Nonselective beta-blockers and hepatic encephalopathy in liver cirrhosis:A meta-analysis of randomized controlled trials

Abstract

BACKGROUND: Liver cirrhosis leads to portal hypertension and related complications, including ascites, esophageal varices, and hepatic encephalopathy (HE). Non-selective beta blockers (NSBBs) decrease portal pressure, but it is not yet clear whether they contribute to HE development. Therefore, we examined the association between NSBB therapy and HE in randomized controlled trials (RCTs) involving patients with cirrhosis. METHODS: We systematically searched PubMed, Web of Science, ScienceDirect, and the Cochrane Library (from inception to December 31, 2024) for RCTs comparing NSBBs with a placebo, endoscopic band ligation, or injection sclerotherapy for variceal bleeding prevention in relation to HE. The risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model. Subgroups were defined according to the comparator, NSBB type, and hepatic function status (weighted mean Child-Pugh score ≤6 vs. >6). The risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2). RESULTS: There were 12 relevant studies, which included 775 NSBB-treated and 771 comparator patients (54 and 57 HE events). NSBB therapy was not associated with a statistically significant change in HE risk (RR 1.04, 95% CI 0.73-1.47; p = 0.84; I² = 0%). Estimates were consistent across all subgroups of hepatic function statuses (compensation, RR 1.18, 0.44-3.14; decompensation, RR 1.02, 0.70-1.48; p = 0.79), comparators (placebo, RR 1.19, 0.79-1.80; endoscopic therapy, RR 0.72, 0.38-1.39; p = 0.20), and NSBB types (propranolol/timolol, RR 1.06, 0.72-1.55; carvedilol, RR 0.95, 0.42-2.15; p = 0.82). CONCLUSION: Current evidence does not indicate a statistically significant association between NSBB therapy and HE development in patients with cirrhosis, regardless of disease severity.