scholarly journals Chronic Hepatitis C Pathogenesis: Immune Response in The Liver Microenvironment and Peripheral Compartment

2021 ◽  
Author(s):  
Daniela Alejandra Rios ◽  
Paola Cecilia Casciato ◽  
María Soledad Caldirola ◽  
María Isabel Gaillard ◽  
Cecilia Giadans ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Immune Cell ◽  
Nk Cell ◽  
Peripheral Compartment ◽  
Advanced Fibrosis ◽  
Tnf Α ◽  
Liver Biopsies ◽  
Ifn Γ

Abstract Background: Chronic hepatitis C pathogenesis is not defined yet, so immune cell populations and cytokines in liver and peripheral blood (PB) were evaluated to elucidate their role in liver disease. B, CTL, Th, Treg, Th1, Th17 and NK cells localization and frequency were evaluated on liver biopsies by immunohistochemistry, while frequency, differentiation, and functional status on PB by flow cytometry. TNF−α, IL−23, IFN−γ, IL−1β, IL−6, IL−8, IL−17A, IL−21, IL−10 and TGF−β expression were quantified in fresh liver biopsy by RT-qPCR and in plasma by CBA/ELISA. Results: Liver CTL and Th1 at lobular area inversely correlated with viral load (r=−0.469, p=0.003 and r=−0.384, p=0.040). Treg correlated with CTL and Th1 at lobular area (r=0.784, p<0.0001; r=0.436, p=0.013). Th17 correlated with hepatic IL-8 (r=0.52, p<0.05) and both were higher in advanced fibrosis cases (Th17 p=0.0312, IL-8 p=0.009). Hepatic cytokines were higher in severe hepatitis cases (IL−1β p=0.026, IL−23 p=0.031, IL−8 p=0.002, TGF−β p=0.037). Peripheral NK (p=0.008) and NK Dim (p=0.018) were diminished while NK Bright (p=0.025) were elevated in patients vs donors. Naïve Th (p=0.011) and CTL (p=0.0007) were decreased, while activated Th (p=0.0007) and CTL (p=0.0003) were increased. IFN−γ production and degranulation activity in NK and CTL were normal. Peripheral cytokines showed an altered profile, particularly elevated IL−6 (p=0.008) and TGF−β (p=0.041). Conclusions: HCV-specific and non-specific hepatic CTLs favored damage. Treg could not prevent fibrogenesis triggered by Th17 and IL-8. Peripheral T-lymphocyte differentiation stages shift, elevated cytokines levels and NK-cell count decrease would contribute to global disease.

scholarly journals Chronic Hepatitis C Pathogenesis: Immune Response in the Liver Microenvironment and Peripheral Compartment

2021 ◽  
Vol 11 ◽  
Author(s):  
Daniela Alejandra Rios ◽  
Paola Cecilia Casciato ◽  
María Soledad Caldirola ◽  
María Isabel Gaillard ◽  
Cecilia Giadans ◽  
...  
Keyword(s):  
Immune Response ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Immune Cell ◽  
Nk Cell ◽  
Peripheral Compartment ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Differentiation Stage

Chronic hepatitis C (CHC) pathogenic mechanisms as well as the participation of the immune response in the generation of liver damage are still a topic of interest. Here, we evaluated immune cell populations and cytokines in the liver and peripheral blood (PB) to elucidate their role in CHC pathogenesis. B, CTL, Th, Treg, Th1, Th17, and NK cell localization and frequency were evaluated on liver biopsies by immunohistochemistry, while frequency, differentiation, and functional status on PB were evaluated by flow cytometry. TNF-α, IL-23, IFN-γ, IL-1β, IL-6, IL-8, IL-17A, IL-21, IL-10, and TGF-β expression levels were quantified in fresh liver biopsy by RT-qPCR and in plasma by CBA/ELISA. Liver CTL and Th1 at the lobular area inversely correlated with viral load (r = −0.469, p =0.003 and r = −0.384, p = 0.040). Treg correlated with CTL and Th1 at the lobular area (r = 0.784, p &lt; 0.0001; r = 0.436, p = 0.013). Th17 correlated with hepatic IL-8 (r = 0.52, p &lt; 0.05), and both were higher in advanced fibrosis cases (Th17 p = 0.0312, IL-8 p = 0.009). Hepatic cytokines were higher in severe hepatitis cases (IL-1β p = 0.026, IL-23 p = 0.031, IL-8 p = 0.002, TGF-β, p= 0.037). Peripheral NK (p = 0.008) and NK dim (p = 0.018) were diminished, while NK bright (p = 0.025) was elevated in patients vs. donors. Naïve Th (p = 0.011) and CTL (p = 0.0007) were decreased, while activated Th (p = 0.0007) and CTL (p = 0.0003) were increased. IFN-γ production and degranulation activity in NK and CTL were normal. Peripheral cytokines showed an altered profile vs. donors, particularly elevated IL-6 (p = 0.008) and TGF-β (p = 0.041). Total hepatic CTLs favored damage. Treg could not prevent fibrogenesis triggered by Th17 and IL-8. Peripheral T-lymphocyte differentiation stage shift, elevated cytokine levels and NK-cell count decrease would contribute to global disease.

scholarly journals Serum IL-33 Levels Are Associated with Liver Damage in Patients with Chronic Hepatitis C

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Juan Wang ◽  
Pingwei Zhao ◽  
Hui Guo ◽  
Xiguang Sun ◽  
Zhenyu Jiang ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Potential Role ◽  
Chinese Patients ◽  
Interleukin 33 ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pathogenic Process

Interleukin-33 (IL-33) is associated with the development of Th2 responses. This study examined the potential role of IL-33 in the pathogenic process of chronic hepatitis C (CHC) in Chinese patients. The levels of serum IL-33 and sST2 in 154 patients with CHC, 24 with spontaneously resolved HCV (SR-HCV) infection and 20 healthy controls (HC), were analyzed by ELISA. The concentrations of serum IL-2, IFN-γ, TNF-α, IL-4, IL-6, and IL-10, HCV loads, ALT, AST, and HCV-Ab were measured. We found that the levels of serum IL-33 in CHC patients were significantly higher than those of SR-HCV and HC but decreased after treatment with interferon for 12 weeks. More importantly, the levels of serum IL-33 were correlated with the concentrations of ALT and AST in CHC patients. The levels of serum sST2, as a decoy receptor of IL-33, were significantly higher in CHC and SR-CHC patients than those in HC, and there was no correlation between the levels of serum sST2 and IL-33. The concentrations of serum IFN-γ and IL-6 in CHC patients were significantly lower than those of SR-HCV. These data suggest that IL-33 may be a pathogenic factor contributing to CHC-related liver injury.

scholarly journals Differential Expression of the CXCR3 Ligands in Chronic Hepatitis C Virus (HCV) Infection and Their Modulation by HCV In Vitro

2008 ◽  
Vol 83 (2) ◽  
pp. 836-846 ◽  
Author(s):  
Karla J. Helbig ◽  
Andrew Ruszkiewicz ◽  
Robert E. Lanford ◽  
Mark D. Berzsenyi ◽  
Hugh A. Harley ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Hcv Infection ◽  
Chemokine Expression ◽  
Tnf Α ◽  
Chronic Hepatitis C Virus ◽  
Ifn Γ

ABSTRACT To investigate chemokine expression networks in chronic hepatitis C virus (HCV) infection, we used microarray analysis to determine chemokine expression in human infection and in chimpanzees experimentally infected with HCV. The CXCR3 chemokine family was highly expressed in both human and chimpanzee infection. CXCL10 was the only CXCR3 chemokine elevated in the serum, suggesting that it may neutralize any CXCR3 chemokine gradient established between the periphery and liver by CXCL11 and CXCL9. Thus, CXCR3 chemokines may not be responsible for recruitment of T lymphocytes but may play a role in positioning these cells within the liver. The importance of the CXCR3 chemokines, in particular CXCL11, was highlighted by replicating HCV (JFH-1) to selectively upregulate its expression in response to gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). This selective upregulation was confirmed at the transcriptional level by using the CXCL11 promoter driving the luciferase reporter gene. This synergistic increase in expression was not a result of HCV protein expression but the nonspecific innate response to double-stranded RNA (dsRNA), as both in vitro-transcribed HCV RNA and the dsRNA analogue poly(I:C) increased CXCL11 expression and promoter activity. Furthermore, we show that CXCL11 is an IRF3 (interferon regulatory factor 3) response gene whose expression is selectively enhanced by IFN-γ and TNF-α. In conclusion, the CXCR3 chemokines are the most significantly expressed chemokines in chronic hepatitis C and most likely play a role in positioning T cells in the liver. Furthermore, HCV can selectively increase CXCL11 expression in response to IFN-γ and TNF-α stimulation that may play a role in the pathogenesis of HCV-related liver disease.

scholarly journals Predictive Value of RNA Protein Kinase and Interferon-γ for HCV Clearance in Patients with Hepatitis C

2021 ◽  
Vol 2 (2) ◽  
Author(s):  
Yuanjiang Liu
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Protein Kinase ◽  
Chronic Hepatitis C ◽  
Predictive Value ◽  
Hcv Infection ◽  
Control Group ◽  
Case Group ◽  
Tnf Α ◽  
Ifn Γ

Objective — To analyze and study the predict value of serum levels of RNA-dependent protein kinase (PKR), tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10) and interferon gamma (INF-γ) for HCV clearance in patients with HCV infection. Methods — A total of 92 patients with chronic HCV infection (case group), 33 patients with HCV spontaneous resolvers (SR group) and 100 healthy persons (control group) during the same period from January 2018 to October 2019 in our hospital's infection department were collected as the study Object. The basic data and routine biochemical indicators of the three groups of subjects were detected and compared, and the levels of serum PKR, TNF-α, INF-γ and IL-10 were detected by enzyme-linked immunosorbent assay. The ROC work curve analysis was used to evaluate the predictive value of the above immune indicators for HCV clearance in patients with hepatitis C. Results — Compared with the control group and the case group, the serum PKR, TNF-α and IFN-γ levels in the SR group increased, while the IL-10 levels decreased, the difference was statistically significant. Predictive analysis of HCV clearance in chronic hepatitis C patients found that the area under the ROC curve of PKR and IFN-γ were 0.784 (95% CI: 0.704-0.864, P <0.001) and 0.645 (95% CI: 0.538-0.751, P = 0.014), and the optimal cut-off points are 7.00 ng / mL and 101.00 pg / mL, respectively. Conclusion — Both PKR and IFN-γ have a certain predictive value for the clearance of HCV in patients with chronic hepatitis C, which can be used as a potential biomarker for predicting the outcome of HCV infection.

scholarly journals Chronic Hepatitis C: An Overview of Evidence on Epidemiology and Management from a Brazilian Perspective

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Rodolfo Castro ◽  
Hugo Perazzo ◽  
Beatriz Grinsztejn ◽  
Valdilea G. Veloso ◽  
Chris Hyde
Keyword(s):  
Public Health ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Public Health Issue ◽  
Advanced Fibrosis ◽  
Noninvasive Methods ◽  
Treatment Protocols ◽  
Major Public Health Issue ◽  
Effectiveness Analysis

Chronic hepatitis C remains one of the main causes of chronic liver disease worldwide and presents a variable natural history ranging from minimal changes to advanced fibrosis and cirrhosis and its complications, such as development of hepatocellular carcinoma. Approximately, 1.45 million people are estimated to be infected by HCV in Brazil representing a major public health issue. The aim of this paper was to review the epidemiology and management of chronic hepatitis C from a Brazilian perspective. The management of chronic hepatitis C has been challenged by the use of noninvasive methods to stage liver fibrosis as an alternative to liver biopsy and the high cost of new interferon-free antiviral treatments. Moreover, the need of cost-effectiveness analysis in hepatitis C and the recent changes in treatment protocols were discussed.

P1099 EXPRESSION OF NK CELL RECEPTORS AS A PREDICTOR OF TREATMENT RESPONSE IN CHILDREN WITH CHRONIC HEPATITIS C

2014 ◽  
Vol 60 (1) ◽  
pp. S444
Author(s):  
A. Mania ◽  
M. Kaczmarek ◽  
P. Kemnitz ◽  
I. Mozer-Lisewska ◽  
M. Figlerowicz ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Treatment Response ◽  
Chronic Hepatitis C ◽  
Nk Cell ◽  
Cell Receptors ◽  
Nk Cell Receptors

scholarly journals Response to Combination Therapy with Interferon Alfa-2a and Ribavirin in Chronic Hepatitis C According to a TNF-α Promoter Polymorphism

Digestion ◽  
2003 ◽  
Vol 68 (1) ◽  
pp. 1-4 ◽  
Author(s):  
U. Schiemann ◽  
J. Glas ◽  
P. Török ◽  
C. Simperl ◽  
K. Martin ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Combination Therapy ◽  
Chronic Hepatitis C ◽  
Promoter Polymorphism ◽  
Interferon Alfa ◽  
Tnf Α

scholarly journals Cytokine profile during occult hepatitis B virus infection in chronic hepatitis C patients

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Camilla Rodrigues de Almeida Ribeiro ◽  
Nathalia Alves Araújo de Almeida ◽  
Katrini Guidolini Martinelli ◽  
Marcia Amendola Pires ◽  
Carlos Eduardo Brandao Mello ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Hepatitis C ◽  
Control Group ◽  
Occult Hepatitis ◽  
Tnf Α ◽  
B Virus ◽  
Occult Hepatitis B

Abstract Background The hepatitis B virus (HBV) is one of the leading causes of acute, chronic and occult hepatitis (OBI) representing a serious public health threat. Cytokines are known to be important chemical mediators that regulate the differentiation, proliferation and function of immune cells. Accumulating evidence indicate that the inadequate immune responses are responsible for HBV persistency. The aim of this study were to investigate the cytokines IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-17A in patients with OBI and verify if there is an association between the levels of these cytokines with the determination of clinical courses during HBV occult infection. Methods 114 patients with chronic hepatitis C were investigated through serological and molecular tests, the OBI coinfected patients were subjected to the test for cytokines using the commercial human CBA kit. As controls, ten healthy donors with no history of liver disease and 10 chronic HBV monoinfected patients of similar age to OBI patients were selected. Results Among 114 HCV patients investigated, 11 individuals had occult hepatitis B. The levels of cytokines were heterogeneous between the groups, most of the cytokines showed higher levels of production detection among OBI/HCV individuals when compared to control group and HBV monoinfected pacients. We found a high level of IL-17A in the HBV monoinfected group, high levels of TNF-α, IL-10, IL-6, IL-4 and IL-2 in OBI/HCV patients. Conclusion These cytokines could be involved in the persistence of HBV DNA in hepatocytes triggers a constant immune response, inducing continuous liver inflammation, which can accelerate liver damage and favor the development of liver cirrhosis in other chronic liver diseases.

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