Future Pharmacological Therapies of Portal Hypertension

To provide an overview of recent pharmacological treatments for portal hypertension evaluated in early clinical trials, with particular emphasis on the pathophysiological basis of their use.

In patients with compensated cirrhosis, even small decreases in portal pressure (as small as 1 mmHg) are associated with a lower probability of decompensation. In patients with decompensated cirrhosis, portal pressure "response" to non-selective beta-blocker (NSBB) therapy is associated with a lower mortality. When present, significant portal hypertension persists even after elimination of the etiology of cirrhosis and this justifies the continued development of new drugs that target portal hypertension.

Over several decades we have gained great depth in the understanding of portal hypertension, its mechanisms and complications. NSBBs, which act by reducing portal venous inflow (an extrahepatic target), are effective in reducing portal pressure and have been the mainstay of therapy for portal hypertension in the last 35 years -being effective in preventing decompensation and variceal hemorrhage. However, because not all patients will have a sufficient response to NSBB and some may be intolerant to NSBB, alternative drugs or drugs that will augment the effect of NSBB on portal pressure are being tested in pre-clinical and early-clinical trials. Many of these drugs target more than one of the intrahepatic or extrahepatic mechanisms implicated in the pathogenesis of portal hypertension in cirrhosis. Out of these proposed therapies, statins have emerged as the most promising new pharmacological therapy for the treatment of portal hypertension.