl-CoA desaturase 1 inhibitor in development for metabolic dysfunction-associated steatohepatitis. Approach and results: Fifty-one patients with metabolic dysfunction-associated steatohepatitis enrolled in the open-label part of the ARMOR trial received Aramchol 300 mg BID and had paired pre-post treatment liver biopsies scored by consensus among 3 hepatopathologists, and separately assessed by a digital image analysis platform (PharmaNest) that generates a continuous phenotypic Fibrosis Composite Severity (Ph-FCS) score. Fibrosis improvement was defined as: ≥1 NASH Clinical Research Network (NASH-CRN) stage reduction; "improved" by ranked pair assessment; reduction in Ph-FCS ("any" for ≥0.3 absolute reduction and "substantial" for ≥25% relative reduction). Fibrosis improved in 31% of patients (NASH-CRN), 51% (ranked pair assessment), 74.5% (any Ph-FCS reduction), and 41% (substantial Ph-FCS reduction). Most patients with stable fibrosis by NASH-CRN or ranked pair assessment had a Ph-FCS reduction (a third with substantial reduction). Fibrosis improvement increased with treatment duration: 25% for <48 weeks versus 39% for ≥48 weeks by NASH-CRN; 43% versus 61% by ranked pair assessment, mean Ph-FCS reduction -0.54 (SD: 1.22) versus -1.72 (SD: 1.02); Ph-FCS reduction (any in 54% vs. 100%, substantial in 21% vs. 65%). The antifibrotic effect of Aramchol was corroborated by reductions in liver stiffness, Pro-C3, and enhanced liver fibrosis. Changes in Ph-FCS were positively correlated with changes in liver stiffness. Conclusions: Continuous fibrosis scores generated in antifibrotic trials by digital image analysis quantify antifibrotic effects with greater sensitivity and a larger dynamic range than conventional pathology.en-USPublisher PolicyLiverLiver cirrhosisNon-alcoholic fatty liver diseaseChalconesArticle