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

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.

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

Journal of Virology ◽

10.1128/jvi.01388-08 ◽

2008 ◽

Vol 83 (2) ◽

pp. 836-846 ◽

Cited By ~ 53

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.

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

Virology Journal ◽

10.1186/s12985-021-01487-2 ◽

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

Mediators of Inflammation ◽

10.1155/2012/819636 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 32

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.

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Cytokine Profile During Occult Hepatitis B Virus Infection in Chronic Hepatitis C Patients

10.21203/rs.3.rs-34180/v2 ◽

2020 ◽

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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Cytokine Profile During Occult Hepatitis B Virus Infection in Chronic Hepatitis C Patients

10.21203/rs.3.rs-34180/v3 ◽

2021 ◽

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 patients. 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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Use of antiviral therapy in patients with chronic hepatitis C

Open Medicine ◽

10.1515/med-2015-0032 ◽

2015 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Natalia Dragomiretskaya ◽

Anna Izha ◽

Nikolay Kalinichenko ◽

Mirosława Szark-Eckardt ◽

Mariusz Klimczyk ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Antiviral Therapy ◽

Chronic Hepatitis C ◽

Adverse Outcomes ◽

Hcv Infection ◽

Blood Analysis ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Hcv Rna

AbstractIntroduction: The presence of background HCV infection cannot be overestimated in view of the prevalence of chronic hepatitis C and the risk of adverse outcomes of this disease. Purpose of this study was to evaluate the effectiveness of the combined use of antiviral therapy (Roferon + Vero-Ribavirin) and resort factors in patients with chronic hepatitis C in the phase of replication. Material and methods: We observed 48 patients with chronic hepatitis C; the minimum level of activity of the process defined the phase of replication. Markers of HCV infection were determined by enzyme linked immunosorbent assay (ELISA) (a-HCV and HCV-Ig M). HCV RNA was determined twice by the polymerase chain reaction (PCR). Genotyping of hepatitis C virus was performed. Biochemical blood analysis and the study of HCV infection markers were carried out four times. Results of therapy were assessed immediately after the end of the resort (spa) treatment, then at 3, 6 and 12 months after starting treatment. At 12 months after starting treatment, all the observed patients had persistent clinical and biochemical remission. Elimination of the virus from the blood was noted in 56% of the control group and 74% of patients in the study group. Conclusions: For patients with moderately active HCV, the replication phase was characterized by asthenic-vegetative syndrome (100% of patients) with severe depression (22.92%), pain (77.08%) and dyspeptic syndrome (33.33%), moderate hypertransferaseemia (100%), slightly pronounced cholestasis (33% of patients), and signs of mesenchymal- inflammatory response.

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Changes in TNF-α mRNA Levels in the Peripheral Blood of Patients with Chronic Hepatitis C Virus (HCV) Infection during α-Interferon and Ribavirin Therapy

Viral Immunology ◽

10.1089/vim.2004.17.580 ◽

2004 ◽

Vol 17 (4) ◽

pp. 580-587 ◽

Cited By ~ 2

Author(s):

Daniel Sypniewski ◽

Magdalena Jurzak ◽

Krzysztof Cholewa ◽

Joanna Gola ◽

Urszula Mazurek ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Peripheral Blood ◽

Hcv Infection ◽

Mrna Levels ◽

Tnf Α ◽

Chronic Hepatitis C Virus

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

10.21203/rs.3.rs-496275/v1 ◽

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.

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Genetic polymorphisms as the predictors of response to antiviral treatment in chronic hepatitis C virus infection

Orvosi Hetilap ◽

10.1556/oh.2011.29113 ◽

2011 ◽

Vol 152 (22) ◽

pp. 876-881

Author(s):

Alajos Pár

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Genetic Polymorphisms ◽

Chronic Hepatitis C ◽

Genome Wide Association Study ◽

Antiviral Treatment ◽

Hcv Infection ◽

Snp Analysis ◽

Chronic Hcv

The review discusses the genetic polymorphisms involved in the pathogenesis of hepatitis C virus (HCV) infection, that may determine the outcome of disease. In this field earlier both certain major histocompatibility complex (MHC) alleles and some cytokine gene variants have also been studied. Recently, the genome-wide association study (GWAS) and targeted single nucleotide polymorphism (SNP) analysis have revealed that a variant in the promoter region of interleukin-28B (IL-28B) gene is strongly linked to viral clearance and it may be the strongest pretreatment predictor of treatment response in chronic hepatitis C. Last year it was shown that two genetic variants leading to inosine triphosphatase deficiency protect against haemolytic anemia in patients receiving ribavirin during antiviral treatment for chronic HCV infection. Orv. Hetil., 2011, 152, 876–881.

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Role of annexin A2 and osteopontin for early diagnosis of hepatocellular carcinoma in hepatitis C virus patients

Egyptian Liver Journal ◽

10.1186/s43066-019-0004-9 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Abd El-Fattah F. Hanno ◽

Fatma M. Abd El-Aziz ◽

Akram A. Deghady ◽

Ehab H. El-Kholy ◽

Aborawy I. Aborawy

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Early Diagnosis ◽

Positive Predictive Value ◽

Negative Predictive Value ◽

Chronic Hepatitis C ◽

Predictive Value ◽

Annexin A2 ◽

Alpha Fetoprotein

Abstract Background Liver cancer is the fifth most common cancer and the second most frequent cause of cancer-related death globally. Early stages of hepatocellular carcinoma (0&A) can be treated with curative procedures. The aim of this work was to evaluate the role of annexin A2 and osteopontin for early diagnosis of hepatocellular carcinoma in hepatitis C virus patients. Methods The study was carried out on 80 patients classified into two groups. Group A had 40 chronic hepatitis C patients without hepatocellular carcinoma, while group B had 40 chronic hepatitis C patients with early hepatocellular carcinoma (stages; 0&A). All patients were subjected to thorough history taking, clinical examination, liver function tests, renal function tests, serum alpha-fetoprotein, serum osteopontin, and serum annexin A2. Results Serum alpha-fetoprotein was found to be statistically significantly higher in patients with the hepatocellular carcinoma group than the chronic hepatitis C group. The ROC curve for alpha-fetoprotein for detection of HCC was significant, its diagnostic performance was 0.818* (p < 0.001*), and the cutoff point for predicting the probability for HCC was 6.0 (ng/ml) with sensitivity of 77.50%, specificity of 82.50%, positive predictive value of 81.60%, negative predictive value of 78.6%, and accuracy of 80%. Serum osteopontin was found to be statistically significantly higher in patients from the hepatocellular carcinoma group than the chronic hepatitis C group. The ROC curve for osteopontin was significant, its diagnostic performance was 0.739* (p < 0.001*), the cutoff point was 13.2 (ng/ml) with sensitivity of 65.0%, specificity of 90.0%, positive predictive value of 86.70%, negative predictive value of 72.0%, and accuracy of 77.0%. Serum annexin A2 was found to be statistically significantly higher in patients from the hepatocellular carcinoma group than the chronic hepatitis C group. The ROC curve for annexin A2 was significant, its diagnostic performance was 0.927* (p < 0.001*), the cutoff point was 10.1(ng/ml) with sensitivity of 85.0%, specificity of 85.0%, positive predictive value of 85.0%, negative predictive value of 85.0%, and accuracy of 85.0%. Conclusions Osteopontin had better specificity but lower sensitivity than serum alpha-fetoprotein for early diagnosis of hepatocellular carcinoma. Annexin A2 had better diagnostic sensitivity and specificity than alpha-fetoprotein for early diagnosis of hepatocellular carcinoma.

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