Improved survival with nonselective beta blockers
Authors: Ulrich Thalheimer, Jaime Bosch, David Patch, Andrew Burroughs
Journal: Hepatology (2008)

We read with interest the study by Lo and colleagues.1 The authors present a follow-up of a previous study2 comparing endoscopic variceal ligation (EVL) versus medical treatment with nonselective beta blockers (NSBBs) plus nitrates for the prevention of variceal rebleeding. The original article2 showed EVL to be more effective for the prevention of variceal rebleeding, even though there was a tendency toward a reduced mortality with medical treatment (15 of 60 patients in the EVL versus 8 of 61 patients in the medical treatment group died) that, however, failed to reach statistical significance. The current study presents the extended follow-up and reports a significant reduction in mortality with medical treatment (42 of 60 patients with EVL versus 30 of 61 patients with medical treatment died, P = 0.013) despite markedly reduced rebleeding with EVL. Furthermore, the number of patients dying from infections or complications of cirrhosis (bleeding, hepatic failure, spontaneous bacterial peritonitis, and hepatorenal syndrome) was higher in the EVL group (29 versus 23 in the medical treatment group). Both NSBBs and endoscopic treatment are known to be effective for the prevention of variceal bleeding. Although endoscopic treatment only acts locally at the level of the varix, NSBBs seem to have a wider effect in the patient with cirrhosis. In a seminal paper, Abraldes and colleagues3 reported a reduction in long-term risk of developing complications of portal hypertension and improved survival in patients who had a hemodynamic response to treatment with NSBBs, with or without nitrates, for the prevention of variceal rebleeding. In a more recent study, Turnes and colleagues4 found the same treatment to reduce the risk for SBP and bacteremia in the setting of primary prevention of variceal bleeding, even with a lesser reduction in hepatic venous pressure gradient than required by the definition of hemodynamic response. We have previously commented on the possible mechanisms of NSBBs beyond the reduction of portal pressure.5, 6 NSBBs seem to have other effects besides reduction in hepatic venous pressure gradient (such as reduction in azygos blood flow and variceal pressure) that contribute to reducing the risk of variceal hemorrhage. These appear to contribute to a reduction of bacterial translocation probably by increasing intestinal motility or decreasing bacterial overgrowth or intestinal permeability. Bacterial translocation seems to be the first step7 in a series of events that eventually lead to bacterial infection and several of the complications of cirrhosis and portal hypertension, such as variceal bleeding, hepatorenal syndrome, and hepatic encephalopathy.5 Interestingly, propranolol has been found, in several other studies, to reduce the incidence of spontaneous bacterial peritonitis and postsurgical infections in patients with cirrhosis.6 We believe that NSBBs have an important role not only in reducing the risk of variceal bleeding or rebleeding in patients with cirrhosis, but also in improving survival perhaps by reduction of bacterial translocation and subsequent complications. NSBBs may indeed reveal themselves as the hepatologist's "aspirin",8 and deserve further evaluation with regard to these other therapeutic effects. Ulrich Thalheimer*, Jaime Bosch , David Patch*, Andrew Burroughs*, * Royal Free Hospital, The Sheila Sherlock, Hepatobiliary, Pancreatic, and Liver Transplantation Unit, London, UK, Hospital Clinic-IDIBAPS, University of Barcelona, Centro de Investigacion Biomedica en Red de Enfermedades, Hepaticas y Digestivas (CIBERehd), Barcelona, Spain.