scholarly journals T Cells with a CD4+CD25+ Regulatory Phenotype Suppress In Vitro Proliferation of Virus-Specific CD8+ T Cells during Chronic Hepatitis C Virus Infection

2005 ◽  
Vol 79 (12) ◽  
pp. 7860-7867 ◽  
Author(s):  
Tobias Boettler ◽  
Hans Christian Spangenberg ◽  
Christoph Neumann-Haefelin ◽  
Elisabeth Panther ◽  
Simonetta Urbani ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
T Cell ◽  
Chronic Hepatitis C ◽  
Hcv Infection ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Regulatory Phenotype

ABSTRACT Chronic hepatitis C virus (HCV) infection is associated with impaired proliferative, cytokine, and cytotoxic effector functions of HCV-specific CD8+ T cells that probably contribute significantly to viral persistence. Here, we investigated the potential role of T cells with a CD4+CD25+ regulatory phenotype in suppressing virus-specific CD8+ T-cell proliferation during chronic HCV infection. In vitro depletion studies and coculture experiments revealed that peptide specific proliferation as well as gamma interferon production of HCV-specific CD8+ T cells were inhibited by CD4+CD25+ T cells. This inhibition was dose dependent, required direct cell-cell contact, and was independent of interleukin-10 and transforming growth factor beta. Interestingly, the T-cell-mediated suppression in chronically HCV-infected patients was not restricted to HCV-specific CD8+ T cells but also to influenza virus-specific CD8+ T cells. Importantly, CD4+CD25+ T cells from persons recovered from HCV infection and from healthy blood donors exhibited significantly less suppressor activity. Thus, the inhibition of virus-specific CD8+ T-cell proliferation was enhanced in chronically HCV-infected patients. This was associated with a higher frequency of circulating CD4+CD25+ cells observed in this patient group. Taken together, our results suggest that chronic HCV infection leads to the expansion of CD4+CD25+ T cells that are able to suppress CD8+ T-cell responses to different viral antigens. Our results further suggest that CD4+CD25+ T cells may contribute to viral persistence in chronically HCV-infected patients and may be a target for immunotherapy of chronic hepatitis C.

scholarly journals Liver Biopsies for Chronic Hepatitis C: Should Nonultrasound-Guided Biopsies Be Abandoned?

2009 ◽  
Vol 23 (6) ◽  
pp. 425-430 ◽  
Author(s):  
Jennifer A Flemming ◽  
David J Hurlbut ◽  
Ben Mussari ◽  
Lawrence C Hookey
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Liver Biopsy ◽  
Chronic Hepatitis C ◽  
Hcv Infection ◽  
Significant Difference ◽  
The Us ◽  
Chronic Hcv Infection ◽  
Liver Biopsies ◽  
Chronic Hcv

BACKGROUND/OBJECTIVE: Liver biopsy has been the gold standard for grading and staging chronic hepatitis C virus (HCV)-mediated liver injury. Traditionally, this has been performed by trained practitioners using a nonimage-guided percutaneous technique at the bedside. Recent literature suggests an expanding role for radiologists in obtaining biopsies using an ultrasound (US)-guided technique. The present study was undertaken study to determine if the two techniques produced liver biopsy specimens of similar quality and hypothesized that at our institution, non-US-guided percutaneous liver biopsies for HCV would be of higher quality than US-guided specimens.METHODS: Liver biopsies from 100 patients with chronic HCV infection (50 consecutive US-guided and 50 consecutive non-US-guided), were retrospectively identified using a hospital histopathology database. All original biopsy slides were coded and prospectively reanalyzed by a single hepatopathologist who was blinded to the technique used in obtaining the biopsy. Additionally, all liver biopsies for chronic HCV infection completed at the centre from 1998 to 2007 were identified and the technique used was recorded. Biopsy quality was determined primarily by the number of complete portal tracts (CPTs) identifiable in the slides. The total length of specimen and the degree of fragmentation were secondary outcome measures.RESULTS: There was a slight difference observed between the US-guided and non-US-guided groups in mean age (46.3 years versus 42.5 years, repectively; P=0.018) but no differences in sex, presence of cirrhosis, bilirubin, creatinine, international normalized ratio, and grade or stage of disease. Biopsies obtained using the US-guided technique produced higher quality specimens than the non-US-guided technique based on our primary outcome of number of CPTs in the biopsy (11.8 versus 7.4; P<0.001). US-guided specimens also were longer (24.4 mm versus 19.7 mm; P=0.001), had less fragmentation (P=0.016), and a higher overall histopathological quality assessment (P=0.026) than the non-US-guided biopsies. However, there was no significant difference between the two groups in the ability to grade and stage the disease (96% US-guided versus 90% in non-US-guided (P=0.20). Over a 10-year period, 763 biopsies for chronic HCV infection were identified with an obvious trend toward the increased use of US-guided technique observed at 2% in 1998 to 85% in 2007.CONCLUSIONS: US-guided liver biopsies for chronic HCV are the most common method of obtaining specimens at the Kingston General Hospital, Kingston, Ontario, and are of higher quality than non-US-guided specimens. However, there is no significant difference in the two techniques in the ability to grade and stage chronic HCV.

scholarly journals Chronic HCV - infection in the Kirov region: Dynamics of indices of disease in adults in 1995-2010

2013 ◽  
Vol 18 (2) ◽  
pp. 33-36
Author(s):  
S. V Baramzina
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Acute Hepatitis ◽  
Chronic Hepatitis C ◽  
Hcv Infection ◽  
Acute Hepatitis C ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
The Given ◽  
Epidemiological Situation

In the given article the analysis of an epidemiological situation concerning chronic forms of HCV infections in adults in the Kirov region in 1995-2010 is presented. In the region during analyzed period stable trend to the elevation of incidence of chronic hepatitis C and a slight decrease in the number of "carriers" of HCV on the background of steadily low indices of the occurrence of acute hepatitis C have been fixed. There are also presented the results of genotyping of HCV-virus in 730 patients with chronic hepatitis C treated at the Kirov Region infectious hospital and polyclinics in Kirov with the dominance of HCV subtypes 1b and 3a .

scholarly journals Treatment options for chronic hepatitis C virus infection

2006 ◽  
Vol 59 (11-12) ◽  
pp. 560-566
Author(s):  
Ivanko Bojic ◽  
Ljubisa Dokic ◽  
Svetlana Minic
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Induction Therapy ◽  
Hcv Infection ◽  
Initiation Factor ◽  
Chronic Hepatitis C Virus ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

Introduction. The incidence of chronic hepatitis C virus (HCV) infection is rather high. Its most frequent consequences are chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Treatment of chronic HCV infection. In treatment of chronic HCV infection, interferons have antiviral, anriproliferative, and immunoregulatory action. Within the cell, they induce protein synthesis, inhibiting viral replication. The most important among them are RNA dependent protein kinase, and eukaryotic initiation factor. However, viral proteins prevent their phosphorylation and activation. In order to overcome this problem, treatment is prolonged, higher doses of IFN are used, as well as induction therapy. The optimal period for viral response is 52 weeks, while induction therapy has shown controversial results. .

scholarly journals Treatment of autoimmune thrombocytopenia in a case of chronic hepatitis C with ursodeoxycholic acid

2009 ◽  
Vol 3 (08) ◽  
pp. 644-646 ◽  
Author(s):  
Hasan Naz ◽  
Vahap Aslan
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Ursodeoxycholic Acid ◽  
Chronic Hepatitis C ◽  
Present Report ◽  
Hcv Infection ◽  
Autoimmune Thrombocytopenia ◽  
Ifn Alpha ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

Pegylated interferon (PEG-IFN) alpha and ribavirin therapy has become the standard treatment in chronic hepatitis C virus (HCH)-infected patients. While thrombocytopenia associated with IFN use is frequently observed among these patients, autoimmune thrombocytopenia is one of the rarely observed adverse effects. In the present report, we present a case with chronic HCV infection in which autoimmune thrombocytopenia developed at week 7 of PEG-IFN alpha 2b plus ribavirin therapy. The patient subsequently received ursodeoxycholic acid (UDCA) treatment. Although there is not an adequate number of studies on this subject, it was concluded that the use of UDCA in cases of autoimmune thrombocytopenia that have developed due to PEG-IFN treatment in chronic HCV infection is a favorable option.

scholarly journals Predictive Clinical Value of Rheumatoid Factor and Anti-Citrullinated Protein Antibodies as Diagnostic Tools in Cases with Non-Arthritic Chronic Hepatitis C Viral Disease

2018 ◽  
Vol 3 (3) ◽  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Rheumatoid Factor ◽  
Chronic Hepatitis C ◽  
Hcv Infection ◽  
P Value ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Antibody Levels ◽  
Citrullinated Protein

Background: Rheumatoid arthritis is a chronic immunological disease that causes destruction and deformity of joints. Chronic hepatitis C infection cases could develop rheumatic like clinical presenting profile. Raised rheumatoid factor in chronic HCV infection considerably reduces the diagnostic privilege of rheumatoid factor for rheumatoid arthritis coexisting with HCV infection. Aim of the work: To determine the value of anti-citrullinated protein antibody levels in cases having chronic HCV infection in comparison to rheumatoid factor. Methodology: The research team recruited 150 non-arthritic study subjects having chronic hepatitis C virus infection rheumatoid factor and anti-citrullinated protein antibody levels were assayed for all study subjects for statistical analysis. Results: Rheumatoid factor +ve study subjects had statistically significantly more frequent within female gender. (p value=0.027) Rheumatoid factor high +ve cases had statistically significantly had more frequent fatty liver and higher platelets than on high RF +ve cases. (P value =0.020, <0.038 consecutively) Conclusion: HCV cases with joint involvement were not implemented in the current research study that prevented statistical estimation of the sensitivity of anti-citrullinated protein antibody for arthritis in this cohort. Racial and ethnic differences should be put in consideration in future research studies that are recommended to be multi centric in fashion.

scholarly journals Altered chemotactic response of myeloid and plasmacytoid dendritic cells from patients with chronic hepatitis C: role of alpha interferon

2008 ◽  
Vol 89 (5) ◽  
pp. 1243-1253 ◽  
Author(s):  
Vito R. Cicinnati ◽  
Jinyu Kang ◽  
Georgios C. Sotiropoulos ◽  
Philip Hilgard ◽  
Andrea Frilling ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Serum Levels ◽  
Hcv Infection ◽  
Alpha Interferon ◽  
Homing Behaviour ◽  
Hepatic Portal ◽  
Chronic Hcv

Dendritic cell (DC) frequencies in the blood of patients with chronic hepatitis C virus (HCV) infection have been shown to be reduced significantly compared with those in healthy individuals. There is a further reduction of circulating myeloid DCs (MDCs) and plasmacytoid DCs (PDCs) in HCV patients receiving alpha interferon (IFN-α)-based antiviral therapy. Altered homing behaviour of DCs may be a possible mechanism for their ‘loss’ in peripheral blood in these clinical conditions. Systemic chemokine levels were measured by ELISA. Phenotypes and migratory properties of MDCs and PDCs from HCV patients were analysed by flow cytometry and chemotaxis assay. Compared with healthy controls, HCV patients had increased serum levels of inflammatory and constitutively expressed chemokines. Spontaneously generated MDCs from HCV patients were less mature, and both MDCs and PDCs showed intrinsic activation of receptors for inflammatory chemokines, thus suggesting an increased propensity to migrate towards inflammatory sites. IFN-α treatment in vitro induced MDC maturation and skewed the migratory response of both MDCs and PDCs towards chemokines expressed constitutively in secondary lymphoid organs. In conclusion, our results hint at altered homing behaviour of DCs during chronic HCV infection. IFN-α therapy may redirect DC migration from inflamed hepatic portal areas towards secondary lymphoid tissue.

scholarly journals Evidence for Protection against Chronic Hepatitis C Virus Infection in Chimpanzees by Immunization with Replicating Recombinant Vaccinia Virus

2008 ◽  
Vol 82 (21) ◽  
pp. 10896-10905 ◽  
Author(s):  
Jin-Won Youn ◽  
Yu-Wen Hu ◽  
Nancy Tricoche ◽  
Wolfram Pfahler ◽  
Mohamed Tarek Shata ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Recombinant Vaccinia Virus ◽  
Hcv Infection ◽  
Recombinant Vaccinia ◽  
Chronic Hepatitis C Virus ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

ABSTRACT Given the failures of nonreplicating vaccines against chronic hepatitis C virus (HCV) infection, we hypothesized that a replicating viral vector may provide protective immunity. Four chimpanzees were immunized transdermally twice with recombinant vaccinia viruses (rVV) expressing HCV genes. After challenge with 24 50% chimpanzee infective doses of homologous HCV, the two control animals that had received only the parental VV developed chronic HCV infection. All four immunized animals resolved HCV infection. The difference in the rate of chronicity between the immunized and the control animals was close to statistical significance (P = 0.067). Immunized animals developed vigorous gamma interferon enzyme-linked immunospot responses and moderate proliferative responses. To investigate cross-genotype protection, the immunized recovered chimpanzees were challenged with a pool of six major HCV genotypes. During the acute phase after the multigenotype challenge, all animals had high-titer viremia in which genotype 4 dominated (87%), followed by genotype 5 (13%). However, after fluctuating low-level viremia, the viremia finally turned negative or persisted at very low levels. This study suggests the potential efficacy of replicating recombinant vaccinia virus-based immunization against chronic HCV infection.

scholarly journals Decreased Frequency of the HLA-DRB1*11 Allele in Patients with Chronic Hepatitis C Virus Infection

2002 ◽  
Vol 76 (4) ◽  
pp. 1787-1789 ◽  
Author(s):  
Ayla Yenigün ◽  
Belma Durupinar
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Class Ii ◽  
Hla Class Ii ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Reduced Frequency ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

ABSTRACT A genetically determined resistance or susceptibility to chronic hepatitis C virus (HCV) infection may make an important contribution to the course of liver disease and may be linked to the human major histocompatibility complex (MHC). The aim of this study was to investigate the HLA class II genotype profile in chronic hepatitis C and to determine the HLA-hepatitis C association. The experimental population was composed of 49 unrelated chronic HCV patients (31 females, 18 males; mean age, 54.4 ± 1.7 years; range, 34 to 73 years). The control population consisted of 43 ethnically matched healthy donors. HLA-DR and -DQ alleles were studied for patients and controls by a PCR-sequence-specific-primer low-resolution method. Anti-HCV was investigated with enzyme-linked immunosorbent assay II, and HCV RNA was investigated with reverse transcriptase nested PCR. The HLA class II allele, DRB1*11, was found at reduced frequency in 49 patients with chronic hepatitis C (anti-HCV and HCV RNA positive) compared to that for controls (22.4 versus 51.0%; P < 0.01, odds ratio = 0.3, confidence interval = 0.1 to 0.7). No further HLA associations with chronic HCV infection were observed, and there was no correlation between the stage of disease and HLA. DRB1*11 was also found at reduced frequency in all HCV antibody-positive patients compared to controls (corrected P = not significant). DRB1*11 was associated with chronic HCV infection, and it is possible that HLA-DRB1*11 may have a protective feature in chronic HCV infection. In addition, DRB1*11 was associated with protection from HCV infection. These findings suggest that host HLA class II genotype is an important factor determining the outcome of infection with HCV.

scholarly journals Hepatitis C Virus (HCV) Sequence Variation Induces an HCV-Specific T-Cell Phenotype Analogous to Spontaneous Resolution

2009 ◽  
Vol 84 (3) ◽  
pp. 1656-1663 ◽  
Author(s):  
Victoria Kasprowicz ◽  
Yu-Hoi Kang ◽  
Michaela Lucas ◽  
Julian Schulze zur Wiesch ◽  
Thomas Kuntzen ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Hcv Infection ◽  
Cell Phenotype ◽  
Cell Responses ◽  
Cognate Antigen ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

ABSTRACT Hepatitis C virus (HCV)-specific CD8+ T cells in persistent HCV infection are low in frequency and paradoxically show a phenotype associated with controlled infections, expressing the memory marker CD127. We addressed to what extent this phenotype is dependent on the presence of cognate antigen. We analyzed virus-specific responses in acute and chronic HCV infections and sequenced autologous virus. We show that CD127 expression is associated with decreased antigenic stimulation after either viral clearance or viral variation. Our data indicate that most CD8 T-cell responses in chronic HCV infection do not target the circulating virus and that the appearance of HCV-specific CD127+ T cells is driven by viral variation.

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