Introduction

The role of proton pump inhibitors (PPIs) in reducing complications after endoscopic band ligation (EBL) of esophageal varices in cirrhotic patients remains uncertain. While PPIs are often prescribed to prevent post-banding ulcers and related bleeding, their clinical benefit in this setting is debated.

Aims & Methods

We conducted a systematic review and meta-analysis to evaluate whether PPI use is associated with reduced risk of bleeding and mortality within 8 weeks after EBL in cirrhotic patients, compared to non-use. A comprehensive search of PubMed, Web of Science, and CENTRAL was performed in January 2025. We included randomized controlled trials (RCTs) and observational studies comparing PPI use versus non-use following EBL. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool for RCTs, ROBINS-I for cohort and case-control studies, and AXIS for cross-sectional studies. A random-effects meta-analysis was conducted using restricted maximum-likelihood estimation. Relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for primary and secondary outcomes.

Results

Eleven studies (4 RCTs, 7 observational) including 7,459 patients with cirrhosis undergoing EBL were included. All studies provided data for the primary outcomes. In the pooled analysis, PPI use was associated with a reduced risk of bleeding within 8 weeks (OR 0.76; 95% CI: 0.62 - 0.92; I² = 29.6%) and lower mortality (OR 0.48; 95% CI: 0.24 - 0.97; I² = 0.0%). However, when analyzing adjusted odds ratios from five eligible observational studies (n = 5,907), PPI use was not significantly associated with reduced bleeding (OR 0.64; 95% CI: 0.33 - 1.23; I² = 72.2%). These negative findings were further supported by the pooled analysis of RCTs alone (n = 445), in which PPI use was not significantly associated with a reduction in bleeding (RR 0.71; 95% CI: 0.39 - 1.30; I² = 0.0%) or mortality (RR 0.75; 95% CI: 0.23 - 2.53; I² = 0.0%). Subgroup analysis based on the indication for EBL (elective vs emergency) also showed no significant differences. Finally, PPIs had no significant impact on the length of hospitalization. Data on post-banding ulcer size and number were inconsistently reported and could not be pooled.

Conclusion

This practice-changing meta-analysis does not support the routine use of PPIs to reduce severe complications after EBL for esophageal varices in patients with cirrhosis.