The Effectiveness and Safety for Mesenchymal Stem Cell for Alcoholic Liver Cirrhosis

Study Overview
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Brief Summary
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Background & Aim: Bone marrow derived mesenchymal stem cells (BM-MSCs) have capacity to differentiate into hepatocytes and anti-fibrotic effect in the experimental model. No study was done in humans with alcoholic liver cirrhosis. The researchers investigated the anti-fibrotic effect of BM-MSCs in alcoholic cirrhosis as Phase II clinical study. Methods: Eleven alcoholic cirrhosis patients (M:F = 10:1) with Child-Pugh's class B and maintenance of alcohol abstinence at least 2 months were enrolled. At baseline, all patients received liver biopsy, hepatic venous pressure gradient (HVPG) measurement and serologic tests. BM-MSCs were isolated from each patient's BM and amplified for one month and injected two times at 4, 8week through Rt. hepatic artery. 5x106cells/mL of BM-MSCs were injected in each session. Follow up biopsy, HVPG and relative expression of tissue transforming growth factor-1 (TGF-β1), α smooth muscle actin (α-SMA) and collagen-1 by real time RT PCR were measured after 12weeks from 2nd BM-MSC injection. The primary outcome was improvement in patients' histology Aim : The researchers aimed to evaluate safety and effectiveness of new therapy with bone marrow derived autologous mesenchymal stem cell for hepatic failure caused by alcoholic liver cirrhosis.

Detailed Description
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Autologous BM-MSCs therapy in alcoholic cirrhosis induces improvement of hepatic fibrosis in histological and quantitative measurements.

Official Title
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The Evaluation of Effectiveness and Safety for New Therapy With Bone Marrow Derived Autologous Mesenchymal Stem Cell for Hepatic Failure Caused by Alcoholic Liver Cirrhosis

Conditions
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Alcoholic Liver Cirrhosis

Intervention / Treatment
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* Biological: mesenchymal stem cell injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Alcoholic liver cirrhosis(child Pugh class B or C, ≥ 7 scores),confirmed by clinically or biopsy. Stop drinking over past 6months. Patients agree with informed consent Patients must satisfy all inclusion criteria. Exclusion Criteria: Patients who did not satisfy inclusion criteria Hepatocellular carcinoma Pregnancy or breast feeding Infective disease(HIV, HBV, HCV..) Other incurable malignancy

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSC injection<br>This study is designed as single interventional arm without comparative arm. MSC injection means hepatic artery catheterizations and mesenchymal stem cell injection through catheter. | Biological: mesenchymal stem cell injection<br>* Hepatic artery catheterization and mesenchymal stem cell injection will be used in alcoholic liver cirrhosis. And before and 1 month after injection, change of liver cirrhosis and portal hypertension will be evaluated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The improvement of Liver Histologic grade | according to Metavir and Laennec fibrosis scoring system | 6 months later | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The evaluation of hepatic dendritic cells activity by immunohistochemistry |  | baseline and 6 months later | 
| Liver fibrosis quantitative analysis using Hydroxyproline contents in liver tissue | Hydroxyproline is a essential component of collange fiber | baseline and 6 months later | 
| Real-Time Polymerase Chain Reaction for relative mRNA expression of TGF-beta, collagen, procollagen, MMP2 or 9 |  | baseline and 6 months later | 
| Hepatic venous pressure gradient(HVPG) | HVPG is a gold standard to measure the portal hypertension. | baseline and 6 months later | 
| Hepatic vein arrival time using microbubble contrast enhanced ultrasonography | Hepatic vein arrival time is related with portal hypertension and intrahepatic inflammation, neoangiogenesis and shunts formation secondary to hepatic fibrosis. | baseline and 6 months later | 
| Liver stiffness measurement with transient elastography | Recently, hepatic fibrosis can be estimated non-invasively using transient elastography (Fibroscan, commercial name) and it can be additive data in estimation of therapeutic response. | baseline and 6 months later | 
| Child-Pugh score |  | baseline and 6 months later | 
| MELD score |  | baseline and 6 months later | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autologous Mesenchymal stem cell, alcoholic liver cirrhosis