Safety and Efficacy of Diverse Mesenchymal Stem Cells Transplantation for Liver Failure

Study Overview
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Brief Summary
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HBV-related liver failure (HBV-LF), a dramatic clinical syndrome, is characterized with massive necrosis of liver cells. Liver transplantation might be the most effective therapy for HBV-LF. However, there are a lot of problems such as lack of donors, surgical complications, transplant rejection, and high cost, which could limit the application of liver transplantation. It is demonstrated that mesenchymal stem cells could directionally differentiate into hepatocytes and cholangiocytes in injured liver, as well as reduce inflammation of the liver by immune regulation. In this study, we assess the safety and efficacy of human bone marrow and umbilical cord mesenchymal stem cells transplantation for patients with HBV-LF.

Official Title
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Clinical Comparison of Safety and Efficacy of Allogeneic Umbilical-Cord and Bone Marrow-derived Mesenchymal Stem Cells Transplantation for HBV-related Liver Failure

Conditions
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Liver Failure

Intervention / Treatment
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* Genetic: Conventional plus BM-MSC treatment
* Genetic: Conventional plus UC-MSC treatment
* Drug: Conventional treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-65 years Liver failure Negative pregnancy test (female patients in fertile age) Written consent HBsAg positive TB≥171 μmol/L or ascend ≥17.1 μmol/L/per day, INR≥1.5 or 20%<PTA≤40% 17≤MELD score≤30 Exclusion Criteria: Hepatocellular carcinoma or other malignancies Severe problems in other vital organs(e.g.the heart,renal or lungs) Pregnant or lactating women Severe bacteria infection Anticipated with difficulty of follow-up observation Liver failure caused by other reasons, such as autoimmune diseases, alcohol, drug and so on Other candidates who are judged to be not applicable to this study by doctors

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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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 72 study visit. | Drug: Conventional treatment<br>* Received conventional treatment including: A.antiviral drugs(Entecavir,Lamivudine,Adefovir dipivoxil,et al); B.Hepatoprotective drugs(Ademetionine1,4-butanethiosulfonate for Injection, Reduced Glutathione for Injection,Polyene Phosphatidylcholine, et al); C.Plasma.<br>* Other names: Plasma;|
| Experimental: Conventional plus BM-MSC treatment<br>Participants will receive conventional treatment plus a dose of BM-MSC(each subgroups with a different dose ) and then be followed until the week 72 study visit. | Genetic: Conventional plus BM-MSC treatment<br>* Received conventional treatment and bone marrow mesenchymal stem cells transplantation by peripheral vein slowly for 30minutes. (1×10e5/Kg,1×10e6/Kg,or 1×10e7/Kg, once a week, 8 times).<br>|
| Experimental: Conventional plus UC-MSC treatment<br>Participants will receive conventional treatment plus a dose of UC-MSC(each subgroups with a different dose ) and then be followed until the week 72 study visit. | Genetic: Conventional plus UC-MSC treatment<br>* Received conventional treatment and bone marrow mesenchymal stem cells transplantation by peripheral vein slowly for 30minutes. (1×10e5/Kg,1×10e6/Kg,or 1×10e7/Kg, once a week, 8 times)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival rate | The survival rate and time | 72 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver function | The levels of serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST),Cholinesterase (CHE) ,Total Bilirubin(TB),Direct Bilirubin(DB), Serum Albumin （ALB） | 72 weeks after treatment | 
| Marker of liver cancer | The level of alpha-fetoprotein (AFP) | 72 weeks after treatment | 
| The degree of hepatic necrosis | The levels of Prothrombin Activity (PA) and Prothrombin Time (PT) | 2 years after treatment | 
| The improvement of symptoms | The improvement of clinical symptoms [including appetite, debilitation, abdominal distension, edema of lower limbs, et al | 72 weeks after treatment | 
| The score for Model for End-Stage Liver Disease |  | 72 weeks after treatment | 
| The improvement of immune function | cluster of differentiation 4 (CD4+)T/ cluster of differentiation 8 (CD8+)T,T helper cell 1 (Th1)/ T helper cell 1(Th2),natural killer cell(NK),natural killer T(NK T),interleukin-1β(IL-1β),interleukin-4(IL-4),interleukin-6(IL-6),interleukin-8(IL-8),interleukin-12(IL-12),interleukin-15(IL-15),interleukin-17A(IL-17A),Tumor necrosis factor-alpha (TNF-α),Interferon-gamma (IFN-γ) | 72 weeks after treatment | 
| complications | The occurrence of complications [including body temperature, tetter and allergy] | Between 0 to 8 hours after MSC transfusion | 
| The incidence of hepatocellular carcinoma |  | 72 weeks after treatment |