“…21,22 Whether portal hypertension can be initiated and sustained by nonfibrotic architectural and functional changes seen in steatosis or steatohepatitis is the subject of long-standing debate. 17,[23][24][25] Numerous observations in animal models of NAFLD have suggested an association between steatosis and increased HVR. Impaired hepatic blood flow due to narrowing of the sinusoidal space has been demonstrated in rats fed choline-deficient diet, 26 New Zealand white rabbits fed high cholesterol diet, 27 the Zucker obese-rat model, 28 rats fed a methionine-choline deficient diet, 29,30 and in the rat model of human NAFLD using the cafeteria diet, 31 In all these reports, increased HVR developed in association with massive steatosis but without significant histological evidence of fibrosis, and without a significant increase in the expression of profibrotic genes, 32 Similarly, when steatohepatitis was induced in rats by high-fat glucose-fructose diet, increased PVP was demonstrated before significant fibrosis developed, 33,34 More recently, digital image analysis of hepatocellular fat and sinusoidal areas in the high-fat glucose-fructose diet model of NAFLD found an inverse correlation between vascular space and PVP.…”