S1018 Fecal Microbiota Transplant Improves Cognitive Function in Patients With Hepatic Encephalopathy: A Systematic Review of Randomized Clinical Trial

Abstract

INTRODUCTION: Hepatic encephalopathy (HE) is a leading cause of readmission, disability, and mortality despite the use of standard of care (Rifaximin + Lactulose) and is associated with microbial dysbiosis. Intestinal dysbiosis with increased gut permeability allows the translocation of pathogen-associated molecules into the systemic circulation. Fecal Microbial Transplant (FMT) may improve microbial dysbiosis and cognitive dysfunction in patients with HE. This review aims to summarize clinical trials using FMT in patients with HE. METHODS: A comprehensive literature search was performed using PubMed, Embase, Web of Science, and Clinicaltrials.gov for the identification of clinical trials. Studies were selected based on the PRISMA guideline. RESULTS: A total of four studies were included. Data were extracted into Table 1. FMT was used in combination with SOC in two studies. In a phase I study (Bajaj et al), FMT was administered via enema, there was no significant change in the MELD score after transplant. SAE was lower in the FMT arm. The number of hospitalization as well as HE episodes was significantly lower. In a phase III study (Woodhouse et al) there was no significant change in the MELD score after transplant but there was a decrease in the ammonia level. Cognitive outcomes: In a phase I study (Bajaj et al 2017), there was improvement in the amount of time taken to complete the Encephaloapp stroop test (FMT arm : tday 0: 247 , Δt (day 0–20): 29.1 ± 27.9 vs Control arm tday 0: 282 Δt (Day 0–20) -43.5 ± -95.7) as well as PHES score (FMT arm : pday 0: -7.4 , Δp (day 0–20) : -3.1 ±-2.1 vs control arm pday 0: -8.6 ,Δp day 0–20: 0.0 ± 3.1). Similar findings were shown in a recent phase I trial (Bajaj et al 2019). In this study, there was improvement in time to complete Encepahloapp stroop test (FMT arm: 245 , 200, 225 at day 0,20 , >1 year vs control arm : 260, 250 , 250 at day 0, 20, >1 year), as well as the PHES scoring system (FMT arm : -7,-4-6 at day 0,20 , >1 year vs control arm: -8,-8,-11). A phase II study (Bloom et al) demonstrated 56-sec improvement in day 0 right after FMT and 22 sec on day 30 using encephaloapp, they also demonstrated 2.6 points improvement in PHES score at day 0 and 3.9 points improvement at day 30. CONCLUSION: The FMT showed improvement in cognition in patients with HE. Large randomized clinical trials are needed to validate the results.Table 1.: Clinical Trial Results of FMT in Patients with Cirrhosis and Hepatic Encephalopathy