Reduction in Neutrophil Count During Hepatitis C Treatment: Drug Toxicity or Predictor of Good Response?

Alvarez-Uria, Gerardo; Day, Jeremy; Nasir, Anisa J.; Russell, Susan K.; Vilar, F. Javier

doi:10.1007/s10620-009-0969-z

Cited by 10 publications

(14 citation statements)

References 18 publications

(23 reference statements)

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“…(A) Absolute neutrophil count (ANC) was significantly high in hepatitis B virus (HBV)-ACLF ( n = 17) and alcoholic-ACLF ( n = 19) than chronic hepatitis B (CHB) ( n = 42) and healthy controls (HC) (24). (B) Bar graph indicates ANC in ACLF survivors ( n = 17) and non-survivors ( n = 17).…”

Section: Resultsmentioning

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: Resultsmentioning

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 SVR improved with higher doses of ribavirin. On the other hand, higher dosages of ribavirin can lead to higher rates of anemia and the requirement for dose reductions 19. It was obvious that the ribavirin regimens and ribavirin dose reduction rules of different trials were distinct.…”

Section: Discussionmentioning

confidence: 99%

“…Based on this fact, PEG-IFN-α2a may be considered as a better choice, as it may lead to a better level of patient compliance. However, since it was possible that a reduction in the neutrophil count was a predictor of SVR,19 the relationship between the effcacies of peginterferon and adverse events needs to be evaluated carefully.…”

Section: Discussionmentioning

confidence: 99%

A meta-analysis that compares the use of either peginterferon-α2a or peginterferon-α2b plus ribavirin for HCV infection

Xiao

Shi

Zhang

2010

HMER

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Background: Two kinds of peginterferons, peginterferon-α2a (PEG-IFN-α2a) and peginterferon-α2b , are used in the treatment of chronic hepatitis C virus (HCV) infection. However, it is unclear which is better in terms of virological responses and patient compliance. We conducted a meta-analysis to assess which peginterferon was better when used with ribavirin. Methods: Relevant clinical trials were identified through the PubMed and EMBASE databases. Primary outcomes included early virological response (EVR), end of treatment response (ETR) and sustained virological response (SVR). Secondary outcomes included biochemical and histological responses and the discontinuation of treatment after adverse events. Meta-analysis was performed using fixed-effect or random-effect methods, depending on absence or presence of significant heterogeneity. Analyses were performed with Review Manager Version 4.2.2. Results: Seven clinical trials were included that involved 3,526 patients in total; six were randomized clinical trials (RCTs) and one was nonrandomized. PEG-IFN-α2a plus ribavirin was better than PEG-IFN-α2b plus ribavirin with regards to ETR (relative risk [RR] = 1.21, 95% confidence interval [CI]: 1.14-1.28). This advantage was less obvious for EVR (RR = 1.12, 95% CI: 1.06-1.19) and SVR (RR = 1.10, 95% CI: 1.02-1.18). Patients who received PEG-IFN-α2a were less likely to discontinue treatment for safety reasons (RR = 0.85, 95% CI: 0.52-1.38). Conclusion:We demonstrated that PEG-IFN-α2a was a better choice than PEG-IFN-α2b in terms of virological responses.

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“…23 In the clinic, a reduction of neutrophils during the treatment of hepatitis C with Peginterferon was associated with a sustained virological response. 24 Passively transferred HBV-specific cytotoxic T cells recruit antigen-nonspecific lymphomononuclear and polymorphonuclear inflammatory cells that contribute to the pathogenesis of liver disease. However, the depletion of neutrophils was associated with diminished recruitment of antigen-nonspecific cells into the liver without affecting the antiviral activity of HBV-specific cytotoxic T cells.…”

Section: Neutrophils In the Defense Against Infectionmentioning

confidence: 99%

The role of neutrophils in the development of liver diseases

et al. 2014

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Liver disease encompasses a wide variety of liver conditions, including liver failure, liver cirrhosis and a spectrum of acute and chronic hepatitis, such as alcoholic, fatty, drug, viral and chronic hepatitis. Liver injury is a primary causative factor in liver disease; generally, these factors include direct liver damage and immune-mediated liver injury. Neutrophils (also known as neutrophilic granulocytes or polymorphonuclear leukocytes (PMNs)) are the most abundant circulating white blood cell type in humans, and PMNs are a major innate immune cell subset. Inappropriate activation and homing of neutrophils to the microvasculature contributes to the pathological manifestations of many types of liver disease. This review summarizes novel concepts of neutrophil-mediated liver injury that are based on current clinical and animal model studies.

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Reduction in Neutrophil Count During Hepatitis C Treatment: Drug Toxicity or Predictor of Good Response?

Cited by 10 publications

References 18 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

A meta-analysis that compares the use of either peginterferon-α2a or peginterferon-α2b plus ribavirin for HCV infection

The role of neutrophils in the development of liver diseases

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Reduction in Neutrophil Count During Hepatitis C Treatment: Drug Toxicity or Predictor of Good Response?

Cited by 10 publications

References 18 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

A meta-analysis that compares the use of either peginterferon-&alpha;2a or peginterferon-&alpha;2b plus ribavirin for HCV infection

The role of neutrophils in the development of liver diseases

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A meta-analysis that compares the use of either peginterferon-α2a or peginterferon-α2b plus ribavirin for HCV infection