Proton Pump Inhibitors after Endoscopic Variceal Ligation: Time to Reconsider the Guidelines?

Abstract Endoscopic variceal ligation (EVL) is the cornerstone of endoscopic therapy for high-risk esophageal varices in cirrhosis. Post-ligation ulcers heal in most patients but can bleed, with mortality reported in up to 5% of bleeding events. The role of acid suppression in preventing this complication has remained unsettled for over two decades. Baveno VII, the AASLD 2024 practice guidance, and the updated APASL 2025 statement all recommend against the routine continuation of proton pump inhibitors after EVL, citing low-quality evidence and the documented association of long-term acid suppression with infections and hepatic encephalopathy in cirrhosis. Yadav et al, in a single-center, single-blind randomized controlled trial of 170 cirrhotic patients undergoing variceal ligation, reported that esomeprazole 40 mg daily for 3 months reduced recurrent bleeding (11.5% versus 28.0%, hazard ratio 0.39) and rebleeding-related mortality, with smaller and fewer post-ligation ulcers on follow-up endoscopy. The trial supplies the largest randomized dataset to date on this question and reopens the case for selective continuation. In this article, we summarize the trial, place it alongside the conflicting prior literature, including a recent 2025 meta-analysis, and consider what it means for current guideline-based practice.