Pre-primary prophylaxis of variceal bleeding

Portosystemic collateral formation, particularly at the gastroesophageal junction, is a most serious consequence of portal hypertension. Increased portal pressure is the most significant force underlying gastroesophageal variceal formation, to which end portal pressure (estimated from the hepatic venous pressure gradient) must reach at least 10 mmHg. Subsequently, splanchnic hyperemia also contributes to variceal development. Portoystemic collaterals result from repermeabilization of pre-extant vessels, vascular remodeling, and angiogenesis. The goal of pre-primary prophylaxis is preventing or delaying the formation of gastroesophageal varices. In experimental models of portal hypertension, early administration of splanchnic vasoconstrictors such as betablockers, nitric oxide synthesis inhibitors, or antiangiogenic substances inhibits portosystemic collateral formation. However, clinical trials of beta-blockers in patients with cirrhosis and no varices to delay variceal formation have failed to yield expected results.