Clinical

Simvastatin decreases hepatic resistance but not portal pressure in cirrhosis

Last Updated: 2004-03-25 16:30:29 -0400 (Reuters Health)

NEW YORK (Reuters Health) - In patients with cirrhosis and portal hypertension, simvastatin enhances hepatic nitric oxide (NO) output and decreases hepatic resistance but does not lower portal hypertension, according to a new study.

"Our findings show no direct therapeutic potential for simvastatin due to the absence of any decrease in portal pressure," Dr. Jaime Bosch from the University of Barcelona, Spain, and colleagues write in the March issue of Gastroenterology.

"Insufficient NO production by endothelial cells in the liver microvasculature seems to be the major factor involved in increased hepatic resistance in cirrhosis," they explain. "It is implicit that delivering NO to the liver circulation should result in a decrease in hepatic resistance."

Therefore, they tested the effects of simvastatin, which is known to increase endothelial NO production, on hepatic hemodynamics and NO output in a group of cirrhotic patients with portal hypertension.

The study involved 30 patents with liver cirrhosis "referred for the hemodynamic evaluation of portal hypertension." Thirteen patients received 40 mg simvastatin and had hemodynamic parameters measured at 30 and 60 minutes, and 17 patients received either placebo or simvastatin either 12 hours or one hour before the study began and had parameters measured at 15, 30, and 45 minutes.

The researchers report that 40 mg simvastatin acutely increased hepatic vein NO levels and reduced hepatic resistance but did not decrease portal hypertension due to a concomitant increase in hepatic blood flow.

Pretreatment with simvastatin but not placebo also raised hepatic vein NO levels after a meal and attenuated the postprandial increase in hepatic venous pressure gradient. The effects were short-lived, however.

"Although there are abundant data indicating that strategies based on supplementing NO enhance the effects of beta-blockers on portal pressure, whether statins might have such an effect remains to be proven," the researchers conclude.

Gastroenterology 2004;126:749-755.