共查询到20条相似文献，搜索用时 15 毫秒
1.
2.
Background:
Hepatitis C virus infection is one of the leading causes of end stage liver diseases. The innate immune response slows down viral replication by activating cytokines such as type I interferon (IFN-α/β), which trigger the synthesis of antiviral proteins and modulate the adaptive immune system. Recently, leucine-rich repeat (in Flightless I) interacting protein-1 (LRRFIP1) was reported contributing to the production of interferon-β in macrophages.Objectives:
The aim of this study was to assess the role of LRRFIP1 in induction of IFN-β and inhibition of HCV infection in hepatocytes.Materials and Methods:
Induction of IFN-β by LRRFIP1 in Huh7 and Huh7.5.1 was determined by real-time PCR and western blotting in vitro. Inhibition of HCV replication by LRRFIP1 overexpression in hepatocytes was assessed.Results:
LRRFIP1 increased the expression of IFN-β in hepatocytes with or without HCV infection. Induction of IFN-β by LRRFIP1 was enhanced with the presence of hepatitis C virus. Overexpression of LRRFIP1 in hepatocytes inhibited HCV replication. However, HCV infection did not regulate intracellular expression of LRRFIP1.Conclusions:
LRRFIP1 and its mediated production of type I interferon play a role in controlling HCV infection. The findings of this study provide new target for HCV treatment and contribute to development of anti-HCV drugs. 相似文献3.
Background:
Hepatitis C virus (HCV) is able to down-regulate innate immune response. It is important to know the immune pathways that this virus interacts with. HCV non-structural protein 3 (NS3) plays an important role in this viral feature. HCV NS3 protein could affect the expression of antiviral protein such as viperin, and interleukin 28whichare important proteins in antiviral response.Objectives:
HCV has developed different mechanisms to maintain a persistent infection, especially by disrupting type I interferon response and subsequent suppression of expression of Interferon stimulatory genes (ISGs). Viperin, a member of ISGs, is considered as a host antiviral protein, which interferes with viral replication. Since it is a good target for some viruses to evade host responses, it is interesting to study if HCV has evolved a mechanism to interfere with this member of ISGs.Materials and Methods:
We evaluated the impact of NS3, NS3/4A and a mutated nonfunctional NS3 on ISGs expression such as viperin and IL-28 after the induction of IFN signaling Jak-STAT pathway using IFN-.Results:
NS3 protein disrupted the expressions of viperin gene and IL-28, an inducer for the expression of ISGs and viperin itself. By comparing the roles of NS3 and NS3/4A protease activities in suppressing the innate immune responses, we also showed that NS3 (without NS4A) has the ability to down-regulate ISGs expression, similar to that of NS3/4A.Conclusions:
ISGs expression is impeded by NS3 protease activity and its interaction with Jak-STAT pathway proteins. In addition, the NS3/4A substrates spectrum seems to be similar to those of NS3. 相似文献4.
Mahdi Dehghan-Manshadi Hossein Hadinedoushan Mohammad Kazem Amirbaigy Fateme Zare Gilda Eslami Seyyed Ali Mirghanizade-Bafghi Mohsen Akhondi-Meybodi 《Hepatitis monthly》2015,15(11)
Background:
Hepatitis C virus (HCV) is an important human pathogen affecting an estimated 120 – 170 million individuals in the world. Toll-Like receptors (TLRs) are pattern-recognition receptors that recognize pathogen-associated molecular patterns, and stimulate immune responses.Objectives:
The aim of this study was to determine the mRNA expression level of TLR2 and TLR7 in HCV-infected patients in comparison with normal controls.Patients and Methods:
Nineteen consecutive patients with HCV infection and nineteen sex and age-matched healthy controls were studied in a case-controlled research.Results:
Our results showed that the expressions of TLR7 in HCV infected samples were significantly increased in comparison those of the controls (P = 0.02), while the expression of TLR2 was similar between the case and the control group (P = 0.8). There were no associations between the expression levels of TLR2 and TLR7 with HCV viral load and HCV genotypes. Also, there was no association between viral load and genotypes of the virus.Conclusions:
Our findings showed that HCV infection could lead to increased expression level of TLR7 mRNA in peripheral blood cells of HCV infected samples. The viral load and genotypes of HCV did not affect the mRNA expression levels of TLR2 and TLR7. 相似文献5.
Wu JM Skill NJ Maluccio MA 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2010,12(9):625-636
Objectives
Lipids are linked to many pathological processes including hepatic steatosis and liver malignancy. This study aimed to explore lipid metabolism in hepatitis C virus (HCV) and HCV-related hepatocellular carcinoma (HCC).Methods
Serum lipids were measured in normal, HCV and HCV-HCC patients. Whole-genome microarray was performed to identify potential signature genes involved in lipid metabolism characterizing normal vs. HCV vs. HCV-HCC conditions.Results
Serum cholesterol was significantly reduced in HCV and HCV-HCC patients compared with normal controls, whereas there was no difference in glucose and triglycerides. Microarray analysis identified 224 probe sets with known functional roles in lipid metabolism (anova, 1.5-fold, P ≤ 0.001). Gene-mediated fatty acid (FA) de novo synthesis and uptake were upregulated in HCV and this upregulation was further enhanced in HCC. Genes involved in FA oxidation were downregulated in both the HCV and HCC groups. The abnormality of cholesterol metabolism in HCV was associated with downregulation of genes involved in cholesterol biosynthesis, absorption and transportation and bile acid synthesis; this abnormality was further intensified in HCC.Conclusions
Our data support the notion that HCV-related lipid metabolic abnormalities may contribute to hepatic steatosis and the development of cancer. Identification of these aberrations would stratify patients and improve treatment algorithms. 相似文献6.
7.
Stephen E Livingston Heike Deubner Dana L Bruden Brian J McMahon Chriss E Homan Lisa J Townshend-Bulson Michael G Bruce Thomas W Hennessy James L Williams David R Gretch 《Journal canadien de gastroenterologie》2010,24(7):445-451
BACKGROUND:
Various factors influence the development and rate of fibrosis progression in chronic hepatitis C virus (HCV) infection.OBJECTIVES:
To examine factors associated with fibrosis in a long-term outcomes study of Alaska Native/American Indian persons who underwent liver biopsy, and to examine the rate of fibrosis progression in persons with subsequent biopsies.METHODS:
A cross-sectional analysis of the demographic, inflammatory and viral characteristics of persons undergoing liver biopsy compared individuals with early (Ishak fibrosis score of lower than 3) with those with advanced (Ishak score of 3 or greater) fibrosis. Persons who underwent two or more biopsies were analyzed for factors associated with fibrosis progression.RESULTS:
Of 253 HCV RNA-positive persons who underwent at least one liver biopsy, 76 (30%) had advanced fibrosis. On multivariate analysis, a Knodell histological activity index score of 10 to 14 and an alpha-fetoprotein level of 8 ng/mL or higher were found to be independent predictors of advanced liver fibrosis (P<0.0001 for each). When surrogate markers of liver inflammation (alanine aminotransferase, aspartate aminotransferase/alanine aminotransferase ratio and alpha-fetoprotein) were removed from the model, type 2 diabetes mellitus (P=0.001), steatosis (P=0.03) and duration of HCV infection by 10-year intervals (P=0.02) were associated with advanced fibrosis. Among 52 persons who underwent two or more biopsies a mean of 6.2 years apart, the mean Ishak fibrosis score increased between biopsies (P=0.002), with progression associated with older age at initial biopsy and HCV risk factors.CONCLUSIONS:
The presence of type 2 diabetes mellitus, steatosis and duration of HCV infection were independent predictors of advanced fibrosis in the present cohort, with significant fibrosis progression demonstrated in persons who underwent serial biopsies. 相似文献8.
Background
Hepatitis infection represents one of the important causes of morbidity and mortality in developing countries, however there is not any effective vaccine against hepatitis C which is one of the significant problems in vaccine project.Objectives
The aim of the present study is to evaluate the role of HCV core protein in inducing IFN-Gamma secretion and TCL activities as a vaccine in Balb/C mice.Material and Methods
Our previous cloned plasmid (HCV Core gene into pETDuet-1) applied for protein expression in bacteria. The expressed and purified recombinant protein together with Freund’s adjuvant was injected to 15 Balb/c mice. The total IgG and IgG2a of immunized mice sera were evaluated after a week. Two weeks after booster injection, we studied the proliferation and IFNγ secretion of spleens, inguinal and popliteal lymph nodes lymphocytes by ELISA and ELISPOT.Results
The FSFC (Frequency of spot forming cells) of secreting cells of immunized mice with HCV/Core protein and sera IgG2a were considerably higher than the control groups.Conclusions
The core protein together with proper adjuvant can be a candidate vaccine against of HCV infection. 相似文献9.
Background:
Previous studies using pegylated interferon (Peg-IFN) and ribavirin (RBV) combination therapy suggested that patients with hepatitis C virus (HCV) genotype 1 and low pretreatment HCV RNA level who achieved rapid virological response (RVR) can be treated for 24 weeks without compromising sustained virological response (SVR) rate.Objectives:
The current study aimed to investigate the efficacy of Peg-IFN-alfa-2a plus RBV administered for a 24-week treatment course in patients with chronic HCV genotype 1 infection and possessing the following criteria: low baseline serum HCV RNA level, absence of significant fibrosis and achievement of RVR.Patients and Methods:
In this case-control study, 20 patients with HCV genotype 1 infection and favorable baseline characteristics and on-treatment response were treated with Peg-IFN and RBV for 24 weeks as the case group. Furthermore, 23 patients with the same characteristics who underwent a 48-week treatment course were selected as the control group.Results:
The majority of patients had no fibrosis on liver elastography. There was no statistical difference regarding age, gender, alanine transaminase (ALT) level, rs12979860 polymorphism and the level of fibrosis between the two studied groups. All patients in the 24-week treatment course achieved SVR and all the subjects who received the 48-week treatment course achieved SVR as well (P > 0.99).Conclusions:
The current study confirmed that the efficacy of a 24-week regimen of Peg-IFN-alfa-2a plus RBV was similar to the 48-week treatment in the patients infected with HCV genotype 1, and low baseline HCV RNA level who achieved RVR. Response guided therapy can be efficient and cost-effective among the selected HCV genotype 1-infected patients. 相似文献10.
11.
12.
Christine Hartoonian Zargham Sepehrizadeh Mojtaba Tabatabai Yazdi Yong Suk Jang Lida Langroudi Parisa Amir Kalvanagh Babak Negahdari Ali Karami Massoumeh Ebtekar Kayhan Azadmanesh 《Hepatitis monthly》2014,14(3)
Background:
Using molecular adjuvants offers an attractive strategy to augment DNA vaccine-mediated immune responses. Several studies have revealed that an efficient HCV vaccine model should be able to induce both humoral and cell mediated immune responses targeting the conserved regions of the virus to circumvent the immune escape mutants. The beta chemokine Macrophage Inflammatory Protein 3-beta (MIP-3beta) is a key modulator of dendritic cells (DCs) and T-cells interaction, functions during immune response induction and is secreted specifically by cells in the lymphoid tissues.Objectives:
In the present study, we questioned whether co-administration of MIP-3beta gene could enhance the immune responses to HCV core in DNA vaccination.Materials and Methods:
Expression and biological activity of MIP-3beta expressing plasmid were evaluated by ELISA and transwell migration assays, respectively. HCV core DNA vaccine ± plasmid expressing MIP-3beta were electroporated subcutaneously to the front foot pads of BALB/c mice on days 0 and 14, and HCV core protein booster was applied to all core-DNA-vaccine received mice on the day 28. Both cell mediated immunity (proliferation, IFN-γ and IL-4 cytokine release, IFN-γ ELISpot and cytotoxic Granzyme B release assays) and humoral immune responses (total IgG and IgG2a/IgG1 subtyping) were evaluated ten days after final immunization.Results:
Mice covaccinated with MIP-3beta elicited an enhanced Th1 biased systemic immune response as evidenced by higher IFN-γ/IL-4 and anti-core IgG2a/IgG1 ratio, lymphoproliferation, strong cytolytic GrzB release and enhanced population of IFN-γ producing immunocytes. Likewise, the humoral immune response assumed as the total anti-core IgG level was augmented by MIP-3beta co-delivery.Conclusions:
These results exhibited the immuno potentiator effects of MIP-3beta plasmid when coadministrated with the HCV core DNA vaccine. Complimentary studies integrating MIP-3beta as a genetic adjuvant in HCV-core-DNA vaccination models are warranted. 相似文献13.
Maryam Moini Mazyar Ziyaeyan Shapoor Aghaei Mohammad Mahdi Sagheb Seyed Alireza Taghavi Mahsa Moeini Marzieh Jamalidoust Laleh Hamidpour 《Hepatitis monthly》2013,13(6)
Background
End-stage renal disease patients on chronic hemodialysis are among high risk groups for hepatitis C virus (HCV) infection for whom routine HCV screening is recommended. Anti-HCV antibody (ab) testing may not be reliable to detect all infected cases because of the blunted ab response due to depressed immune state in these patients. Using a more reliable, cost-effective and non-complex HCV screening test may be necessary in this group of patients for case finding and management, and also for prevention of infection spread.Objectives
The aim of this study was to find the prevalence of HCV infection in HCV ab negative hemodialysis patients by Real time PCR and total HCV core antigen (ag) test and comparing the results of the two tests.Patients and Methods
From a single hemodialysis center, 181 anti- HCV ab negative patients were screened by total HCV core ag using an ELISA kit. Real time PCR was used for determination of the virus and viral load quantity.Results
Among the 181 anti-HCV ab negative patients, 13 (7.2%) were positive for HCV core ag and 11 (6%) had detectable HCV RNA with a range of 40-336543 IU/ml by PCR. The two tests had a high measurement agreement (Kappa=0.82, P<0.001). Of the 13 patients with positive HCV core ag test results, 3 were negative for HCV RNA. Considering real time PCR for HCV RNA as the gold standard for HCV infection determination in this patient population, HCV core ag assay yielded a sensitivity of 90.9%, specificity of 98.2%, positive predictive value of 76.9% and negative predictive value of 99.4%.Discussion
The rate of HCV infection among HCV ab negative hemodialysis patients was high. HCV core ag testing could be used as a sensitive method for HCV infection screening in this group of patients. 相似文献14.
Jordanna E Kapeluto Matthew Kadatz Andrew Wormsbecker Kiran Sidhu Eric M Yoshida 《Journal canadien de gastroenterologie》2014,28(6):315-318
BACKGROUND:
Hepatitis B virus (HBV) and hepatitis C virus (HCV) represent an increasing health burden and morbidity in Canada. Viral hepatitis, specifically HCV, has high prevalence among persons born between 1945 and 1965, with 45% to 85% of infected adults asymptomatic and unaware of their infection. Screening has been shown to be cost effective in the detection and treatment of viral hepatitis.OBJECTIVE:
To quantify incidence and identify undocumented HBV and HCV infection in hospitalized patients at a single centre with secondary analysis of risk factors as part of a quality improvement initiative.METHODS:
A one-time antibody test was conducted in patients admitted to the acute medicine and gastroenterology services.RESULTS:
Over a 12-week period, hospital screening for HBV and HCV was performed in 37.3% of 995 admitted patients. There was identification of 15 previously undiagnosed cases of HCV (4%) and 36 undocumented cases of occult (ie, antihepatitis B core antigen seropositive) or active (ie, hepatitis B surface antigen seropositive) HBV (9.7%). Among patients with positive screens, 60% of seropositive HCV patients had no identifiable risk factors.CONCLUSIONS:
The prevalence of HBV and HCV infection among hospitalized patients in Vancouver was higher than that of the general population. Risk factors for contraction are often not identified. These results can be used as part of an ongoing discussion regarding a ‘seek and treat’ approach to the detection and treatment of chronic blood-borne viral illnesses. 相似文献15.
Imran Tipu Fiona Marriage Zia-ur-Rahman Farooqi Hazel Platt Muhammad Amin Athar Philip John Day Andrea Short 《Hepatitis monthly》2014,14(3)
Background
Polymorphisms in the interferon λ (INF λ) genes on chromosome 19 have been associated with clearance of hepatitis C virus (HCV) induced by interferon and ribavirin therapy however there is no such data available for Pakistani patients with HCV infection.Objectives
In this study, the effects of single nucleotide polymorphisms (SNPs) have been investigated in response to treatment with interferon-α and ribavirin in a cohort of 75 HCV genotype 3a patients.Patients and Methods
A total number of 50 SNPs from the Interferon λ region on chromosome 19 were genotyped to investigate allelic associations with the treatment response in HCV type 3a patients. Thirteen SNPs were associated with HCV clearance, with the most significant alleles being RS8109886 (Fisher’s P = 0.0001), RS8113007 (Fisher’s P = 0.0001) and RS12979860 (Fisher’s P = 0.0002).Results
These SNPs were found to be the most suitable SNPs for predicting treatment response in the present study. These findings support those reported previously. This could be used to improve HCV treatment strategies and suggest that Pakistani patients should be genotyped for the relevant SNPs to identify the patients who are more likely to respond to interferon and ribavirin therapy.Conclusions
This therapy is costly and can be accompanied by several adverse side-effects, hence pre-treatment prediction of patients who are most likely to benefit would have both economic and patient benefits in the long term. 相似文献16.
Saleh Sandoughdaran Seyed Moayed Alavian Heidar Sharafi Bita Behnava Shima Salimi Leila Mehrnoush Pegah Karimi Elizee Maryam Keshvari 《Hepatitis monthly》2015,15(1)
Background:
Most thalassemic patients with chronic hepatitis C virus (HCV) infection do not respond to therapy with pegylated interferon (Peg-IFN) plus ribavirin (RBV) due to hepatic siderosis and RBV dose reduction caused by RBV-induced anemia.Objectives:
In the present study, we recruited HCV genotype 1-infected thalassemic patients who had relapsed after a 48-week treatment with Peg-IFN plus RBV in order to evaluate the efficacy of a 72-week regimen of Peg-IFN plus RBV.Patients and Methods:
In this retrospective study, 23 thalassemic patients with HCV genotype 1 infection who had prior relapse after treatment with Peg-IFN and RBV for 48 weeks were consecutively enrolled in this study for evaluation of the efficacy of a 72-week treatment regimen.Results:
For the 21 included cases, mean age was 29.7 years; 81% were men and 28.6% had cirrhosis. At the end of the treatment, nine (42.9%) patients had an undetectable level of HCV RNA in their sera. However, six months after treatment completion four of these patients relapsed and a sustained virological response (SVR) was found in five (23.8%) patients. Undetectable HCV RNA level at week 4 (P = 0.03) and undetectable HCV RNA level at week 12 (P < 0.01) were found to be predictors of SVR. There was an average 47.9% increase in blood transfusion during therapy and treatment was discontinued for 12 (57.1%) patients prematurely.Conclusions:
The present study suggests that thalassemic patients with chronic hepatitis C genotype 1 infection who did not achieve SVR after a course of therapy with Peg-IFN and RBV may benefit from being retreated with a 72-week regimen. 相似文献17.
Background:
Hepatitis C virus (HCV) is known for the eminent global disease burden responsible for encumbering public health. Development of an effective vaccine is the major need of the day; however, several obstacles loom ahead of this objective. One of the major barriers is that as a RNA virus, it mutates rapidly resulting in high sequence divergence and several viral isolates in the world. Theglycoprotein 2 (gpE2) is the primary component of HCV envelope with direct interaction with the host cell surface receptors; it is an indispensable target of neutralizing antibodies and hence, should be a fundamental component of vaccine design.Objectives:
This study focused on B-cells and T-cells epitopes prediction in HCV gpE2, particularly in 3a genotype, in Pakistan and identification of the conserved epitopes among various 3a isolates at global level, principally conserved across HCV major genotypes.Materials and Methods:
Epitope finding was done by using online available bioinformatics tools including Immune Epitope Database (IEDB), ProPred-I, and ProPred. Conservation of these epitopes was found by aligning selected gpE2 sequences using MultAlin online software and conservancy analysis tool available at IEDB.Results:
Many B-cell and T-cell epitopes predicted in gpE2 were found conserved among HCV 3a genotypes whereas few were conserved in other genotypes anticipating these epitopes as potential candidates of producing strong B-cell and T-cell response against HCV 3a and other genotypes.Conclusions:
HCV gpE2 is an ideal target for HCV vaccine. Prediction of epitope immunogenicity and characterization on the basis of peptide sequences will be significantly helpful for development of a heterologous vaccine against HCV variants. 相似文献18.
Mihajlo Jakovljevic Zeljko Mijailovic Biljana Popovska Jovicic Predrag Canovic Olgica Gajovic Mirjana Jovanovic Dejan Petrovic Olivera Milovanovic Natasa Djordjevic 《Hepatitis monthly》2013,13(6)
Background
Pegylated interferon alfa plus ribavirin protocol is currently considered the most efficient hepatitis C treatment. However, no evidence of costs comparison among common viral genotypes has been published.Objectives
We aimed to assess core drivers of hepatitis C medical care costs and compare cost effectiveness of this treatment among patients infected by hepatitis C virus with genotypes 1 or 4 (group I), and 2 or 3 (group II).Patients and Materials
Prospective bottom-up cost-effectiveness analysis from societal perspective was conducted at Infectious Diseases Clinic, University Clinic Kragujevac, Serbia, from 2007 to 2010. There were 81 participants with hepatitis C infection, treated with peg alpha-2a interferon plus ribavirin for 48 or 24 weeks. Economic data acquired were direct inpatient medical costs, outpatient drug acquisition costs, and indirect costs calculated through human capital approach.Results
Total costs were significantly higher (P = 0.035) in group I (mean ± SD: 12,751.54 ± 5,588.06) compared to group II (mean ± SD: 10,580.57 ± 3,973.02). In addition, both direct (P = 0.039) and indirect (P < 0.001) costs separately were significantly higher in group I compared to group II. Separate comparison within direct costs revealed higher total cost of medical care (P = 0.024) in first compared to second genotype group, while the similar tendency was observed for total drug acquisition (P = 0.072).Conclusion
HCV genotypes 1 and 4 cause more severe clinical course require more care and thus incur higher expenses compared to HCV 2 and 3 genotypes. Policy makers should consider willingness to pay threshold differentially depending upon HCV viral genotype detected. 相似文献19.
20.