Circulating and inducible IL-32α in chronic hepatitis C virus infection

2019 ◽  
Vol 2 (1) ◽  
pp. 23-30
Author(s):  
Mark Collister ◽  
Julia Rempel ◽  
Jiaqi Yang ◽  
Kelly Kaita ◽  
Zach Raizman ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Chronic Hepatitis C Virus ◽  
Chronic Hcv

Background: Interleukin 32 (IL-32) is a recently described pro-inflammatory cytokine implicated in chronic hepatitis C virus (HCV)-related inflammation and fibrosis. IL-32α is the most abundant IL-32 isoform. Methods: Circulating IL-32α levels were documented in patients with chronic HCV infections ( n = 31) and compared with individuals who spontaneously resolved HCV infection ( n = 14) and HCV-naive controls ( n = 20). In addition, peripheral blood mononuclear cells (PBMC) from the chronic HCV ( n = 12) and HCV-naive ( n = 9) cohorts were investigated for responses to HCV core and non-structural (NS)3 protein induced IL-32α production. Finally, correlations between IL-32α levels, hepatic fibrosis and subsequent responses to interferon-based therapy were documented in patients with chronic HCV. Results: Circulating IL-32α levels in patients with chronic HCV were similar to those of spontaneously resolved and HCV-naive controls. HCV protein induced IL-32α responses were similar in chronic HCV patients and HCV-naive controls. In patients with chronic HCV, serum IL-32α levels correlated with worsening METAVIR fibrosis (F) scores from F0 to F3 ( r = 0.596, P < 0.001) as did NS3 induced IL-32α responses ( r = 0.837, P < 0.05). However, these correlations were not sustained with the inclusion of IL-32α levels at F4 scores, suggesting events at F4 interfere with IL-32α synthesis or release. In chronic HCV patients who underwent treatment ( n = 28), baseline in vivo and in vitro induced IL-32α concentrations were not predictive of therapeutic outcomes. Conclusions: IL-32α activity is associated with worsening fibrosis scores in non-cirrhotic, chronic HCV patients.

scholarly journals Synergy of Small Molecular Inhibitors of Hepatitis C Virus Replication Directed at Multiple Viral Targets

2006 ◽  
Vol 81 (6) ◽  
pp. 3005-3008 ◽  
Author(s):  
David L. Wyles ◽  
Kelly A. Kaihara ◽  
Florin Vaida ◽  
Robert T. Schooley
Keyword(s):  
Clinical Trials ◽  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Mechanisms Of Action ◽  
Systematic Assessment ◽  
Chronic Hepatitis C Virus ◽  
Small Molecular Inhibitors

ABSTRACT Chronic hepatitis C virus (HCV) infection is a significant worldwide health problem with limited therapeutic options. A number of novel, small molecular inhibitors of HCV replication are now entering early clinical trials in humans. Resistance to small molecular inhibitors is likely to be a significant hurdle to their use in patients. A systematic assessment of combinations of interferon and/or novel anti-hepatitis C virus agents from several different mechanistic classes was performed in vitro. Combinations of inhibitors with different mechanisms of action consistently demonstrated more synergy than did compounds with similar mechanisms of action. These results suggest that combinations of inhibitors with different mechanisms of action should be prioritized for assessment in clinical trials for chronic hepatitis C virus infection.

scholarly journals The Interplay between Zinc, Vitamin D and, IL-17 in Patients with Chronic Hepatitis C Liver Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Randa Reda ◽  
Amal A. Abbas ◽  
Mai Mohammed ◽  
Shahira F. El Fedawy ◽  
Hala Ghareeb ◽  
...  
Keyword(s):  
Vitamin D ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Disease Severity ◽  
Chronic Hepatitis C ◽  
Healthy Subjects ◽  
Serum Levels ◽  
Chronic Hepatitis C Virus ◽  
Chronic Hcv

Objectives. To assess zinc (Zn) and vitamin D (Vit. D) status in chronic Hepatitis C virus- (HCV) infected patients and their relationship to interleukin- (IL-) 17 and disease severity and then investigate whether Zn and Vit. D3 modulate IL-17 expression in chronic HCV patients.Methods. Seventy patients and fifty healthy subjects were investigated. Serum levels of Zn, Vit. D, and IL-17 were assessed in the patients group and subgroups. Patients lymphocytes were activatedin vitroin the presence or absence of Zn or Vit. D3 and then intracellular IL-17 production was assessed using flow cytometry.Results. Zn and Vit. D were significantly decreased in HCV patients. Increasing disease severity leads to more reduction in Zn level opposed by increasing IL-17 level. Zn potently reduced IL-17 production in a dose-related fashion; however it did not exert any toxic effects. Although Vit. D apparently increases IL17 expression, it is unclear whether it is due to its toxic effect on cell count or lack of definite association between Vit. D and both IL-17 and disease severity.Conclusions. This study demonstrates that Zn modulates IL-17 expression and provides a rationale for evaluating this compound as a supplementary agent in the treatment of chronic HCV.

scholarly journals Patients With Chronic Hepatitis C Virus Infection Are at an Increased Risk of Colorectal Cancer: A Nationwide Population-Based Case-Control Study in Taiwan

2021 ◽  
Vol 10 ◽  
Author(s):  
Fu-Hsiung Su ◽  
Chyi-Huey Bai ◽  
Thi Nga Le ◽  
Chih-Hsin Muo ◽  
Shih-Ni Chang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Case Control Study ◽  
Case Control ◽  
Chronic Hepatitis C Virus ◽  
Chronic Hcv ◽  
Control Study

AimStudies evaluating colorectal cancer (CRC) risk associated with chronic hepatitis C virus (HCV) infection are limited.MethodsIn this case-control study, we identify 67,670 CRC cases newly diagnosed from 2005 to 2011 and randomly selected 67,670 controls without HCV and CRC from the same database, frequency matched by age and sex of cases.ResultsResults of logistic regression analysis revealed that the adjusted odds ratio (aOR) of CRC was 1.16 (95% confidence interval [CI] = 1.08–1.24, p &lt; 0.001) in association with chronic HCV. The CRC risk was slightly greater for women than for men. The risk decreased with age, with the aOR decreased from 2.26 (95% CI = 1.32–3.87, p = 0.003) in patients under 45 years old to 1.31 (95% CI = 1.10–1.55, p = 0.03) in patients aged 50–59, and 1.10 (95% CI = 1.00–1.22, p = 0.061) in patients aged over 70.ConclusionsOur findings suggested that patients with chronic HCV infection are at an elevated risk of developing CRC. Our data also imply that the CRC prevention programs are needed to target younger HCV patients.

scholarly journals Effect of alpha interferon (IFN-alpha) on 2'-5' oligoadenylate synthetase activity in peripheral blood mononuclear cells of patients with chronic hepatitis C: relationship to the antiviral effect of IFN-alpha.

1996 ◽  
Vol 40 (2) ◽  
pp. 320-324 ◽  
Author(s):  
J M Pawlotsky ◽  
A G Hovanessian ◽  
F Roudot-Thoraval ◽  
N Robert ◽  
M Bouvier ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Antiviral Effect ◽  
Peripheral Blood Mononuclear ◽  
Ifn Alpha

Alpha interferon (IFN-alpha) is, to date, the only treatment with proven efficacy in patients with chronic hepatitis C. However, less than 15% of the patients have a sustained response to IFN-alpha. Interferon acts through the induction of various cellular enzymes. Among them, the 2'-5' oligoadenylate synthetase (2-5OAS) is (at least in part) responsible for a direct antiviral effect of IFN-alpha. The aim of this study was to determine whether basal and IFN-alpha-induced in vivo and in vitro 2-5OAS activities measured in peripheral blood mononuclear cells predict biochemical and virological responses to IFN-alpha in patients with chronic hepatitis C. 2-5OAS activity in peripheral blood mononuclear cells and the antiviral effect of IFN-alpha were studied in 36 patients with chronic hepatitis C (27 men and 9 women; mean age, 44.7 years). Basal in vivo 2-5OAS activity (mean +/- standard error of the mean) was 4.41 +/- 0.69 nmol/10(6) cells. It was significantly induced at month 3 of IFN-alpha therapy (18.07 +/- 2.74 nmol/10(6) cells; P = 0.0001). No significant differences were found in basal in vivo 2-5OAS activities, in IFN-alpha-induced/basal in vitro 2-5OAS activity ratios, in IFN-alpha-induced in vivo 2-5OAS activities, and in IFN-alpha-induced/basal in vivo 2-5OAS activity ratios between the patients with and without a biochemical response (normal alanine aminotransferase activity in serum) or a virological response (normal alanine aminotransferase activity in serum and negative hepatitis C virus RNA detection) at any step of the study. At month 3 of therapy, p69, which is considered to be the active isoform of 2-5OAS, was induced, as demonstrated by Western blot (immunoblot) analysis in 50% of the patients, and induction of the p100 isoform was observed in 70% of the patients. No significant relationship with the response to IFN-alpha therapy was observed. Our results suggest that a deficiency of the IFN-alpha-dependent 2-5OAS system, which could be genetically determined, is unlikely to be responsible for the failure to achieve biochemical and virological responses to IFN-alpha therapy in patients with chronic hepatitis C.

Hepatocellular Carcinoma and Non-Hodgkin Lymphoma in a Patient With Chronic Hepatitis C and Cirrhosis

2000 ◽  
Vol 124 (10) ◽  
pp. 1532-1534 ◽  
Author(s):  
Arief Suriawinata ◽  
Ming Q. Ye ◽  
Sukru Emre ◽  
James Strauchen ◽  
Swan N. Thung
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Hodgkin Lymphoma ◽  
Chronic Hepatitis C ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Hilar Lymph Node ◽  
Non Hodgkin Lymphoma ◽  
Chronic Hcv

Abstract Hepatitis C virus (HCV) is a hepatotropic virus, but its genome and replicative intermediates also have been detected in peripheral blood mononuclear cells in patients with chronic hepatitis C. Chronic HCV infection may lead to hepatocellular carcinoma and, in a small percentage of cases, to B-cell non-Hodgkin lymphoma. To our knowledge, coexistence of these 2 tumors has not been reported previously. We describe a case of chronic hepatitis C and cirrhosis with 2 small hepatocellular carcinomas and incidental non-Hodgkin lymphoma of a hilar lymph node found during liver transplantation. Although the mechanisms of HCV oncogenesis in hepatocellular carcinoma and in lymphoma are unclear, the presence of these 2 tumors in a single patient are in agreement with the tropism of HCV and its role in oncogenesis.

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