Umbilical Cord Mesenchymal Stem Cells Transplantation Combined With Plasma Exchange for Patients With Liver Failure

Study Overview
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Brief Summary
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Liver failure (LF) is a dramatic clinical syndrome with massive necrosis of liver cells. Although liver transplantation provides an option to cure patients suffering with LF, lack of donors, postoperative complications, especially rejection, and high cost limit its application. Previous study showed that bone marrow derived mesenchymal stem cells (BM-MSCs) the novel and promising therapeutic strategy, BM-MSCs can replace hepatocytes in injured liver, and effectively rescue experimental liver failure and contribute to liver regeneration. Plasma exchange (PE) can improve internal environment by removing endotoxin, it helps the liver regeneration and functional recovery and make UC-MSC differentiation into hepatocyte like cells, and exert immunomodulatory function. In this study, safety and efficacy of human umbilical cord mesenchymal stem cells (UC-MSCs) transplantation combined with plasma exchange (PE) for patients with liver failure caused by hepatitis B Virus will be evaluated.

Detailed Description
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To investigate safety and efficacy of human umbilical cord mesenchymal stem cells (UC-MSCs) transplantation combined with plasma exchange (PE) for patients with liver failure caused by hepatitis B virus.

Official Title
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Safety and Efficacy of Human Umbilical Cord Mesenchymal Stem Cells Transplantation Combined With Plasma Exchange for Patients With Acute-on-Chronic Liver Failure Caused by Hepatitis B Virus (HBV)

Conditions
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Liver Failure

Intervention / Treatment
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* Other: Conventional plus UC-MSC treatment
* Other: Conventional plus PE treatment
* Other: Conventional plus UC-MSC and PE therapy
* Other: Conventional treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Acute-on-Chronic liver failure caused by hepatitis B virus Model for End-Stage Liver Disease (MELD) <30 Exclusion Criteria: Liver failure caused by other reasons, such as autoimmune diseases, alcohol, drug and so on History of severe hepatic encephalopathy or variceal bleeding during the last two months before enrollment Severe problems in other vital organs(e.g. the heart, renal or lungs) Severe bacteria infection Tumor on ultrasonography, CT or MRI examination Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conventional treatment<br>Participants will receive conventional treatment and then be followed until the week 48 study visit. | Other: Conventional treatment<br>* Received conventional treatment including antiviral drugs, lowering aminotransferase and jaundice medicine.<br>|
| Experimental: Conventional plus UC-MSC treatment<br>Participants will receive conventional treatment plus a dose of UC-MSC and then be followed until the week 48 study visit. | Other: Conventional plus UC-MSC treatment<br>* Received conventional treatment and umbilical cord mesenchymal stem cells transplantation by peripheral vein slowly for 30minutes. (1×105/Kg, once a week, 4 times).<br>|
| Experimental: Conventional plus PE treatment<br>Participants will receive conventional treatment plus plasma exchange and then be followed until the week 48 study visit. | Other: Conventional plus PE treatment<br>* Received conventional treatment plus 2000 milliliter plasma exchange (every 3 days, 3 times).<br>|
| Experimental: Conventional plus UC-MSC and PE therapy<br>Participants will receive conventional treatment plus umbilical cord mesenchymal stem cells transplantation combined with plasma exchange. Participants will then be followed until the week 48 study visit. | Other: Conventional plus UC-MSC and PE therapy<br>* Received conventional treatment plus 2000 milliliter plasma exchange (every 3 days, 3 times). Meantime taken i.v umbilical cord mesenchymal stem cells transplantation slowly for 30minutes (1×105/Kg, once a week, 4 times), the first two times is taken after plasma exchange.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival rate and time |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improve biochemical indexes [alanine aminotransferase (ALT), albumin (ALB), total bilirubin (TBIL), prothrombin time (PT), INR and so on] |  | 24 weeks after treatment | 
| The clinical symptom improvement [including appetite, debilitation, abdominal distension, edema of lower limbs, et al] |  | 24 weeks after treatment | 
| Liver function evaluation using Child-Pugh score and MELD score |  | 24 weeks after treatment | 
| Immune function improvement [including Th1/Th2] |  | 24 weeks after treatment | 
| The occurrence of complications [including body temperature, tetter and allergy] |  | Between 0 to 8 hours after UC-MSCs transfusion | 
| Incidence of hepatocellular carcinoma |  | 48 weeks after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mesenchymal stem cells, plasma exchange, liver failure, hepatitis B virus