This is a single-center, prospective, open-label, parallel-group exploratory clinical study designed to evaluate the safety and preliminary efficacy of fecal microbiota transplantation combined with standard medical therapy in patients with refractory overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. The study also aims to explore whether adjunctive prebiotic supplementation may improve clinical outcomes and support gut microbiota reconstruction after fecal microbiota transplantation.
A total of 26 participants with recurrent overt hepatic encephalopathy after TIPS despite standard therapy with rifaximin and lactulose will be enrolled. All participants will continue to receive standard medical therapy, including rifaximin and lactulose. During an episode of overt hepatic encephalopathy, all participants will receive fecal microbiota transplantation via a nasojejunal tube at a dose of 100 mL per administration, twice daily, for 3 consecutive days. Participants will be assigned in a 1:1 ratio to either the fecal microbiota transplantation group or the fecal microbiota transplantation plus prebiotic group. Participants in the combination group will receive dietary fiber prebiotic supplementation at 24 g/day for 4 weeks in addition to the same fecal microbiota transplantation and standard medical therapy.
Participants will be followed for up to 6 months. The primary efficacy assessment will focus on recurrence of hepatic encephalopathy, including recurrence rate, time to first recurrence, episode grade, and duration. Secondary assessments will include time to reversal of hepatic encephalopathy, West Haven grade, blood ammonia, liver and kidney function, inflammatory markers, liver function scores, neurocognitive function, and changes in gut microbiota composition. Safety assessments will include adverse events, fecal microbiota transplantation-related adverse events, infection, worsening hepatic encephalopathy, hospitalization, and serious adverse events. This study is expected to provide preliminary clinical evidence for a microbiota-based therapeutic strategy in patients with refractory overt hepatic encephalopathy after TIPS.
Age: 18 - 75 years old, both genders are eligible
Successful implementation of covered stent TIPS
Those who experienced recurrence of hepatic encephalopathy after TIPS surgery and still used lactulose and rifaximin (within 6 months after intervention with rifaximin and lactulose, West Haven grade ≥ 2 hepatic encephalopathy occurred at least 2 times)
Meet the conditions for receiving fecal microbiota transplantation through nasogastric tube (no severe anatomical abnormalities in the upper digestive tract; basic intestinal motility is normal; can tolerate the insertion of nasogastric tube and the subsequent infusion process)
Patients with active gastrointestinal bleeding or perforation accompanied by severe damage to the intestinal barrier due to various reasons
Patients with congenital or acquired immunodeficiency diseases, those who have received high-risk immunosuppressive or cytotoxic drug treatment within the recent 3 months, and those with severe immunosuppression (neutrophil count < 1.5×10⁶ cells/L; CD4+ T cell count < 2.0×10⁵ cells/L)
Patients with malignant tumors of the liver or gastrointestinal tract, patients with spontaneous bacterial peritonitis, and patients with Budd-Chiari syndrome
Patients with severe heart, kidney, or lung dysfunction (NYHA III-IV grade or unstable heart failure; eGFR < 30 ml/min/1.73m² or requiring dialysis; respiratory failure or requiring long-term oxygen therapy)
Parallel
Fecal Microbiota Transplantation
Biological/VaccineFecal microbiota transplantation is used to reconstruct gut microbiota structure, regulate intestinal microecological homeostasis, improve intestinal barrier function, reduce systemic endotoxin load and inflammatory level, for the prevention and treatment of refractory hepatic encephalopathy after TIPS. The preparation is made from stool of qualified screened donors, processed under sterile conditions.
Rifaximin、Lactulose
DrugRifaximin is a non-absorbable oral rifamycin antibiotic, used as standard medical therapy for hepatic encephalopathy, to reduce intestinal urease-producing bacteria and intestinal ammonia production.Lactulose is a synthetic disaccharide laxative, used as first-line standard medical therapy for hepatic encephalopathy, to acidify the intestinal lumen, reduce ammonia production and promote ammonia excretion.
Dietary Fiber Prebiotic
Dietary supplementParticipants assigned to the FMT plus prebiotic group will receive dietary fiber prebiotic supplementation in addition to fecal microbiota transplantation and standard medical therapy. The prebiotic will be administered at a total dose of 24 g per day, given as 12 g twice daily, starting on the day of fecal microbiota transplantation and continuing for four weeks. Standard medical therapy with rifaximin and lactulose will be continued during the study period.
Incidence and severity of treatment-related adverse events (AEs) and serious adverse events (SAEs)
Record the number, incidence, severity (graded by NCI-CTC v3.0 criteria), correlation with trial intervention, and outcome of all AEs, FMT-related AEs and SAEs in subjects from randomization to the end of follow-up. Key monitoring includes gastrointestinal reactions, infection, exacerbation of hepatic encephalopathy and other intervention-related adverse events.
Reversal time of hepatic encephalopathy
The reversal time of hepatic encephalopathy is defined as the time required from the start of fecal microbiota transplantation treatment until the patient's clinical consciousness state recovers to the remission state of hepatic encephalopathy. Hepatic encephalopathy remission is defined as a significant improvement in the West Haven classification compared to the baseline and a return to grade 0-1, with significant relief of related neurological and mental symptoms. The reversal time is recorded in hours or days and is used to assess the speed of improvement in hepatic encephalopathy after treatment.
Recurrent rate of hepatic encephalopathy
The recurrent rate of hepatic encephalopathy is defined as the proportion of subjects who experienced overt hepatic encephalopathy again during the follow-up period after receiving fecal microbiota transplantation treatment. Overt hepatic encephalopathy is evaluated according to the West Haven classification, and is defined as a hepatic encephalopathy event with a West Haven grade of ≥2. During the study period, the time of the first recurrence, the number of recurrences, and the severity of recurrence of the subjects were recorded, and the recurrence rates at each follow-up time point and throughout the entire follow-up period were calculated.
The colonization status of the intestinal microbiota
The survival rate (%) of the donor microbiota in the patient's intestinal tract
Changes in the α diversity of the intestinal microbiota
Using metagenomic sequencing technology, the α diversity of the intestinal microbiota (Shannon index, Simpson index) was evaluated.
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