Fecal Microbiota Transplantation for Liver Failure

Study Overview
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Brief Summary
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To investigate the safety, adverse reactions and therapeutic effects of fecal microbiota transplantation on patients with liver failure;to investigate the effect of fecal microbiota transplantation on the intestinal microecology and gut-liver axis immune system of liver failure, and further optimization of fecal microbiota transplantation technology.

Official Title
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The Clinical Efficacy and Safety of Fecal Microbiota Transplantation in Patients With Acute-on-chronic Liver Failure

Conditions
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Liver Failure

Intervention / Treatment
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* Other: fecal microbiota transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients willing to sign informed consent Patients aged 18-65 According to the diagnosis standard of liver failure in the guide for diagnosis and treatment of liver failure (2018 Edition), the eligible patients are included, that is, on the basis of chronic liver disease, the syndrome with acute jaundice deepening and coagulation dysfunction as the manifestation of liver failure caused by various inducements can be combined with complications such as Hepatoencephalopathy, ascites, electrolyte disorder, infection, hepatorenal syndrome, hepatopulmonary syndrome, etc And extrahepatic organ failure. The patient's jaundice deepened rapidly, the serum TBIL ≥ 10 × ULN or the daily rise ≥ 17.1 μ mol / L; there was bleeding, PTA ≤ 40% (or INR ≥ 1.5) Exclusion Criteria: Patients with severe heart failure, COPD, cerebrovascular accident, nephrotic syndrome, etc; Patients with gastrointestinal bleeding, pulmonary infection, septicemia, etc Patients with liver cancer, lung cancer, lymphoma and other malignant tumors Patients taking anticoagulants, mental diseases and immune diseases for a long time Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: fecal microbiota transplantation<br>The fecal bacteria were transplanted once every 5 days for a total of 4 times. | Other: fecal microbiota transplantation<br>* The fecal bacteria were transplanted once every 5 days for a total of 4 times<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver function change | The investigators need to monitor the changes in liver and kidney function before and after faecal bacteria transplantation，such as ALT、AST、GGT 、TBIL(The units of these indices are U/L). | Blood samples were collected 1 week before faecal bacteria transplantation, and followed up at 5 day, 10 day, 15 day, 20 day, 4 and 8 weeks after faecal bacteria transplantation, respectively | 
| Coagulation function change | Prothrombin activity are one of the indexes to evaluate the degree of liver failure in patients.The units of this indices is %. | Blood samples were collected 1 week before faecal bacteria transplantation, and followed up at 5 day, 10 day, 15 day, 20 day, 4 and 8 weeks after faecal bacteria transplantation, respectively | 
| Model for end-stage liver disease score change | The model for end-stage liver disease (MELD) score is a prospectively developed and validated scale for the severity of end-stage liver disease.The higher the MELD score, the more severe the liver disease and the greater the risk of death. The fatality rate of patients with MELD between 20 and 30 was more than 30%, that of patients with MELD between 30 and 40 was more than 50%, and that of patients with MELD >40 was more than 70%. | Model for end-stage liver disease score were obtained separately in 1 week before faecal bacteria transplantation, and to access once again at 5 day, 10 day, 15 day, 20 day, 4 and 8 weeks after faecal bacteria transplantation, respectively | 
| gut microbiota change | Gene sequencing and metabonomics analysis of fecal flora. | Fecal samples were collected 1 week before faecal bacteria transplantation, and change from at 5 day, 10 day, 15 day, 20 day, 4 and 8 weeks after faecal bacteria transplantation, respectively | 
| Observe the clinical manifestations, safety and adverse reactions of the patients | Safety and adverse events were assessed including fever, diarrhea and elevated inflammatory markers (such as C-reactive protein and procalcitonin) before and after faecal bacteria transplantation. | These indicators were collected 1 week before faecal bacteria transplantation, and change from at 5 day, 10 day, 15 day, 20 day, 4 and 8 weeks after faecal bacteria transplantation, respectively | 
| proinflammatory cytokine change | IL-17,IL-6,TNF-α, TGF-β, IFN-γ and other cytokines were detected by ELISA(The units of these indices are pg/mL). | Blood samples were collected 1 week before faecal bacteria transplantation, and followed up at 5 day, 10 day, 15 day, 20 day, 4 and 8 weeks after faecal bacteria transplantation, respectively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fecal microbiota transplantation, gut-liver axis, liver failure