Study on Effect of Intestinal Microbiota Transplantation in Hepatitis B Virus Induced Cirrhosis

Study Overview
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Brief Summary
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Chronic hepatitis B (CHB) is a common infectious disease affecting up to 2 billion people worldwide. Around 650 thousand people died of liver failure, cirrhosis and primary liver cancer caused by chronic hepatitis B every year. 3%-5% compensatory liver cirrhosis develop to decompensated cirrhosis and suffer from series symptoms such as fatigue, edema, portal hypertension, splenomegaly, hemorrhage, hepatic encephalopathy, hepatorenal syndrome and so on. Chronic hepatitis B is closely related to the imbalance of intestinal microbiota, and the intestinal microbiota of patients is significantly different from healthy people. The response of patients to hepatitis B virus can be influenced by reconstructing intestinal flora, while Intestinal microbiota transplantation(IMT) is a significant method to achieve it. In a previous study using IMT to treat HBeAg positive chronic hepatitis B patients combined with antiviral therapy, 80% of them has reached HBeAg clearance. The investigators propose a randomized trial of IMT in patients with HBV induced cirrhosis. Patients will be randomized to either control group or IMT group over a 12 months period.

Detailed Description
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A group of 60 patients with HBV induced cirrhosis will be recruited for study, which involved a 4 times IMT with gastroduodenoscopy and the time interval is generally 2 weeks. Participants can keep taking their present treatment. All participants will be assessed at baseline, after 3 months, 6 months, 12 months from baseline in order to evaluate the possible changes in: (1)Imaging changes: Color Doppler ultrasound of portal vein, CT/MRI, Fibroscan score of liver fibrosis and steatosis, Grading of varicosity under gastroscopy(GI); (2)Basic information and symptoms; (3)Biochemical indexes: Liver function, four items of liver fiber, lipid metabolism, blood routine, coagulation function, blood ammonia, inflammation, oxidative stress, urine routine; sugar metabolism indicators (blood glucose, glycosylated hemoglobin, insulin level and insulin resistance level). (4) Changes of gut microbiota: The changes of gut microbiota will be assessed by High-throughput sequencing (16S rRNA) on baseline, 3 months, 6 months and 12 months after treatment samples to assess changes associated with IMT.

Official Title
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A Randomised Study on Intestinal Microbiota Transplantation for Hepatitis B Virus Induced Cirrhosis

Conditions
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Cirrhosis, Liver

Intervention / Treatment
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* Other: intestinal microbiota transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent/assent as appropriate, able to keep treatment 18 to 50 years of age Chronic hepatitis B, definitely diagnosed as hepatic fibrosis/cirrhosis through Fibroscan/Biopsy of liver biopsy Exclusion Criteria: Drug treatment(immunosuppressive drugs, biological agents, high dose vitamins or other immunosuppressive drugs Other immune related diseases Gastrointestinal organic lesions such as gastroesophageal reflux disease, inflammatory bowel disease, intestinal tumor Medical or social condition which in the opinion of the principal investigator would interfere with or prevent regular follow up Participating in other clinical trials

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Interventional Model Description: a open-label, self-control study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: patients with HBV induced cirrhosis<br>patients with HBV induced cirrhosis will be recruited for study, which involved a 4 times intestinal microbiota transplant and the time interval is generally 2 weeks. | Other: intestinal microbiota transplant<br>* All participants take 4 times IMT by gastroduodenoscopy with 2-week intervals<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of liver Fibroscan score | Fibroscan score of liver fibrosis and steatosis | 3 months, 6 months, 12months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptoms | The onset and duration of gastrointestinal symptoms will be assessed by Evaluation Score Table of Gastrointestinal Symptoms. | 3 months, 6 months, 12months | 
| Changes of gut microbiota | The changes of gut microbiota will be assessed by High-throughput sequencing (16S rRNA) in fecal samples from recruited patients. | 3 months, 6 months, 12months | 
| Color Doppler ultrasound of portal vein | Doppler ultrasonography is medical ultrasonography that employs the Doppler effect to generate imaging of the movement of tissues and body fluids (usually blood), and their relative velocity to the probe. By calculating the frequency shift of a particular sample volume, for example flow in an artery or a jet of blood flow over a heart valve, its speed and direction can be determined and visualized. Color Doppler is the presentation of the velocity by color scale. Color Doppler images are generally combined with grayscale (B-mode) images to display duplex ultrasonography images, allowing for simultaneous visualization of the anatomy of the area. This is particularly useful in cardiovascular studies (sonography of the vascular system and heart) and essential in many areas such as determining reverse blood flow in the liver vasculature in portal hypertension. | 3 months, 6 months, 12months | 
| CT | A CT scan, also known as computed tomography scan, makes use of computer-processed combinations of many X-ray measurements taken from different angles to produce cross-sectional (tomographic) images (virtual slices) of specific areas of a scanned object, allowing the user to see inside the object without cutting. Other terms include computed axial tomography (CAT scan) and computer aided tomography. | 3 months, 6 months, 12months | 
| MRI | Hepatobiliary MR is used to detect and characterize lesions of the liver, pancreas, and bile ducts. Focal or diffuse disorders of the liver may be evaluated using diffusion-weighted, opposed-phase imaging, and dynamic contrast enhancement sequences. Extracellular contrast agents are used widely in liver MRI and newer hepatobiliary contrast agents also provide the opportunity to perform functional biliary imaging. | 3 months, 6 months, 12months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HBV induced cirrhosis, intestinal microbiota transplantation, microbiota