A Prospective Exploratory Study on Fecal Microbiota Transplantation for the Treatment of Refractory Hepatic Encephalopathy After TIPS Surgery

Hepatic encephalopathy is one of the most common and clinically significant complications after transjugular intrahepatic portosystemic shunt. After TIPS, portosystemic shunting may increase the systemic exposure to gut-derived neurotoxins and inflammatory mediators, thereby increasing the risk of overt hepatic encephalopathy. Although lactulose and rifaximin are widely used as standard medical therapy, some patients continue to experience recurrent overt hepatic encephalopathy despite adequate treatment. For patients with refractory overt hepatic encephalopathy after TIPS, current therapeutic options remain limited, particularly in terms of rapid recovery of consciousness, prevention of recurrence, and restoration of gut microbial homeostasis.

Fecal microbiota transplantation may provide a microbiota-based therapeutic approach by reshaping the intestinal microbial ecosystem, modulating gut-derived toxin production, improving intestinal barrier and metabolic function, and regulating the gut-liver-brain axis. Previous studies have suggested that fecal microbiota transplantation may be safe and potentially effective in patients with cirrhosis-related hepatic encephalopathy. However, clinical evidence remains limited in patients with refractory overt hepatic encephalopathy specifically occurring after TIPS. In addition, prebiotics may support the growth and engraftment of beneficial bacterial taxa after fecal microbiota transplantation by providing fermentable dietary substrates. Therefore, this study is designed to evaluate the safety and preliminary efficacy of fecal microbiota transplantation combined with standard therapy in patients with refractory overt hepatic encephalopathy after TIPS, and to compare the clinical and microbiome-related effects of fecal microbiota transplantation with or without adjunctive prebiotic supplementation.

This is a single-center, prospective, open-label, parallel-group exploratory clinical study. A total of 26 eligible participants with refractory overt hepatic encephalopathy after TIPS will be enrolled. Eligible participants will be adults aged 18 to 75 years who have successfully undergone covered-stent TIPS and have experienced at least two episodes of overt hepatic encephalopathy with West Haven grade 2 or higher within 6 months despite treatment with rifaximin and lactulose. Participants must also be suitable for fecal microbiota transplantation via a nasojejunal tube and able to tolerate tube placement and subsequent infusion procedures. Key exclusion criteria include active major gastrointestinal bleeding or perforation, severely impaired intestinal barrier function, congenital or acquired immunodeficiency, recent high-risk immunosuppressive or cytotoxic therapy, hepatic or gastrointestinal malignancy, spontaneous bacterial peritonitis, Budd-Chiari syndrome, severe cardiac, renal, or pulmonary dysfunction, unstable vital signs, recent gastrointestinal surgery, planned liver transplantation within 6 months, recent fecal microbiota transplantation, alcohol dependence, use of medications that may affect neuropsychiatric status, other neuropsychiatric disorders, pregnancy or lactation, and poor compliance as judged by the investigator.

All enrolled participants will continue to receive standard medical therapy. Standard therapy consists of rifaximin 0.4 g three times daily, with a total daily dose of 1200 mg, and lactulose 25 mL twice daily, adjusted as clinically needed. During an episode of overt hepatic encephalopathy, all participants will receive fecal microbiota transplantation via a nasojejunal tube. The fecal microbiota suspension will be administered at 100 mL per infusion, twice daily, for 3 consecutive days. The fecal microbiota product will be prepared from rigorously screened healthy donors under standardized conditions, with controlled storage and traceability. Participants will be assigned in a 1:1 ratio to the fecal microbiota transplantation group or the fecal microbiota transplantation plus prebiotic group, with 13 participants in each group. Participants in the combination group will receive additional dietary fiber prebiotic supplementation at a total dose of 24 g/day, administered as 12 g twice daily, starting on the day of fecal microbiota transplantation and continuing for 4 weeks.

Efficacy and safety will be systematically assessed during treatment and follow-up. Clinical assessments will include vital signs, mental status, West Haven grade, time to reversal of hepatic encephalopathy, recurrence of hepatic encephalopathy, hospitalization, and adverse events. Laboratory assessments will include complete blood count, liver function, renal function, coagulation function, plasma ammonia, hepatitis B virus DNA when applicable, alpha-fetoprotein, endotoxin, C-reactive protein, and interleukin-6. Liver disease severity will be assessed using Child-Pugh and MELD scores. Minimal hepatic encephalopathy testing and neurocognitive assessments will be performed when clinically feasible.