Safety and Efficacy Study of Peripheral Blood Mononucleated Cells for Treatment of Liver Cirrhosis

Study Overview
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Brief Summary
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The investigators aim to investigate the safety and efficacy of peripheral blood monocyte for the treatment of patients with advanced liver cirrhosis.

Detailed Description
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G-colony stimulating factor(5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis. On the day 4th, plasmapheresis will be done to collect peripheral blood mononucleated cells . And then we are going to infuse the collected peripheral blood mononucleated cells of their own through the portal vein of each patients under ultrasonographic guidance.

Official Title
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The Role of Peripheral Mononuclear Cells for Treatment of Advanced Liver Cirrhosis

Conditions
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Liver Cirrhosis

Intervention / Treatment
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* Drug: G-colony stimulating factor
* Other: Infusion of the mobilized monocyte cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20 =< Age < 80 Advanced liver cirrhosis with Child-Pugh score 8 or 9 (including patients who have no radiologic evidence of remnant HCC for more than 2 years after treatment) Exclusion Criteria: HBsAg-positive Active status of hepatocellular carcinoma (HCC) (except patients who have no radiologic evidence of remnant HCC for more than 2 years after treatment) History of hemochromatosis and/or autoimmune hepatitis Pregnant women or lactating women Hemoglobin < 8g/dL (male), 7.5g/dL (female) or white blood cell (WBC) <1,500 mm3 or Neutrophils <500/mm3 or platelet count <50,000/mm3 Serum creatinine> 1.5 x normal upper limit or creatinine clearance <60 ml/min Presence of signs of malignant tumors or tumor suspected symptoms, or history of malignant tumors with recurrence rate greater than 20% within two years Gastrointestinal bleeding within the last 3 months or if there is a history of spontaneous bacterial peritonitis Presence of portal vein thrombosis Presence of acute infections

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 79 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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Three patients with liver cirrhosis of this arm will not receive any intervention regarding to peripheral blood mononucleated cells. | |
| Active Comparator: G-colony stimulating factor<br>G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. | Drug: G-colony stimulating factor<br>* G-colony stimulating factor (5ug/kg/day)will be administered subcutaneously to three patients with liver cirrhosis of this arm.<br>* Other names: Filgrastim;|
| Experimental: Infusion of the mobilized monocyte cells<br>G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. On the day 4th, leukapheresis will be done to collect peripheral blood mononucleated cells . And then we are going to infuse the collected peripheral blood mononucleated cells of their own through the portal vein of each patients under ultrasonographic guidance. | Other: Infusion of the mobilized monocyte cells<br>* G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. On the day 4th, leukapheresis will be done to collect peripheral blood mononucleated cells. And then we are going to infuse the collected peripheral blood mononucleated cells of their own through the portal vein of each patients under ultrasonographic guidance.<br>* Other names: leukapheresis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Severe Adverse Events | No serious adverse event. Minor adverse events (not considered to be related to this study), as follows; Control: 6 events (ascites and pleural tapping, gum bleeding, ascties tapping x3, diarrhea) G-colony stimulating factor group: 6 events (percutaneous vertebroplasty, abdominal pain and nausea, hyperkalemia, ascties tapping, diarrhea, liver transplantation) Infusion of the mobilized peripheral blood mononucleated cells group: 1 event (hepatic encephalopathy) | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score | The efficacy (mean change in Child-Pugh score and Model For End-Stage Liver Disease score [at weeks 24]) of ultrasound-guided percutaneous portal transplantation of peripheral blood monocyte cell in cirrhotic patients. MELD Score = (0.957 * ln(Serum Cr) + 0.378 * ln(Serum Bilirubin) + 1.120 * ln(INR) + 0.643 ) * 10 (if hemodialysis, value for Creatinine is automatically set to 4.0) (minimum <9: 1.9% mortality; maximum 40 or more: 71.3% mortality). Child-Pugh score = Bilirubin (mg/dl): <2 (1 point),2-3 (2 points), >3 (3 points) + Albumin (g/dl): >3.5 (1 point),3.5-2.8 (2 points), <2.8 (3 points) + PT prolongation (INR): <4 seconds (<1.7) (1 point), 4-6 seconds (1.7-2.3) (2 points),>6 seconds (>2.3) (3 points) + Ascites: Absent (1 point), Slight (2 points), Moderate (3 points) + Encephalopathy: Absent (1 point), Mild (I-II) (2 points), Severe (III-IV) (3 points) ; Class A: 5-6, Class B: 7-9, Class C: 10-15 (minimum 5, maximum 15; higher Child-Pugh score with worse prognosis) | Baseline and Week 24 |