Steatosis as main determinant of portal hypertension through a restriction of hepatic sinusoidal area in a dietary rat nash model.

Autor: Barberá A; Liver Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain, Barcelona, Spain., Raurell I; Liver Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain, Barcelona, Spain., García-Lezana T; Icahn School of Medicine at Mount Sinai, New York, NY, USA., Torres-Arauz M; Liver Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain, Barcelona, Spain., Bravo M; Liver Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain, Barcelona, Spain., Hide D; Liver Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain, Barcelona, Spain., Gil M; Liver Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain, Barcelona, Spain., Salcedo MT; Pathology Department, Hospital Universitari Vall d´Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain., Genescà J; Liver Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain, Barcelona, Spain.; Centro De Investigación Biomédica En Red De Enfermedades Hepáticas y Digestivas, Instituto De Salud Carlos III, Madrid, Spain., Martell M; Liver Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain, Barcelona, Spain.; Centro De Investigación Biomédica En Red De Enfermedades Hepáticas y Digestivas, Instituto De Salud Carlos III, Madrid, Spain., Augustin S; Liver Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain, Barcelona, Spain.; Centro De Investigación Biomédica En Red De Enfermedades Hepáticas y Digestivas, Instituto De Salud Carlos III, Madrid, Spain.
Jazyk: angličtina
Zdroj: Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2020 Nov; Vol. 40 (11), pp. 2732-2743. Date of Electronic Publication: 2020 Oct 13.
DOI: 10.1111/liv.14632
Abstrakt: Background & Aims: Portal hypertension (PH) can be present in pre-cirrhotic stages, even in absence of fibrosis in non-alcoholic steatohepatitis (NASH) patients. Liver endothelial dysfunction (ED) has been shown as responsible for this effect in short-term dietary animal models. We evaluated the persistence of PH and underlying mechanisms in a long-term rat model of NASH.
Methods: Sprague-Dawley rats were fed 8 or 36 weeks with control diet or high-fat high-glucose/fructose diet. Metabolic parameters, histology, ED and haemodynamics were characterized. Structural characteristics of liver sections were analysed using image analysis.
Results: Both interventions reproduced NASH histological hallmarks (with steatosis being particularly increased at 36 weeks), but neither induced fibrosis. The 36-week intervention induced a significant increase in portal pressure (PP) compared to controls (12.1 vs 8.7 mmHg, P < .001) and the 8-week model (10.7 mmHg, P = .006), but all features of ED were normalized at 36 weeks. Image analysis revealed that the increased steatosis at 36-week was associated to an increase in hepatocyte area and a significant decrease in the sinusoidal area, which was inversely correlated with PP. The analysis provided a critical sinusoidal area above which animals were protected from developing PH and below which sinusoidal flux was compromised and PP started to increase.
Conclusion: Liver steatosis per se (in absence of fibrosis) can induce PH through a decrease in the sinusoidal area secondary to the increase in hepatocyte area in a long-term diet-induced rat model of NASH. Image analysis of the sinusoidal area might predict the presence of PH.
(© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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