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

Ron C. Gaba, Nasya Mendoza-Elias, Daniel P. Regan, Kelly D. Garcia, R. Peter Lokken, Regina M. Schwind, Michael Eichner, Faith M. Thomas, Lauretta A. Rund, Lawrence B. Schook, Kyle M. Schachtschneider

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1194-1202.e1
JournalJournal of Vascular and Interventional Radiology
Volume29
Issue number8
DOIs
StatePublished - Aug 2018

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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    Gaba, R. C., Mendoza-Elias, N., Regan, D. P., Garcia, K. D., Lokken, R. P., Schwind, R. M., Eichner, M., Thomas, F. M., Rund, L. A., Schook, L. B., & Schachtschneider, K. M. (2018). Characterization of an Inducible Alcoholic Liver Fibrosis Model for Hepatocellular Carcinoma Investigation in a Transgenic Porcine Tumorigenic Platform. Journal of Vascular and Interventional Radiology, 29(8), 1194-1202.e1. https://doi.org/10.1016/j.jvir.2018.03.007