S2769 Adjunctive Fecal Microbiota Transplantation Lowers Recurrence of Overt Hepatic Encephalopathy Without Added Harm: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: Hepatic encephalopathy (HE) recurs in approximately 40% of cirrhotic patients despite taking lactulose and rifaximin, driven partly by persistent gut dysbiosis. Fecal microbiota transplantation (FMT) rapidly re-establishes eubiotic flora and may therefore avert relapse. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing adjunctive FMT to prevent recurrent overt HE. Methods: A systematic search of PubMed, Embase, Scopus, and Cochrane Library identified randomized controlled trials (RCTs) analyzing adjunctive fecal microbiota transplantation (FMT) for preventing recurrent overt hepatic encephalopathy in cirrhosis up to May 2025. Data were analyzed using RevMan 4.2.1. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using Mantel-Haenszel methods. Random- or fixed-effects models were applied based on heterogeneity (Higgins’ I²). Statistical significance was set at P < 0.05. Risk of bias was assessed using RoB 2.0. Results: Three RCTs (Bajaj 2017, 2019 and 2025; 35 FMT vs 35 standard-of-care [SOC] participants) met eligibility. Adjunctive FMT conferred a clinically meaningful and statistically significant reduction in recurrent overt HE within 180 days (risk ratio [RR] 0.23, 95% CI 0.08–0.66; I² = 0%, P = 0.006). Numerically fewer hospital readmissions (RR 0.42, 95% CI 0.17–1.05; I² = 0%, P = 0.06) and composite adverse events (RR 0.41, 95% CI 0.13–1.36; I² = 60%, P = 0.15) were observed, but these did not reach conventional significance. All-cause mortality was low and comparable between groups (RR 0.60, 95% CI 0.08–4.24; I² = 0%, P = 0.61). Importantly, no FMT-related serious adverse events were reported across trials, regardless of delivery route or dosing schedule. Conclusion: Collectively, the current published literature shows that adjunctive FMT provides a clinically meaningful, safe means of curbing early HE recurrence, underscoring the therapeutic value of microbiome modulation in cirrhosis. The consistent direction of benefit across differing delivery protocols strengthens biological plausibility, yet the small, single-center nature of available trials limits certainty for secondary endpoints. Larger, multicenter studies powered for patient-centered outcomes, mechanistic biomarkers and cost-effectiveness are needed to refine donor selection, optimize dosing frequency and confirm long-term sustainability before routine implementation.