Soluble inflammatory markers as predictors of liver histological changes in patients with chronic hepatitis C virus infection
ABSTRACT Host immune response seems to be mainly responsible for the progression of liver disease among patients with hepatitis C virus (HCV) infection. Immune activation involves the release of cytokines and their receptors that can be measured in plasma samples. The study aimed to evaluate the association between plasma levels of chemokines and soluble tumor necrosis factor receptors (sTNFR) and liver histological changes among patients with chronic HCV infection. Seventy-one treatment-naive patients were included. Plasma levels of CCL2, CCL3, CCL11, CCL24, CXCL9, CXCL10, sTNFR1, and sTNFR2 were measured and liver histological findings were reviewed. Plasma levels of CXCL9, sTNFR1, and sTNFR2 were significantly associated with liver fibrosis, with higher median levels found among patients with moderate/severe fibrosis (F >or= 2) if compared to those with no or mild fibrosis (p = 0.014; p = 0.012; p = 0.009, respectively). Plasma sTNFR2 levels were significantly associated with necroinflammatory activity, with higher median levels among patients with moderate/severe activity (A >or= 2) if compared to those with no or mild activity (2.34 ng/mL vs. 1.99 ng/mL; p = 0.019). In conclusion, plasma levels of CXCL9, sTNFR1, and sTNFR2 were independently associated with liver histological changes, suggesting a role of TNF activation and Th1-type cell-mediated immune response in the pathogenesis of HCV infection.
- SourceAvailable from: Manoel Otávio da Costa Rocha
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- "Other authors (Diago et al. 2006) propose that elevated CXCL10 levels may result in an accumulation of effector T cells in the liver and the selective pressure imposed by this accumulation may foster outgrowth of immune escape HCV mutants that would be more difficult to eradicate with combined therapy (Diago et al. 2006). The observed association between CXCL10 levels and therapeutic response was not mediated by liver histological changes, as plasma levels of this chemokine were not associated with liver inflammatory activity or fibrosis in a subanalysis of the dataset (Moura et al. 2010). CXCL9, which binds the same chemokine receptor as CXCL10 (i.e., CXC3), did not show an association with virological response in our study, in accordance with findings from a previous study conducted by Butera et al. (2005) "
ABSTRACT: The host immune response plays an important role in viral clearance in patients who are chronically infected with hepatitis C virus (HCV) and are treated with interferon and ribavirin. Activation of the immune system involves the release of pro and anti-inflammatory molecules that can be measured in plasma samples. The present study aimed to evaluate the association between pretreatment plasma levels of chemokines and soluble tumor necrosis factor receptors (sTNF-R) and the virological response in treated patients with chronic hepatitis C infection. Forty-one chronically-infected HCV patients that were being treated with interferon-α (IFN-α) plus ribavirin were included in the study. Socio-demographic, clinical and laboratory data were collected and pretreatment plasma levels of chemokine CCL2, CCL3, CCL11, CCL24, chemokine CXCL9, CXCL10, sTNF-R1 and sTNF-R2 were measured. The virological response was assessed at treatment week 12, at the end of treatment and 24 weeks after treatment. Pretreatment CXCL10 levels were significantly higher in patients without an early virological response (EVR) or sustained virological response (SVR) compared to responders [512.9 pg/mL vs. 179.1 pg/mL (p = 0.011) and 289.9 pg/mL vs. 142.7 pg/mL (p = 0.045), respectively]. The accuracy of CXCL10 as a predictor of the absence of EVR and SVR was 0.79 [confidence interval (CI) 95%: 0.59-0.99] and 0.69 (CI 95%: 0.51-0.87), respectively. Pretreatment plasma levels of the other soluble inflammatory markers evaluated were not associated with a treatment response. Pretreatment CXCL10 levels were predictive of both EVR and SVR to IFN-α and ribavirin and may be useful in the evaluation of candidates for therapy.Memórias do Instituto Oswaldo Cruz 02/2011; 106(1):38-43. DOI:10.1590/S0074-02762011000100006 · 1.57 Impact Factor
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ABSTRACT: Persistently high serum levels of soluble tumor-necrosis factor (TNF) receptor 2 (sTNFR2) have been observed in septic shock and many inflammatory diseases. However, its origin and regulation during these pathological processes are still largely unknown. In this study, murine bone marrow (BM) chimeras selectively expressing TNFR2 on either BM-derived or non-BM-derived cells were generated and challenged with lipopolysaccharide (LPS). The results show that TNFR2 expression on non-BM-derived cells is crucial for both the sensitivity of mice to LPS and the downregulation of sTNFR2 in serum. Most importantly, sTNFR2 was released from both BM- and non-BM-derived cells. Non-BM TNFR1 expression influenced the sensitivity of mice to LPS challenge but not the level of serum sTNFR2. These results provide the first in vivo evidence for the origin and regulation of sTNFR2 in serum and could aid in the development of novel anti-TNF strategies against septic shock.Cellular & molecular immunology 01/2011; 8(2):164-71. DOI:10.1038/cmi.2010.79 · 4.19 Impact Factor
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ABSTRACT: Information about the stage of liver fibrosis is important for managing patients with chronic hepatitis C (CHC). The aim of this study was to evaluate 12 plasma markers for differentiating no/mild liver fibrosis from cirrhosis among patients with CHC genotype 1. Transient elastography was used to assess the stage of fibrosis for the patients included in the study. Forty patients were included (21 cirrhotic). Plasma levels of tumor necrosis factor-α (TNF-α), interleukin 8 (IL-8), interferon-γ inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), soluble urokinase-type plasminogen activator (suPAR), monokine induced by γ-interferon (MIG), human hepatocyte growth factor (HGF), insulin, interleukin 6 (IL-6), interleukin 1-β (IL-1β), leptin, and nerve growth factor (NGF) were analyzed. Concentrations of TNF-α (median 15.0 vs. 25.1 pg/ml, area under the receiver operating characteristic curve [AUC] 0.91), IL-8 (48.7 vs. 103.3 pg/ml, AUC 0.85), IP-10 (176 vs. 566 pg/ml, AUC 0.83), MCP-1 (449 vs. 735 pg/ml, AUC 0.78), suPAR (3.5 vs. 5.2 ng/ml, AUC 0.78), MIG (100 vs. 152 pg/ml, AUC 0.75), and HGF (3.69 vs. 5.58 ng/ml, AUC 0.71) were significantly higher in patients with cirrhosis. In conclusion, several of the investigated markers showed promise for differentiating cirrhosis from no/mild fibrosis among patients with CHC genotype 1.European Journal of Clinical Microbiology 06/2011; 30(6):761-6. DOI:10.1007/s10096-010-1149-y · 2.54 Impact Factor