icon-folder.gif   Conference Reports for NATAP  
 
  38th Annual Meeting of the European Association for the Study of the Liver
 
Istanbul, Turkey. March 28-April 1, 2003
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SIMVASTATIN AMMELIORATES THE INCREASED HEPATIC VASCULAR TONE IN PATIENTS WITH CIRRHOSIS
 
 
  C. Zafra, J.G. Abraldes*, C. Cortez, A. Berzigotti, I. Tarantino, J.C. Garcia-Pagan, J. Bosch, *Presenting Author Hepatic Hemodynamic Laboratory. Liver Unit. Hospital Clinic. IDIBAPS. University Of Barcelona., Barcelona, Spain
 
An insufficient intrahepatic production of NO in cirrhotic liver contributes to increase hepatic resistance and portal hypertension, and enhances the postprandial increase in portal pressure. Simvastatin increases NO production by enhancing AKT-dependent eNOS phosphorylation. Therefore, simvastatin may decrease hepatic resistance in cirrhosis. This was evaluated in a group of patients with cirrhosis and portal hypertension. Methods: Protocol 1. 13 patients had measurements of mean arterial pressure, cardiac output, systemic vascular resistance, HVPG and hepatic blood flow (HBF) before and 30 and 60 min after receiving 40 mg of simvastatin. Protocol 2. 17 patients were randomized to receive placebo or simvastatin (40mg) 12 h and 1 h before the study. After baseline measurements, a standard liquid meal was given and measurements were repeated at 15, 30 and 45 min. Results: Protocol 1. Acute simvastatin did not modify HVPG but increased HBF (+21 13% and +14 23% at 30 and 60 min respectively;p=0.04) and decreased estimated hepatic sinusoidal resistance by 1411% and 1117% (p=0.01). Systemic hemodynamics were not modified. Protocol 2. With respect to placebo, pretreatment with simvastatin significantly attenuated the postprandial increase in portal pressure (+88% vs +177% at 15 min, +66% vs +188% at 30 min, +89 vs +158% at 45 min;p=0.03). HBF increased equally in the two groups. Hepatic resistance decreased in simvastatin group but not in placebo (-1710% vs -58% at 30 min;p=0, 03). Conclusions: Simvastatin effectively decreases hepatic resistance in patients with cirrhosis, without deleterious effects on systemic circulation.