Evaluation of Liver Regeneration With Autologous Peripheral Stem Cells

Study Overview
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Brief Summary
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For patient with liver cirrhosis who need to right or extended right hepatectomy, we will treat with autologous peripheral stem cells transplantation to facilitate liver regeneration. We will asses liver regeneration by evaluation of liver volume and liver function test.

Detailed Description
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Patients: 30 patients (10 patients in each 3 group) Indication: Patients with Primary hepatocellular carcinoma combined liver cirrhosis (Hepatitis B, C, Non-B Non-C) Planned to right hepatectomy or extended right hepatectomy Patients who need right portal vein embolization due to insufficient expected remnant liver volume (< 40%) or severe hepatic dysfunction(ICGR15>10%) Child A classification ICG R15 < 25% Age : 20 - 70 years old Expected life period > 3months The patients who agreed to this study. Contraindication Patients who planned liver transplantation Age <20 or >70 years old Pregnant women Patients on acute infection Acute hepatic failure Child class B or C Heart failure Existence of bleeding tendency : platelet < 30,000, INR > 2.2, Cr >2.5 Patients who did not agree to this study. Allocation: We will allocate patients randomly to three group including control group. Methods Group 1: 4 days injection of G-CSF -> Plasma pheresis, Selection of CD34 cell -> Right portal vein embolization and infusion of CD34 cell into left portal vein. Group 2: 4 days injection of G-CSF -> Plasma pheresis -> Right portal vein embolization and infusion of mononuclear cell into left portal vein. Group 3 (control): Right portal vein embolization ( -> after 4 weeks, operation will be performed) Evaluation: Change of liver volume, liver function test before and after portal vein embolization

Official Title
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Evaluation of Liver Regeneration With Autologous Peripheral Stem Cells Transplantation in the Patient Needed Extensive Hepatectomy

Conditions
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Liver Cirrhosis

Intervention / Treatment
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* Procedure: Plasma pheresis, Right portal vein embolization


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Primary hepatocellular carcinoma combined liver cirrhosis (Hepatitis B, C, Non-B Non-C) Planned to right hepatectomy or extended right hepatectomy Patients who need right portal vein embolization due to unsufficient expected remnant liver volume (< 40%) or severe hepatic dysfunction (ICG R15 > 10%) Child A classification ICG R15 < 25% Age: 20 - 70 years old Expected life period > 3months The patients who agreed to this study Exclusion Criteria: Patients who planned liver transplantation Age < 20 or > 70 years old Pregnant women Patients on acute infection Acute hepatic failure Child class B or C Heart failure Existence of bleeding tendency : platelet < 30,000, INR > 2.2, Cr >2.5 Patients who did not agree to this study

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1. CD34<br>4 days injection of G-CSF (10μg/kg, Subcutaneous infusion) On 5th day, plasmapheresis will be performed to select mononuclear cells. (at least 4x10(9) of mononuclear cells) CD 34 cells will be selected by CliniMACS (Miltenyi Biotec, Bergisch- Gladbach, Germany) (at least 1x10(7) of CD 34 cell) In same day, right portal vein embolization with infusion of CD 34 cells into left portal vein will be performed. | Procedure: Plasma pheresis, Right portal vein embolization<br>* Plasma pheresis : With insertin of 2 intravenous line, plasmapheresis will be done with COBE BCT Inc. It will be performed under supervision of clinical laboratorians and doctors. Right portal vein : Under ultrasonography guided, left portal vein be punctured. Right portal vein will be embolized by coil or gelfoam.<br>* Other names: COBE BCT Inc : for plasmapheresis;|
| Active Comparator: 2. Mononucelar cell<br>4 days injection of G-CSF (10μg/kg, Subcutaneous infusion) On 5th day, plasma pheresis will be performed to select mononuclear cells. (at least 4x10(9) of mononuclear cells) In same day, right portal vein embolization with infusion of mononuclear cells into left portal vein will be performed. | Procedure: Plasma pheresis, Right portal vein embolization<br>* Plasma pheresis : With insertin of 2 intravenous line, plasmapheresis will be done with COBE BCT Inc. It will be performed under supervision of clinical laboratorians and doctors. Right portal vein : Under ultrasonography guided, left portal vein be punctured. Right portal vein will be embolized by coil or gelfoam.<br>* Other names: COBE BCT Inc : for plasmapheresis;|
| Other: 3. Control<br>Without infusion of G-CSF, patients will be performed just right portal vein embolization | Procedure: Plasma pheresis, Right portal vein embolization<br>* Plasma pheresis : With insertin of 2 intravenous line, plasmapheresis will be done with COBE BCT Inc. It will be performed under supervision of clinical laboratorians and doctors. Right portal vein : Under ultrasonography guided, left portal vein be punctured. Right portal vein will be embolized by coil or gelfoam.<br>* Other names: COBE BCT Inc : for plasmapheresis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and efficacy, short term outcome | After portal vein embolization, we will compare liver volume by CT and liver function test by blood test in 3 groups. (Second and forth week) | 4 weeks after procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and efficacy. | After 4 weeks of portal vein embolization, hepatectomy woul be performed in indicated patients. After hepatectomy, until 12 weeks, we will compare remnant liver volume by CT and liver function test by blood test. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver cirrhosis, liver regeneration, liver volume, liver function, hepatocellular carcinoma, extensive, hepatectomy