VCU news

By Carla Davis

Transferring stool from a healthy donor to cirrhosis patients who suffer from recurrent hepatic encephalopathy offers positive long-term outcomes including reduced hospitalizations and improved cognition, according to extended data from a previously published study led by a researcher at Virginia Commonwealth University.

Extended results of the study were recently published online in the journal Gastroenterology.  

“The current study extends the experience of the first randomized clinical trial of fecal microbiota transplant after antibiotics in cirrhosis and recurrent hepatic encephalopathy over more than 12 months,” said the paper’s lead author, Jasmohan Bajaj, M.D., an associate professor in the VCU School of Medicine and a staff physician at Hunter Holmes McGuire VA Medical Center. Bajaj led the team of researchers who oversaw fecal microbiota transplants in cirrhosis patients at McGuire.

Cirrhosis, a disease characterized by permanent scarring and damage to the liver, is caused by a variety of conditions including chronic alcohol abuse and hepatitis. Cirrhosis affects about 1 in 400 adults and is the most common reason adults need liver transplants, according to the National Institutes of Health.

A complication of cirrhosis, hepatic encephalopathy is characterized by the loss of brain function. The disorder can lead to significant behavior, mood and speech impairments, and even death. In research findings published in the Journal of Hepatology and Scientific Reports, Bajaj revealed a relationship between bacteria found in the intestinal tract and stool, called microbiota, and hepatic encephalopathy.

In the published safety trial informed by those findings, Bajaj and his colleagues randomly assigned a small number of cirrhosis patients with recurrent hepatic encephalopathy to receive either a fecal microbiota transplant with pre-treatment antibiotics orstandard care. . Fecal transplantation has been used to treat other conditions, but this was the first randomized trial of its kind in liver disease and cirrhosis.

After five months, the researchers found the fecal transplantation was safe, offered short-term cognitive improvements and reduced hospitalizations. Encouraged by those findings, the researchers followed the study subjects for 12 to 15 months after the initial fecal microbiota transplant. 

“Our aim was to determine the long-term impact of FMT on cognition, hospitalizations and hepatic encephalopathy by extending results of this trial,” Bajaj said. “What we found, to our surprise, was that the patients with liver disease who received the transplant, compared to the people who received standard care, maintained their ability to reduce hospitalizations and reduce episodes of hepatic encephalopathy. And this was accompanied by continued improvement in their brain function. Basically, we were able to induce a lasting change in the gut-liver-brain axis with that one fecal transplant.”

This preliminary experience demonstrates that fecal transplantation after antibiotics may be safe and effective in preventing long-term recurrence of hepatic encephalopathy in patients with liver cirrhosis.

“This is truly very exciting if it is confirmed with larger trials,” Bajaj said. “This treatment can potentially improve the suffering of these patients and their families.”

As a next step, a randomized clinical trial is planned for a larger population of cirrhosis patients. Performing fecal microbiota transplant using both oral capsules and enemas, Bajaj and his colleagues will determine the improvement in brain function between the different delivery methods. 

Donor materials were provided by nonprofit stool bank OpenBiome, a collaborator on the study. Funding was provided by the National Institutes of Health and a U.S. Department of Veterans Affairs Merit Review grant.