Altered Frequencies of Dendritic Cells and <scp>IFN</scp>‐γ‐secreting T Cells with Granulocyte Colony‐Stimulating Factor (G‐<scp>CSF</scp>) Therapy in Acute‐on‐Chronic Liver Failure

Khanam, Arshi; Trehanpati, Nirupama; Garg, Vishal; Kumar‐Sinha, Chandan; Garg, Hitendra; Sharma, Barjesh Chander; Sarin, Shiv Kumar

doi:10.1111/liv.12415

Cited by 66 publications

(49 citation statements)

References 31 publications

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“…It would be possible to address key targets to prevent organ damage, thereby inhibiting progression toward liver failure, which will ultimately reduce the requirement for liver transplantation. We have recently shown that reduction in intrahepatic dendritic cells and increased interferon gamma (IFN-γ)-producing CD8+ T cells has an important role in hepatocellular injury which correlates with high mortality in ACLF (3). …”

Section: Introductionmentioning

confidence: 99%

Blockade of Neutrophil’s Chemokine Receptors CXCR1/2 Abrogate Liver Damage in Acute-on-Chronic Liver Failure

et al. 2017

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BackgroundNeutrophils serve as critical players in the pathogenesis of liver diseases. Chemokine receptors CXCR1 and CXCR2 are required for neutrophil chemotaxis to the site of inflammation/injury and are crucial in hepatic inflammatory response. However, key mechanism of neutrophil-mediated liver injury in acute-on-chronic liver failure (ACLF) remains highly elusive; which could be targeted for the development of new therapeutic interventions.MethodsTo demonstrate the role of CXCR1/CXCR2-expressing neutrophils in hepatic injury, we investigated CXCR1/CXCR2 receptor expression in 17 hepatitis B virus-related ACLF patients in comparison to 42 chronic hepatitis B and 18 healthy controls. Mechanism of neutrophil-mediated cell death was analyzed by in vitro coculture assays and correlated with the patient data. In addition, to find out any etiological-based variations in ACLF, 19 alcohol-related ACLF patients were also included.ResultsIn ACLF, neutrophils have high expression of CXCR1/CXCR2 receptors, which potentially participate in hepatocyte death through early apoptosis and necrosis in contact-dependent and -independent mechanisms. Importantly, blockade of CXCR1/CXCR2 with SCH 527123 antagonist significantly reduced cell death by targeting both the mechanisms. No etiology-based differences were seen between ACLF groups. Importantly, absolute neutrophil count was particularly higher in clinically severe ACLF patients and non-survivors (p < 0.0001). Multivariate analysis demonstrated ANC and CXCL8/IL-8 as a predictor of mortality. Further, receiver operating characteristics curve confirmed the cutoff of ANC >73.5% (sensitivity: 76.5% and specificity: 76.5%) and CXCL8/IL-8 >27% (sensitivity: 70% and specificity: 73%) in prediction of mortality.ConclusionBlockade of CXCR1/CXCR2 diminished the production of inflammatory mediators and reduced cell death; therefore, pharmacological neutralization of CXCR1/CXCR2 could provide novel therapeutic target in the management of ACLF.

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Section: Introductionmentioning

confidence: 99%

Blockade of Neutrophil’s Chemokine Receptors CXCR1/2 Abrogate Liver Damage in Acute-on-Chronic Liver Failure

et al. 2017

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“…The frequency of intrahepatic myeloid and plasmacytoid dendritic cells is reduced with increased interferon gamma producing CD8 T cells in patients with ACLF. Decreased frequency of DCs and high IFN-c levels correlate with poor patient survival [75].…”

Section: Sepsis In Aclfmentioning

confidence: 99%

Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014

et al. 2014

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The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. Due to the rapid advancements in the knowledge and available information, a consortium of members from countries across Asia Pacific, ''APASL ACLF Research Consortium (AARC),'' was formed in 2012. A large cohort of retrospective and prospective data of ACLF patients was collated and followed up in this data base. The current ACLF definition was reassessed based on the new AARC data base. These initiatives were concluded on a 2-day meeting in February 2014 at New Delhi and led to the development of the final AARC consensus. Only those statements which were based on the evidence and were unanimously recommended were accepted. These statements were circulated again to all the experts and subsequently presented at the annual conference of the APASL at Brisbane, on March 14, 2014. The suggestions from the delegates were analyzed by the expert panel, and the modifications in the consensus were made. The final consensus and guidelines document was prepared. After detailed deliberations and data analysis, the

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“…Moreover, circulating myeloid and plasmacytoid dendritic cells and T cells were shown to increase following G-CSF therapy, while IFN-γ production by CD8-T cells was decreased [75,77]. These findings have also been documented in a cohort of patients with HBV-associated ACLF [78].…”

Section: Gut Microbiotamentioning

confidence: 64%

Immunotherapy in the Treatment and Prevention of Infection in Acute-on-chronic Liver Failure

et al. 2015

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Chronic liver disease, depicted by gradual destruction and fibrosis of the liver, is a condition with high and probably increasing prevalence worldwide. Its deterioration, acute-on-chronic liver failure (ACLF), is characterized by an in-hospital mortality of up to 65%. Infectious complications are the main precipitants eliciting ACLF and concurrently the main cause of death from ACLF. Patients have a marked susceptibility to bacterial infections, which is thought to arise a consequence of an inadequate immune response to microbial challenge, termed immuneparesis. The pathophysiologic mechanisms remain poorly understood. Treatments aimed at restoring the patients' immune function may prevent onset of ACLF and death from secondary infections. A number of drugs approved for patients with liver disease bear immunomodulatory potential such as albumin, glucocorticoids, N-acetylcysteine. Specific targets have been defined that may lead to development of new immunotherapeutic agents. Here, we summarize the pathophysiology of immuneparesis in ACLF and drug candidates to restore immune function and improve survival in the future.

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Altered Frequencies of Dendritic Cells and IFN‐γ‐secreting T Cells with Granulocyte Colony‐Stimulating Factor (G‐CSF) Therapy in Acute‐on‐Chronic Liver Failure

Cited by 66 publications

References 31 publications

Blockade of Neutrophil’s Chemokine Receptors CXCR1/2 Abrogate Liver Damage in Acute-on-Chronic Liver Failure

Blockade of Neutrophil’s Chemokine Receptors CXCR1/2 Abrogate Liver Damage in Acute-on-Chronic Liver Failure

Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014

Immunotherapy in the Treatment and Prevention of Infection in Acute-on-chronic Liver Failure

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