Document Type

Conference Proceeding

Publication Date

10-2026

Publication Title

Hepatology

Abstract

Background: Gastroesophageal variceal bleeding carries significant morbidity and mortality in patients with portal hypertension. Multiple pharmacological, endoscopic, and interventional strategies have emerged for prophylaxis, yet no network meta-analysis has comprehensively compared the full treatment spectrum across both primary and secondary prophylaxis settings. We aimed to evaluate their relative efficacy within a single unified framework. Methods: We conducted a systematic review and frequentist random-effects NMA of RCTs comparing propranolol, nadolol, carvedilol, EBL, combination therapy (EBL plus beta-blocker), and TIPS. Databases searched included PubMed/MEDLINE, Embase, Cochrane CENTRAL, Scopus, and ClinicalTrials.gov through January 2026 (PROSPERO: CRD420261304355). Outcomes included bleeding/rebleeding risk and all-cause mortality. Risk of bias was assessed using Cochrane RoB 2. Treatment ranking used SUCRA values. Consistency was evaluated using design-by-treatment interaction models and TSA assessed conclusiveness of mortality evidence. Results: Thirty-four RCTs enrolling 3,674 patients were included. In primary prophylaxis, combination therapy (RR 0.30, 95% CI 0.11-0.81; SUCRA 0.86) and carvedilol (RR 0.40, 95% CI 0.26-0.63; SUCRA 0.76) significantly reduced first bleeding versus propranolol. In secondary prophylaxis, TIPS (RR 0.49, 95% CI 0.29-0.84; SUCRA 0.92) and carvedilol (RR 0.54, 95% CI 0.36-0.80; SUCRA 0.88) most effectively reduced rebleeding. No intervention demonstrated a statistically significant mortality benefit in either setting; carvedilol showed consistent directional trends toward lower mortality in both primary (RR 0.73, 95% CI 0.38-1.42) and secondary (RR 0.35, 95% CI 0.08-1.59) prophylaxis, though TSA confirmed evidence remains below the required information size. Sensitivity analyses were robust to exclusion of high-risk-of-bias studies. Conclusion: This first comprehensive NMA across the full prophylaxis spectrum demonstrates that combination therapy is the most effective strategy for primary prophylaxis, while TIPS leads in secondary prophylaxis. Carvedilol's consistent directional mortality advantage warrants investigation in adequately powered trials. These findings provide a comparative framework to inform clinical practice and guideline development.

Volume

84

Issue

S1

First Page

S639

Comments

American Association for the Study of Liver Diseases (AASLD) Liver Meeting, November 5-9, 2026, Denver, CO

Last Page

S640

DOI

10.1097/01.HEP.0001249252.53649.9f

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