AMSTERDAM — Patients with recurrent episodes of hepatic encephalopathy experience cognitive improvements and significantly fewer hospitalizations after fecal microbiota transplantation than after standard care, according to a phase 1 study designed to evaluate the safety of this treatment.
Fecal microbiota transplantation "is a safe procedure in this population with advanced hepatic encephalopathy," said Jasmohan Bajaj, MD, from Virginia Commonwealth University in Richmond. "We were pleasantly surprised when we saw efficacy."
Recurrent episodes of hepatic encephalopathy are a leading cause of hospital admission, and can occur despite treatment with lactulose and rifaximin. The condition is characterized by personality changes, intellectual impairment, and a depressed level of consciousness.
"This is the first randomized trial to show that fecal transplantation may be of benefit to patients with hepatic encephalopathy," Tom Karlsen, MD, PhD, from the Department of Transplantation Medicine at Oslo University Hospital Rikshospitalet in Norway, who is secretary general of the European Association for the Study of the Liver (EASL), said in a statement.
Dr Bajaj presented the findings during a well-attended session that generated a lot of interest during the question-and-answer period here at the International Liver Congress 2017.
For 150 days, Dr Bajaj and his colleagues followed 20 men with cirrhosis who had experienced at least two overt hepatic encephalopathy episodes. All patients had Model for End Stage Liver Disease (MELD) scores of 17 or less, and all received lactulose and rifaximin. The 10 patients randomized to the transplant group also received a combination of high-dose antibiotics for 5 days to clear their gut flora, and on day 6 underwent fecal transplantation. Microbiota were delivered with an enema.
The fecal microbiota came from a single bowel movement from a "rationally derived stool donor." The researchers selected the donor from OpenBiome, a nonprofit organization in Massachusetts that provides fecal microbiota to physicians around the world. The donor was chosen because he had the best profile of the Lachnospiraceae and Ruminococcaceae families of bacteria. "These are markers of everything going well in our body," Dr Bajaj explained.
The main objective of the study was to determine whether fecal transplantation is safe in this patient population. "When pumping someone else's poop into someone who is immunocompromised, we are really worried about infection," Dr Bajaj said during a news conference held in advance of his presentation.
During the 150-day study period, fewer patients in the transplant group than in the standard-care group were hospitalized (2 vs 8). And some patients in the standard-care group were hospitalized more than once.
Table. Events Occurring During the 150-Day Study Period
|Event||Transplant Group, n||Standard-Care Group, n|
|Hospitalization related to hepatic encephalopathy||0||6|
The two hospitalized patients in the transplant group were admitted because of chest pain and because of acute kidney injury from dehydration. The two patients in the standard-care group hospitalized for reasons other than hepatic encephalopathy were admitted because of a Clostridium difficile infection and because of pneumonia.
In addition to being safe, the procedure was shown to be well tolerated — no serious adverse events occurred — and effective.
Patients in the transplant group also experienced improvement in cognitive function — assessed with the Psychometric Hepatic Encephalopathy Score (PHES) and Stroop test app — from baseline to day 150, whereas those in the standard-care group did not.
The one patient in the transplant group who experienced a decline in cognitive function had higher baseline levels of Proteobacteria(a group of bacteria that includes pathogens such as Escherichia, Salmonella, Vibrio, and Helicobacter), which did not respond to fecal transplantation.
Fecal transplantation also significantly restored gut microbial diversity, including Lactobacillaceae and Bifidobacteriaceae, after antibiotic-associated loss, and was not associated with infections.
"It is nice to see a reduction in events," said session moderator Annalisa Berzigotti, MD, PhD, from the University Clinic for Visceral Surgery and Medicine Inselspital at the University of Berne in Switzerland.
"As was clearly stated, this study was devoted to safety and we cannot extrapolate more; it's too early to come to any other conclusions. But now that safety is not an issue, it's open to further study on the clinical importance," she told Medscape Medical News.
After his presentation, Dr Bajaj was asked by a member of the audience why an enema was used to deliver the fecal microbiota.
"That's a very important question," he replied. "We were struggling with this, and this approach had the least logistic issues in our endoscopy lab." In addition, he pointed out, enemas are the least invasive method, so could have minimized procedure-related adverse events. "Next we are looking at a capsule," he reported.
The same audience member asked about the donor. "He was a 36-year-old very muscular young man, which helped me convince my veterans with cirrhosis" to agree to the procedure, Dr Bajaj said.
"Does the volume of the transplant matter, and does a probiotic help?" another audience member asked.
"As I said, it was a safety study. We started with the lowest amount of variables. But these are all important questions — duration, frequency, and coexisting microbial-changing medications — in these patients," Dr Bajaj responded.
Studies are needed in women, patients who do not receive antibiotics before transplantation, and those with higher MELD scores, he added.
"The encouraging findings open new avenues of research to determine how to best manipulate the gut microbiota in patients with hepatic encephalopathy," Dr Karlsen explained. "They also show proof of concept for the likely beneficial impact of such interventions, adding to what is already known about nonabsorbable antibiotics like rifaximin."
Dr Bajaj, Dr Berzigotti, and Dr Karlsen have disclosed no relevant financial relationships.
International Liver Congress (ILC) 2017: Abstract PS-085. Presented April 21, 2017.
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Cite this: Fecal Transplant Safe for Hepatic Encephalopathy - Medscape - Apr 27, 2017.