Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial

Abstract

Recurrent hepatic encephalopathy (HE) is a leading cause of readmission despite standard of care (SOC) associated with microbial dysbiosis. Fecal microbiota transplantation (FMT) may improve dysbiosis; however, it has not been studied in HE. We aimed to define whether FMT using a rationally-derived stool donor is safe in recurrent HE compared to SOC alone. An open-label, randomized clinical trial with a 5 month follow-up in outpatient cirrhotic men with recurrent HE on SOC was conducted with 1:1 randomization. FMT-randomized patients received 5-days of broad-spectrum antibiotic pre-treatment then a single FMT enema from the same donor with the optimal microbiota deficient in HE. Follow-up occurred on days 5, 6, 12, 35 and 150 post-randomization. The primary outcome was safety of FMT compared to SOC using FMT-related serious adverse events (SAE). Secondary outcomes were AEs, cognition, microbiota and metabolomic changes. Participants in both arms were similar on all baseline criteria and were followed till study-end. FMT with antibiotic pre-treatment was well-tolerated. Eight (80%) SOC participants had a total of 11 SAE compared to two (20%) FMT participants with SAEs (both FMT-unrelated, p=0.02). Five SOC and no FMT participants developed further HE (p=0.03). Cognition improved in FMT, but not SOC group. MELD score transiently worsened post-antibiotics, but reverted to baseline post-FMT. Post-antibiotics, beneficial taxa and microbial diversity reduction occurred with Proteobacteria expansion. However, FMT increased diversity and beneficial taxa. SOC microbiota and MELD score remained similar throughout. Conclusions: FMT from a rationally selected donor reduced hospitalizations, improved cognition and dysbiosis in cirrhosis with recurrent HE.

The use of faecal microbiota transplant as treatment for recurrent or refractoryClostridium difficileinfection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines

“…To date, there have been a total of 71 such studies investigating the role of FMT in IBD; of these, only four are prospective randomised controlled trials, limited to patients with ulcerative colitis 136–139. Five other reviewed randomised studies investigated the use of FMT in IBS,140 slow transit constipation,141 hepatic encephalopathy142 and metabolic syndrome 143 144…”

“…One small study has investigated the role of FMT in the management of hepatic encephalopathy 142. This RCT randomised 20 male patients with cirrhosis with refractory hepatic encephalopathy to receive either 5 days of broad spectrum antibiotic pretreatment followed by a single FMT enema or standard of care.…”

Intensive Care Therapy for Patients with Advanced Liver Diseases

“…Organ dysfunction is defined as an increase of 2 points in the Sequential Organ Failure Assessment (SOFA) score [72][73][74] (table 4). Currently under investigation Flumazenil (synthetic benzodiazepine antagonist) [59] Pre-/probiotics [60] Fecal microbiome transfer [61] In patients with liver cirrhosis and sepsis, intensive care therapy is aimed to restore organ perfusion (as described above) along with fast identification and elimination of the infectious site(s) and trigger(s). More information on this particular aspect can be found in the contribution by Engelmann and Berg [75] in this focus issue of Visceral Medicine.…”

Proton Pump Inhibitors Are Associated With Minimal and Overt Hepatic Encephalopathy and Increased Mortality in Patients With Cirrhosis

“…In fact, gut bacteria are responsible for the formation and release of products such as ammonia and endotoxins, implicated in the pathophysiology of HE . Moreover, treatments able to modify the gut flora such as antibiotics, disaccharides, probiotics, and fecal transplantation have been shown to have a beneficial effect on HE. Thus, factors able to modify the gut microbiota may affect HE.…”