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

Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Journal of the Chinese Medical Association (Impact Factor: 0.75). 01/2012; 75(1):3-9. DOI: 10.1016/j.jcma.2011.10.008
Source: PubMed

ABSTRACT 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.
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.
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.
The presence of a high degree of portosystemic shunting without significant liver damage may not be adequate for the development of HE.

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    ABSTRACT: Eur J Clin Invest 2012 ABSTRACT: Background  Sorafenib, a multikinase inhibitor that inhibits angiogenesis and carcinogenesis, has been used for patients with advanced hepatocellular carcinoma. However, sporadic cases have been reported with the development of hepatic encephalopathy (HE) after sorafenib treatment, mostly in those with cirrhosis. Liver function impairment, portal-systemic collaterals and brain oxidative stress participate in the pathogenesis of HE. The study therefore aimed to investigate the potential influences of sorafenib on HE and the relevant risk factors in cirrhotic rats. Methods  Liver cirrhosis was induced in Spraque-Dawley rats with common bile duct ligation (CBDL). CBDL rats received sorafenib 1 mg/kg/day or distilled water (DW) via oral gavage since the 15th day post surgery for 2 weeks. On the 28th day, after motor activities measurements, mean arterial pressure, portal pressure and heart rate were checked. Thereafter, cerebral cortex and cerebellum were dissected for oxidative stress study and blood was collected for liver biochemistry survey. Results  Sorafenib significantly reduced portal pressure (22%) and collateral shunting degree (15%) in cirrhotic rats. Alanine transaminase, aspartate transaminase, total bilirubin and ammonia were similar in sorafenib- and DW-treated groups. Motor activities were not significantly altered by sorafenib. In cerebrum, the oxidant and antioxidant substances activities were not significantly different between the two groups, whereas they were divergent in cerebellum and hippocampus. Conclusion  By surveying three main aspects involved in the pathogenesis of HE, this study demonstrates that sorafenib does not increase the risk of HE in cirrhotic rats.
    European Journal of Clinical Investigation 10/2012; · 3.37 Impact Factor


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May 22, 2014