Comparable effects of Sildenafil, Vardenafil, and Tadalafil – the three licensed inhibitors of phosphodiesterase 5– on portal haemodynamics

Introduction: Most complications of liver cirrhosis are caused by or linked to portal hypertension (PH). Beta-blockers, organic nitrates or vasopressin derivatives lower portal pressure by a decrease of portal venous inflow. We had previously shown that Vardenafil, an inhibitor of phosphodiesterase 5 (PDE-5), decreases intrahepatic sinusoidal resistance, increases portal flow and lowers portal pressure. We investigated whether this effect can be found with Sildenafil and Tadalafil as well.

Methods and patients: In 10 healthy male individuals liver haemodynamics were measured by Doppler ultrasonography before and after 100mg Sildenafil. Corresponding measurements were performed in 5 healthy persons and 5 patients with liver cirrhosis after 10mg Tadalafil. The data were compared with the results obtained in 18 healthy individuals and 18 patients with liver cirrhosis Child A after 10mg of Vardenafil (Deibert P et al. Aliment Pharmacol Ther 2006). In 5 of the Vardenafil patients with liver cirrhosis wedged and free hepatic vein pressure was measured by current invasive procedures.

Results: With all three inhibitors of PDE-5 comparable results were obtained.

1. Portal venous blood flow increased significantly in controls and in patients with liver cirrhosis by 20–30% and reversed to base-line after 48h.

2. Celiac and hepatic artery resistivity indices rose significantly.

3. Resistivity indices of the superior mesenteric artery remained constant. The effect on portal blood flow is not caused by an increased blood inflow in the splanchnic system.

4. Systemic hemodynamic parameters (heart rate and blood pressure) showed only minor changes in cirrhotics.

5. The increase of portal blood flow was demonstrable within 15 minutes after oral administration of Sildenafil, Vardenafil, and Tadalafil. Only very low concentrations of the inhibitors of PDE-5 are sufficient to influence hepatic haemodynamics.

6. In 4/5 patients with liver cirrhosis hepatic venous pressure gradient decreased by >15% after Vardenafil.

Conclusion: The three inhibitors of phosphodiesterase 5 are candidates for a novel therapy of portal hypertension. Since a continuous effect on portal pressure is required long acting inhibitors may be the most suitable substances for this indication.