dc.contributor.author | Ratziu, Vlad | |
dc.contributor.author | Yılmaz, Yusuf | |
dc.contributor.author | Lazas, Don | |
dc.contributor.author | Friedman, Scott L. | |
dc.contributor.author | Lackner, Caroline | |
dc.contributor.author | Behling, Cynthia | |
dc.contributor.author | Cummings, Oscar W. | |
dc.contributor.author | Chen, Li | |
dc.contributor.author | Petitjean, Matthieu | |
dc.contributor.author | Gilgun-Sherki, Yossi | |
dc.contributor.author | Gorfine, Tali | |
dc.contributor.author | Kadosh, Shaul | |
dc.contributor.author | Eyal, Eli | |
dc.contributor.author | Sanyal, Arun J. | |
dc.date.accessioned | 2024-07-19T10:42:16Z | |
dc.date.available | 2024-07-19T10:42:16Z | |
dc.date.issued | 2024 | en_US |
dc.identifier.citation | 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.0000000000000980 | en_US |
dc.identifier.issn | 0270-9139 | |
dc.identifier.issn | 1527-3350 | |
dc.identifier.uri | https://doi.org/10.1097/HEP.0000000000000980 | |
dc.identifier.uri | https://hdl.handle.net/11436/9200 | |
dc.description.abstract | 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. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Wolters Kluwer Medknow Publications | en_US |
dc.rights | info:eu-repo/semantics/closedAccess | en_US |
dc.title | Aramchol improves hepatic fibrosis in MASH: Results of multimodality assessment using both conventional and digital pathology | en_US |
dc.type | article | en_US |
dc.contributor.department | RTEÜ, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü | en_US |
dc.contributor.institutionauthor | Yılmaz, Yusuf | |
dc.relation.journal | Hepatology | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |