Characterization of an Inducible Alcoholic Liver Fibrosis Model for Hepatocellular Carcinoma Investigation in a Transgenic Porcine Tumorigenic Platform.

Autor:	Gaba RC; Department of Radiology, University of Illinois Health, 1740 West Taylor Street, MC 931, Chicago, Illinois, 60612., Mendoza-Elias N; College of Medicine, University of Illinois at Chicago, Chicago, Illinois., Regan DP; Flint Animal Cancer Center, Colorado State University, Fort Collins, Colorado., Garcia KD; Biological Resources Laboratory, University of Illinois at Chicago, Chicago, Illinois., Lokken RP; Department of Radiology, University of Illinois Health, 1740 West Taylor Street, MC 931, Chicago, Illinois, 60612., Schwind RM; Department of Radiology, University of Illinois Health, 1740 West Taylor Street, MC 931, Chicago, Illinois, 60612., Eichner M; Biological Resources Laboratory, University of Illinois at Chicago, Chicago, Illinois., Thomas FM; Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana and Champaign, Illinois., Rund LA; Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana and Champaign, Illinois., Schook LB; Department of Radiology, University of Illinois Health, 1740 West Taylor Street, MC 931, Chicago, Illinois, 60612; Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana and Champaign, Illinois., Schachtschneider KM; Department of Radiology, University of Illinois Health, 1740 West Taylor Street, MC 931, Chicago, Illinois, 60612. Electronic address: kschach2@uic.edu.
Jazyk:	angličtina
Zdroj:	Journal of vascular and interventional radiology : JVIR [J Vasc Interv Radiol] 2018 Aug; Vol. 29 (8), pp. 1194-1202.e1. Date of Electronic Publication: 2018 Jun 07.
DOI:	10.1016/j.jvir.2018.03.007
Abstrakt:	Purpose: This study used the Oncopig Cancer Model (OCM) to develop alcohol-induced fibrosis in a porcine model capable of developing hepatocellular carcinoma. Materials and Methods: Liver injury was induced in 8-week-old Oncopigs (n = 10) via hepatic transarterial infusion of 0.75 mL/kg ethanol-ethiodized oil (1:3 v/v). Feasibility was assessed in an initial Oncopig cohort (n = 5) by histologic analysis at 8 weeks after induction, and METAVIR results were compared to age- and sex-matched healthy controls (n = 5). Liver injury was then induced in a second OCM cohort (n = 5) for a time-course study, with post-induction disease surveillance via biweekly physical exam, lab analysis, and liver biopsies until 20 weeks after induction. Results: In Cohort 1, 8-week post-induction liver histologic analysis revealed median METAVIR F3 (range, F3-F4) fibrosis, A2 (range, A2-A3) inflammation, and 15.3% (range, 5.0%-22.9%) fibrosis. METAVIR and inflammation scores were generally elevated compared to healthy controls (F0-F1, P = 0.0013; A0-A1, P = .0013; median percent fibrosis 8.7%, range, 5.8%-12.1%, P = .064). In Cohort 2, histologic analysis revealed peak fibrosis severity of median METAVIR F3 (range, F2-F3). However, lack of persistent alcohol exposure resulted in liver recovery, with median METAVIR F2 (range, F1-F2) fibrosis at 20 weeks after induction. No behavioral or biochemical abnormalities were observed to indicate liver decompensation. Conclusions: This study successfully validated a protocol to develop METAVIR F3-F4 fibrosis within 8 weeks in the OCM, supporting its potential to serve as a model for hepatocellular carcinoma in a fibrotic liver background. Further investigation is required to determine if repeated alcohol liver injury is required to develop an irreversible METAVIR grade F4 porcine cirrhosis model. (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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