Use of non-selective beta blockers in cirrhosis: the evidence we need before closing (or not) the window

Non selective beta blockers (NSBBs) are used in primary and secondary prophylaxis of portal hypertension-related bleeding in patients with cirrhosis. The efficacy of NSBBs treatment is predicted by hemodynamic response in term of reduction of the hepatic venous pressure gradient (HVPG) below 12 mmHg or at least 20% of the basal value. Nevertheless a relevant number of patients who do not achieve this HVPG reduction during NSBBs therapy do not bleed during follow up; this evidence suggests an additional non-hemodynamic advantage of NSBBs treatment to modify the natural history of cirrhosis. Recent studies have questioned the efficacy and safety of NSBBs in patients with advanced stage of liver disease characterized by refractory ascites and/or spontaneous bacterial peritonitis. These studies have suggested the existence of a defined and limited period to modify the natural history of cirrhosis by NSBBs: the "window hypothesis". According with this hypothesis, patients with cirrhosis benefit from the use of NSBBs from the appearance of varices up to the development of an advanced stage of cirrhosis. Indeed, in patients with refractory ascites and/or spontaneous bacterial peritonitis the hemodynamic effects of NSBBs may expose to a high risk of further complications such as renal insufficiency and/or death. Methodological concerns and contrasting results counterbalance the evidence produced up to now on this issue and are the main topic of this editorial.