“
“Abbreviations: HCC, hepatocellular carcinoma; HRS, hepatorenal syndrome; HVPG, hepatic venous pressure gradient; NSBB, nonselective beta-blocker; RCT, randomized controlled trial; SBP, spontaneous bacterial peritonitis. Patients with cirrhosis are at risk for developing complications that can negatively impact their survival.1 These complications include the development of hepatocellular carcinoma (HCC), sepsis, renal failure, and gastrointestinal bleeding, mainly variceal. The risk of bleeding is mainly related to the development of varices from portal hypertension. Bleeding from varices, whether

selleck kinase inhibitor esophageal or gastric, is associated with a mortality risk of 40% at 1 year.2 Twenty-nine years ago, a randomized controlled trial (RCT) from France involving 74 patients with cirrhosis with a history of gastrointestinal bleeding showed that propranolol, a nonselective beta-blocker (NSBB), significantly reduced the risk of rebleeding from esophageal varices.3 Since then, 615 articles have been published in the English literature on the use of propranolol or nadolol (the other NSBB) in cirrhosis, both for primary and secondary prophylaxis. In fact, NSBBs have become one of the most effective preventative therapies in patients with cirrhosis against variceal bleeding.4 The advantage of using NSBBs, however,

must be weighed against the risks associated with their chronic use. NSBBs are contraindicated in patients with refractory asthma, respiratory failure, advanced atrio-ventricular block, and severe arterial hypotension. In order to improve Erlotinib the risk/benefit ratio, administration of beta-blockers is recommended only in patients with a substantial risk of bleeding such as those patients with medium or large varices or patients with small esophageal varices who have Child-Pugh class C cirrhosis.5,

6 If possible, hepatic venous pressure gradient (HVPG) should be measured before and 1-2 months after NSBB administration to identify responders (those Resveratrol with a final HVPG < 12 mm Hg or those who show a decrease of ≥20% in HVPG versus the pretreatment value) who are most likely to benefit from NSBB prophylaxis. Nonresponders should discontinue therapy so to prevent the development of side effects when their chances of any therapeutic benefits are small.7 In the ensuing 29 years since the original description of the effectiveness of propranolol in preventing variceal bleeding, many other drugs such as angiotensin receptor antagonists, selective beta-blockers, nitrates, alpha-receptor antagonists, and endothelin receptor antagonists, to name a few, have been investigated for their ability to decrease portal pressures. None of these agents has shown a more favorable profile than NSBBs in the prophylaxis against variceal bleeding.