Portosystemic collaterals are not prerequisites for the development of hepatic encephalopathy in cirrhotic rats

Background: Liver functions and portosystemic collaterals influence the development and severity of hepatic encephalopathy (HE) in cirrhosis. However, it has not been examined which factor has a greater influence or if shunts can be used to determine the presence and severity of HE. The expression of tumor necrosis factor-α (TNF-α) is increased in cirrhosis, and its role in HE deserves further evaluation. Methods: Portal hypertension was induced by portal vein ligation (PVL; a model of high-degree portosystemic shunting without significant liver damage) and liver cirrhosis was induced by bile duct ligation (BDL; a model of low-degree shunting with liver cirrhosis) in male Spraque-Dawley rats. Sham-operated rats were used as controls. Motor activity counts, hemodynamic parameters, plasma levels, liver biochemistry parameters, TNF-α, and a flow-pressure curve study of portosystemic collaterals (where a higher slope indicates fewer portosystemic collaterals) were performed on Day 7 after PVL and Week 5 after BDL. Results: Portal pressure was significantly higher in the PVL and BDL groups than in controls. The liver biochemistry parameters, TNF-α, and motor activities were not significantly different between the PVL and PVL-control groups. In the BDL group, TNF-α, AST, and total bilirubin levels were significantly higher and the motor activity counts were lower than in the BDL-control group. Moreover, in the BDL rats, TNF-α (p= 0.037, R = -0.490), AST (p= 0.007, R = -0.595) and total bilirubin (P = 0.001, R = -0.692) levels, but not the slopes of the flow-pressure curves, were significantly and negatively correlated with the motor activity counts. Conclusion: The presence of a high degree of portosystemic shunting without significant liver damage may not be adequate for the development of HE.