Beta blockers in cirrhosis: The window re-opens

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Non-selective beta blockers (NSBB) have been the mainstay of therapy for portal hypertension for the past 25 years, ever since Lebrec et al. demonstrated in a randomized controlled trial (RCT) that propranolol reduced portal pressure in 18 patients with cirrhosis and variceal hemorrhage [1]. The authors theorized that the reduction in portal pressure likely resulted from a decrease in splanchnic blood flow as a consequence of a demonstrated reduction in cardiac output. Since then, knowledge of the mechanisms that lead to portal hypertension have advanced and studies from Groszmann et al. determined that the portal hypertensive state is maintained despite the formation of collaterals because of splanchnic vasodilatation leading to an increase in portal venous inflow [2]. These studies also demonstrated that propranolol reduced portal pressure by reducing portal flow mainly due to beta-2 adrenergic blockade leading to an unopposed alpha-adrenergic vasoconstrictive effect on the splanchnic circulation [3]. The clinical efficacy of propranolol and other NSBB has since been extensively shown both in the prevention of first variceal hemorrhage and in the prevention of recurrent variceal hemorrhage [4]. In the former, the recommendation is to use either NSBB or ligation. In the latter, the combination of NSBB plus ligation is recommended; however, ligation is only effective inasmuch as it is combined with NSBB. Evidence in a meta-analysis shows that NSBB therapy alone is almost as effective as combination therapy in preventing re-bleeding with a tendency to decrease mortality [5]. This is not surprising as, unlike NSBB, ligation is a local therapy that does not affect pathophysiological mechanisms that lead to portal hypertension. In fact, NSBBinduced reductions in portal pressure have been associated not only with a decreased incidence of variceal hemorrhage but also with a reduction in the development of other complications of cirrhosis (ascites, encephalopathy) and improved survival [6,7]. Patients with both compensated and decompensated cirrhosis have been included in RCTs comparing NSBB vs. no therapy/placebo and almost none of the individual RCTs report