Novel Rat Model of Repetitive Portal Venous Embolization Mimicking Human Non-Cirrhotic Idiopathic Portal Hypertension

Klein, Sabine; Hinüber, C; Hittatiya, Kanishka; Schierwagen, Robert; Uschner, Frank Erhard; Strassburg, Christian P.; Fischer, Hans‐Peter; Spengler, Ulrich; Trebicka, Jonel

doi:10.1371/journal.pone.0162144

Cited by 20 publications

(10 citation statements)

References 26 publications

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“…There are several proposed animal models of IPH . Unfortunately, these models only partially reproduce the phenotypic characteristics of human IPH.…”

Section: Pathophysiology Etiology and Risk Factorsmentioning

confidence: 99%

Idiopathic Portal Hypertension

et al. 2018

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Idiopathic portal hypertension (IPH) is a rare disorder characterized by clinical portal hypertension in the absence of a recognizable cause such as cirrhosis. Laboratory tests often reveal a preserved liver function with anemia, leukopenia, and thrombocytopenia due to splenomegaly. Imaging studies reveal signs of portal hypertension, whereas liver stiffness and portal pressure values are usually normal or slightly elevated. Liver biopsy is considered mandatory in order to rule out other causes of portal hypertension, mainly cirrhosis. Liver histology may only show subtle or mild changes, and the definite diagnosis of IPH often requires an expert pathologist and a high-quality specimen. The most frequent clinical presentation is variceal bleeding. Ascites is rarely observed initially, although it may occasionally appear during follow-up. Typical histological findings associated with IPH have been described in patients without portal hypertension, probably representing early stages of the disease. Although the pathophysiology of this entity remains largely unknown, it is frequently associated with underlying immunological disorders, bacterial infections, trace metal poisoning, medications, liver circulatory disturbances, and thrombotic events. The long-term prognosis of patients with IPH, where ascites and the underlying condition are important prognostic factors, is better than in patients with cirrhosis. Treatments that modify the natural history of the disease remain an unmet need, and management of IPH is frequently restricted to control of portal hypertension-related complications.

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“…There are several proposed animal models of IPH . Unfortunately, these models only partially reproduce the phenotypic characteristics of human IPH.…”

Section: Pathophysiology Etiology and Risk Factorsmentioning

confidence: 99%

Idiopathic Portal Hypertension

et al. 2018

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“…Alcoholic liver disease [6,7,[31][32][33][34] NASH/HCC (WD + CCl 4 ) Knock-out mice HFD HF-HC MCD Non-alcoholic liver disease [1,7,9,[35][36][37][38][39][40][41][42][43][44] Xenograft Isograft DEN DEN + CCL 4 NASH/HCC (WD + CCl 4 ) Hepatocarcinoma [7,9,[45][46][47][48][49] Hemodynamic assays Monitoring protocols HVPG CT-or MRI-based cross imaging Portal hypertension [39,[50][51][52] Knock-out mice, retroviral, lentiviral, sh/siRNA knock-down, CRISPR/Cas9-based method Angiogenesis [53][54][55][56] A-DW: alcohol in drinking water; APAP: acetaminophen; HF-HC: high fat/high cholesterol; HFD: high-fat diet; LPS: lipopolysaccharide; MACS: magnetic-activated cell sorting; MCD: methionine choline deficient; NIAAA: mouse model of chronic and binge ethanol feeding.…”

Section: Methods Application Referencesmentioning

confidence: 99%

Recent Advances in Practical Methods for Liver Cell Biology: A Short Overview

Torres

Abdullah²,

Brol

et al. 2020

IJMS

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Molecular and cellular research modalities for the study of liver pathologies have been tremendously improved over the recent decades. Advanced technologies offer novel opportunities to establish cell isolation techniques with excellent purity, paving the path for 2D and 3D microscopy and high-throughput assays (e.g., bulk or single-cell RNA sequencing). The use of stem cell and organoid research will help to decipher the pathophysiology of liver diseases and the interaction between various parenchymal and non-parenchymal liver cells. Furthermore, sophisticated animal models of liver disease allow for the in vivo assessment of fibrogenesis, portal hypertension and hepatocellular carcinoma (HCC) and for the preclinical testing of therapeutic strategies. The purpose of this review is to portray in detail novel in vitro and in vivo methods for the study of liver cell biology that had been presented at the workshop of the 8th meeting of the European Club for Liver Cell Biology (ECLCB-8) in October of 2018 in Bonn, Germany.

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“…This preclinical model and the experimental method may also have a significant impact on the preclinical evaluation of locoregional HCC therapies and provide further benefit research in this area. Previously, creating an animal model of PVT, PHT, or vena thrombosis has been successfully attempted [12][13][14][15]. However, no effective models of cirrhosis with PVT have been introduced.…”

Section: Biomed Research Internationalmentioning

confidence: 99%

“…In other cases, PVT in cirrhosis was triggered by a genetic predisposition and inflammation effects [8][9][10][11]. Previous techniques have successfully induced animal models of PVT, PHT, and vena thrombosis [12][13][14][15]. However, the established animal model of PVT in cirrhosis remains an unsolved issue to date.…”

Section: Introductionmentioning

confidence: 99%

A Preclinical Porcine Model of Portal Vein Thrombosis in Liver Cirrhosis

Zhang

Jiang

et al. 2020

BioMed Research International

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Background. This study aimed at presenting a novel method of developing a porcine model of portal vein thrombosis (PVT) in cirrhosis by intravenous administration of thrombin and insertion of a fibered coil. We further investigated changes of biochemical parameters, coagulation, and proinflammatory cytokine expression in the cirrhosis-PVT group. Methods. Twelve male pigs were randomized into the control group (n=3) and cirrhosis group (n=9). In cirrhotic pigs, three were randomly selected to establish PVT by ultrasound-guided percutaneous puncture of the main portal vein (MPV) followed by intravenous thrombin administration and fibered coil insertion. Thrombosis in the MPV was detected by abdominal enhanced computer tomography (CT). The changes of hepatic function, coagulation system, and inflammation cytokines were compared among normal, cirrhosis, and cirrhosis with PVT groups. Results. As manifested by the presence of a filling defect in MPV on portal venous-phase CT angiography, fibrin thrombi were formed in the MPV in cirrhotic pigs within one week and persisted for four weeks. Five weeks after surgery, abnormal liver functions occurred in association with PVT formation in cirrhosis. Both coagulation and thromboelastography parameters showed that cirrhosis-PVT pigs exhibited a procoagulant state through hyperfunction of platelets and clotting factors. Interleukin 6 (IL-6) as a potential inflammatory marker stimulated PVT-mediated inflammation activation in cirrhosis. Conclusions. Our study provides in vivo evidence that intravenous injection of a coil and thrombin into MPV under interventional guided devices enables a feasible method in thrombus creation. Further exploration and validation of large-sample cases are required to characterize utilities of this model.

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Novel Rat Model of Repetitive Portal Venous Embolization Mimicking Human Non-Cirrhotic Idiopathic Portal Hypertension

Cited by 20 publications

References 26 publications

Idiopathic Portal Hypertension

Idiopathic Portal Hypertension

Recent Advances in Practical Methods for Liver Cell Biology: A Short Overview

A Preclinical Porcine Model of Portal Vein Thrombosis in Liver Cirrhosis

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