Early cirrhosis and a preserved bone marrow niche favour regenerative response to growth factors in decompensated cirrhosis

Background Exogenous growth factor‐mobilized bone marrow (BM) stem cells have shown a differential response in the management of decompensated cirrhosis (DC). This study was designed to evaluate potential clinical benefit of adding Erythropoietin (EPO) in granulocyte‐colony stimulating factor (G‐CSF...

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Bibliographic Details
Published in:Liver international 2019-01, Vol.39 (1), p.115-126
Main Authors: Anand, Lovkesh, Bihari, Chhagan, Kedarisetty, Chandan K., Rooge, Sheetalnath B., Kumar, Dhananjay, Shubham, Smriti, Kumar, Guresh, Sahney, Amrish, Sharma, Manoj K., Maiwall, Rakhi, Kumar, Anupam, Sarin, Shiv K.
Format: Article
Language:English
Subjects:
Adult
Ascites
Biopsy
Bone growth
Bone marrow
bone marrow stem cells
CD163 antigen
Cirrhosis
Colony-stimulating factor
Combined Modality Therapy
Double-Blind Method
Encephalopathy
Erythropoietin
Erythropoietin - administration & dosage
Female
Granulocyte Colony-Stimulating Factor - administration & dosage
Growth factors
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
Humans
India
Inflammation
Leukocytes (granulocytic)
Liver
Liver - pathology
Liver cirrhosis
Liver Cirrhosis - mortality
Liver Cirrhosis - pathology
Liver Cirrhosis - therapy
Liver diseases
liver regeneration
Logistic Models
Macrophages
Male
Middle Aged
Multivariate Analysis
Patients
Refilling
Regeneration
Severity of Illness Index
Stem Cell Niche
Stem cells
Therapy
transplant‐free survival
Treatment Outcome
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Summary:Background Exogenous growth factor‐mobilized bone marrow (BM) stem cells have shown a differential response in the management of decompensated cirrhosis (DC). This study was designed to evaluate potential clinical benefit of adding Erythropoietin (EPO) in granulocyte‐colony stimulating factor (G‐CSF)‐mobilized stem cell therapy, possible mechanisms of regeneration and predictive factors of regenerative response. Methods Sixty consecutive DC patients received either G‐CSF with EPO (Group A; n = 30) or G‐CSF and placebo (Group B; n = 30) for 2 months and were carefully followed up for 1 year. Baseline and post‐treatment liver biopsy, BM biopsy and BM aspirate were analysed for fibro‐inflammatory and regenerative response and BM hematopoietic reservoir. Results Addition of EPO to G‐CSF showed a significant improvement in Child‐Pugh score (P = 0.03) and MELD score (P = 0.003) as compared to G‐CSF alone, with reduction in mortality (16.6% vs 36.7%, P = 0.09). The combination arm also demonstrated a decreased incidence of acute kidney injury (P 
ISSN:1478-3223
1478-3231
DOI:10.1111/liv.13923