- Decline in mental function (hepatic encephalopathy HE) occurs with
advanced liver disease which is associated with poor quality of life and
- 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
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
‘Fecal transplant not only improves the mental decline occurring in advanced liver disease but also reduces the rate of recurrence and subsequent hospitalizations.’
study authors feel that current forms of
treatment, though effective in treatment of hepatic encephalopathy, are nevertheless associated with recurrent episodes
microbiota transplant (FMT) could potentially address the gaps in the current treatment
it is safe with no
Details of the Study
a randomized trial, 20 men with
due to advanced liver disease with recurrent episodes of hepatic
encephalopathy before the study were chosen.
Results of the Study
- The participants were randomly
chosen to either receive the standard treatment of lactulose plus
or a five day course of broad spectrum antibiotics followed by fecal
microbiota transplant (FMT) from a healthy donor while continuing the
- The FMT was administered as an enema. The patients were monitored for upto 150 days
following the randomization.
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.
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
, 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
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.
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.
have shown that there is significant alteration in the gut flora (dysbiosis)
in hepatic encephalopathy
patients with a shift towards ammonia
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
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.
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
What is Fecal Microbiota Transplant
Microbiota Transplant (FMT) is a procedure wherein fecal matter, or stool, obtained from a healthy
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.
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,"
- 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/)