Investigational Microbiota Restoration Therapeutic for Hepatic Encephalopathy
Investigational Microbiota Restoration Therapeutic for Hepatic Encephalopathy
Individuals with cirrhosis are likely to develop overt hepatic encephalopathy for which
 diagnostic modalities and treatment options are limited. The purpose of this study is to
 determine if individuals with cirrhosis who experience hepatic encephalopathy would benefit
 from investigational microbiota restoration therapy due to their inherent cognitive
 alterations. Analysis for a correlation between changes in microbiome composition and
 specific blood biomarkers could allow for earlier diagnosis of HE which could then be treated
 earlier and with novel treatments.
The investigators hypothesize that changes in an individual's cognition due to HE-related
 liver cirrhosis can be stabilized and/or improved through investigational microbiota
 restoration therapeutic treatment. The main objective of this study is to determine if
 investigational microbiota restoration therapeutic treatment alters the cognitive function in
 individuals with cirrhosis who have been previously diagnosed with overt hepatic
 encephalopathy (HE). Once individuals have one HE episode, they are more likely to experience
 additional episodes, even after complying with standard of care. The number of HE episodes
 each study group experiences during the post-treatment follow-up will be compared among
 treatment groups. It is also anticipated that cognitive improvement will correlate with
 specific changes in the intestinal microbiota composition of these individuals likely
 shifting their microbiome away from baseline samples and becoming more like donor samples.
 Novel blood biomarkers potentially related to episodes of HE will be assessed in individuals
 before and after treatment.
Inclusion Criteria

 1. Individuals who are male or female and are between the ages of 18 and 70 years.

 2. Individuals with a current diagnosis of liver cirrhosis as evidenced by one or more of
 the following:

 a. Liver Biopsy

 OR a clinical suspicion of cirrhosis based on the presence of one or more of the
 following criteria:

 1. Radiologic evidence of varices, cirrhosis or portal hypertension

 2. Laboratory evidence of platelet count <100,000 or AST/ALT ratio >1

 3. Endoscopic evidence of varices or portal gastropathy

 4. Elastography (i.e. Fibroscan)

 3. Individuals must have at least one previously documented episode of HE.

 4. Individuals must be able to read and write in the English language.

 5. Individuals must be able and willing to utilize the electronic device necessary to
 measure cognitive function without assistance from outside individuals once the
 training phase has been completed.

 6. Individuals must be able to provide valid informed consent prior to any study related
 procedures.

 Exclusion Criteria

 1. Individuals who are color-blind.

 2. Individuals actively using psychotropic substances including alcohol.

 3. Individuals who are pregnant, breastfeeding, or unwilling to practice birth control
 during participation in the study. Study individuals are expected to attest to this
 fact during their participation time. Females who are not surgically sterile or having
 undergone greater than one year of menopause will receive urine pregnancy tests at
 screening and initial drug dosing.

 4. Presence of TIPS (transjugular intrahepatic portosystemic shunt).

 5. Individuals with an active bacterial infection and are taking antibiotics for those
 infections at time of consent.

 6. Individuals with ANC <800 (neutropenia).

 7. Individuals with MELD >17.

 8. Individuals with platelet count <35,000/mm3.

 9. Individuals who are immunocompromised due any of the following reasons:

 1. HIV infection (CD4 count <200/mm3) or AIDS diagnosis

 2. Inherited/primary immunodeficiency disorders

 3. Treatment with any anti-neoplastic agent within the last 3 months (excluding
 locoregional therapy for hepatocellular carcinoma)

 4. Treatment with any immunosuppressant medications [including but not limited to
 monoclonal antibodies to B cells or T cells, anti-TNF agents, glucocorticoids,
 antimetabolites (azathioprine, 6-mercaptopurine), calcineurin inhibitors
 (tacrolimus, cyclosporine), mycophenolate mofetil] within the last 3 months

 10. Individuals who have previously undergone FMT.

 11. Individuals with a history of colorectal cancer (all stages).

 12. Individuals with a history of chronic intrinsic GI diseases such as inflammatory bowel
 disease (ulcerative colitis, Crohn's disease or microscopic colitis), eosinophilic
 gastroenteritis, celiac disease or irritable bowel syndrome as determined by Rome III
 criteria.

 13. Individuals with a history of colectomy, major gastro-intestinal surgery, or
 intra-abdominal surgery.

 14. Individuals with a history of Clostridium difficile infection six months prior to
 study enrollment.

 15. Individuals with a history of chronic diarrhea.

 16. Individuals currently participating in a research trial that involves drug or device
 intervention.

 17. Individuals who are unable to fulfill all study criteria.

 18. Individuals that the PI determines are not capable of participating in the research
 study.