Faecal transplants improve encephalopathy in people with advanced liver disease

24 Apr 2019 Liz Highleyman
Originally published on www.infohep.org

Faecal microbiota transplantation (FMT), which helps restore a healthy mix of bacteria in the gut, can help reverse brain function impairment in people with liver failure, according to a report at the International Liver Congress last week in Vienna.

FMT capsules led to the restoration of bacterial diversity in the gut and improvement of cognitive function in people with hepatic encephalopathy as a consequence of advanced cirrhosis, Dr Jasmohan Bajaj of Virginia Commonwealth University reported.

Over years or decades, chronic hepatitis B or C, fatty liver disease, heavy alcohol consumption and other causes of liver injury can lead to cirrhosis, hepatocellular carcinoma and end-stage liver failure requiring a transplant.

In people with decompensated cirrhosis, the liver can no longer carry out its vital functions due to the accumulation of scar tissue and blockage of blood flow. Complications may include ascites (fluid build-up in the abdomen), bleeding veins in the oesophagus and hepatic encephalopathy, which occurs when the liver can no longer filter out ammonia and other toxins.

Symptoms of hepatic encephalopathy may include impaired cognition, poor concentration, confusion, personality changes and coma. Over time, recurrent bouts of encephalopathy can lead to lasting brain damage, according to Dr Bajaj. Treatments include lactulose, a non-digestible sugar that absorbs ammonia and acts as a laxative, and the non-absorbable antibiotic rifaximin.

Lactulose and antibiotics can change the makeup of bacteria in the intestines, known as the gut microbiome. Some types of gut bacteria produce ammonia, which worsens encephalopathy, while others trigger systemic inflammation.

Studies have shown that altering the gut microbiome can help prevent or improve hepatic encephalopathy. For example, research presented at the 2013 International Liver Congress showed that a probiotic supplement reduced ammonia levels, improved cognitive function and prevented encephalopathy progression in people with advanced liver disease.

Transplanting gut bacteria from a healthy individual is another way to restore a beneficial microbiome. FMT involves transferring donor faeces via an enema formulation or oral capsules.

Dr Bajaj and colleagues previously showed that FMT via enema improved cognitive function and reduced hospitalisations in people with advanced liver cirrhosis. They then evaluated the safety, tolerability and effectiveness of a capsule formulation, which is more convenient and can deliver beneficial bacteria to the small intestine, not just the colon.

This phase I study included 20 people with cirrhosis and recurrent hepatic encephalopathy who were receiving lactulose and rifaximin. Participants were randomly assigned to receive 15 FMT capsules or similar placebo capsules in addition to their existing therapy.

The capsules were prepared using stool from a single donor – the same so-called 'super pooper' who donated for the enema FMT study – with high levels of beneficial Lachnospiraceae and Ruminococcaceae bacteria species. Dr Bajaj stressed that the capsules "do not smell like poop and do not taste like poop."

At the start of the study, microbial diversity in stool samples and biopsy samples from the small intestine (duodenum) and large intestine (sigmoid colon) was similar in both groups. After two to four week of treatment, however, people in the FMT group saw an increase in bacterial diversity, with more Ruminococcaceae and Bifidobacteriaceae bacteria and a decrease in Streptococcaceae and Veillonellaceae species. Duodenum biopsy samples also showed a reduction in biomarkers of inflammation.

Cognitive function scores using a standardised assessment test improved in the FMT group compared with the placebo group. Just one participant required hospitalisation or died in the FMT group while six did so in the placebo group. The total number of hospitalisations was also significantly lower in the FMT group. No safety issues were identified during the study.

"Faecal microbiota transplant using a single stool donor enriched with bacterial species we know are deficient in this population is a promising approach to the potential treatment of patients with cirrhosis and recurrent hepatic encephalopathy," Dr Bajaj said. "The way to the brain is through the gut."