This proposal translates a hypothesis driven basic research into clinical setting to determine the potential of using autologous CD133+ cells to reverse fibrosis and improve clinical outcome for patients with end stage cirrhosis. This has significant impact on the management of cirrhosis.
This is a 2 arm randomised study patients with decompensated liver cirrhosis involving minimum of 23 and maximum of 33 patients in each arm. The investigators propose that transplantation of mobilized autologous CD133+ cells harvested from the bone marrow directly into the liver has the ability to replace and regenerate the damaged sinusoidal endothelium as well as normalize macrophage and Natural Killer (NK) cell function. The niche provided by the refenestrated endothelium can polarize the macrophage to antifibrotic phenotype as well as directly inactivate the activated myofibroblast, resulting in reversal of liver fibrosis and improvement in liver function. Transplantation of cells will be via intraportal route delivered by percutaneous cannulation of the portal vein system.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
66
5 doses of GCSF injection will be injected under the skin on the abdomen to mobilize the bone marrow cells.
Endothelial progenitor cells are harvested by CD133+ MACS (magnetic activated cell sorting) sort selection of bone marrow and a minimum of 1x 10\^6 and up to 50-100 x 10\^6 cells are transplanted to one lobe of the liver via a percutaneous catheter inserted into the portal venous system by percutaneous transhepatic approach for engraftment.
National University Hospital
Singapore, Singapore
RECRUITINGImprovement of Fibrosis Staging (Ishak)
Improvement of Fibrosis Staging (Ishak) \> 1 point
Time frame: 3 months
Improvement of liver fibrosis on MRE (magnetic resonance elastography)
Improvement of liver fibrosis on MRE (magnetic resonance elastography) \> 2 point
Time frame: 6 months
Improvement of MELD (Model of End stage Liver Disease) score or Child Pugh State
Improvement of MELD (Model of End stage Liver Disease) score or Child Pugh State by at least 2 points
Time frame: 6 months
Improvement of quantitative fibrosis
Improvement of quantitative fibrosis on histology \> 10%
Time frame: 1 year
Overall Survival and Improvement
Overall Survival
Time frame: 1 year
Overall Improvement in Liver Function Tests
Improvement in Liver Function Tests, especially Total Bilirubin, Albumin and Prothrombin Time
Time frame: 1 year
Improvement of Hepatic Venous Pressure
Improvement of Hepatic Venous Pressure
Time frame: 3 months
Incidence of clinical decompensation
Frequency of Incidence of clinical decompensation
Time frame: 1 year
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Overall Improvement of Patient Reported outcome
Improvement of Patient Reported outcome (quality of life Short Form Health Survey SF-36 for liver cirrhosis)
Time frame: 6 months
Overall Improvement of MELD score
Rate of deterioration of MELD score (Kaplan Meier analysis)
Time frame: 1 year