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

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