Evaluation of Liver Regeneration With Autologous Peripheral Stem Cells

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

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.

Study Overview

• Status: Unknown
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Procedure: Plasma pheresis, Right portal vein embolization

Detailed Description

1. Patients: 30 patients (10 patients in each 3 group)

2. 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.

3. 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.
4. Allocation: We will allocate patients randomly to three group including control group.

5. 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)

6. Evaluation: Change of liver volume, liver function test before and after portal vein embolization

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ho-Seong Han, PhD; Phone Number: 82-31-787-7099; Email: hanhs@snubh.org
• Study Contact Backup: Name: Keun Soo Ahn, MD; Phone Number: 82-31-787-7099; Email: ahnks@snubh.org

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Seongnam, Gyeonggi-do, Korea, Republic of
      • Recruiting
      • Ho-Seong Han

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with Primary hepatocellular carcinoma combined liver cirrhosis (Hepatitis B, C, Non-B Non-C)
2. Planned to right hepatectomy or extended right hepatectomy
3. Patients who need right portal vein embolization due to unsufficient expected remnant liver volume (< 40%) or severe hepatic dysfunction (ICG R15 > 10%)
4. Child A classification
5. ICG R15 < 25%
6. Age: 20 - 70 years old
7. Expected life period > 3months
8. The patients who agreed to this study

Exclusion Criteria:

1. Patients who planned liver transplantation
2. Age < 20 or > 70 years old
3. Pregnant women
4. Patients on acute infection
5. Acute hepatic failure
6. Child class B or C
7. Heart failure
8. Existence of bleeding tendency : platelet < 30,000, INR > 2.2, Cr >2.5
9. Patients who did not agree to this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1. CD34; 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; 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.; Other Names: COBE BCT Inc : for plasmapheresis
ACTIVE_COMPARATOR: 2. Mononucelar cell; 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; 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.; Other Names: COBE BCT Inc : for plasmapheresis
OTHER: 3. Control; Without infusion of G-CSF, patients will be performed just right portal vein embolization	Procedure: Plasma pheresis, Right portal vein embolization; 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.; Other Names: COBE BCT Inc : for plasmapheresis

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Seoul National University Bundang Hospital
• Investigators: Principal Investigator: Ho-Seong Han, PhD, Chairman of surgery, Seoul National University Bundang Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (ANTICIPATED): December 1, 2011
• Study Completion (ANTICIPATED): December 1, 2011

Study Registration Dates

• First Submitted: April 20, 2010
• First Submitted That Met QC Criteria: April 21, 2010
• First Posted (ESTIMATE): April 22, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): December 15, 2010
• Last Update Submitted That Met QC Criteria: December 14, 2010
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: Liver cirrhosis; liver function; hepatectomy; liver volume; liver regeneration; hepatocellular carcinoma, extensive
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: SNUBH-GS-HBP3; B-0901-068-003 (OTHER: Seoul National University Bundang Hospital)