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3593290 
Journal Article 
The anticoagulant Rivaroxaban lowers portal hypertension in cirrhotic rats mainly by deactivating hepatic stellate cells 
Vilaseca, M; García-Calderó, H; Lafoz, E; García-Irigoyen, O; Avila, M; Reverter, JC; Bosch, J; Hernández-Gea, V; Gracia-Sancho, J; García-Pagán, JC 
2017 
Yes 
Hepatology
ISSN: 0270-9139
EISSN: 1527-3350 
English 
28142199 
BACKGROUND & AIMS: In cirrhosis, increased intrahepatic vascular resistance (IHVR) is the primary factor for portal hypertension development. Hepatic Stellate Cells (HSC) play a major role increasing IHVR as when activated are contractile and promote fibrogenesis. Protease activated receptors (PARs) can activate HSC, through thrombin and factor Xa which are known PARs agonists, and cause microthrombosis in liver microcirculation. This study investigates the effects of the oral anticoagulant rivaroxaban, a direct anti-factor Xa, on HSC phenotype, liver fibrosis, liver microthrombosis and portal hypertension in cirrhotic rats.

METHODS: Hepatic and systemic hemodynamic, NO bioavailability, liver fibrosis, HSC activation and microthrombosis were evaluated in CCl4 and thioacetamide-cirrhotic rats treated with rivaroxaban (20 mg/kg/day) or its vehicle for two weeks.

RESULTS: Rivaroxaban significantly decreased portal pressure in both models of cirrhosis without changes in portal blood flow, suggesting a reduction in IHVR. Rivaroxaban reduced oxidative stress, improved NO bioavailability and ameliorated endothelial dysfunction. Rivaroxaban deactivated HSC, with decreased α-SMA and mRNA expression of other HSC activation markers. Despite this marked improvement in HSC phenotype, no significant changes in liver fibrosis were identified. Rivaroxaban markedly reduced fibrin deposition suggesting reduced intrahepatic microthrombosis.

SUMMARY AND CONCLUSION: Rivaroxaban decreases portal pressure in two rat models of cirrhosis. This effect is mostly associated to decreased IHVR, enhanced NO bioavailability, HSC deactivation and reduced intrahepatic microthrombosis. Our findings suggest that rivaroxaban deserves further evaluation as a potential treatment for cirrhotic portal hypertension. This article is protected by copyright. All rights reserved.