Steatosis as main determinant of portal hypertension through a restriction of hepatic sinusoidal area in a dietary rat nash model.
Liver Int
; 40(11): 2732-2743, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32770818
ABSTRACT
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Hepatopatia Gordurosa não Alcoólica
/
Hipertensão Portal
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article