Evaluation of the Outcome of Fecal Microbiota Transplantation

A Clinical Randomized Controlled Study on the Prevention and Treatment of Drug-refractory Hepatic Encephalopathy After TIPS With Fecal Microbiota Transplantation

This study is a randomized, placebo-controlled, exploratory phase II clinical trial led by Professor Han Gyeong-ho from the Digestive Disease Hospital of Xi'an International Medical Center. The study enrolled 40 patients who had experienced recurrence of hepatic encephalopathy despite treatment with rifaximin and lactulose. These patients were randomly divided 1:1 into the experimental group and the control group. After obtaining informed consent from the patients, fecal microbiota transplantation or placebo control was performed. The fecal microbiota was sourced from the feces of healthy individuals who had a rich composition of the Muribaculaceae, Ruminococcaceae, and Bifidobacteriaceae families and did not contain pathogenic bacteria. The safety and efficacy of the treatment were followed up, and blood and fecal samples were collected for sequencing analysis. The aim was to provide new solutions for patients with hepatic encephalopathy who did not respond to the treatment with rifaximin and lactulose after TIPS surgery; and to explore the impact of microbiota changes and translocation on the recurrence of hepatic encephalopathy after TIPS surgery.

This study is a single-center, randomized, placebo-controlled, exploratory phase II clinical trial. A total of 40 patients aged 18-75 years who had drug-refractory hepatic encephalopathy after transjugular intrahepatic portosystemic shunt surgery and experienced at least 2 West Haven grade ≥2 hepatic encephalopathy episodes within 6 months of treatment with lactulose and rifaximin were planned to be enrolled: These patients were randomly assigned in a 1:1 ratio to the fecal microbiota transplantation group and the placebo group. Both groups received basic standard treatment: 1200mg/day of rifaximin + 25ml/once of lactulose, twice/day; The FMT group was additionally infused with fecal suspension (100mL/once, twice/day, for 3 consecutive days) through the nasal jejunostomy tube combined with oral enteric-coated freeze-dried fecal capsules (7 capsules each time, for 1 week), while the placebo group was given the same volume of placebo solution and placebo capsules, with the same frequency and duration as the FMT group. All subjects were followed up at 15 days, 1 month, 3 months, and 6 months after transplantation. The primary outcomes were the safety (adverse events, severe adverse events, FMT-related adverse events) and efficacy (hepatic encephalopathy recurrence rate, time to first recurrence, West Haven classification) of FMT; The secondary outcomes were changes in intestinal flora colonization and diversity, liver function, blood ammonia levels, and health-related quality of life (CLDQ scale). Fecal and blood samples were collected at each follow-up time point for multi-omics detection and analysis. Statistical analysis of the trial data was performed using Kaplan-Meier method, Log-rank test, and Cox proportional hazards regression model.

Inclusion Criteria:

• Aged between 18 and 75 years old
• Patients who have experienced esophageal-gastric variceal bleeding or recurrent refractory ascites and meet the inclusion criteria, and for whom conservative treatment has failed, are planned to undergo elective TIPS surgery
• Patients with recurrent hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS), despite treatment with lactulose and rifaximin (at least 2 episodes of West Haven grade ≥2 HE within 6 months under lactulose and rifaximin intervention)
• Provided written informed consent from the patient

Exclusion Criteria:

• Malignant tumors of the liver, gastrointestinal tract or other systems
• Uncontrolled severe active infection (>grade 2) or sepsis
• Spontaneous bacterial peritonitis
• Complicated with severe cardiac, renal or pulmonary insufficiency
• Other neuropsychiatric diseases, including dementia
• Budd-Chiari syndrome
• Alcohol dependence or use of psychotropic drugs (benzodiazepines, opioids, etc.)
• History of gastrointestinal surgery (e.g., colectomy) within 3 months before enrollment
• Pregnant or lactating subjects
• Poor compliance judged by the investigator
• Model for End-Stage Liver Disease (MELD) score >17
• Tumor, immunodeficiency, or receiving immunosuppressive therapy within 3 months before enrollment
• Patients who have used other prebiotics, probiotics or fecal microbiota transplantation (FMT) before enrollment