Fecal Microbiota Transplant from a Rational Stool Donor Improves Hepatic Encephalopathy: A Randomized Clinical Trial.

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Title: Fecal Microbiota Transplant from a Rational Stool Donor Improves Hepatic Encephalopathy: A Randomized Clinical Trial.
Author(s): Bajaj, JS
Kassam, Z
Fagan, A
Gavis, EA
Liu, E
Cox, IJ
Kheradman, R
Heuman, D
Wang, J
Gurry, T
Williams, R
Sikaroodi, M
Fuchs, M
Alm, E
John, B
Thacker, LR
Riva, A
Smith, M
Taylor-Robinson, SD
Gillevet, PM
Item Type: Journal Article
Abstract: Recurrent hepatic encephalopathy (HE) is a leading cause of readmission despite standard of care (SOC) associated with microbial dysbiosis. Fecal microbiota transplantation (FMT) may improve dysbiosis; however, it has not been studied in HE. We aimed to define whether FMT using a rationally-derived stool donor is safe in recurrent HE compared to SOC alone. An open-label, randomized clinical trial with a 5 month follow-up in outpatient cirrhotic men with recurrent HE on SOC was conducted with 1:1 randomization. FMT-randomized patients received 5-days of broad-spectrum antibiotic pre-treatment then a single FMT enema from the same donor with the optimal microbiota deficient in HE. Follow-up occurred on days 5, 6, 12, 35 and 150 post-randomization. The primary outcome was safety of FMT compared to SOC using FMT-related serious adverse events (SAE). Secondary outcomes were AEs, cognition, microbiota and metabolomic changes. Participants in both arms were similar on all baseline criteria and were followed till study-end. FMT with antibiotic pre-treatment was well-tolerated. Eight (80%) SOC participants had a total of 11 SAE compared to two (20%) FMT participants with SAEs (both FMT-unrelated, p=0.02). Five SOC and no FMT participants developed further HE (p=0.03). Cognition improved in FMT, but not SOC group. MELD score transiently worsened post-antibiotics, but reverted to baseline post-FMT. Post-antibiotics, beneficial taxa and microbial diversity reduction occurred with Proteobacteria expansion. However, FMT increased diversity and beneficial taxa. SOC microbiota and MELD score remained similar throughout. CONCLUSIONS: FMT from a rationally selected donor reduced hospitalizations, improved cognition and dysbiosis in cirrhosis with recurrent HE.
Publication Date: 6-Jun-2017
Date of Acceptance: 5-Jun-2017
URI: http://hdl.handle.net/10044/1/49643
DOI: https://dx.doi.org/10.1002/hep.29306
ISSN: 0270-9139
Publisher: Wiley
Start Page: 1727
End Page: 1738
Journal / Book Title: Hepatology
Volume: 66
Issue: 6
Sponsor/Funder: National Institutes of Health
Funder's Grant Number: 5R01AA020203-02
Copyright Statement: © 2017 the American Association for the Study of Liver Diseases. This is the accepted version of the following article: Bajaj, J. S., Kassam, Z., Fagan, A., Gavis, E. A., Liu, E., Cox, I. J., Kheradman, R., Heuman, D., Wang, J., Gurry, T., Williams, R., Sikaroodi, M., Fuchs, M., Alm, E., John, B., Thacker, L. R., Riva, A., Smith, M., Taylor-Robinson, S. D. and Gillevet, P. M. (), Fecal Microbiota Transplant from a Rational Stool Donor Improves Hepatic Encephalopathy: A Randomized Clinical Trial. Hepatology. Accepted Author Manuscript. doi:10.1002/hep.29306, which has been published in final form at https://dx.doi.org/10.1002/hep.29306
Keywords: 1103 Clinical Sciences
1101 Medical Biochemistry And Metabolomics
Gastroenterology & Hepatology
Publication Status: Published
Appears in Collections:Division of Surgery
Faculty of Medicine



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