Aramchol improves hepatic fibrosis in MASH: Results of multimodality assessment using both conventional and digital pathology
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Erişim
info:eu-repo/semantics/closedAccessTarih
2024Yazar
Ratziu, VladYılmaz, Yusuf
Lazas, Don
Friedman, Scott L.
Lackner, Caroline
Behling, Cynthia
Cummings, Oscar W.
Chen, Li
Petitjean, Matthieu
Gilgun-Sherki, Yossi
Gorfine, Tali
Kadosh, Shaul
Eyal, Eli
Sanyal, Arun J.
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Ratziu, V., Yilmaz, Y., Lazas, D., Friedman, S. L., Lackner, C., Behling, C., Cummings, O. W., Chen, L., Petitjean, M., Gilgun-Sherki, Y., Gorfine, T., Kadosh, S., Eyal, E., & Sanyal, A. J. (2024). Aramchol improves hepatic fibrosis in MASH: Results of multimodality assessment using both conventional and digital pathology. Hepatology (Baltimore, Md.), 10.1097/HEP.0000000000000980. Advance online publication. https://doi.org/10.1097/HEP.0000000000000980Özet
Background and aims: Antifibrotic trials rely on conventional pathology (CP) despite recognized limitations. We compared single fiber digital image analysis (DIA) with CP to quantify the antifibrotic effect of Aramchol, a stearoyl-CoA desaturase 1 inhibitor in development for metabolic-dysfunction associated steatohepatitis (MASH).
Approach and results: 51 MASH patients 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 three hepatopathologists, and separately assessed by a DIA platform (PharmaNest®) that generates a continuous phenotypic Fibrosis Composite Severity Score (Ph-FCS). Fibrosis improvement was defined as: >1 NASH-CRN stage reduction; "improved" by ranked pair assessment (RPA); reduction in Ph-FCS ("any" for >0.3 absolute reduction, "substantial" for >25% relative reduction). Fibrosis improved in 31% of patients (NASH-CRN), 51% (RPA), 74.5% (any Ph-FCS reduction) and 41% (substantial Ph-FCS reduction). Most patients with stable fibrosis by NASH-CRN or RPA had a Ph-FCS reduction (a third with substantial reduction). Fibrosis improvement increased with treatment duration: 25% for <48 weeks vs. 39% for >48 weeks by NASH-CRN; 43% vs. 61% by RPA, mean Ph-FCS reduction -0.54 (sd 1.22) vs. -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 ELF. Changes in Ph-FCS were positively correlated with changes in liver stiffness.
Conclusions: Continuous fibrosis scores generated in antifibrotic trials by DIA quantify antifibrotic effects with greater sensitivity and larger dynamic range than CP.