Long-acting nitrates in portal hypertension: to be or not to be?

The major complication of portal hypertension is represented by gastrointes tinal haemorrhage from ruptured oesophageal varices. Gold standard prophyla xis with non selective beta-blockers is able to decrease the risk of bleedi ng or rebleeding only in a fraction of patients, thus additional forms of t reatment are under investigation. Long-acting nitrates have been considered the best candidates to improve the pharmacological response. The rationale for the use of nitrates in portal hypertension is primarily based on the f act that they lead to a decrease in the hepatic venous pressure gradient an d on the knowledge that deficient intrahepatic nitric oxide release could b e one of the mechanisms involved in the development of increased portal res istance in early cirrhosis. Ten randomised controlled trials have, so far i nvestigated the clinical usefulness of long-acting nitrates in portal hyper tension. Five of them explored the field of primary prophylaxis and the oth ers, the use of nitrates in the prevention of rebleeding. The results of th ese randomised controlled trials are partially contradictory as far as conc erns prevention of bleeding or rebleeding, survival and treatment-related c omplications. A common finding emerging from most of these studies suggests that the potential for a beneficial or detrimental effect of nitrates depe nds on the stage of liver disease and the extension of portal collaterals. Thus, in the early stage of cirrhosis, it would be desirable to target nitr ates to the liver microvasculature, while, in a later stage, nitrates could be deleterious by aggravating the hyperdynamic syndrome through the expans ion of the vascular bed. Whether or not nitrates may have a role in the pri mary and/or secondary prophylaxis of bleeding needs to be addressed in furt her long-term studies.