Fecal microbiota transplantation produces sustained improvements in cognitive and clinical outcomes

Liver cirrhosis is a leading cause of morbidity and mortality, with complications such as HE resulting in recurrent emergency hospitalizations, irreversible brain injury, and a poor prognosis.2-5 There is some evidence that HE patients have a reduced relative abundance of certain beneficial gut microbiota (e.g. Lachnospiraceae and Ruminococcaceae) and an enrichment of potentially pathogenic Enterobacteriaceae ¬- a microbial profile that has been linked to cognitive impairment and systemic inflammation in cirrhotic patients with HE.1 Faecal microbiota transplants have been used successfully to correct dysbiotic conditions such as recurrent Clostridium difficile and ulcerative colitis,6-8 and a preliminary report suggested that FMT may be promising in the management of HE.9

'In conducting the original study, we primarily wanted to evaluate whether FMT was safe in patients with recurrent HE compared with SOC alone', explained Dr Jasmohan Bajaj from Virginia Commonwealth University and McGuire VA Medical Center in Richmond, USA, and lead author of the study. 'We identified a single stool donor from a universal donor bank who had the highest relative abundance of Lachnospiraceae and Ruminococcaceae, and FMT enemas were prepared using a single stool specimen provided by this donor'.

The long-term analysis of this study followed all participants from the original 5-month study1 who were still alive and without liver transplant for an additional 6 months, assessing both cognitive and clinical outcomes. At 1 year after randomization, one participant in the FMT arm and three in the SOC arm had died or undergone liver transplant. Amongst the remaining participants, a median of 1.5 (IQR 0.75-2.75) HE episodes and 3.0 (IQR 0.75-5.75) hospitalizations were reported during the subsequent 6 months of the study in the SOC arm compared with 0 (range 0-1.0) and 0 (range 0-1.5) in the FMT arm (p<0.05 and p<0.02, respectively). The FMT arm also demonstrated sustained and significant improvements in cognitive function at 1 year compared with both baseline and SOC.

'Although this was a small randomized trial, we believe it confirms that FMT from a rationally selected donor was safe and associated with substantial long-term improvements in both clinical and cognitive outcomes in patients with cirrhosis and recurrent HE', said Dr Bajaj. 'These findings now need to be confirmed in a larger patient population'.

'Hepatic encephalopathy is a debilitating condition and a major burden to patients and caregivers, and new therapies are urgently needed', said Prof. Annalisa Berzigotti from the University of Bern, Switzerland, and EASL Governing Board Member. 'This study provides an important piece of evidence. The encouraging long-term results of FMT in HE strongly support the need for a larger, multicentre study of this intervention'.

About The International Liver Congress™

This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Attending specialists present, share, debate and conclude on the latest science and research in hepatology, working to enhance the treatment and management of liver disease in clinical practice. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. The International Liver Congress™ 2018 will take place from 11¬-15 April 2018 at the Paris Convention Centre, Paris, France.

About The European Association for the Study of the Liver (EASL)

Since its foundation in 1966, this not-for-profit organization has grown to over 4,000 members from all over the world, including many of the leading hepatologists in Europe and beyond. EASL is the leading liver association in Europe, having evolved into a major European association with international influence, and with an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

Contact

For more information, please contact the ILC Press Office at:

* Email: press@easloffice.eu" title="mailto:press@easloffice.eu">press@easloffice.eu

* Telephone: +41 (0) 22 807 29 88

Onsite location reference

Session title: Poster

Time, date and location of session: 14. April 2018, 09:00 AM -- 05:00 PM, Poster area

Presenter: Jasmohan S Bajaj, USA

Abstract: Sustained long-term improvement in clinical and cognitive outcomes after fecal microbiota transplantation in cirrhosis (3161)

Author disclosures

None reported.

References

14. Bajaj JS, et al. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: a randomized clinical trial. Hepatology. 2017;66(6):1727-38.

15. American Association for the Study of Liver Diseases; European Association for the Study of the Liver. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Hepatol. 2014;61(3):642-59.

16. Bajaj JS, et al. Persistence of cognitive impairment after resolution of overt hepatic encephalopathy. Gastroenterology. 2010;138(7):2332-40.

17. Stepanova M, et al. In-hospital mortality and economic burden associated with hepatic encephalopathy in the United States from 2005 to 2009. Clin Gastroenterol Hepatol. 2012;10(9):1034-41.e1.

18. Ellul MA, et al. Hepatic encephalopathy due to liver cirrhosis. BMJ. 2015;351:h4187.

19. van Nood E, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407-15.

20. Moayyedi P, et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology. 2015;149(1):102-109.e6.

21. Kelly CR, et al. Effect of fecal microbiota transplantation on recurrence in multiply recurrent clostridium difficile infection: a randomized trial. Ann Intern Med. 2016;165(9):609-16.

22. Kao D, et al. Fecal microbiota transplantation in the management of hepatic encephalopathy. Hepatology. 2016;63(1):339-40.