S1062 Effect of Fecal Microbiota Transplant on Hepatic Encephalopathy Varies by Donor and Recipient Factors

Introduction: Early data suggests fecal microbiota transplant (FMT) may treat hepatic encephalopathy (HE). Optimal FMT donor and recipient characteristics are unknown. We assessed the safety and efficacy of FMT in patients with prior overt HE, while comparing 5 FMT donors (NCT03420482). Methods: We performed an open-label study of FMT capsules, administered 5 times over 3 weeks, in patients with prior overt HE. Five healthy donors provided FMT to 1-3 patients each. Primary outcomes were change in Psychometric HE Score (PHES) and serious adverse events. Serial stool samples underwent shallow shotgun metagenomic sequencing. Results: Ten patients completed FMT administration and 6-month follow-up. MELD score did not change after FMT (14 vs. 14, P=0.51). Thirteen minor adverse events and 3 serious adverse events (2 unrelated to FMT) were reported. One SAE was extended-spectrum beta-lactamase E. coli bacteremia (DeFilipp & Bloom et al, NEJM, 2019). PHES improved after 3 doses of FMT (+2.1, P< 0.05), after 5 doses of FMT (+2.9, P=0.007), and 4 weeks after the 5th dose of FMT (+3.1, P=0.02; Figure 1). Mean change in PHES ranged from -1 to +6 by donor. Two taxa were identified by random forest analysis and confirmed by linear regression to predict PHES: Bifidobacterium adolescentis (adjusted R2 = 0.27) and Bifidobacterium angulatum (adjusted R2 = 0.25), both short-chain fatty acid [SCFA] producers. Patients who responded to FMT had higher levels of Bifidobacterium, as well as other known beneficial taxa, at baseline and throughout the study. The FMT donor with poorest cognitive outcomes in recipients had the lowest fecal SCFA levels. Compared to baseline, venous ammonia did not change after 5 doses of FMT (73 µmol/L vs. 75 µmol/L, P=0.73), nor did serum TNF-alpha (P=0.09), IL-6 (P=0.55), or IFN-gamma (P=0.30). Conclusion: FMT capsules appear to improve cognition in HE, with an effect varying by donor and recipient factors, and possibly mediated by SCFAs.Figure 1.: Change in Cognitive Tests with Fecal Transplant.