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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388685PMC
http://dx.doi.org/10.1016/j.jvir.2018.03.007DOI Listing

Publication Analysis

Top Keywords

liver injury
12
histologic analysis
12
median metavir
12
metavir range
12
liver
9
fibrosis
8
model hepatocellular
8
hepatocellular carcinoma
8
injury induced
8
cohort n =
8

Similar Publications

Background: Selective androgen receptor modulators (SARMs) are small-molecule compounds that exert agonist and antagonist effects on androgen receptors in a tissue-specific fashion. Because of their performance-enhancing implications, SARMs are increasingly abused by athletes. To date, SARMs have no Food and Drug Administration approved use, and recent case reports associate the use of SARMs with deleterious effects such as drug-induced liver injury, myocarditis, and tendon rupture.

View Article and Find Full Text PDF

Role of hepatocyte-specific FOXO1 in hepatic glucolipid metabolic disorders induced by perfluorooctane sulfonate.

Environ Pollut

January 2025

Department of Toxicology, School of Public Health, Hebei Medical University, Shijiazhuang, 050017, PR China; Hebei Key Laboratory of Environment and Human Health, Hebei Province, Shijiazhuang, 050017, PR China. Electronic address:

Perfluorooctane sulfonate (PFOS), a prevalent perfluoroalkyl substance (PFAS), is widely present in various environmental media, animals, and even human bodies. It primarily accumulates in the liver, contributing to the disruption of hepatic metabolic homeostasis. However, the precise mechanism underlying PFOS-induced hepatic glucolipid metabolic disorders remains elusive.

View Article and Find Full Text PDF

Complex wound closure scenarios necessitate the development of advanced wound dressings that can effectively address the challenges of filling irregularly shaped wounds and managing fatigue failures encountered in daily patient activities. To tackle these issues, we develop a multifunctional hydrogel from natural polysaccharides and polypeptides with injectability and self-healing properties for promoting full-time and multipurpose wound healing. Synthesized through dynamic Schiff base linkages between oxidized hyaluronic acid (OHA), ε-polylysine (ε-PL), and quaternized chitosan (QCS), the OHA/ε-PL/QCS hydrogel can gel rapidly within 50 s.

View Article and Find Full Text PDF

Tetrahydroberberrubine improves hyperlipidemia by activating the AMPK/SREBP2/PCSK9/LDL receptor signaling pathway.

Eur J Pharmacol

January 2025

State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology, College of Pharmacy, and Department of Cardiology, the Second Affiliated Hospital, Harbin Medical University, Harbin 150081, China; State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, and Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin 150081, China; Research Unit of Noninfectious Chronic Diseases in Frigid Zone (2019RU070), Chinese Academy of Medical Sciences, Harbin 150081, China. Electronic address:

Hyperlipidemia is a major risk factor for hypertension, coronary heart disease, diabetes and stroke, triggering an intensified research efforts into its prevention and treatment. Tetrahydroberberrubine (THBru) is a derivative of berberine (BBR) that has been shown to have higher bioavailability and lower toxicity compared to its parent compound. However, its impact on hyperlipidemia has not been fully explored.

View Article and Find Full Text PDF

Host hepatocyte senescence determines the success of hepatocyte transplantation in a mouse model of liver injury.

J Hepatol

January 2025

Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, EH16 4UU, United Kingdom. Electronic address:

Background & Aims: Hepatocyte transplantation has shown promise for genetic diseases of the hepatocytes but to date has shown limited efficacy for non-genetic forms of severe liver injury. Limited cell engraftment and poor function of donor hepatocytes in recipient livers impacts the clinical utility of hepatocyte cell therapy. The mechanisms underpinning this are poorly understood.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!