Re-Evaluating the Role of Proton Pump Inhibitors After Endoscopic Band Ligation of Esophageal Varices in Cirrhotic Patients: A Systematic Review and Meta-Analysis

INTRODUCTION: The benefit of proton pump inhibitors (PPIs) in improving outcomes after endoscopic band ligation (EBL) of esophageal varices in cirrhosis remains uncertain. We aimed to evaluate whether PPI use reduces bleeding and mortality after EBL compared with nonuse. METHODS: Major databases were systematically searched until January 2025. Randomized clinical trials (RCTs) and observational studies comparing PPI use vs nonuse after EBL of esophageal varices in patients with cirrhosis were included. Random-effects meta-analyses were conducted using restricted maximum likelihood estimation. Risk ratios (RR), odds ratios (ORs), or standardized mean differences with 95% confidence intervals (CIs) were calculated for outcomes. RESULTS: Eleven studies (4 RCTs and 7 observational) comprising 7,459 patients with cirrhosis undergoing EBL were included. In pooled unadjusted analyses, PPI use was associated with reduced post-EBL bleeding (OR 0.76; 95% CI 0.62–0.92; I 2 = 29.6%) and all-cause mortality (OR 0.48; 95% CI 0.24–0.97; I 2 = 0.0%). More rigorous analyses showed no benefit: adjusted observational data for post-EBL bleeding and RCT data for post-EBL bleeding and all-cause mortality were not significant ( P > 0.05). Similarly, for the mechanistic outcome of post-EBL ulcer bleeding, RCT data showed no statistically significant effect (RR 0.54; 95% CI 0.25–1.16; I 2 = 0.0%). Trial sequential analysis confirmed the cumulative RCT evidence for bleeding is underpowered. DISCUSSION: Current evidence is insufficient to support routine PPI use after EBL. RCT data remain underpowered and inconclusive, emphasizing the need for adequately powered trials.