Role of Granulocyte Colony-stimulating Factor Therapy in Cirrhosis, ‘Inside Any Deep Asking Is the Answering’

Philips, Cyriac Abby; Augustine, Philip; Ahamed, Rizwan; Rajesh, Sasidharan; George, Tom; Valiathan, Gopakumar C.; John, S. K. P.

doi:10.14218/jcth.2019.00034

Cited by 5 publications

(12 citation statements)

References 64 publications

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“…G-CSF stimulates the BM to release neutrophils and CD34+ HSC into the circulation. CD133+ cells are a subset of CD34+ cells that can differentiate more easily 84 . G-CSF acts as a chemoattractant and a mitogen for oval cells in vitro.…”

Section: G-csf Mobilized Hsc Therapymentioning

confidence: 99%

Hepatic Regeneration in Cirrhosis

Jindal

Jagdish

Kumar

2022

Journal of Clinical and Experimental Hepatology

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: G-csf Mobilized Hsc Therapymentioning

confidence: 99%

Hepatic Regeneration in Cirrhosis

Jindal

Jagdish

Kumar

2022

Journal of Clinical and Experimental Hepatology

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“…The regenerative role of G-CSF in damaged tissues has been extensively studied. 5,6 The use of G-CSF for acute-on-chronic liver failure has shown promising results in adult patients. 4,6,7 The administration of G-CSF elicits the mobilization of CD34+, a marker of the hematopoietic stem cell, from the bone marrow to the peripheral blood.…”

Section: Introductionmentioning

confidence: 99%

“…4,6,7 The administration of G-CSF elicits the mobilization of CD34+, a marker of the hematopoietic stem cell, from the bone marrow to the peripheral blood. 5 The clinical use of G-CSF in the pediatric population has been applied in treating congenital, febrile, and post-chemotherapy neutropenia. [8][9][10][11] The use of G-CSF in pediatric decompensated liver cirrhosis has not yet been reported.…”

Section: Introductionmentioning

confidence: 99%

Granulocyte Colony-stimulating Factor as Bridging Therapy for Pediatric Decompensated Liver Cirrhosis Prior to Liver Transplantation: an Open-label Randomised Controlled Trial

Rahayatri

Kekalih

Harahap

et al. 2021

Preprint

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Decompensated cirrhosis in children is a leading indication of liver transplantation (LT). Granulocyte-colony stimulating factor (G-CSF) therapy has shown promising results in adult decompensated cirrhosis. Our study aimed to investigate the effect of G-CSF on liver function, Pediatric End-stage liver disease (PELD) score, CD34+ cells mobilization, nutritional status, short-term side effects, and survival in children indicated for liver transplantation (LT).We performed an open-label, randomized controlled trial with decompensated liver cirrhosis between 3 months to 12 years old. The intervention group received a subcutaneous injection of G-CSF (5 μg/kg/day) for twelve courses in addition to standard medical treatment (SMT) for liver cirrhosis. We measured liver function, PELD scores, CD34+ cell mobilization, the change of leucocyte and neutrophil count, nutritional status, side effects, and survival within three months. Thirty-five pediatric patients were randomized into 17 interventional groups and 18 control groups. During the trial, 14 (82%) of the interventional group completed the intervention course. The median age was 18 months in the interventional group and 14.5 months in the control group. The alanine aminotransferase (ALT) level showed significant improvement in the intervention group, while other liver parameters, PELD score, nutritional status, and survival, did not. CD34+ cells mobilization rose in the interventional group but was statistically insignificant. Minor side effects of G-CSF were found in the intervention group.Multiple doses of G-CSF significantly improve ALT but did not improve PELD score, nutritional status, and survival in three months.

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“…( 11 ) Similarly, G‐CSF has also been observed to improve neutrophil phagocytosis and generation of ROS. ( 22,23 ) Clinical trials treating patients with compensated and decompensated cirrhosis with G‐CSF demonstrate contradictory results. ( 23‐27 )…”

mentioning

confidence: 99%

“…( 22,23 ) Clinical trials treating patients with compensated and decompensated cirrhosis with G‐CSF demonstrate contradictory results. ( 23‐27 )…”

mentioning

confidence: 99%

Loss of Coordinated Neutrophil Responses to the Human Fungal Pathogen, Candida albicans, in Patients With Cirrhosis

et al. 2021

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Neutrophils are the most abundant white blood cell in the body and are key participants in the defense against fungal infections. Fungal infections occur often in patients with cirrhosis and are associated with increased 30‐day and 90‐day mortality. Previous studies have shown that specific neutrophil functions are abnormal in patients with cirrhosis, although the extent of neutrophil dysfunction is not well understood. We tested the ability of neutrophils from 21 hospitalized patients with cirrhosis and 23 healthy control patients to kill Candida albicans, a common fungal pathogen in patients with cirrhosis. Using an assay, we also measured the ability of neutrophils to coordinate multicellular, synchronized control of C. albicans hyphae through a process known as swarming. We found that neutrophils from patients with cirrhosis have significantly decreased fungicidal capacity compared with healthy control neutrophils (53% vs. 74%, P < 0.0001) and diminished ability to control hyphal growth normalized as a ratio to healthy control (0.22 vs. 0.65, P < 0.0001). Moreover, serum from patients with cirrhosis decreases the ability of healthy control neutrophils to kill C. albicans (from 60% to 41%, P < 0.003). Circulating concentration of the inflammatory cytokines tumor necrosis factor α, interleukin‐6, and interleukin‐8 were found to be significantly elevated in patients with cirrhosis compared to healthy controls. Following pretreatment with granulocyte‐colony stimulating factor and granulocyte‐macrophage colony‐stimulating factor, neutrophil function was restored to almost that of healthy controls. Conclusion: Our data establish profound neutrophil dysfunction against, and altered swarming to, C. albicans in patients with cirrhosis. This dysfunction can be partially reversed with cytokine augmentation ex vivo.

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Role of Granulocyte Colony-stimulating Factor Therapy in Cirrhosis, ‘Inside Any Deep Asking Is the Answering’

Cited by 5 publications

References 64 publications

Hepatic Regeneration in Cirrhosis

Hepatic Regeneration in Cirrhosis

Granulocyte Colony-stimulating Factor as Bridging Therapy for Pediatric Decompensated Liver Cirrhosis Prior to Liver Transplantation: an Open-label Randomised Controlled Trial

Loss of Coordinated Neutrophil Responses to the Human Fungal Pathogen, Candida albicans, in Patients With Cirrhosis

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