Cognitive Impairment In Liver Failure Treated With Fecal Microbiota Transplant

Fecal microbiota transplant from a healthy donor improves the impaired mental function in liver failure patients significantly compared to standard treatment.

Highlights:

Decline in mental function (hepatic encephalopathy HE) occurs with advanced liver disease which is associated with poor quality of life and increased mortality
Standard treatment involves giving lactulose and rifaximin which target the gut microbiota.
Current study shows fecal microbiota transplant (FMT) may be better in improving the deterioration in mental function associated with HE than standard therapy

Fecal transplant from a healthy person may be more effective in improving the reduced mental function of advanced liver disease compared to standard forms of treatment, according to a recent randomized study by scientists at the Virginia Commonwealth University, Richmond, United States of America.

Reason for Study

Autism Therapy Could Lie in Fecal Microbial Transplant
Fecal microbial transplant in patients with autism increases good bacteria in the gut and could be an effective therapy for autism.

‘Fecal transplant not only improves the mental decline occurring in advanced liver disease but also reduces the rate of recurrence and subsequent hospitalizations.’

The study authors feel that current forms of treatment, though effective in treatment of hepatic encephalopathy, are nevertheless associated with recurrent episodes necessitating frequent hospitalizations.

Fecal microbiota transplant (FMT) could potentially address the gaps in the current treatment forms; additionally it is safe with no adverse effects.

Details of the Study

Ulcerative Colitis May be Treated Using Fecal Transplants
Ulcerative colitis causes inflammation and ulcers in the lining of the colon, which can lead to rectal bleeding and abdominal discomfort.

In a randomized trial, 20 men with cirrhosis due to advanced liver disease with recurrent episodes of hepatic encephalopathy before the study were chosen.

The participants were randomly chosen to either receive the standard treatment of lactulose plus rifaximin, or a five day course of broad spectrum antibiotics followed by fecal microbiota transplant (FMT) from a healthy donor while continuing the standard treatment.
The FMT was administered as an enema. The patients were monitored for upto 150 days following the randomization.

Results of the Study

The cognitive function of the participants was assessed using standard tests to assess the cognition such as Psychometric Hepatic Encephalopathy Score (PHES) and the Stroop App.

Comparing Fecal Transplant to the Existing Standard of Care for Clostridium Difficile
Over the last decade, fecal transplantation (FT) has re-emerged as a promising treatment for recurrent Clostridium difficile infection.

The results were as follows:

The improvement in cognition in the FMT was significantly higher than the standard of care group.
Number of hospitalizations in the FMT during the followup period was 2 compared to 11 in the standard of care group.
Hospital admissions due to recurrent HE was zero in the FMT group compared to 6 in the standard of care group.
There was a significant increase in good gut bacteria following FMT including Bifidobacteriaceae and Lactobacillaceae but not in the standard of care group.
Persons who received the standard of care treatment did not show significant changes in cognition, gut bacteria or MELD score which is used to assess severity of liver disease.

Jasmohan Bajaj, Virginia Commonwealth University, Richmond, America, and lead author of the study said, "The results from this study demonstrate that in patients with hepatic encephalopathy, a fecal transplant improves brain function more than standard of care as well as reducing the number of hospital admissions, including those for recurrent hepatic encephalopathy. Fecal transplantation is an innovative and promising approach to treat this condition, and we look forward to more studies being conducted to confirm our results."

Hepatic Encephalopathy – Why It Occurs

Liver Cirrhosis - Causes, Symptoms, Diagnosis, Treatment & Prevention
Liver cirrhosis is a chronic liver disease that arises due to alcoholism, hepatitis, or other conditions. Liver failure patients are treated with transplantation.

Hepatic encephalopathy (HE) refers to mental impairment, often seen in advanced liver disease. It can range from mild confusion and forgetfulness to severe confusion seizures coma and even death.

The reason for these mental changes is the accumulation of ammonia a toxin, which is to a large extent derived in our body by activity of bacteria in the gut.

Studies have shown that there is significant alteration in the gut flora (dysbiosis) in hepatic encephalopathy patients with a shift towards ammonia producing organisms.

Normally the ammonia is detoxified in the liver and eliminated from the body. In liver disease, the ammonia therefore accumulates in the blood and affects the brain function leading to the features of hepatic encephalopathy.

How Treatments Targeting Gut Bacteria Work

The gut bacteria which lead ammonia formation and accumulation are urease forming organisms. Treatment of HE aims at altering the gut microbial flora from urease forming to non-urease forming organisms, consequently reducing levels of ammonia in the blood.

Both standard treatments such as lactulose and rifaximin or FMT therapy exert their effects by targeting the gut flora and shifting it towards non-urease producing organisms.

What is Fecal Microbiota Transplant

Fecal Microbiota Transplant (FMT) is a procedure wherein fecal matter, or stool, obtained from a healthy tested donor is mixed with a saline or other solution and then introduced into the intestine of the patient by an enema, colonoscopy or sigmoidoscopy.

The aim of FMT is to introduce good bacteria to replace the bad disease causing bacteria that have populated the colon due to various reasons.
Other diseases in addition to HE where fecal transplant has shown benefit is Clostridium difficile colitis caused by prolonged antibiotic therapy. Other conditions where its potential use is being studied include inflammatory bowel diseases, irritable bowel syndrome (IBS) and obesity to name a few.

In conclusion, this study has paved the way for future research as to how gut bacteria could be modified or manipulated to treat hepatic encephalopathy.

In the words of Prof Tom Karlsen, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Norway and EASL Vice-Secretary, "This is the first randomised trial to show that fecal transplantation may be of benefit to patients with hepatic encephalopathy. The encouraging findings open new avenues of research to determine how to best manipulate the gut microbiota in patients with hepatic encephalopathy. They also show proof-of-concept for the likely beneficial impact of such interventions, adding to what is already known for non-absorbable antibiotics like rifaximin,"

References:

Faecal microbiota transplantation: applications and limitations in treating gastrointestinal disorders - (https://www.ncbi.nlm.nih.gov/pubmed/15025256)
Role of gut bacteria in the therapy of hepatic encephalopathy with lactulose and antibiotics - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873946/)
Management of Hepatic Encephalopathy in the Hospital - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128786/)
The role of microbiota in hepatic encephalopathy - (http://thefecaltransplantfoundation.org/what-is-fecal-transplant/)
What is FMT? - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153779/)

Source-Medindia