Fecal Microbiota Transplant as Treatment of Hepatic Encephalopathy

By Dr. Katie E. Golden, MD

CMIT is collaborating with Dr. Patricia Pringle and Dr. Raymond Chung from Massachusetts General Hospital (MGH) on a new study that is investigating the potential role of fecal microbiota transplantation (FMT) as a treatment for hepatic encephalopathy. They will be providing stool sample analysis and genomic sequencing as the clinical investigators study the correlation between changes in the microbiome and clinical outcomes in liver disease patients.

Hepatic Encephalopathy (HE) is a common complication of liver cirrhosis, and is associated with alterations in mental status and cognition that can have a significant impact on a patient’s quality of life and morbidity. HE is believed to be the result of increased levels of ammonia in the blood (the diseased liver has decreased metabolism of gut-derived ammonia), which then crosses the blood-brain barrier and toxic to neurons. This leads to confusion, lethargy, and in more severe causes, dangerous swelling of the brain.

Recent research has highlighted the contribution of a patient’s microbiome the development of HE. Not only is the microbiome known to be dysbiotic in cirrhosis patients, but there is also evidence that cirrhotic patients with HE have greater abundance of ammonia-producing bacteria in the intestine. There is already published case reports and data to suggest successful use of FMT to treat cognitive dysfunction in HE, however the available research is limited and requires further investigation.

Clinical researchers at MGH, with the help of CMIT, are conducting a two-part clinical trial to evaluate the safety and utility of FMT in HE. The first phase will be a pilot phase to investigate the efficacy of the intervention in a small number of patients, and the second phase will isolate material from the most effective donors in a larger cohort of patients (and compare this to outcomes in a placebo population). Stool samples from both donors and recipients will be collected and analyzed, at multiple time points throughout the study, to understand how changes in the gut microbial populations correlate with clinical symptoms and treatment efficacy. The primary outcome is improvement in the patient’s cognitive function. The secondary outcomes include the safety and tolerability of treatment, changes in recipient microbiome composition, as well as changes in serum and stool biomarkers. Researchers hope to not only develop improved treatment options for those suffering from HE, but also better characterize the mechanism behind the microbiome’s contribution to this specific disease and broader neurocognitive disease.