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Sample records for chronic hcv infection

  1. THE CYTOKINE IP-10 IN CHRONIC HBV AND HCV INFECTION

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    Nina S. Nikolova

    2013-08-01

    Full Text Available Introduction: IP-10 it has been studied as a predictor of treatment response in chronic HCV infected patients. The data for the HBV infection are not enough.Aim: To compare IP-10 levels in patients with chronic HBV /CHB/ and HCV infection /CHC/ and their relation to liver disease and treatment response. Material and methods: 20 patients - with CHC genotype 1 infection /on standard bi-therapy/ and 32 patients with CHB /21 pts - NUC; 11 pts - IFN/. Results: The IP-10 did not correlate with sex, age, ALT and liver fibrosis. The basal IP-10 were lower in patients with CHB (p=0,017. There was a difference in IP-10 baseline levels among the HCV patients with or without RVR (p=0,007. A negative correlation was found between basal IP-10 and RVR (r= -0,508; p=0,008. Conclusion: IP-10 could predict virological response in patients with CHC on standard bi-therapy, but not in HBV infected patients on standard therapy.

  2. Endothelial Dysfunction Correlates with Liver Fibrosis in Chronic HCV Infection

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    Michele Barone

    2015-01-01

    Full Text Available Background. Hepatitis C virus (HCV infection can exert proatherogenic activities due to its direct action on vessel walls and/or via the chronic inflammatory process involving the liver. Aims. To clarify the role of HCV in atherosclerosis development in monoinfected HCV patients at different degrees of liver fibrosis and with no risk factors for coronary artery disease. Methods. Forty-five patients were included. Clinical, serological, and anthropometric parameters, liver fibrosis (transient liver elastometry (fibroscan and aspartate aminotransferase to platelet ratio index (APRI, carotid intima-media thickness (c-IMT, and brachial artery flow-mediated vasodilatation (FMD were assessed. Patients were divided into 3 tertiles according to fibroscan values. Results. Patients in the third tertile (fibroscan value >11.5 KPa showed FMD values were significantly lower than second and first tertiles (4.7±1.7% versus 7.1±2.8%, p=0.03. FMD values were inversely related to liver elastomeric values. c-IMT values were normal. The risk for endothelial dysfunction development in the third tertile (p=0.02 was 6.9 higher than the first tertile. A fibroscan value >11.5 KPa had a positive predictive power equal to 79% for endothelial dysfunction. Conclusions. HCV advanced liver fibrosis promotes atherosclerosis by inducing endothelial dysfunction independently of common cardiovascular risk factors.

  3. Function of monocytes in chronic HCV infection: Role for IL-10 and interferon

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    B. Liu (Bi Sheng)

    2011-01-01

    textabstractHepatitis C virus (HCV) establishes persistent infection in about 80% of the infected individuals. The symptoms are initially mild in those persistently infected patients, and it may take decades before the serious consequences of chronic HCV infection become apparent. Up to 20% of infec

  4. Increased microRNA-155 expression in the serum and peripheral monocytes in chronic HCV infection

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    Bala Shashi

    2012-07-01

    Full Text Available Abstract Background Hepatitis C Virus (HCV, a single stranded RNA virus, affects millions of people worldwide and leads to chronic infection characterized by chronic inflammation in the liver and in peripheral immune cells. Chronic liver inflammation leads to progressive liver damage. MicroRNAs (miRNA regulate inflammation (miR-155, -146a and -125b as well as hepatocyte function (miR-122. Methods Here we hypothesized that microRNAs are dysregulated in chronic HCV infection. We examined miRNAs in the circulation and in peripheral monocytes of patients with chronic HCV infection to evaluate if specific miRNA expression correlated with HCV infection. Results We found that monocytes from chronic HCV infected treatment-naïve (cHCV but not treatment responder patients showed increased expression of miR-155, a positive regulator of TNFα, and had increased TNFα production compared to monocytes of normal controls. After LPS stimulation, miR-155 levels were higher in monocytes from cHCV patients compared to controls. MiR-125b, which has negative regulatory effects on inflammation, was decreased in cHCV monocytes compared to controls. Stimulation of normal monocytes with TLR4 and TLR8 ligands or HCV core, NS3 and NS5 recombinant proteins induced a robust increase in both miR-155 expression and TNFα production identifying potential mechanisms for in vivo induction of miR-155. Furthermore, we found increased serum miR-155 levels in HCV patients compared to controls. Serum miR-125b and miR-146a levels were also increased in HCV patients. Serum levels of miR-122 were elevated in cHCV patients and correlated with increased ALT and AST levels and serum miR-155 levels. Conclusion In conclusion, our novel data demonstrate that miR-155, a positive regulator of inflammation, is upregulated both in monocytes and in the serum of patients with chronic HCV infection. Our study suggests that HCV core, NS3, and NS5 proteins or TLR4 and TLR8 ligands can mediate

  5. Prevalence of occult HBV infection in haemodialysis patients with chronic HCV

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    Vedat Goral; Hamza Ozkul; Selahattin Tekes; Dede Sit; Ali Kemal Kadiroglu

    2006-01-01

    AIM: To study the prevalence and clinical effects of occult HBV infection in haemodialysis patients with chronic HCV.METHODS: Fifty chronic hemodialysis patients with negative HbsAg, and positive anti-HCV were included in the study. These patients were divided into two groups:HCV-RNA positive and HCV-RNA negative, based on the results of HCV-RNA PCR. HBV-DNA was studied using the PCR method in both groups.RESULTS: None of the 22 HCV-RNA positive patients and 28 HCV-RNA negative patients revealed HBV-DNA in serum by PCR method. The average age was 47.2 ± 17.0 in the HCV-RNA positive group and 39.6 ± 15.6 in the HCV-RNA negative group.CONCLUSION: The prevalence of occult HBV infection is not high in haemodialysis patients with chronic HCV in our region. This result of our study has to be evaluated in consideration of the interaction between HBsAg positivity (8%-10%) and frequency of HBV mutants in our region.

  6. Broad Anti-Hepatitis C Virus (HCV) Antibody Responses Are Associated with Improved Clinical Disease Parameters in Chronic HCV Infection

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    Swann, Rachael E.; Cowton, Vanessa M.; Robinson, Mark W.; Cole, Sarah J.; Barclay, Stephen T.; Mills, Peter R.; Thomson, Emma C.; McLauchlan, John

    2016-01-01

    ABSTRACT During hepatitis C virus (HCV) infection, broadly neutralizing antibody (bNAb) responses targeting E1E2 envelope glycoproteins are generated in many individuals. It is unclear if these antibodies play a protective or a pathogenic role during chronic infection. In this study, we investigated whether bNAb responses in individuals with chronic infection were associated with differences in clinical presentation. Patient-derived purified serum IgG was used to assess the breadth of HCV E1E2 binding and the neutralization activity of HCV pseudoparticles. The binding and neutralization activity results for two panels bearing viral envelope proteins representing either an intergenotype or an intragenotype 1 group were compared. We found that the HCV load was negatively associated with strong cross-genotypic E1E2 binding (P = 0.03). Overall, we observed only a modest correlation between total E1E2 binding and neutralization ability. The breadth of intergenotype neutralization did not correlate with any clinical parameters; however, analysis of individuals with genotype 1 (gt1) HCV infection (n = 20), using an intragenotype pseudoparticle panel, found a strong association between neutralization breadth and reduced liver fibrosis (P = 0.006). A broad bNAb response in our cohort with chronic infection was associated with a single nucleotide polymorphism (SNP) in the HLA-DQB1 gene (P = 0.038), as previously reported in a cohort with acute disease. Furthermore, the bNAbs in these individuals targeted more than one region of E2-neutralizing epitopes, as assessed through cross-competition of patient bNAbs with well-characterized E2 antibodies. We conclude that the bNAb responses in patients with chronic gt1 infection are associated with lower rates of fibrosis and host genetics may play a role in the ability to raise such responses. IMPORTANCE Globally, there are 130 million to 150 million people with chronic HCV infection. Typically, the disease is progressive and is a

  7. Increased microRNA-155 expression in the serum and peripheral monocytes in chronic HCV infection

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    Bala Shashi; Tilahun Yaphet; Taha Odette; Alao Hawau; Kodys Karen; Catalano Donna; Szabo Gyongyi

    2012-01-01

    Abstract Background Hepatitis C Virus (HCV), a single stranded RNA virus, affects millions of people worldwide and leads to chronic infection characterized by chronic inflammation in the liver and in peripheral immune cells. Chronic liver inflammation leads to progressive liver damage. MicroRNAs (miRNA) regulate inflammation (miR-155, -146a and -125b) as well as hepatocyte function (miR-122). Methods Here we hypothesized that microRNAs are dysregulated in chronic HCV infection. We examined mi...

  8. HCV-RNA positivity in peripheral blood mononuclear cells of patients with chronic HCV-infection: does it really mean viral replication?

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    Volker Meier; Sabine Mihm; Perdita Wietzke-Braun; Guliano Ramadori

    2001-01-01

    AIM To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC)and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication,METHODS HCV-RNA was monitored in serumand PBMC preparations from 15 patients with chronic HCV infection before, during and after an IFN-α therapy using a nested RT/ PCRtechnique. In a second approach, PBMC from healthy donors were incubated in HCV positive plasma.RESULTS In the IFN-α responding patients,HCV-RNA disappeared first from total RNApreparations of PBMC and then from serum. In contrast, in relapsing patients, HCV-RNAreappeared first in serum and then in PBMC. A quantitative analysis of the HCV-RNAconcentration in serum was performed before and after transition from detectable to nondetectable HCV-RNA in PBMC-RNA and vice versa. When HCV-RNA was detectable in PBMCpreparations, the HCV concentration in serum was significantly higher than the serum HCV-RNA concentration when HCV-RNA in PBMC was not detectable. Furthermore, at no time during the observation period was HCV specific RNA observed in PBMC, if HCV-RNA in serum was under the detection limit. Incubation of PBMCfrom healthy donors with several dilutions of HCV positive plasma for two hours showed a concentration-dependent PCR-positivity for HCV-RNA in reisolated PBMC.CONCLUSION The detectability of HCV-RNA in total RNA from PBMC seems to depend on the HCV concentration in serum. Contamination or passive adsorption by circulating virus could be the reason for detection of HCV-RNA in PBMCpreparations of chronically infected patients.

  9. Cyclosporine as Monotherapy for Psoriasis in the Setting of Chronic HCV Infection: A Forgotten Therapeutical Option

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    Alexandra Maria Giovanna Brunasso

    2012-05-01

    Full Text Available Background: Treatment of psoriasis in the setting of chronic hepatitis C virus (HCV infection is diffcult, because standard therapies like methotrexate are associated with increased hepatic toxicity. Due to the HCV suppressive effect. Cyclosporine may represent a valid systemic alternative for psoriatic-HCV patients.Objectives: In this study, we report the successful usage of intermittent cycles of cyclosporine in the setting of chronic HCV infection and we try to call the attention once again in a very effective and forgotten therapeutic option for severe chronic plaque psoriasis.Observation: We describe a 48 years - old patient who has a 20 year history of severe chronic plaque psoriasis and HCV infection (aminotransferase levels are three times normal; HCV genotype 2a-2c and HCV-RNA titer of 2.050.000 UI-ml. Five courses (range of duration of three to six months of oral cyclosporine (5 mg/kg/day were followed during a 38 month period. The viral load and the transaminases’ levels diminished during the 38 months of intermittent cyclosporine therapy to the lowest level measured at 36th month. The good psoriatic response was associated to a slight improvement of the liver condition, even though the HCV-RNA was reduced by less than 1 log10 without normalization of aminotransferase’ levels.Conclusions: The reduced liver toxicity, the potential anti-HCV properties and the well-known systemic anti-inflammatory effect, make cyclosporine a good alternative for recalcitrant psoriatic patients with HCV-liver disease.

  10. Anti-soluble liver antigen (SLA) antibodies in chronic HCV infection.

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    Vitozzi, Susana; Lapierre, Pascal; Djilali-Saiah, Idriss; Marceau, Gabriel; Beland, Kathie; Alvarez, Fernando

    2004-05-01

    Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.

  11. Single Clinical Practice's Report of Testing Initiation, Antibody Clearance, and Transmission of Hepatitis C Virus (HCV) in Infants of Chronically HCV-Infected Mothers.

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    Bal, Aswine; Petrova, Anna

    2016-01-01

    Background.  Perinatally acquired hepatitis C virus (HCV) is the main source of pediatric HCV infection. However, the best time for initiation of screening and follow up of these infants is still unknown. Analysis of the clinical data of infants born to HCV-infected mothers, transmission rates, and pathway of HCV testing could be important for optimization of their management. Methods.  Children of mothers with chronic HCV infection, who were observed between 1998 and 2013 at the pediatric infectious disease clinic for the first 18 months of their life, were eligible for enrollment. We analyzed the factors influencing initiation of HCV testing in these children and rate of HCV transmission as demonstrated by consecutive HCV antibody and HCV ribonucleic acid (RNA) amplification testing. Results.  One hundred and forty-two mother-infant pairs were enrolled. The majority of mothers were intravenous drug users, had carried to term, and delivered vaginally. A high proportion of infants had at least 1 positive anti-HCV antibody assay without viremia. True HCV infection and intermittent viremia were recorded in 3.5% and 1.4% of infants, respectively. Initiation of HCV testing after 10 months of age was associated with a significant decline in the probability of obtaining a positive HCV antibody of maternal origin. Conclusions.  The low likelihood for detection and confirmation of true HCV transmission before 10 months of age could challenge the early initiation of HCV screening of infants exposed to maternal HCV infection but may affect the parental need for early monitoring and counseling. PMID:26985444

  12. Recent advances in managing chronic HCV infection: Focus on therapy in patients with severe liver disease

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    R. Maan (Raoel); A.J.P. van der Meer (Adriaan)

    2016-01-01

    textabstractChronic hepatitis C virus (HCV) infection still represents a major public health problem, as it is thought to be responsible for more than 350,000 deaths around the globe on a yearly basis. Fortunately, successful eradication of the virus has been associated with improved clinical outcom

  13. Factors Associated with Hepatitis C Infection among Chronic HCV Egyptian Patients.

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    Ekram W Abd El-Wahab

    2014-11-01

    Full Text Available Identification of risk factors of acute hepatitis C virus (HCV infection in Egypt is crucial for developing appropriate prevention strategies. There are few community-based studies on the epidemiology and risk factors of hepatitis C infection in Egypt, which could not provide enough information. Clear identification of past and current risk factors for infection is of utmost importance so that intervention programs can be appropriately focused. This study aims to provide up-to-date information about changes in the incidence of individual risk factors for HCV infection transmission in Egypt.A total of 396 chronic HCV patients on follow-up treatment at liver center in El-Qabbary General Hospital in Alexandria were evaluated retrospectively regarding the potential iatrogenic, community acquired and behavioral HCV risk factors. Risk factors for HCV transmission were found in all study populations.At least three identifiable risk factors were reported by each participant. Some behavioral and community-acquired exposures that entail several risky behaviors particularly, unsafe sexual practices were exclusively established among males. We report a significant decline in prevalence of HCV transmission through blood transfusion, parenteral treatment, hospitalization, surgery, non medicalized circumcision, Hijiama done by informal practitioner, tattooing, folk body piercing and threading, sharing hygiene and sharp items, and the use of communal barber or manicure sets among younger age cluster.The pattern of risk differed among older patients compared to younger age group suggesting improved medical care and infection control measures and raised public health awareness regarding the different modes of viral transmission.

  14. Immunogenetic Aspects Of Pathogenesis Of Chronic Hcv-Infection (Review

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    Khamid Karimov

    2012-10-01

    Full Text Available Viral hepatitis B and C is a relevant issue because of high prevalence and degree of chronicity, late diagnosis and poor prognosis. Today, protein products of numerous genes are involved in the pathogenesis of viral pathology of the liver. In this review, the authors analyzed 42 literature sources on genetic basis of susceptibility to various infectious diseases. Study of the role of immunogenetic factors is of great practical importance to develop methods for predicting outcomes of viral hepatitis.

  15. Interferon Response in Hepatitis C Virus (HCV) Infection: Lessons from Cell Culture Systems of HCV Infection.

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    Sung, Pil Soo; Shin, Eui-Cheol; Yoon, Seung Kew

    2015-01-01

    Hepatitis C virus (HCV) is a positive-stranded RNA virus that infects approximately 130-170 million people worldwide. In 2005, the first HCV infection system in cell culture was established using clone JFH-1, which was isolated from a Japanese patient with fulminant HCV infection. JFH-1 replicates efficiently in hepatoma cells and infectious virion particles are released into the culture supernatant. The development of cell culture-derived HCV (HCVcc) systems has allowed us to understand how hosts respond to HCV infection and how HCV evades host responses. Although the mechanisms underlying the different outcomes of HCV infection are not fully understood, innate immune responses seem to have a critical impact on the outcome of HCV infection, as demonstrated by the prognostic value of IFN-λ gene polymorphisms among patients with chronic HCV infection. Herein, we review recent research on interferon response in HCV infection, particularly studies using HCVcc infection systems.

  16. HCV Infection and B-Cell Lymphomagenesis

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    Masahiko Ito

    2011-01-01

    Full Text Available Hepatitis C virus (HCV has been recognized as a major cause of chronic liver diseases worldwide. It has been suggested that HCV infects not only hepatocytes but also mononuclear lymphocytes including B cells that express the CD81 molecule, a putative HCV receptor. HCV infection of B cells is the likely cause of B-cell dysregulation disorders such as mixed cryoglobulinemia, rheumatoid factor production, and B-cell lymphoproliferative disorders that may evolve into non-Hodgkin's lymphoma (NHL. Epidemiological data indicate an association between HCV chronic infection and the occurrence of B-cell NHL, suggesting that chronic HCV infection is associated at least in part with B-cell lymphomagenesis. In this paper, we aim to provide an overview of recent literature, including our own, to elucidate a possible role of HCV chronic infection in B-cell lymphomagenesis.

  17. Assessment of immunological changes in Epstein-Barr virus co-infection in Egyptian chronic HCV patients

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    Sahar Shoman

    2014-09-01

    Full Text Available Epstein-Barr virus (EBV plays a major role in liver pathology. Similar to other members of the herpesvirus family, EBV establishes a persistent infection in more than 90% of adults. The aim of this study was to evaluate the impact of EBV and chronic hepatitis C co-infection (HCV on biochemical and immunological responses in patients. The study was conducted in 62 patients and 33 apparently healthy controls. Patients were divided into three groups: group I, consisting of 31 patients with chronic hepatitis C infection (CHC, group II, consisting of eight patients with EBV infection and without HCV infection and group III, consisting of 23 patients with EBV and chronic HCV. The percentage of CD3+ cells, helper CD4+ cells and CD19+ B-cells was measured by flow cytometry. Human interferon-γ (IFN-γ and interleukin (IL-15 levels were measured by an ELISA. The levels of liver alanine aminotransferase and aspartate aminotransferase enzymes were higher in EBV/HCV patients compared to that in EBV and HCV mono-infected patients. EBV/HCV patients had significantly reduced percentages of CD3+ and CD4+ cells compared to EBV patients. Serum IFN-γ levels were significantly reduced in EBV/HCV patients (3.86 pg/mL compared to CHC patients (6.76 pg/mL and normal controls (4.69 pg/mL. A significant increase in serum IL-15 levels was observed in EBV/HCV patients (67.7 pg/mL compared to EBV patients (29.3 pg/mL. Taken together, these observations suggest that HCV and EBV co-infection can potentiate immune response dampening in patients.

  18. Antiviral Therapy for Chronic HCV Infection: Virological Response and Long-Term Outcome

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    A.J.P. van der Meer (Adriaan)

    2014-01-01

    markdownabstract__Abstract__ Hepatitis C is a major global health problem which is responsible for over 350,000 deaths each year.1 In total, there are thought to be around 150 million hepatitis C virus (HCV) carriers, which comprise about 3% of the world population. The prevalence of HCV infection,

  19. T-cell homeostasis in chronic HCV-infected patients treated with interferon and ribavirin or an interferon-free regimen

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    Hartling, Hans Jakob; Birch, Carsten; Gaardbo, Julie C;

    2015-01-01

    Direct-acting antiviral has replaced pegylated interferon-α and ribavirin-based treatment in the treatment of chronic hepatitis C virus (HCV) infection. While interferon-α is immune modulating and causes lymphopenia, interferon-free regimens seem to be well-tolerated. This study aimed to compare T......-cell homeostasis before, during, and after HCV treatment with or without interferon-α in patients with chronic HCV infection. A total of 20 patients with chronic HCV infection were treated with pegylated interferon-α and ribavirin, and six patients were treated with an interferon-free regimen. All patients were...

  20. CD4⁺ and CD8⁺ regulatory T cells (Tregs) are elevated and display an active phenotype in patients with chronic HCV mono-infection and HIV/HCV co-infection

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    Hartling, H J; Gaardbo, J C; Ronit, A;

    2012-01-01

    The aim of this study was to examine regulatory T cells (Tregs) in peripheral blood and liver tissue in patients with chronic hepatitis C virus (HCV) mono-infection and in patients with HIV/HCV co-infection. In a cross-sectional study were included 51 patients with chronic HCV infection, 24...... patients with HIV/HCV co-infection and 24 healthy individuals. CD4⁺ and CD8⁺ Tregs were determined using flow cytometry. Fibrosis was examined by transient elastography. Inflammation, fibrosis and Tregs were determined in liver biopsies from 12 patients. Increased frequency of CD4⁺ and CD8⁺ Tregs was found...... in HIV/HCV co-infected patients [median: 6.4% (IQR: 5.7-6.9) and 1.0% (0.7-1.2), respectively] compared to HCV mono-infected patients [5.6% (4.2-6.3), P = 0.01 and 0.5% (0.3-0.7), P HCV mono-infected patients had increased frequencies of Tregs compared with healthy...

  1. A New Twist to a Chronic HCV Infection: Occult Hepatitis C

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    Bashar M. Attar

    2015-01-01

    Full Text Available Background. The prevalence of occult hepatitis C infection (OCI in the population of HCV-RNA negative but anti-HCV positive individuals is presently unknown. OCI may be responsible for clinically overt recurrent disease following an apparent sustained viral response (SVR weeks to years later. Purpose. To review the available current literature regarding OCI, prevalence, pathogenic mechanisms, clinical characteristics, and future directions. Data Sources. Searching MEDLINE, article references, and national and international meeting abstracts for the diagnosis of OCI (1990–2014. Data Synthesis. The long-term followup of individuals with an OCI suggests that the infection can be transient with the loss of detectable HCV-RNA in PPBMCs after 12–18 months or alternatively exist intermittently and potentially long term. The ultimate outcome of HCV infection is decided by interplay between host immune responses, antiviral therapies, and the various well-identified viral evasion mechanisms as well as the presence of HCV infection within extrahepatic tissues. Conclusion. The currently widely held assumption of a HCV-cure in individuals having had “SVR” after 8–12 weeks of a course of DAA therapy as recently defined may not be entirely valid. Careful longitudinal followup utilizing highly sensitive assays and unique approaches to viral isolation are needed.

  2. HCV virological response during treatment of chronic hepatitis C is associated with liver histological Improvement in patients with HCV/HIV co-infection

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    Gleusa Castro

    2008-06-01

    Full Text Available Liver histological improvement after treatment for chronic hepatitis C in patients co-infected with human immunodeficiency virus-1 (HIV-1 has been described. Paired liver biopsies in twenty six HCV/HIV co-infected patients were compared to determine factors possibly associated with histological improvement. The patients were submitted to a liver biopsy before treatment for hepatitis C and 25 months after the end of treatment. Fragments of the liver biopsy obtained before and after treatment were compared regarding the following parameters: histological activity index (HAI and degree of fibrosis (Knodell; intensity of collagen deposits (Sirius Red staining and degree of stellate cell activation (alpha-smooth muscle actin labeling. The ratios of the post and pre-treatment variables were related through logistic regression to body mass index (BMI, alcohol ingestion, HCV genotype, HCV viremia, presence of hepatic iron and pre-treatment hepatic steatosis. A negative RNA test in the 24th week of treatment was associated with improvement in fibrosis, collagen deposits and stellate cell numbers. The other variables analyzed did not correlate to an improvement in hepatic histology after hepatitis C treatment. Reduction in HCV viremia during treatment may result in reduced hepatic fibrosis even in patients without a sustained virological response.

  3. Epidemiology of HCV infection.

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    Baldo, V; Baldovin, T; Trivello, R; Floreani, A

    2008-01-01

    It is estimated that approximately 130-170 million people worldwide are infected with hepatitis C virus (HCV). According to data from WHO community and blood donor surveys, the African and Eastern Mediterranean countries report the highest prevalence rates (>10%). The rates of infection in the general population and the incidence of newly-acquired cases indicate an appreciable change in the epidemiology of the infection in recent years. Prior to the widespread screening of blood donations, infected blood and blood products represented a common source of infection. On the other hand, the high peak in HCV antibodies among the elderly in Italian epidemiological studies on the population at large reflects a cohort effect due to an epidemic of HCV infection occurring after the Second World War. According to data reported by the CDC Surveillance System, the incidence of acute hepatitis C has declined since the late 1980s. In 2005, as in previous years, the majority of such cases in North America and Northern Europe occurred among young adults and injected drug use was the most common risk factor. Other, less commonly reported modes of HCV acquisition are occupational exposure to blood, high-risk sexual activity, tattooing, body piercing and other forms of skin penetration. Finally, the overall rate of mother-to-child transmission from HCV-infected, HIV-negative mothers has been estimated at around 5% (coinfection with HIV raises this figure to 19.4%). HCV prevention relies on identifying and counseling uninfected persons at risk of contracting hepatitis C. PMID:18673187

  4. Effect of interferon therapy on radionuclide imaging in chronic liver diseases due to HCV infection

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    Ghaffar, Y.; Dorgham, L.; Lotfy, N. [Ain Shams Univ., Imbaba, Giza (Egypt)]|[Menofia Unif., Shebin El Kom (Egypt)] [and others

    1995-09-01

    Interferon (alpha-IFN) exerts a modulating effect on the immune system. Kupffer cells of the liver play an important immunological role by their uptake of various agents and particles, including colloids. We sought to discover if alpha-IFN could enhance the colloid uptake function of the Kupffer cells. The effect of alpha-IFN therapy on radioisotope scans of the liver was studied in 20 patients with chronic liver disease due to hepatitic C virus (HCV) infection who received therapy at a dose of 3 million IU for 6 mo, in another patients who received the same therapy for 12 mo and in matched control groups (10 patients with HCV infection for each study group) who did not received alpha-IFN. A {sup 99m}Tc-sulfur colloid scan of the liver was obtained for each group before and after therapy and, for control subjects, at the start and end of the study periods. The liver-to-spleen geometric mean ratio of colloid uptake was assessed. In the first study group, the mean rate of improvement in the liver-to-spleen ratio was 48% in 70% of the patients, compared to 8% in 20% of controls (p<0.05). In the second study group, mean liver-to-spleen ratio was 88% in 85% of patients, compared to 12% in 40% of controls (p<0.001). Alpha-IFN therapy appears to enhance the colloidal uptake function of Kupffer cells, which adds a new dimension to the immunomodulatory effect of interferon. 13 refs., 2 tabs.

  5. Rheumatoid Case with HCV Infection

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    Bita Behnava

    2005-03-01

    infection.2- It may be suggested that combination of antiviral treatment with interferon alpha plus ribavirin should be initiated as a part of the therapeutic regimen in HCV-related arthritis. Low dose corticosteroids, NSAIDs or hydroxychloroquine can be added to antiviral drugs.Options in FutureFurther research should be directed toward a better understanding of the pathogenesis of HCV-related arthritis. Also, additional research is needed to determine the optimal treatment of HCV-related arthritis and safety of IFN and anti-tumor agents in these patients.References1. Buskila D. Hepatitis C-associated arthritis. Curr Opin Rheumatol 2000; 12: 295-92. Mc Murry RW, Elbourne K. Hepatitis C virus infection and autoimmunity. Semin Arthritis Rheum 1997; 26: 689-7013. Gordon SC. Extrahepatic manifestations of hepatitis C. Dig Dis 1996; 14: 157-84. Remoroza R, Bonkovsky H. Extrahepatic manifestations of chronic hepatitis C. August 2003, available at www.hcvadvocate.org5. Zuckerman E, Yeshurun D, Rosner I. Management of hepatitis C virus-related arthritis. BioDrugs 2001; 15: 547- 846. Kessel A, Rosner I, Zuckerman E, et al. Use of antikeratin antibodies to distinguish between rheumatoid arthritis and polyarthritis associated with hepatitis C infection. J Rheumatol 2000; 29: 610-27. Lovy MR, Starkebaum G, Uberoi S. Hepatitis C infection presenting with rheumatic manifestations: a mimic of rheumatoid arthritis. J Rheumatol 1996; 23: 979-838. Rivera J, Abergo ID, Pozuelo DE, Alarcon E. Fibromyalgia associated HCV infection. B J Rheumatol 1997; 36: 981-59. Palazzi C, Olivieri I, Cacciatore P, Pennese E, D’Amico E. Management of hepatitis C virus-related arthritis. Expert Opin Pharmacother 2005; 6: 27-3410. Parke FA, Revielle JD. Anti-tumor necrosis factor agents for rheumatoid arthritis in the setting of chronic hepatitis C infection. Arthritis Rheum 2004; 51: 800-411. Peterson JR, Hsu FC, Simkin PA, Wener MH. Effect of tumour necrosis factor alpha antagonists on serum transaminases

  6. Viral genotype and HLA class II alleles influence on extra-hepatic manifestations of chronic HCV infection

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    M. Galeazzi

    2011-09-01

    Full Text Available Objective: To test whether an association between HCV genotype, HLA class II alleles distribution and extra-hepatic manifestations (EHM can be demonstrated in a group of Italian patients with chronic HCV infection . Methods: Sixty patients affected by HCV infection with EHM were consecutively enrolled. 163 HCV patients without EHM were tested as controls for the prevalence of HCV genotypes, while we referred to literature as to the controls for HLA distribution. HCV-RNA was quantified by a RT-PCR. HLA class II alleles typing was performed using a standard microlymphocytotoxicity assay. We used chi-square or Fisher test (p<0.05 significant. Odds Ratio (OR was performed by 2X2 contingency table. Results: HCV 2c genotype was found in 63.46% of patients compared to 19.63% of controls (p<0.0001; OR=7.11. Furthermore, it correlated with carpal tunnel syndrome (p=0.03; OR=4.5 and autoimmune thyroiditis (p=0.02; OR=9.2. On the contrary, 1b genotype protected from EHM in toto (p=0.0004; OR=0.21 and particularly from carpal tunnel syndrome (p=0.0014; OR=0.07. Moreover, 3a genotype prevented HCV people from having cryoglobulinemia (p=0.05; OR=0.11. As to HLA, DR6 seemed to facilitate EHM in HCV patients (p=0.041; OR=1.61, while DQ2 (p=0.03; OR=0.5 and DQ3 (p=0.002; OR= 0.5 may play a protective role. In addition, HLA DR3 was associated with cryoglobulinemia (p=0.02; OR=9.5. Conclusions: According to our findings, 2c genotype can be considered as a major risk factor for developing HCVrelated EHM, while 1b genotype seems to prevent their onset; there are also evidences suggesting that HLA might play a role in chronic HCV infected patients.

  7. Unexpected spontaneous remission of HCV in a patient with chronic HIV infection

    Directory of Open Access Journals (Sweden)

    Roberto Manfredi

    2010-03-01

    Full Text Available We report an exceptional case of resolution of HCV infection in a HIV-infected patient. The patient, a 49-year-old male with history of drugs addiction, suffered from an evolutive liver disease never treated with specific anti-HCV compounds during two decades. The case report highlights a rare phenomenon, seldom reported in medical literature (a PubMed search retrieved only 8 similar cases, and underlines the importance of a deeper investigation of all the virologic, immunological, pathogenetic, and therapeutic implications.

  8. Role of IL-28B polymorphisms in virologic response to combined pegylated interferon and ribavirin therapy in genotype 4 chronic HCV infected patients with and without cirrhosis

    Directory of Open Access Journals (Sweden)

    Amira Youssef Shaala

    2015-09-01

    Conclusion: In Egypt, where chronic HCV genotype 4 and schistosoma coinfection predominate, both schistosoma infection and cirrhosis are more potent than IL28B polymorphisms as strong baseline negative predictors of hepatitis C treatment response.

  9. Chronic polyarthritis in a patient affected by sarcoidosis and chronic HCV infection. Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    A. Carcassi

    2011-09-01

    Full Text Available Sarcoidosis is a systemic granulomatous disease of unknown etiology that has a wide variety of clinical manifestation. Lung involvement may slowly undergo pulmonary fibrosis. Chronic sarcoid arthritis is a rare, usually non destructive arthropathy; may be a mono, oligo or polyarthritis. Knees, ankles, shoulders, wrists and small joint of the hands and feet may be involved. It can involve skin, eyes, exocrine glands such as salivary and lacrimal glands, and many other tissues. We describe the case of a 77 years old woman with a history of rhinopharyngitis with epistaxis and chronic laryngitis since youth; a dry mouth and throat, a erytematous, infiltrative skin lesion in the forehead and in the nape of the neck, a purple lesion of the left ear and nose, skin distrophy of the hands from 30 years before. She underwent an operation for a left femoral fracture with emotrasfusion 14 years ago. Then she developed a polyarthritis of the small joints of the hands (II, III and IV right DIP, I, III, e V left DIP; III and V bilateral PIP, knees, tarsi, toes and left elbow. An HCV chronic hepatitis was discovered 6 years before. She is affected by productive cough, dysphonia, dyspnea at rest, feveret, cephalea and asthenia for over 5 years. Laboratory examination revealed leukopenia, HCV hepatitis with anti HCV, HCV-RNA, transaminases elevated and cryoglobulinemia. HCV may be involved in the etiopathogenesis of rheumatic diseases, lung fibrosis and may moreover contribuite to the onset or progression of sarcoidosis; the possible pathogenesis is discussed.

  10. Patient Characteristics and Prescribing Patterns Associated with Sofosbuvir Treatment for Chronic HCV Infection in a Commercially Insured Population

    Science.gov (United States)

    Tambourine, Brent M.; Sadeghi, Arash; Yang, Jianing; Stockl, Karen M.; Lew, Heidi C.; Solow, Brian K.; Tran, Josephine N.

    2016-01-01

    Background In December 2013, the US Food and Drug Administration (FDA) approved sofosbuvir (Sovaldi) for the treatment of patients with chronic hepatitis C virus (HCV) infection. Given the potential “warehousing” of patients before the launch of sofosbuvir and the possibility that some patients and providers may have elected to continue deferring treatment in anticipation of more promising, interferon-free therapies in the pipeline, the early landscape for sofosbuvir treatment is difficult to ascertain. Objective To describe the demographics, clinical characteristics, and prescribing patterns associated with members requesting treatment with sofosbuvir in a commercially insured population in the United States. Methods A descriptive analysis was conducted using a randomly selected sample of commercially insured members who were identified as having a prior authorization request for sofosbuvir between March and June 2014. Member and provider characteristics, as well as treatment information, were collected using a prior authorization database from OptumRx, a national pharmacy care services company. The results were analyzed using descriptive statistics. Results A total of 338 members were selected for inclusion in the analysis. Chronic HCV genotype 1 infection was present in 74.3% of the members. Chronic HCV genotype 2, 3, or 4 was identified in 13.9%, 9.5%, and 1.2% of the members, respectively. Gastroenterologists and hepatologists accounted for 90% of providers. Among the 251 members with chronic HCV genotype 1, an interferon-free regimen was requested for 59.4% (N = 149) of them; the most frequently requested (51.4%) regimen for members with chronic HCV genotype 1 was the off-label combination of sofosbuvir plus simeprevir. Of the members with chronic HCV genotype 1, 19.1% had liver fibrosis equivalent to METAVIR stage F0 to F2 fibrosis, and 24.7% had liver fibrosis equivalent to METAVIR stage F3 to F4 fibrosis. For the remaining 56.2%, the degree of liver

  11. Evidence for immune selection of hepatitis C virus (HCV) putative envelope glycoprotein variants: potential role in chronic HCV infections.

    Science.gov (United States)

    Weiner, A J; Geysen, H M; Christopherson, C; Hall, J E; Mason, T J; Saracco, G; Bonino, F; Crawford, K; Marion, C D; Crawford, K A

    1992-01-01

    E2/nonstructural protein 1, the putative envelope glycoprotein (gp72) of HCV, possesses an N-terminal hypervariable (E2 HV) domain from amino acids 384 to 414 of unknown significance. The high degree of amino acid sequence variation in the E2 HV domain appears to be comparable to that observed in the human immunodeficiency virus type 1 gp120 V3 domain. This observation and the observation that the HCV E2 HV domain lacks conserved secondary structure imply that, like the V3 loop of human immunodeficiency virus 1 gp120, the N-terminal E2 region may encode protective epitopes that are subject to immune selection. Antibody-epitope binding studies revealed five isolate-specific linear epitopes located in the E2 HV region. These results suggest that the E2 HV domain is a target for the human immune response and that, in addition to the three major groups of HCV, defined by nucleotide and amino acid sequence identity among HCV isolates, E2 HV-specific subgroups also exist. Analysis of the partial or complete E2 sequences of two individuals indicated that E2 HV variants can either coexist simultaneously in a single individual or that a particular variant may predominate during different episodes of disease. In the latter situation, we found one individual who developed antibodies to a subregion of the E2 HV domain (amino acids 396-407) specific to a variant that was predominant during one major episode of hepatitis but who lacked detectable antibodies to the corresponding region of a second variant that was predominant during a later episode of disease. The data suggest that the variability in the E2 HV domain may result from immune selection. The findings of this report could impact vaccine strategies and drug therapy programs designed to control and eliminate HCV. PMID:1314389

  12. ELISA in serodiagnosis of HCV infection.

    Science.gov (United States)

    Pillot, J; Rioche, M; Lazizi, Y

    1994-07-01

    A high level of anti-HCV is generally associated with viral replication and the number of recognized epitopes appears to be correlated with the viral charge. Nevertheless, the absence of detectable antibodies in about 60% of patients during the acute phase of the disease and in 10% of chronically infected (generally immunocompromised subjects) are heavy handicaps for HCV serology. Moreover, low levels of anti-HCV antibodies can persist after complete recovery, and HCV viremia does not appear to be associated with the presence of a special antibody specificity. The immunoblots presented as 'confirmatory test' always appear to be less sensitive than the screening tests and therefore are unable to discriminate between post-infection antibodies and false-positive reactions, as rare as they can be. In these cases, as in non-responder patients, PCR appears essential. The possible reasons of immune response limitations and the possible improvements of HCV serology are discussed. PMID:7522020

  13. Accumulation of Intrahepatic TNF-α-Producing NKp44+ NK Cells Correlates With Liver Fibrosis and Viral Load in Chronic HCV Infection

    Science.gov (United States)

    Nel, Isabelle; Lucar, Olivier; Petitdemange, Caroline; Béziat, Vivien; Lapalus, Martine; Bédossa, Pierre; Debré, Patrice; Asselah, Tarik; Marcellin, Patrick; Vieillard, Vincent

    2016-01-01

    Abstract In the setting of chronic hepatitis C virus (HCV) infection, changes in natural killer (NK) cells have been shown to reflect activation in response to virus stimulation. The contribution of individual natural cytotoxicity receptors to HCV infection remains to be clarified. NKp44 is the sole specific natural cytotoxicity receptor expressed only on activated NK cells. In this study, peripheral blood and liver NK-cell subsets were purified from 31 patients with chronic C hepatitis or nonalcoholic steatohepatitis, and then characterized by flow cytometry. Their polyfunctional activity was determined by expression of the CD107a degranulation marker, together with intracellular cytokine production. Unlike the patients with nonalcoholic steatohepatitis, patients with chronic HCV infection had a higher frequency of NKp44+ NK cells in the liver than in their peripheral blood (P < 0.0001). Intrahepatic NKp44+ NK cells from HCV+ individuals produced higher levels of tumor necrosis factor-α than did NKp44− NK cells (P = 0.0011). Importantly, the frequency of intrahepatic NKp44+ NK cells was correlated with both HCV-RNA levels (P = 0.0234) and stage of fibrosis (P = 0.0003). Our findings suggest that the accumulation of intrahepatic tumor necrosis factor-α-producing NKp44+ resident NK cells play a role in the liver damage associated with chronic HCV infection. PMID:27175704

  14. Usefulness of non-invasive serum markers for predicting liver fibrosis in Egyptian patients with chronic HCV infection.

    Science.gov (United States)

    El Guesiry, Dalal; Moez, Pacinte; Hossam, Nermine; Kassem, Mohamed

    2011-01-01

    Accurate monitoring of liver fibrosis changes in patients with hepatitis C virus (HCV) infection would be helpful in defining the need to intervene, implement the appropriate response in treatment and to minimize the use of liver biopsy. We aimed to evaluate the diagnostic utility of the different serum markers and indices in detecting liver fibrosis in study patients. Initial liver biopsy, routine liver function tests, estimation of hyaluronic acid, MMP-1, and PIIINP levels was performed for 30 Egyptian patients with HCV and 15 controls. Marker algorithms based on common laboratory such APRI score, Fibrotest and Actitest. PIIINP and MMP-1 serum markers were combined and entered into a stepwise logistic regression analysis with formulation of a score equation for fibrosis staging. Combined PIIINP and MMP-1 yielded different cut off scores to estimate two clinically relevant fibrosis stages: "significant fibrosis" versus "extensive fibrosis. Apri score also showed AUC of 1.0 with 100 % sensitivity and specificity to exclude the presence of cirrhosis and was significantly correlated to Metavair fibrosis stage in early fibrosis. On the other hand, PIIINP, Fibrotest and acti test were significantly correlated to Metavair fibrosis stage in both early and late fibrosis. In conclusion, integrating PIIINP/MMP-1 score was able to provide reliable information about the degree of liver fibrosis in chronic hepatitis C patients using different cut-offs values. A combination of liver markers as well as its related indices is an emerging tool to differentiate early from advanced liver fibrosis in HCV patients. PMID:23082465

  15. 77 FR 30293 - Recommendations for the Identification of Hepatitis C Virus (HCV) Chronic Infection

    Science.gov (United States)

    2012-05-22

    ... chronic infection, which places infected persons at risk for liver cirrhosis, liver cancer or... liver disease that ranges in severity from a mild illness lasting a few weeks to a serious, lifelong... health services to prevent additional harm to the liver (e.g., hepatitis A virus and hepatitis B...

  16. CCR5△32 mutation does not influence the susceptibility to HCV infection, severity of liver disease and response to therapy in patients with chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Ankur Goyal; PV Suneetha; GT Kumar; Deepak K Shukla; Naveen Arora; Shiv K Sarin

    2006-01-01

    AIM: To study whether CCR5△32 mutation was associated with viral infection and severity of liver disease.METHODS: Two hundred and fifty two histologically proven, chronic HCV patients (mean age: 41 ± 14 years;M/F: 164/88) were genotyped. PCR based genotyping of 32 bp deletion at the CCR5 locus was done. Fourhundred and eight matched healthy controls were studied to assess susceptibility to HCV infection. To assess correlation of immune gene polymorphism with severity of HCV related liver disease, patients with chronic HCV infection were divided into those with a fibrosis score of ≤ 2 (mild) or > 2 (severe) and histological activity index (HAI) of ≤ 5 or > 5. For correlation between CCR5△32 mutations and response to therapy, 129 patients who completed therapy were evaluated.RESULTS: The majority (89.4%) of the patients were infected with genotype 3. The frequency of homozygous CCR5△32 mutants was comparable to HCV patients as compared to the healthy controls (0.7% vs 0%, P = 0.1).Further more, the frequency of CCR5△32 mutation was comparable in patients with mild or severe liver disease.(P = NS). There was also no association observed with response to therapy and CCR5△32 mutation.CONCLUSION: CCR5△32 mutation does not have a role in disease susceptibility, severity or response to therapy in patients with chronic hepatitis C infection.

  17. Modulation of monocyte/macrophage-derived cytokine and chemokine profile by persistent Hepatitis C virus (HCV infection leads to chronic inflammation

    Directory of Open Access Journals (Sweden)

    Penelope Mavromara

    2012-02-01

    Full Text Available HCV infection presents a major public health problem, with more than 170 million people infected worldwide. Chronicity and persistence of infection constitute the hallmark of the disease. Although HCV is a hepatotropic virus, subsets of immune cells have been found to be permissive to infection and viral replication. Peripheral blood monocytes, attracted to the site of infection and differentiated into macrophages, and resident hepatic macrophages, known as Kupffer cells, are important mediators of innate immunity, through production of several chemokines and cytokines in addition to their phagocytic activity. HCV proteins have been shown to modulate the cytokine and chemokine production profile of monocytes/macrophages, as it is suggested by both in vitro and clinical studies. This modified expression profile appears crucial for the establishment of aberrant inflammation that leads to liver cirrhosis and hepatocellular carcinoma.

  18. Early quantification of HCV core antigen may help to determine the duration of therapy for chronic genotype 2 or 3 HCV infection

    DEFF Research Database (Denmark)

    Alsiö, A; Jannesson, A; Langeland, N;

    2012-01-01

    The aim of the present study was to evaluate the utility of hepatitis C virus (HCV) core antigen (coreAg) assessment for the identification of candidates for short-term therapy. Plasma samples from HCV genotype 2 or 3-infected patients participating in the NORDynamIC trial (n = 382) comparing 12...... and 24 weeks of combination treatment with pegylated interferon-α2a and a fixed dose of 800 mg ribavirin daily were analyzed for coreAg. Among the 126 patients (33% of the intention-to-treat population) achieving HCV coreAg levels in plasma below 0.2 pg/mL when assayed on treatment day 3, sustained viral...... were 89% and 95%, respectively. Twelve weeks of combination treatment may be sufficient for genotype 2 or 3-infected patients achieving HCV coreAg levels below 0.2 pg/mL by day 3, signaling a rapid clearance of HCV viremia....

  19. The influence of HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV-positive individuals

    Directory of Open Access Journals (Sweden)

    Vogel M

    2010-03-01

    Full Text Available Abstract Objective This study was performed to investigate the impact of HAART versus no HAART and nucleoside free versus nucleoside containing HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV/HCV co-infected patients. In addition a control group of HCV mono-infected patients undergoing anti-HCV therapy was evaluated. Methods Multicenter, partially randomized, controlled clinical trial. HIV-negative and -positive patients with chronic HCV infection were treated with pegylated interferon alfa-2a and ribavirin (800 - 1200 mg/day for 24 - 48 weeks in one of four treatment arms: HIV-negative (A, HIV-positive without HAART (B and HIV-positive on HAART (C. Patients within arm C were randomized to receive open label either a nucleoside containing (C1 or a nucleoside free HAART (C2. Results 168 patients were available for analysis. By intent-to-treat analysis similar sustained virological response rates (SVR, negative HCV-RNA 24 weeks after the end of therapy were observed comparing HIV-negative and -positive patients (54% vs. 54%, p = 1.000. Among HIV-positive patients SVR rates were similar between patients off and on HAART (57% vs. 52%, p = 0.708. Higher SVR rates were observed in patients on a nucleoside free HAART compared to patients on a nucleoside containing HAART, though confounding could not be ruled out and in the intent-to-treat analysis the difference was not statistically significant (64% vs. 46%, p = 0.209. Conclusions Similar response rates for HCV therapy can be achieved in HIV-positive and -negative patients. Patients on nucleoside free HAART reached at least equal rates of sustained virological response compared to patients on standard HAART.

  20. Effect of oral care gel on the quality of life for oral lichen planus in patients with chronic HCV infection

    OpenAIRE

    Sata Michio; Nagao Yumiko

    2011-01-01

    Abstract Background Oral lichen planus (OLP) decreases the quality of life because it can cause spontaneous pain during eating and tooth-brushing and an uncomfortable feeling in the mouth. In addition, OLP may be associated with HCV-related liver disease. We investigated the visual analogue scale (VAS) and effects of oral care gel, REFRECARE-H®, on patients with OLP associated with HCV infection. Results Nine OLP patients (mean age 67.9 ± 7.6 years) with HCV-related liver diseases were recrui...

  1. Personality disorders do not affect treatment outcomes for chronic HCV infection in Spanish prisoners: the Perseo study

    OpenAIRE

    Marco, Andrés; Antón, José J.; Trujols, Joan; Saíz de la Hoya, Pablo; Juan, José; Faraco, Inmaculada; Caylà, Joan A; ,

    2015-01-01

    Background The link between infection with hepatitis C virus (HCV) and personality disorders (PD) has not been investigated in detail. The aim of this study was to compare the effectiveness of HCV treatment in prisoners with and without PD. Methods We performed a prospective multicentre study in inmates from 25 Spanish prisons who had been treated with pegylated interferon alfa-2a plus ribavirin in 2011. PD diagnosis was based on the Personality Diagnostic Questionnaire-4+. We calculated adju...

  2. Highly-Immunogenic Virally-Vectored T-cell Vaccines Cannot Overcome Subversion of the T-cell Response by HCV during Chronic Infection.

    Science.gov (United States)

    Swadling, Leo; Halliday, John; Kelly, Christabel; Brown, Anthony; Capone, Stefania; Ansari, M Azim; Bonsall, David; Richardson, Rachel; Hartnell, Felicity; Collier, Jane; Ammendola, Virginia; Del Sorbo, Mariarosaria; Von Delft, Annette; Traboni, Cinzia; Hill, Adrian V S; Colloca, Stefano; Nicosia, Alfredo; Cortese, Riccardo; Klenerman, Paul; Folgori, Antonella; Barnes, Eleanor

    2016-01-01

    An effective therapeutic vaccine for the treatment of chronic hepatitis C virus (HCV) infection, as an adjunct to newly developed directly-acting antivirals (DAA), or for the prevention of reinfection, would significantly reduce the global burden of disease associated with chronic HCV infection. A recombinant chimpanzee adenoviral (ChAd3) vector and a modified vaccinia Ankara (MVA), encoding the non-structural proteins of HCV (NSmut), used in a heterologous prime/boost regimen induced multi-specific, high-magnitude, durable HCV-specific CD4+ and CD8+ T-cell responses in healthy volunteers, and was more immunogenic than a heterologous Ad regimen. We now assess the immunogenicity of this vaccine regimen in HCV infected patients (including patients with a low viral load suppressed with interferon/ribavirin therapy), determine T-cell cross-reactivity to endogenous virus, and compare immunogenicity with that observed previously in both healthy volunteers and in HCV infected patients vaccinated with the heterologous Ad regimen. Vaccination of HCV infected patients with ChAd3-NSmut/MVA-NSmut was well tolerated. Vaccine-induced HCV-specific T-cell responses were detected in 8/12 patients; however, CD4+ T-cell responses were rarely detected, and the overall magnitude of HCV-specific T-cell responses was markedly reduced when compared to vaccinated healthy volunteers. Furthermore, HCV-specific cells had a distinct partially-functional phenotype (lower expression of activation markers, granzyme B, and TNFα production, weaker in vitro proliferation, and higher Tim3 expression, with comparable Tbet and Eomes expression) compared to healthy volunteers. Robust anti-vector T-cells and antibodies were induced, showing that there is no global defect in immunity. The level of viremia at the time of vaccination did not correlate with the magnitude of the vaccine-induced T-cell response. Full-length, next-generation sequencing of the circulating virus demonstrated that T-cells were

  3. Highly-Immunogenic Virally-Vectored T-cell Vaccines Cannot Overcome Subversion of the T-cell Response by HCV during Chronic Infection

    Directory of Open Access Journals (Sweden)

    Leo Swadling

    2016-08-01

    Full Text Available An effective therapeutic vaccine for the treatment of chronic hepatitis C virus (HCV infection, as an adjunct to newly developed directly-acting antivirals (DAA, or for the prevention of reinfection, would significantly reduce the global burden of disease associated with chronic HCV infection. A recombinant chimpanzee adenoviral (ChAd3 vector and a modified vaccinia Ankara (MVA, encoding the non-structural proteins of HCV (NSmut, used in a heterologous prime/boost regimen induced multi-specific, high-magnitude, durable HCV-specific CD4+ and CD8+ T-cell responses in healthy volunteers, and was more immunogenic than a heterologous Ad regimen. We now assess the immunogenicity of this vaccine regimen in HCV infected patients (including patients with a low viral load suppressed with interferon/ribavirin therapy, determine T-cell cross-reactivity to endogenous virus, and compare immunogenicity with that observed previously in both healthy volunteers and in HCV infected patients vaccinated with the heterologous Ad regimen. Vaccination of HCV infected patients with ChAd3-NSmut/MVA-NSmut was well tolerated. Vaccine-induced HCV-specific T-cell responses were detected in 8/12 patients; however, CD4+ T-cell responses were rarely detected, and the overall magnitude of HCV-specific T-cell responses was markedly reduced when compared to vaccinated healthy volunteers. Furthermore, HCV-specific cells had a distinct partially-functional phenotype (lower expression of activation markers, granzyme B, and TNFα production, weaker in vitro proliferation, and higher Tim3 expression, with comparable Tbet and Eomes expression compared to healthy volunteers. Robust anti-vector T-cells and antibodies were induced, showing that there is no global defect in immunity. The level of viremia at the time of vaccination did not correlate with the magnitude of the vaccine-induced T-cell response. Full-length, next-generation sequencing of the circulating virus demonstrated that T

  4. Highly-Immunogenic Virally-Vectored T-cell Vaccines Cannot Overcome Subversion of the T-cell Response by HCV during Chronic Infection

    Science.gov (United States)

    Swadling, Leo; Halliday, John; Kelly, Christabel; Brown, Anthony; Capone, Stefania; Ansari, M. Azim; Bonsall, David; Richardson, Rachel; Hartnell, Felicity; Collier, Jane; Ammendola, Virginia; Del Sorbo, Mariarosaria; Von Delft, Annette; Traboni, Cinzia; Hill, Adrian V. S.; Colloca, Stefano; Nicosia, Alfredo; Cortese, Riccardo; Klenerman, Paul; Folgori, Antonella; Barnes, Eleanor

    2016-01-01

    An effective therapeutic vaccine for the treatment of chronic hepatitis C virus (HCV) infection, as an adjunct to newly developed directly-acting antivirals (DAA), or for the prevention of reinfection, would significantly reduce the global burden of disease associated with chronic HCV infection. A recombinant chimpanzee adenoviral (ChAd3) vector and a modified vaccinia Ankara (MVA), encoding the non-structural proteins of HCV (NSmut), used in a heterologous prime/boost regimen induced multi-specific, high-magnitude, durable HCV-specific CD4+ and CD8+ T-cell responses in healthy volunteers, and was more immunogenic than a heterologous Ad regimen. We now assess the immunogenicity of this vaccine regimen in HCV infected patients (including patients with a low viral load suppressed with interferon/ribavirin therapy), determine T-cell cross-reactivity to endogenous virus, and compare immunogenicity with that observed previously in both healthy volunteers and in HCV infected patients vaccinated with the heterologous Ad regimen. Vaccination of HCV infected patients with ChAd3-NSmut/MVA-NSmut was well tolerated. Vaccine-induced HCV-specific T-cell responses were detected in 8/12 patients; however, CD4+ T-cell responses were rarely detected, and the overall magnitude of HCV-specific T-cell responses was markedly reduced when compared to vaccinated healthy volunteers. Furthermore, HCV-specific cells had a distinct partially-functional phenotype (lower expression of activation markers, granzyme B, and TNFα production, weaker in vitro proliferation, and higher Tim3 expression, with comparable Tbet and Eomes expression) compared to healthy volunteers. Robust anti-vector T-cells and antibodies were induced, showing that there is no global defect in immunity. The level of viremia at the time of vaccination did not correlate with the magnitude of the vaccine-induced T-cell response. Full-length, next-generation sequencing of the circulating virus demonstrated that T-cells were

  5. Association between IL28B rs12979860 single nucleotide polymorphism and the frequency of colonic Treg in chronically HCV-infected patients.

    Science.gov (United States)

    Mehta, Minesh; Hetta, Helal F; Abdel-Hameed, Enass A; Rouster, Susan D; Hossain, MdMonir; Mekky, Mohamed A; Khalil, Nasr K; Mohamed, Wegdan A; El-Feky, Mohamed A; Ahmed, Shabaan H; Daef, Enas A; El-Mokhtar, Mohamed A; Abdelwahab, Sayed F; Medhat, Ahmed; Sherman, Kenneth E; Shata, Mohamed Tarek M

    2016-11-01

    The IL28B gene is associated with spontaneous or treatment-induced HCV viral clearance. However, the mechanism by which the IL28B single nucleotide polymorphism (SNP) affects the extra-hepatic HCV immune responses and its relationship to HCV pathogenesis have not been thoroughly investigated. To examine the mechanism by which IL28B affects HCV clearance. Forty Egyptian patients with chronic HCV infection receiving an Interferon/ribavirin treatment regimen were enrolled into this study. There were two groups: non-responders (NR; n = 20) and sustained virologic responders (SVR; n = 20). The initial plasma HCV viral loads prior to treatment and IL28B genotypes were determined by quantitative RT-PCR and sequencing, respectively. Liver biopsies were examined to determine the inflammatory score and the stage of fibrosis. Colonic regulatory T cell (Treg) frequency was estimated by immunohistochemistry. No significant association between IL28B genotypes and response to therapy was identified, despite an odds ratio of 3.4 to have the TT genotype in NR compared to SVR (95 % confidence interval 0.3-35.3, p = 0.3). Patients with the TT-IL28Brs12979860 genotype (unfavorable genotype) have significantly higher frequencies of colonic Treg compared to the CT (p = 0.04) and CC (p = 0.03) genotypes. The frequency of colonic Treg cells in HCV-infected patients had a strong association with the IL-28B genotype and may have a significant impact on HCV clearance.

  6. Alcohol and HCV Chronic Infection Are Risk Cofactors of Type 2 Diabetes Mellitus for Hepatocellular Carcinoma in Italy

    Directory of Open Access Journals (Sweden)

    Massimiliano Balbi

    2010-03-01

    Full Text Available Type 2 diabetes mellitus (DM2 has been associated with hepatocellular carcinoma (HCC development. To study this relationship, we enrolled 465 HCC patients compared with 618 Cirrhotic cases and 490 Controls. The prevalence of DM2 is significantly higher in HCC patients with an Odds Ratio of 3.12 versus Controls. In HCC cases with alcohol abuse, the frequency of DM2 is the highest. In our HCC patients, when HCV infection is associated with alcohol abuse, the liver cancer develops earlier. In addition, multivariate analysis shows that alcohol consumption is an independent risk factor for HCC more relevant than HCV infection.

  7. Undetectable hepatitis C virus RNA during syphilis infection in two HIV/HCV-co-infected patients

    DEFF Research Database (Denmark)

    Salado-Rasmussen, Kirsten; Knudsen, Andreas; Krarup, Henrik Bygum;

    2014-01-01

    BACKGROUND: Treponema pallidum, the causative agent of syphilis, elicits a vigorous immune response in the infected host. This study sought to describe the impact of syphilis infection on hepatitis C virus (HCV) RNA levels in patients with HIV and chronic HCV infection. METHODS: Patients...... with chronic HIV/HCV and syphilis co-infection were identified by their treating physicians from 1 October 2010 to 31 December 2013. Stored plasma samples obtained before, during, and after syphilis infection were analysed for interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor alpha (TNF......-α), interferon gamma (IFN-γ), and IFN-γ-inducible protein 10 kDa (IP-10). RESULTS: Undetectable HCV RNA at the time of early latent syphilis infection was observed in 2 patients with HIV and chronic HCV infection. After treatment of the syphilis infection, HCV RNA levels increased again in patient 1, whereas...

  8. Relation between C.32 A>T Polymorphism In TLR7 and Response to Treatment in Chronic HCV-Infection

    Directory of Open Access Journals (Sweden)

    SA Taghavi

    2009-07-01

    (p=0.046. Conclusion: c.32A>T single nucleotide polymorphism of TLR-7, by impairment of TLR-7 function, can be considered among host factors that had unfavorable effect on response rate to treatment of patients with chronic HCV hepatitis. Keywords: Hepatitis C virus, Toll like receptor 7 (TLR7, Sustained Virologic Response, End treatment response (ETR

  9. Intracellular expression of the proliferative marker Ki-67 and viral proteins (NS3, NS5A and C in chronic, long lasting hepatitis C virus (HCV infection.

    Directory of Open Access Journals (Sweden)

    Karolina Olejniczak

    2008-01-01

    Full Text Available Hepatitis C virus (HCV continues to represent the main causative agent of the hepatitis, which leads to chronic transformation of the process in 60-80% individuals. It remains unclear how far cellular expression of HCV proteins in vivo may represent an index of progression of the disease and of proliferative activity in the liver in chronic hepatitis C. Aim of the studies included detection and subcellular localization of three HCV proteins (NS3, NS5A and C in liver biopsies from adults (n=19 with chronic, long lasting hepatitis C as related to hepatocyte proliferative activity. The immunocytochemical ABC (avidin biotin-peroxidase complex technique was applied, alone or associated with the ImmunoMax technique. Results of the immunocytochemical tests were compared to histological alterations in liver biopsies, proliferation index and with selected clinical data. A significantly higher expression of NS3 protein was noted, as compared to expressions of NS5A and C proteins. In all the patients, cytoplasmic localization of all proteins dominated over nuclear localization (p0.05. At the level of electron microscopy, protein localization in endoplasmic reticulum (ER membranes, mitochondria, perinuclear region and/or in hepatocyte cell nucleus was observed. No direct relationships could be demonstrated between expressions of HCV proteins and of Ki-67 antigen. No correlations could also be demonstrated between cellular expression of any HCV protein on one hand and grading or staging, alanine transaminase (ALT, serum level of HCV RNA or alpha-fetoprotein (AFP on the other. However, positive correlations were disclosed between proliferative activity of hepatocytes on one hand and patient's age, grading and staging on the other. Advanced hepatic fibrosis correlated also with serum levels of AFP. The studies were supplemented with data on subcellular localization of HCV proteins. Moreover, they indicated that in HCV infection grading and staging

  10. Addressing HCV infection in Europe: reported, estimated and undiagnosed cases

    DEFF Research Database (Denmark)

    Merkinaite, Simona; Lazarus, Jeff; Gore, Charles

    2008-01-01

    The hepatitis C virus (HCV) is a major public health problem due to its high prevalence, high rate of onward transmission and health complications. As many as 85% of people infected with HCV may go on to become chronic carriers of the disease with the risk of developing liver cancer or cirrhosis...... cirrhosis and liver cancer. Additionally, as previous studies in central and eastern Europe show, evidence-based measures to prevent and manage HCV among IDUs, where most current transmission is concentrated, remain limited. Therefore, there is a strong need for intensified advocacy to put HCV higher...

  11. 增强丙型肝炎病毒DNA疫苗免疫原性的策略%Progress in the development and immunogenicity improvement of DNA vaccine against chronic HCV infection

    Institute of Scientific and Technical Information of China (English)

    殷霄; 文波; 谭文杰

    2011-01-01

    当前全世界有超过1.7亿慢性丙型肝炎(CHC)感染者,目前尚无有效的疫苗.最近丙型肝炎病毒(HCV)实验性疫苗的研制有不少进展.本文综述了增强HCV DNA疫苗免疫原性的策略及相关进展.%More than 170 million people are currently affected by chronic hepatitis C virus (HCV) infection worldwide. Currently,there is no vaccine available. There are many HCV experimental vaccines developed and progressed recently. Here, we would discuss strategies of enhancing immunogenicity of DNA vaccine and review some progress towards development of DNA vaccine against chronic HCV infection.

  12. High prevalence of human parvovirus 4 infection in HBV and HCV infected individuals in shanghai.

    Science.gov (United States)

    Yu, Xuelian; Zhang, Jing; Hong, Liang; Wang, Jiayu; Yuan, Zhengan; Zhang, Xi; Ghildyal, Reena

    2012-01-01

    Human parvovirus 4 (PARV4) has been detected in blood and diverse tissues samples from HIV/AIDS patients who are injecting drug users. Although B19 virus, the best characterized human parvovirus, has been shown to co-infect patients with hepatitis B or hepatitis C virus (HBV, HCV) infection, the association of PARV4 with HBV or HCV infections is still unknown.The aim of this study was to characterise the association of viruses belonging to PARV4 genotype 1 and 2 with chronic HBV and HCV infection in Shanghai.Serum samples of healthy controls, HCV infected subjects and HBV infected subjects were retrieved from Shanghai Center for Disease Control and Prevention (SCDC) Sample Bank. Parvovirus-specific nested-PCR was performed and results confirmed by sequencing. Sequences were compared with reference sequences obtained from Genbank to derive phylogeny trees.The frequency of parvovirus molecular detection was 16-22%, 33% and 41% in healthy controls, HCV infected and HBV infected subjects respectively, with PARV4 being the only parvovirus detected. HCV infected and HBV infected subjects had a significantly higher PARV4 prevalence than the healthy population. No statistical difference was found in PARV4 prevalence between HBV or HCV infected subjects. PARV4 sequence divergence within study groups was similar in healthy subjects, HBV or HCV infected subjects.Our data clearly demonstrate that PARV4 infection is strongly associated with HCV and HBV infection in Shanghai but may not cause increased disease severity.

  13. Cryoglobulinemia in elderly patients with HCV-related chronic hepatitis

    Institute of Scientific and Technical Information of China (English)

    Francesco; Giuseppe; Foschi; Anna; Chiara; Dall’Aglio; Arianna; Lanzi; Giorgio; Marano; Sara; Savini; Pietro; Andreone; Mauro; Bernardi; Giuseppe; Francesco; Stefanini

    2010-01-01

    Hepatitis C virus(HCV) infection affects about 3% of the world’s population and often leads to chronic liver disease.In some industrialized countries,HCV prevalence increases with age,but the optimal management of older patients has not been accurately defined.HCV infection can also lead to lymphoproliferative disorders,the most common being mixed cryoglobulinemia(MC),and also for this condition that frequently affects elderly patients,the optimal therapeutic strategy is still debated.We report the case of a 77-year-old Caucasian woman with HCV-related chronic hepatitis and cutaneous manifestations consisting of urticaria and pruritus related to MC resistant to antihistamines.The patient underwent a treatment with interferon and ribavirin.Such a treatment led to early biochemical and virological response associated with the resolution of cryoglobulinemia and cutaneous symptoms.After the end of treatment,HCV replication relapsed,but cryoglobulinemia and cutaneous symptoms did not recur.In the absence of definite treatment guidelines in this particular context,our experience suggests that the presence of symptoms related to HCV-infection that deeply affect patient quality of life warrants antiviral therapy even beyond the age limits that currently exclude patients from treatment.

  14. Raltegravir, tenofovir, and emtricitabine in an HIV-Infected patient with HCV chronic hepatitis, NNRTI intolerance and protease inhibitors-induced severe liver Toxicity

    Directory of Open Access Journals (Sweden)

    Ortu F

    2010-02-01

    Full Text Available Abstract Background in HIV-infected patients with HCV-related chronic hepatitis, liver impairment and drug toxicity may substantially reduce the number of possible therapeutic options. Case Description we here describe the case of an HCV-HIV coinfected woman who had repeated severe episodes of drug-related liver toxicity with indinavir, saquinavir, fosamprenavir, and darunavir, with minimal further therapeutic options left in this class. Previous treatment-limiting side effects with efavirenz and nevirapine also precluded use of non-nucleoside reverse transcriptase inhibitors. Introduction of an integrase-inhibitor regimen based on raltegravir, tenofovir, and emtricitabine allowed a prompt achievement of undetectable viral load and a substantial rise of CD4 count to high levels, with no subsequent episodes of hepatic toxicity, and no other side effects. Conclusions given the relatively common prevalence of HCV-related chronic hepatitis among people with HIV, raltegravir might represent an important alternative option for a substantial number of patients who cannot be treated with protease inhibitors or NNRTI because of drug-related hepatic toxicity.

  15. Drug Authorization for Sofosbuvir/Ledipasvir (Harvoni for Chronic HCV Infection in a Real-World Cohort: A New Barrier in the HCV Care Cascade.

    Directory of Open Access Journals (Sweden)

    Albert Do

    Full Text Available New treatments for hepatitis C (HCV infection hold great promise for cure, but numerous challenges to diagnosing, establishing care, and receiving therapy exist. There are limited data on insurance authorization for these medications.We performed a retrospective chart review of patients receiving sofosbuvir/ledipasvir (SOF/LED from October 11-December 31, 2014 to determine rates and timing of drug authorization. We also determined predictors of approval, and those factors associated with faster decision and approval times.Of 174 patients prescribed HCV therapy during this period, 129 requests were made for SOF/LED, of whom 100 (77.5% received initial approval, and an additional 17 patients (13.9% ultimately received approval through the appeals process. Faster approval times were seen in patients with Child-Pugh Class B disease (14.4 vs. 24.7 days, p = 0.048. A higher proportion of patients were initially approved in those with Medicare/Medicaid coverage (92.2% vs. 71.4%, p = 0.002 and those with baseline viral load ≥ 6 million IU/mL (84.1% vs. 62.5%, p = 0.040. Linear regression modeling identified advanced fibrosis, high Model of End Stage Liver Disease (MELD score, and female gender as significant predictors of shorter decision and approval times. On logistic regression, Medicare/Medicaid coverage (OR 5.96, 95% CI 1.66-21.48 and high viral load (OR 4.52, 95% CI 1.08-19.08 were significant predictors for initial approval.Early analysis of real-world drug authorization outcomes between October-December 2014 reveals that nearly one in four patients are initially denied access to SOF/LED upon initial prescription, although most patients are eventually approved through appeal, which delays treatment initiation. Having Medicare/Medicaid and advanced liver disease resulted in a higher likelihood of approval as well as earlier decision and approval times. More studies are needed to determine factors resulting in higher likelihood of denial and to

  16. Prevalence of mixed hepatitis C virus (HCV genotypes among recently diagnosed dialysis patients with HCV infection

    Directory of Open Access Journals (Sweden)

    Mohammed A Al Balwi

    2011-01-01

    Full Text Available Hepatitis C virus (HCV infection is considered a major health problem recognized globally. HCV is a major cause of chronic liver disease that may lead to cirrhosis and hepatocellular carcinoma. The aim of this study was to investigate the prevalence of multiple (mixed HCV genotypes in Saudi patients recently diagnosed with HCV infection and their association with various clinical risk factors. We examined a total of 1,292 newly diagnosed HCV-positive cases between January 2006 and July 2009 at the Molecular Pathology Laboratory, King Abdulaziz Medical City, Riyadh. The clinical and laboratory data of the study patients were collected. The HCV-RNA viral load and its genotyping were carried out with RT-PCR technology to assist in the follow-up and management of HCV-infected patients undergoing antiviral therapy. Twenty-two patients (1.7% were found to have mixed HCV genotypes; of them, mixed genotypes associated with genotype-4 were seen in 19 patients (86%, mixed genotypes associated with genotype-1 were found in 68.4%, with genotype-3 in 26.3% and with genotype-2 in 5.3%. Additionally, mixed genotypes associated with genotype-1 were seen in three cases (13.6%; they were associated with genotype-2 in two (66.7% and with genotype-5 in one patient (33.3%. In conclusion, the prevalence rate of mixed HCV genotypes in the cohort of the newly infected Saudi patients was 1.7%, with genotype-4 being the most frequent genotype encountered.

  17. SNP rs8099917 in Gene IL28B Might Be Associated with Risk of Chronic Infection by HCV but Not with Response to Treatment

    Directory of Open Access Journals (Sweden)

    Simone Regina Souza da Silva Conde

    2014-01-01

    Full Text Available Aim. The aim of this study was to characterize the genetic profile of patients with chronic hepatitis C virus (HCV infection relative to polymorphisms rs12979860 and rs8099917 in gene IL28B and the association of those polymorphisms with the response to treatment with pegylated interferon and ribavirin, performed at a reference center in Brazilian Amazonia. Methods. A total of 75 individuals with chronic hepatitis C and 98 healthy individuals from both genders over 18 years old were assessed. DNA samples were collected from leukocytes and subjected to real-time polymerase chain reaction to genotype polymorphisms rs12979860 and rs8099917. Results. Analysis of the allelic and genotypic frequencies of the investigated polymorphisms showed that both groups were in Hardy-Weinberg equilibrium; polymorphism rs12979860 exhibited no significant difference between the groups. For polymorphism rs8099917, allele T was significantly less frequent (P=0.0195 among the patients (63.3% than the controls (75.5%, and the patients were 1.7 times as likely to exhibit allele G. No difference in response to treatment was associated with SNP patterns. Conclusion. The results suggest a possible association of SNP rs8099917 with higher odds of chronic HCV infection but do not indicate a putative influence of the investigated SNPs on the sustained virologic response.

  18. The natural course of hepatitis C virus infection after 22 years in a unique homogenous cohort: spontaneous viral clearance and chronic HCV infection

    OpenAIRE

    Barrett, S; Goh, J; Coughlan, B; Ryan, E.; Stewart, S; Cockram, A; O'Keane, J; Crowe, J

    2001-01-01

    BACKGROUND/AIMS—The cohort of Irish women infected with hepatitis C virus (HCV) genotype 1b via contaminated anti-D immunoglobulin in 1977 represent a unique homogenous group to investigate the natural course of HCV infection.
METHODS—The clinical status of 87 polymerase chain reaction (PCR) positive and 68 PCR negative women was investigated at diagnosis (1994/95) and after 4-5 years of follow up (21/22 years after inoculation). Other features investigated included: histological status/progr...

  19. Effect of oral care gel on the quality of life for oral lichen planus in patients with chronic HCV infection

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    Sata Michio

    2011-07-01

    Full Text Available Abstract Background Oral lichen planus (OLP decreases the quality of life because it can cause spontaneous pain during eating and tooth-brushing and an uncomfortable feeling in the mouth. In addition, OLP may be associated with HCV-related liver disease. We investigated the visual analogue scale (VAS and effects of oral care gel, REFRECARE-H®, on patients with OLP associated with HCV infection. Results Nine OLP patients (mean age 67.9 ± 7.6 years with HCV-related liver diseases were recruited and their VAS score determined along with a biochemical examination of the blood. Types of OLP included erosive (6 patients and reticular (3. REFRECARE-H®, an oral care gel (therapeutic dentifrice containing hinokitiol, was applied by each patient as a thin layer on the oral membrane, after each meal and at bedtime for 30 days. Application of REFRECARE-H® improved the quality of life in all terms of dry mouth, breath odor, oral freshness, oral pain during rest, oral pain at a mealtimes, taste disorder, loss of appetite, sleep disorder, depressive mood and jitteriness. VAS scores of dry mouth, breath odor, oral freshness, and sleep disorder were significantly increased 30 days after application of REFRECARE-H® (P = 0.01, P = 0.05, P = 0.03, P = 0.04. VAS scores of oral pain at a mealtimes and taste disorder were increased 30 days after application of REFRECARE-H® (P = 0.06. There was an absence of side effects. Conclusions REFRECARE-H® improved the quality of life for OLP. It is necessary for the hepatologist to educate patients regarding oral hygiene, as well as provide treatment of liver disease.

  20. Prevalence of hepatitis C virus (HCV infection and HCV genotypes of hemodialysis patients in Salvador, Northeastern Brazil

    Directory of Open Access Journals (Sweden)

    Silva L.K.

    2006-01-01

    Full Text Available Hepatitis C virus (HCV infection has been identified as the major cause of chronic liver disease among patients on chronic hemodialysis (HD, despite the important reduction in risks obtained by testing candidate blood donors for anti-HCV antibodies and the use of recombinant erythropoietin to treat anemia. A cross-sectional study was performed to estimate the prevalence of HCV infection and genotypes among HD patients in Salvador, Northeastern Brazil. Anti-HCV seroprevalence was determined by ELISA in 1243 HD patients from all ten different dialysis centers of the city. HCV infection was confirmed by RT-PCR and genotyping was performed by restriction fragment length polymorphism. Anti-HCV seroprevalence among HD patients was 10.5% (95% CI: 8.8-12.3 (Murex anti-HCV, Abbott Murex, Chicago, IL, USA. Blood samples for qualitative HCV detection and genotyping were collected from 125/130 seropositive HD patients (96.2%. HCV-RNA was detected in 92/125 (73.6% of the anti-HCV-positive patients. HCV genotype 1 (77.9% was the most prevalent, followed by genotype 3 (10.5% and genotype 2 (4.6%. Mixed infections of genotypes 1 and 3 were found in 7.0% of the total number of patients. The present results indicate a significant decrease in anti-HCV prevalence from 23.8% detected in a study carried out in 1994 to 10.5% in the present study. The HCV genotype distribution was closely similar to that observed in other hemodialysis populations in Brazil, in local candidate blood donors and in other groups at risk of transfusion-transmitted infection.

  1. Addressing HCV infection in Europe: reported, estimated and undiagnosed cases.

    Science.gov (United States)

    Merkinaite, Simona; Lazarus, Jeffrey V; Gore, Charles

    2008-09-01

    The hepatitis C virus (HCV) is a major public health problem due to its high prevalence, high rate of onward transmission and health complications. As many as 85% of people infected with HCV may go on to become chronic carriers of the disease with the risk of developing liver cancer or cirrhosis. At present, it is the most common cause of chronic liver disease and liver transplantation in a number of countries, with an estimated 250,000 people dying annually from HCV-related causes. Despite the magnitude of the problem, the virus does not receive adequate attention from either the general public or from health policy-makers. This study assesses HCV prevalence from both estimated totals and undiagnosed cases in selected European countries. Secondary sources were assessed and experts in 17 European countries were interviewed about HCV prevalence, reporting strategies and transmission. Available data suggest that only between 10% and 40% of people with HCV in Europe are aware of their infection (up to 90% of the prevalent pool are undiagnosed in such countries as Germany or Poland). Though the virus affects people of all ages, races and backgrounds, in Europe, between 20% and 90% of new HCV cases have been identified among past or current injecting drug users (IDUs). It is of the utmost importance to improve both public awareness and access to early testing and counselling, with the goal of prevention of further infections, maintenance of health and provision of treatment to avoid cirrhosis and liver cancer. Additionally, as previous studies in central and eastern Europe show, evidence-based measures to prevent and manage HCV among IDUs, where most current transmission is concentrated, remain limited. Therefore, there is a strong need for intensified advocacy to put HCV higher on both public health and harm reduction agendas. PMID:18935772

  2. HIV, HCV & Leprosy co-infection.

    Science.gov (United States)

    George, A; Kanish, B

    2014-01-01

    In the era where Hansen's disease has achieved elimination status in India, co-infection with HIV can possibly cause a resurgence of this disease. A young intravenous drug abuser was found to have triple affliction, where HIV and HCV infection were discovered on testing after the patient was clinically diagnosed to have Hansen's disease. To our knowledge, there has been no case reported where leprosy was seen with HIV and HCV infection. We are reporting a patient with lepromatous Hansen's disease in type 2 reaction in whom HIV and HCV was incidentally diagnosed. PMID:26118224

  3. [Consequences of extrahepatic manifestations of hepatitis C viral infection (HCV)].

    Science.gov (United States)

    Pawełczyk, Agnieszka

    2016-01-01

    The hepatitis C virus (HCV) is a primarily hepatotropic virus. However, numerous extrahepatic symptoms are observed in patients chronically infected with HCV, e.g. cryoglobulinemia, lymphoproliferative disorders, kidney diseases, disturbances of the central and peripheral nervous system, thyroid gland, pancreas, lymph nodes and pituitary gland, that develop at various times after the infection. Complex mechanisms underlie these processes, both molecular, related to direct effects of the virus on cells or tissues and indirect mechanisms, resulting from the response of the immune system to infection (via cytokines or oxidative stress), and from the antiviral treatment used. Understanding these mechanisms may contribute to the definition of new prognostic factors, important for the early diagnosis of the infection, which in turn may improve treatment efficacy. This paper is a review of the incidence of selected extrahepatic manifestations of HCV infection and their underlying pathogenetic mechanisms and risk factors. PMID:27117111

  4. Modeling HCV Disease in Animals: Virology, Immunology and Pathogenesis of HCV and GBV-B Infections

    Directory of Open Access Journals (Sweden)

    Cordelia eManickam

    2014-12-01

    Full Text Available Hepatitis C virus (HCV infection has become a global public health burden costing billions of dollars in health care annually. Even with rapidly advancing scientific technologies, this disease still looms large due to a lack of vaccines and affordable treatment options. The immune correlates of protection and predisposing factors towards chronicity remain major obstacles to development of HCV vaccines and immunotherapeutics due, at least in part, to lack of a tangible infection animal model. This review discusses the currently available animal models for HCV disease, with a primary focus on GB virus B (GBV-B infection of New World primates that recapitulates the dual hepacivirus phenotypes of acute viral clearance and chronic pathologic disease. HCV and GBV-B are also closely phylogenetically related, and advances in characterization of the immune systems of New World primates have already led to the use of this model for drug testing and vaccine trials. Herein, we discuss the benefits and caveats of the GBV-B infection model and discuss potential avenues for future development of novel vaccines and immunotherapies.

  5. IP-10 predicts the first phase decline of HCV RNA and overall viral response to therapy in patients co-infected with chronic hepatitis C virus infection and HIV

    DEFF Research Database (Denmark)

    Falconer, Karolin; Askarieh, Galia; Weis, Nina Margrethe;

    2010-01-01

    The aim of this study was to investigate the utility of baseline plasma interferon-gamma inducible protein-10 (IP-10) levels in human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected patients. Baseline IP-10 was monitored during HCV combination therapy in 21 HIV-HCV co......-infected patients (HCV genotype 1 (n = 16), 2 (n = 2), and 3 (n = 3)). Lower baseline IP-10 was significantly associated with a rapid decline in HCV RNA, in particular with the first phase reduction, and similar cut-off levels ( 600 pg/ml) as in HCV mono-infected patients apply. In conclusion, baseline IP......-10 HCV therapy in HIV-HCV co-infected patients, and may thus be useful in encouraging such difficult-to-treat patients to initiate therapy....

  6. Analysis of mutant NS5B proteins encoded by isolates from chimpanzees chronically infected following clonal HCV RNA inoculation

    International Nuclear Information System (INIS)

    We hypothesized that mutations in the HCV NS5B polymerase, which occur during infection, may affect RNA-dependent RNA polymerase (RdRp) activity. NS5B proteins corresponding to a genotype 1a infectious clone and mutants identified in chimpanzees following inoculation with the clone were expressed and purified and their in vitro RdRp activity was compared to a NS5B genotype 1b control. A Gln-65-to-His mutation increased RdRp activity by 1.8-fold as compared to the infectious clone. Moreover, this NS5B1a protein had RdRp activity similar to the NS5B1b control. Three NS5B proteins representing mutations found in another animal had no in vitro RdRp activity. All mutations were maintained in the majority circulating virus for at least 216 weeks. The results demonstrate that some in vivo mutations of NS5B directly enhance in vitro RdRp activity. In addition, they suggest that the in vitro RdRp activity of NS5B may not always reflect in vivo activity within replication complexes

  7. Recent advances in managing chronic HCV infection: focus on therapy in patients with severe liver disease [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Raoel Maan

    2016-03-01

    Full Text Available Chronic hepatitis C virus (HCV infection still represents a major public health problem, as it is thought to be responsible for more than 350,000 deaths around the globe on a yearly basis. Fortunately, successful eradication of the virus has been associated with improved clinical outcome and reduced mortality rates. In the past few years, treatment has improved considerably by the implementation of direct-acting antivirals (DAAs. From 2014 onwards, sofosbuvir, simeprevir, daclatasvir, ledipasvir, paritaprevir, ombitasvir, and dasabuvir have been approved by the US Food and Drug Administration (FDA and European Medicines Agency (EMA. Regimens with various combinations of these new drugs, without the use of interferon (IFN, proved to be very effective and well tolerated, even among patients with advanced liver disease. Moreover, treatment duration could be shortened to 12 weeks in the majority of patients. The high costs of these DAAs, however, limit the availability of IFN-free therapy worldwide. Even in wealthy countries, it is deemed necessary to prioritize DAA treatment in order to limit the immediate impact on the health budget. As patients with advanced liver disease are in most need of HCV clearance, many countries decided to treat those patients first. In the current review, we focus on the currently available IFN-free treatment options for patients with cirrhosis. We discuss the virological efficacy as well as the clinical relevance of these regimens among this specific patient population.

  8. [Control of HCV, HBV and HIV Infections in Hemodialysis].

    Science.gov (United States)

    Fabrizi, Fabrizio; Martin, Paul; Messa, Piergiorgio

    2013-01-01

    Infections with blood-borne pathogens are still common among patients on maintenance dialysis all over the world. The control of infection due to blood-borne viruses (particularly HBV) within dialysis units has been a major goal in the management of patients with chronic kidney disease in the industrialized world. Standard precautions and specific procedures have been recommended to prevent infections with HBV, HCV and HIV within dialysis units. Isolation of HBsAg positive patients by dialysis rooms, staff and machines continues to be an important step to control HBV infection within dialysis units, according to the CDC and other regulatory agencies. Some prospective observational studies have reported the complete prevention of HCV transmission to hemodialysis patients in the absence of any isolation policy, and the use of dedicated dialysis machines for HCV-infected patients is not recommended by clinical guidelines. Isolation of HCV-infected patients should be considered in special circumstances only. Vaccination is an important tool against transmission of HBV among patients on long-term dialysis even if the immune response towards the hepatitis B vaccine remains unsatisfactory. Hemodialysis is considered a low risk setting for the transmission of human immunodeficiency virus (HIV) infection, providing that standard and specific procedures are carefully observed. HIV-infected patients do not have to be isolated from other patients or dialyzed separately on dedicated machines.

  9. HBV-DNA in hemodialysis patients infected by HCV

    Directory of Open Access Journals (Sweden)

    Arababadi Mohammad

    2009-01-01

    Full Text Available End-stage renal disease patients on chronic hemodialysis (HD patients are at risk for both hepatitis B virus (HBV and hepatitis C virus (HCV infection, and they may coexist. To de-termine the prevalence and clinical impact of HBV and HCV infection, we studied poly chain reaction (PCR and reverse transcription (RT-PCR on the blood samples of 90 HD patients in Kerman, Iran. ELISA test was used to detect anti-HBc, anti-HBs and HBsAg. We found that 30 out of 90 (33.3% patients were PCR-RT-PCR positive for HCV-RNA. No HBV-DNA (0% was detected through the PCR study in both positive and negative HCV-RNA patient groups. Though none of the samples was HBsAg positive, 10 (33.3% HCV-RNA positive patients were anti-HBc positive, and 12 (40.7% were anti-HBs positive. We conclude that prevalence of hepatitis C infection is high in HD patients in our region, but not associated with active HBV infection.

  10. Hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infections in alcoholics.

    Science.gov (United States)

    Prakash, Om; Mason, Andrew; Luftig, Ronald B; Bautista, Abraham P

    2002-07-01

    Approximately 400,000 individuals in the United States are co-infected with hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) and it is likely that almost one in two of these subjects consumes alcohol. The majority of these patients suffer an accelerated course of liver disease as manifested by the onset of cirrhosis within 5 to 10 years of developing HCV infection, as well as an increased risk of developing hepatocellular carcinoma (HCC). It is thought that chronic alcohol abuse mediates liver damage as a result of increased production of free radicals and proinflammatory cytokines. In the setting of chronic HCV infection, alcohol ingestion has an additional effect of diminishing immune clearance and increasing viral burden to hasten the onset of cirrhosis and HCC. Likewise, chronic HCV and HIV-1 co-infection results in a net increase in HCV burden; higher prevalence rates of HCV transmission to sexual partners and offspring, as well as an accelerated progression to end stage liver disease as compared to individuals with HCV infection alone. Thus, the synergistic effects of alcohol abuse and HIV-1 greatly impact on the morbidity and mortality for patients with HCV coinfection. Ultimately, this cumulative disease process will require far more aggressive management with abstinence and counseling for alcohol abuse; highly active antiretroviral therapy (HAART) for HIV infection and combination anti-viral therapy for HCV infection to stem the rapid progression to end stage liver disease. PMID:12086918

  11. Impact of Immunogenetic IL28B Polymorphism on Natural Outcome of HCV Infection

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    Valli De Re

    2014-01-01

    Full Text Available With the aim of investigating whether interleukin 28B gene (IL28B rs1297860 polymorphism is associated with different hepatitis C (HCV infection statuses, we compared IL28B allelic distribution in an Italian case series of 1050 patients with chronic infection and different outcomes, 47 individuals who spontaneously cleared HCV, and 178 blood donors. Furthermore, we compared IL28B variants among 3882 Caucasian patients with chronic infection, 397 with spontaneous clearance, and 1366 blood donors reported in PubMed. Overall data confirmed a relation between IL28B C allele and HCV spontaneous clearance. Furthermore, we found that IL28B T allele had a weak relation with chronic HCV progression to hepatocellular carcinoma. Study findings are in accordance with the hepatocellular carcinogenic model where IL28B TT genotype, by promoting a persistent chronic hepatitis which leads to both hepatocyte injury and chronic inflammation, could facilitate HCC development. Conversely, patients with lymphoproliferative disorders had not any significantly different IL28B rs1297860 allelic distribution than those with chronic HCV, but, like all chronic HCV-related diseases, they showed a lower CC frequency than patients who spontaneously cleared HCV. Study results confirmed the model of persistent HCV infection as a risk factor for the pathogenesis of both liver and lymphoproliferative disorders.

  12. Point-of-care testing for HCV infection: recent advances and implications for alternative screening.

    Science.gov (United States)

    Parisi, Maria Rita; Soldini, Laura; Vidoni, Gianmarino; Mabellini, Chiara; Belloni, Teresa; Brignolo, Livia; Negri, Silvia; Schlusnus, Karin; Dorigatti, Fernanda; Lazzarin, Adriano

    2014-10-01

    Over the last few years, hepatitis C virus (HCV) infection has emerged as one of the most significant causes of chronic liver disease worldwide, with an estimated prevalence ranging from 2.2 to 3.0%. In Italy, approximately 2% of subjects are infected with HCV. Considering that acute HCV infection is usually asymptomatic, early diagnosis is rare. Those people who develop chronic infection, even though undiagnosed, may suffer serious liver damage, making chronic HCV infection a major health problem. New initiatives are needed to identify a submerged portion of patients with chronic viral hepatitis and to propose controls and antiviral treatments to avoid the progression to liver cirrhosis or hepatocellular carcinoma (HCC). Since January 2011, the Infectious Diseases Department of San Raffaele Scientific Institute in Milan has been carrying out a prevention program called "EASY test project", using a new oral test, the OraQuick® HCV rapid antibody test (OraSure technologies, Inc.). The main objective of the project is to evaluate the acceptability of an alternative, free and anonymous HCV test offer, available in different settings (Points of Care, STDs Prevention clinics and General Practitioner clinics). From January 2011 to April 2014, 29,600 subjects were approached to inform them about HCV infection and other sexually transmitted diseases; 4,507 (15.2% of the contacted subjects) of them, total eligible volunteers, performed HCV tests on saliva and completed the interview in the alternative POCTs. Twenty-seven subjects (0.6% of the total) turned HCV oral test reactive (27/4.507) during the evaluation period; all of them were confirmed by conventional test. All 27 patients were asymptomatic and without a history of HCV-re- lated symptoms. The results from this analysis suggest that the promotion of alternative HCV test screening has not yet been fully developed as a strategy to increase levels of HCV testing among people at risk for HCV infection. Increasing

  13. Prevalence and coexistence of diabetes in HIV, HCV and HIV/HCV co- infection in Kermanshah -Iran

    Directory of Open Access Journals (Sweden)

    Alireza Janbakhsh

    2012-01-01

    Full Text Available Background: Beside various factors for producing diabetes, it seems that chronic hepatitis C, HIV/HCV co-infection, and anti-retroviral treatment especially including protease inhibitors may predispose to diabetes. This study conducted to determine prevalence of diabetes in HIV and HCV patients.Methods: The registries of 150 HCV patients, 50 HIV patients and 90 HIV/HCV co-infected patients in Hepatic Clinics and consulting center for behavioral disorders in Kermanshah Western Iran was studied. The patients selected using convenience sampling method. Variables including age, sex, duration of disease, injecting drug usage, liver enzymes level, CD4 count, treatment with anti retroviral, treatment with interferon and blood sugar level were collected. Subjects with FBS≥126 or BS≥200 mg/dl described as diabetic. Data analyzed using chi-square and Fisher tests and SPSS software.Results: The prevalence of diabetes was 2.7%, 4% and 2.2% among patients infected with HCV, HIV and HIV/HCV co infection respectively. None of the variables such as age, sex, liver enzymes, injecting drug usage, CD4 count, antiretroviral treatment and interferon determined as risk factors for diabetes.Conclusion: Our finding showed that hepatitis C is not a definitive risk factor for diabetes. Although prevalence of diabetes in these patients was determined lower than general Kermanshah population, but factors such as difference in mean age and body mass index (BMI may contribute in diabetes incidence. Infection with HIV and co-infection with HIV/HCV and treatment with anti retroviral drugs were not risk factors for diabetes.

  14. Quantification of serum hepatitis C virus core protein level in patients chronically infected with different hepatitis C virus genotypes.

    OpenAIRE

    Orito, E; M. Mizokami; Tanaka, T.; Lau, J. Y.; Suzuki, K; Yamauchi, M.; Ohta, Y.; Hasegawa, A; Tanaka, S.; Kohara, M

    1996-01-01

    BACKGROUND/AIM: A novel fluorescent enzyme immunoassay (FEIA) for the detection and quantification of serum hepatitis C virus (HCV) core protein was developed. The aim of this study was to evaluate the relation among serum HCV core protein level, HCV RNA level, and HCV genotype in patients with chronic HCV infection. PATIENTS AND METHODS: Serum HCV core protein, HCV RNA, HCV genotype were determined in 175 patients using the FEIA, branched DNA assay (Quantiplex HCV RNA ver 1.0), and serologic...

  15. Socioeconomic status in HCV infected patients – risk and prognosis

    DEFF Research Database (Denmark)

    Omland, Lars Haukali; Osler, Merete; Jepsen, Peter;

    2013-01-01

    It is unknown whether socioeconomic status (SES) is a risk factor for hepatitis C virus (HCV) infection or a prognostic factor following infection.......It is unknown whether socioeconomic status (SES) is a risk factor for hepatitis C virus (HCV) infection or a prognostic factor following infection....

  16. Safety of interferon treatment for chronic HCV hepatitis

    Institute of Scientific and Technical Information of China (English)

    D Festi; L Sandri; G Mazzella; E Roda; T Sacco; T Staniscia; S Capodicasa; A Vestito; A Colecchia

    2004-01-01

    Hepatitis C is a major cause of liver-related morbidity and mortality worldwide, In fact, chronic hepatitis C is considered as one of the primary causes of chronic liver disease, cirhosis and hepatocellular carcinoma, and is the most common reason for liver transplantation. The primary objectives for the treatment of HCV-related chronic hepatitis is to eradicate infection and prevent progression of the disease. The treatment has evolved from the use of α-interferon (TFNα)alone to the combination of IFNα plus ribavirin, with a significant improvement in the overall efficacy, and to the newer PEG-IFNs which have further increased the virological response, used either alone or in combination with ribavirin.Despite these positive results, in terms of efficacy, concerns are related to the safety and adverse events. Many patients must reduce the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable percentage of subjects are not suitable owing to intolerance toward drugs. IFNβ represents a potential therapeutic alternative for the treatment of chronic viral hepatitis and in some countries it plays an important role in therapeutic protocols. Aim of the present paper was to review available data on the safety of IFNβ treatment in HCV-related chronic hepatitis.The rates of treatment discontinuation and/or dose modification due to the appearance of severe side effects during IFNβ are generally low and in several clinical studies no requirements for treatment discontinuation and/or dose modifications have been reported. The most frequent side effects experienced during IFNβ treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No differences in terms of side-effect frequency and severity between responders and non-responders have been reported.A more recent study, performed to compare IFNβ alone or in combination with ribavirin, confirmed the good safety profile of both treatments. Similar trends of adverse event

  17. APOPTOSIS SYSTEM AND ITS RELATIONS TO HEPATOCELLULAR DAMAGE AND SOME INDEXES OF LOCAL CYTOKINE PROFILE CHRONIC HCV INFECTION

    Directory of Open Access Journals (Sweden)

    L. Ph. Skljar

    2008-01-01

    Full Text Available Abstract. At present time, some conflicting data concern a possible importance of apoptosis in pathogenesis of chronic hepatitis C. A significant role is ascribed to FAS/FAS-L, as a factor of hepatocyte apoptosis. CD95+ levels at the cell surfaces were studied in liver homogenates. A significant decrease in CD95+ cells was revealed in liver samples from the patients with higher histological indexes of hepatitis activity and fibrosis. A reverse relationship between CD95+ level and local concentrations of cytokines (TNFα, IL-1, IL-10, as well as significant direct correlation with IFNγ, IL-2 values were detected, thus suggesting a failure of compensatory mechanisms of immune regulation, and predominance of anti-apoptotic viral potential over protective cellular responses. (Med. Immunol., vol. 10, N 4-5, pp 415-422.

  18. Response rates of standard interferon therapy in chronic HCV patients of Khyber Pakhtunkhwa (KPK

    Directory of Open Access Journals (Sweden)

    Ahmad Bashir

    2012-01-01

    Full Text Available Abstract Background Interferon based therapy is used to eradicate the Hepatitis C Virus from the bodies of the infected individuals. HCV is highly prevalent in Khyber Pakhtunkhwa (KPK that is why it is important to determine the response of standard interferon based therapy in Chronic HCV patients of the region. Study design A total of 174 patients were selected for interferon based therapy. The patients were selected from four different regions of KPK. After confirmation of active HCV infection by Real Time PCR, standard interferon with ribavirn was given to patients for 6 months. After completion of therapy, end of treatment virologic response (ETR was calculated. Results Out of total 174 patients, 130 (74.71% showed ETR and 44 (25.28% did not show ETR. In district Bunir, out of 52 patients, 36 (69.23% showed ETR and 16 (30.79% did not show ETR. In district Mardan, out of the total 74 patients, 66 (89.18% were negative for HCV RNA and 8 (10.81% were resistant to therapy. In Peshawar, out of 22, 16 (60% were negative and 6 (40% were positive for HCV RNA at the end of 6 months therapy. In the Federally Administered Tribal Area (FATA, out of 18 only 10 (55.5% were negative and 8 (44.45% were positive for active HCV infection. Conclusion It is concluded that the response of antiviral therapy against HCV infection in chronic HCV patients of KPK province is 74.71%. The high response rate may be due to the prevalence of IFN-responsive HCV genotypes (2 and 3 in KPK.

  19. A Predictive Model for Selecting Patients with HCV Genotype 3 Chronic Infection with a High Probability of Sustained Virological Response to Peginterferon Alfa-2a/Ribavirin.

    Directory of Open Access Journals (Sweden)

    Tarik Asselah

    Full Text Available Access to direct-acting antiviral agents (DAAs is restricted in some settings; thus, the European Association for the Study of the Liver recommends dual peginterferon/ribavirin (PegIFN/RBV therapy wherever DAAs are unavailable. HCV genotype (GT 3 infection is now the most difficult genotype to eradicate and PegIFN/RBV remains an effective option. The goal of this study was to devise a simple predictive score to identify GT3 patients with a high probability of achieving a sustained virologic response (SVR with PegIFN alfa-2a/RBV therapy.Relationships between baseline characteristics and SVR were explored by multiple logistic regression models and used to develop a simple scoring system to predict SVR using data from 1239 treatment-naive GT3 patients who received PegIFN alfa-2a/RBV for 24 weeks in two large observational cohort studies.The score was validated using a database of 473 patients. Scores were assigned for six factors as follows: age (years (≤40: 2 points; >40 but ≤55: 1; bodyweight (kg (200: 2; ≥100 but <200: 1; HCV RNA (<400,000 IU/mL: 1. The points are summed to arrive at a score ranging from 0‒10 where higher scores indicate higher chances of SVR; 141, 123, 203, 249, 232, and 218 patients had total scores of 0‒4, 5, 6, 7, 8, and 9-10, respectively, among whom SVR rates were 45%, 62%, 72%, 76%, 84%, and 89%. Among 622 patients who had scores of 6‒10 and HCV RNA <50 IU/mL by treatment week 4 the SVR rate was 86% (532/622.A simple baseline scoring system involving age, bodyweight, cirrhosis status, ALT level, platelet count and HCV RNA level can be used to identify treatment-naive Caucasian patients with HCV GT3 infection with a high probability of SVR with PegIFN alfa-2a/RBV therapy.

  20. High rate of hepatitis C virus (HCV) recurrence in HIV-infected individuals with spontaneous HCV RNA clearance

    DEFF Research Database (Denmark)

    Peters, L; Mocroft, A; Soriano, V;

    2014-01-01

    OBJECTIVES: Following resolution of hepatitis C virus (HCV) infection, recurrence has been shown to occur in some persons with repeated exposure to HCV. We aimed to investigate the rate and factors associated with HCV RNA recurrence among HIV-1-infected patients with prior spontaneous HCV RNA...... clearance in the EuroSIDA cohort. METHODS: All HIV-infected patients with documented prior spontaneous HCV clearance, and at least one subsequently collected plasma sample, were examined. The last sample was tested for HCV RNA and those with HCV RNA ≥ 615 IU/mL were defined as having HCV recurrence...... and their characteristics were compared with those of patients who were still aviraemic. Logistic regression was used to identify factors associated with HCV recurrence. RESULTS: Of 191 eligible patients, 35 [18.3%; 95% confidence interval (CI) 12.8-23.8%] had HCV recurrence. Thirty-three (94.3%) were injecting drug users...

  1. HIV and HCV: from Co-infection to Epidemiology, Transmission,Pathogenesis, and Treatment

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Human immunodeficiency virus (HIV) is the infectious agent causing acquired immunodeficiency syndrome (AIDS), a deadliest scourge of human society. Hepatitis C virus (HCV) is a major causative agent of chronic liver disease and infects an estimated 170 million people worldwide,resulting in a serious public health burden. Due to shared routes of transmission, co-infection with HIV and HCV has become common among individuals who had high risks of blood exposures. Among hemophiliacs the co-infection rate accounts for 85%; while among injection drug users (IDU) the rate can be as high as 90%. HIV can accelerate the progression of HCV-related liver disease, particularly when immunodeficiency has developed. Although the effect of HCV on HIV infection is controversial,most studies showed an increase in mortality due to liver disease. HCV may act as a direct cofactor to fasten the progression of AIDS and decrease the tolerance of highly active antiretroviral therapy(HARRT). Conversely, HAART-related hepatotoxicity may enhance the progression of liver fibrosis.Due to above complications, co-infection with HCV and HIV-1 has imposed a critical challenge in the management of these patients. In this review, we focus on the epidemiology and transmission of HIV and HCV, the impact of the two viruses on each other, and their treatment.

  2. Immune biomarker differences and changes comparing HCV mono-infected, HIV/HCV co-infected, and HCV spontaneously cleared patients.

    Directory of Open Access Journals (Sweden)

    Lauren E Kushner

    Full Text Available BACKGROUND: Immune biomarkers are implicated in HCV treatment response, fibrosis, and accelerated pathogenesis of comorbidities, though only D-dimer and C-reactive protein have been consistently studied. Few studies have evaluated HIV/HCV co-infection, and little longitudinal data exists describing a broader antiviral cytokine response. METHODS: Fifty immune biomarkers were analyzed at baseline (BL and HCV end of treatment follow-up(FU time point using the Luminex 50-plex assay in plasma samples from 15 HCV-cleared, 24 HCV mono- and 49 HIV/HCV co-infected patients receiving antiretroviral treatment, who either did or did not receive pegylated-interferon/ribavirin HCV treatment. Biomarker levels were compared among spontaneous clearance patients, mono- and co-infected, untreated and HCV-treated, and sustained virologic responders (SVR and non-responders (NR at BL and FU using nonparametric analyses. A Bonferroni correction, adjusting for tests of 50 biomarkers, was used to reduce Type I error. RESULTS: Compared to HCV patients at BL, HIV/HCV patients had 22 significantly higher and 4 significantly lower biomarker levels, following correction for multiple testing. There were no significantly different BL levels when comparing SVR and NR in mono- or co-infected patients; however, FU levels changed considerably in co-infected patients, with seven becoming significantly higher and eight becoming significantly lower in SVR patients. Longitudinally between BL and FU, 13 markers significantly changed in co-infected SVR patients, while none significantly changed in co-infected NR patients. There were also no significant changes in longitudinal analyses of mono-infected patients achieving SVR or mono-infected and co-infected groups deferring treatment. CONCLUSIONS: Clear differences exist in pattern and quantity of plasma immune biomarkers among HCV mono-infected, HIV/HCV co-infected, and HCV-cleared patients; and with SVR in co-infected patients treated

  3. Logical Analysis of Regulation of Interleukin-12 Expression Pathway Regulation During HCV Infection.

    Science.gov (United States)

    Farooqi, Zia-Ur-Rehman; Tareen, Samar H K; Ahmed, Jamil; Zaidi, Najam-Us-Sahar S

    2016-01-01

    Hepatitis C virus (HCV) triggers coordinated innate and adaptive response in host cell. HCV genome and proteins of the replicating virus are recognized as non-self-antigens by host cell to activate Toll Like Receptors (TLRs). Activated TLRs ultimately express cytokines, which can clear virus either by activating interferon (IFN), protein kinase C (PKC) and RNA Lase system or through activation of cytotoxic T-lymphocytes. Interleukin-12 (IL-12) is a potent antiviral cytokine, capable of clearing HCV by bridging both innate and adaptive antiviral immune response. Activation of TLR-4 on macrophages surface induces expression of IL-12 via NF-κB and AP-1 transcriptional pathway. After expression, IL- 12 releases IFN-γ, which activates anti-HCV cytotoxic lymphocytes. Conversely, in chronic HCV infection downregulation of IL-12 has been reported instead of by number of studies. Keeping in view of the above mentioned facts, this study was designed to evaluate HCV-core mediated down-regulation of IL-12 transcriptional pathway by employing a logical modeling approach based on the Ren´e Thomas formalism. The logical parameters of entities were estimated by using SMBioNet. The Logical model represents all possible dynamics of protein expression involved during course of HCV pathology. Results demonstrated that at chronic stage of infection, though TLR-4 was constantly active but yet it failed to express the NF-κB, AP-1, IL-12 and IFN-γ. This mechanism was indicative of incorporation of core mediated changes in IL-12 regulatory pathway. Moreover, results also indicate that HCV adopts different trajectories to accomplish the persistence of chronic phase of infection. It also implicated that human immune system tries to clear HCV but core is capable of inducing system oscillations to evade the immunity.

  4. HCV triple therapy in co-infection HIV/HCV is not associated with a different risk of developing major depressive disorder

    Directory of Open Access Journals (Sweden)

    Renata Fialho

    2014-11-01

    Full Text Available Introduction: Hepatitis C (HCV treatment options have changed with the development of direct activity antivirals (DAAs and the availability of triple therapies have improved HCV cure rates. A common neuropsychiatric side effect of pegylated-interferon and ribavirin treatment is major depressive disorder (MDD, however little is known about such adverse events with protease inhibitor-based triple therapy. The aim of this study was to assess the rate of MDD in co-infected HIV HCV patients undergoing different HCV treatments. Methods: All participants were co-infected HIV HCV attending the Royal Sussex County Hospital Brighton hepatology outpatient clinic between 2010 and 2014. Participants were assessed for DSM-IV MDD and depression severity (using the Hamilton depression scale (HAMD at baseline and monthly after treatment initiation. HIV and HCV stages, genotype, reinfection and standard demographic variables were recorded. Influence of HCV stage (acute vs. chronic and type of treatment (classic vs triple, emergence of MDD and clearance outcomes were analyzed using repeated measures and logistic regression models. Results: Fifty participants with a mean age of 42.65 years (SD=10.32 were included; most were male (98%. The majority had contracted HCV genotype 1 (64% or 4 (26%. The HCV stage and treatment groups were matched for age and depression at baseline. No significant differences were found on virological outcomes considering HCV stage and treatment. From baseline to SVR, there was a significant increase in HAMD scores, F(4,36=10.09, p<.001; this was not significantly influenced by HCV stage, F(4,35=0.54, p=.708 or HCV treatment group, F(4,35=0.60, p=.664. Those with chronic HCV were more likely to transition to MDD than acute infection (OR 7.77, 95% CI 2.04–29.54, p=.003. No differences were found for depression emergence by HCV treatment group (OR 0.83, 95% CI 0.22–3.13, p=.787. Conclusions: HCV triple therapy was not associated with a

  5. Prevalence and Risk Factors of Hepatitis C Infection (HCV in Birjand, Iran, 2014

    Directory of Open Access Journals (Sweden)

    Ebrahimzadeh

    2016-01-01

    Full Text Available Background Hepatitis C virus (HCV infection is an important global concern, with a frequency of 3% (i.e., 170 million of the population has HCV-Ab. Additionally, 50% of HCV and 80% of transfusion transmitted infections (TTI are chronic. In 20% of cases, HCV occurs as an acute infection, and in the remaining 80% of cases, it becomes chronic. In chronic patients, risk of cirrhosis is up to 44%, risk of hepatocellular carcinoma (HCC is 13%, and risk of mortality is 14%. As there is no vaccine available for the virus yet, and since most of the cases are asymptomatic, attention to the epidemiology of the disease among the population is a pressing concern. Objectives The aim of this study is to determine the prevalence and risk factors of HCV in Birjand city. Patients and Methods In this descriptive-analytical study, 5,235 people who live in Birjand city were selected; after gaining permission for the study, a signed consent form was obtained from each patient. Prevalence of HCV was determined by ELISA test, and positive cases underwent Polymerase chain reaction (PCR and genotyping for confirmation. Results The mean age of the participants was 39.7 ± 14.4. Among them, 52.2% were female and 29.9% had university degrees. Prevalence of HCV-Ab+ was about 0.2% with ELISA, and 0.14% of entire group were confirmed by PCR. No significant relationship was found for age, sex, and education (P > 0.05. Also, there was no significant relationship found with risk factors such as endoscopy, blood transfusion, surgery, hospitalization, phlebotomy, and alcohol drinking (P > 0.05. HCV-Ab was 200 times more prevalent in IV-drug abusers compared to non-addicted people. Also, the prevalence of HCV-Ab in non-IV-drug abuser addicts was 9.3 times higher than in non-addict patients. Prevalence of HCV-Ab in patients who reported illicit sexual activities was 13.3 times higher. In patients with a familial history of HCV, infection was 26.3 times more prevalent than in patients

  6. Identification and Linkage to Care of HCV-Infected Persons in Five Health Centers - Philadelphia, Pennsylvania, 2012-2014.

    Science.gov (United States)

    Coyle, Catelyn; Viner, Kendra; Hughes, Elizabeth; Kwakwa, Helena; Zibbell, Jon E; Vellozzi, Claudia; Holtzman, Deborah

    2015-05-01

    Approximately three million persons in the United States are infected with hepatitis C virus (HCV), a blood-borne pathogen that is an increasing cause of liver disease and mortality in the United States. Treatments for HCV are curative, of short duration, and have few associated side effects, increasing the importance of identifying HCV-infected persons. Many persons with HCV infection were infected decades ago, before implementation of prevention measures and most are unaware of their infection, regardless of when it occurred. Most newly diagnosed cases are associated with injection drug use. Persons born during 1945-1965 have a fivefold higher risk of HCV infection than other adults and the highest risk for HCV-related morbidity and mortality. CDC recommends testing for this group, for persons who inject drugs, and others at risk for HCV infection. From October 2012 through July 2014, the National Nursing Centers Consortium (NNCC) carried out a project to integrate routine HCV testing and linkage-to-care in five federally qualified health centers in Philadelphia, PA, that primarily serve homeless persons and public housing residents. During the project period, 4,514 patients across the five centers were tested for HCV. Of these, 595 (13.2%) were HCV-antibody positive and 550 (92.4%) had a confirmatory HCV-RNA test performed. Of those who had a confirmatory HCV-RNA test performed, 390 (70.9%) were identified as having current (i.e., chronic) HCV infection (overall prevalence = 8.6%). Of those currently infected with HCV, 90% were informed of their status, 78% were referred to an HCV care specialist, and 62% went to the referred specialist for care. Replicable system modifications that improved HCV testing and care included enhancements to electronic medical records (EMRs), simplification of HCV testing protocols, and addition of a linkage-to-care coordinator. Findings from this project highlight the need for innovative strategies for HCV testing, care, and

  7. Intrahepatic mRNA Expression of FAS, FASL, and FOXP3 Genes Is Associated with the Pathophysiology of Chronic HCV Infection

    Science.gov (United States)

    Amoras, Ednelza da Silva Graça; Gomes, Samara Tatielle Monteiro; Freitas, Felipe Bonfim; Santana, Bárbara Brasil; Ishak, Geraldo; Ferreira de Araújo, Marialva Tereza; Demachki, Sâmia; Conde, Simone Regina Souza da Silva; Ishak, Marluísa de Oliveira Guimarães; Ishak, Ricardo; Vallinoto, Antonio Carlos Rosário

    2016-01-01

    This study aimed to evaluate the relative mRNA expression of Fas receptor (FAS), Fas ligand (FASL), and forkhead box protein 3 (FOXP3) in liver biopsy specimens obtained from patients with viral and non-viral chronic hepatitis and correlate their expression with the fibrosis stage. A total of 51 liver biopsy specimens obtained from HBV (n = 6), HCV (n = 28), and non-viral hepatic disease (NVHD) (n = 9) patients and from individuals with normal liver histology (n = 8) (control—CT) were analyzed. Quantifications of the target genes were assessed using qPCR, and liver biopsies according to the METAVIR classification. The mRNA expression levels of FAS and FASL were lower in the CT group compared to the groups of patients. The increase in the mRNA expression of FAS and FASL was correlated with higher levels of inflammation and disease progression, followed by a decline in tissues with cirrhosis, and it was also associated with increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Higher mRNA expression of FOXP3 was observed in the HCV and NVHD groups, with the peak observed among patients with cirrhosis. The increased FOXP3 mRNA expression was positively correlated with increased FAS and FASL mRNA expression and the AST and ALT levels in all patients. Conclusions: These results suggest that regardless of the cause, the course of chronic liver disease may be modulated by the analyzed genes and correlated with an increase in regulatory T cells during the liver damage followed by hepatocyte destruction by Fas/FasL system and subsequent non specific lymphocytic infiltrate accumulation. PMID:27243827

  8. Maternal HCV infection is associated with intrauterine fetal growth disturbance

    Science.gov (United States)

    Huang, Qi-tao; Hang, Li-lin; Zhong, Mei; Gao, Yun-fei; Luo, Man-ling; Yu, Yan-hong

    2016-01-01

    Abstract Since the evidence regarding the association between maternal hepatitis C virus (HCV) infection and impaired intrauterine fetal growth had not been conclusive, the aim of the present study was to evaluate the risk of maternal HCV infection in association with intrauterine fetal growth restriction (IUGR) and/or low birth weight infants (LBW). We performed an extensive literature search of PubMed, MEDLINE, and EMBASE through December 1, 2015. The odds ratios (ORs) of HCV infection and IUGR/LBW were calculated and reported with 95% confidence intervals (95% CIs). Statistical analysis was performed using RevMen 5.3 and Stata 10.0. Seven studies involving 4,185,414 participants and 5094 HCV infection cases were included. Significant associations between HCV infection and IUGR (OR = 1.53, 95% CI: 1.40–1.68, fixed effect model) as well as LBW were observed (OR = 1.97, 95% CI: 1.43–2.71, random effect model). The results still indicated consistencies after adjusting for multiple risk factors which could affect fetal growth, including maternal age, parity, maternal smoking, alcohol abuse, drugs abuse, coinfected with HBV/HIV and preeclampsia. Our findings suggested that maternal HCV infection was significantly associated with an increased risk of impaired intrauterine fetal growth. In clinical practice, a closer monitoring of intrauterine fetal growth by a series of ultrasound might be necessary for HCV-infected pregnant population. PMID:27583932

  9. Therapeutic vaccination against chronic hepatitis C virus infection

    NARCIS (Netherlands)

    Ip, Peng Peng; Nijman, Hans W.; Wilschut, Jan; Daemen, Toos

    2012-01-01

    Approximately 170 million people worldwide are chronic carriers of Hepatitis C virus (HCV). To date, there is no prophylactic vaccine available against HCV. The standard-of-care therapy for HCV infection involves a combination of pegylated interferon-α and ribavirin. This therapy, which is commonly

  10. [Pulmonary vasculitis as a clinical mask of HCV infection: efficiency of interferon-free antiviral therapy].

    Science.gov (United States)

    Stelmakh, V V; Kozlov, V K; Sukhanov, D S; Skipsky, I M

    2014-01-01

    The paper describes a clinical case of pulmonary vasculitis caused by hepatitis C virus (HCV). Its diagnosis was established on the basis of in-depth laboratory testing and an investigation of the molecular biological markers of viremia (polymerase chain reaction--PCR--HCV RNA) in peripheral blood mononuclear cells. By taking into account of extrahepatic HCV replication and contraindications to interferon therapy, the female patient was given an interferon-free antiviral therapy cycle using an interferonogenic inductor in combination with ribavirin. Pathogenic therapy (methylpred and ursodeoxycholic acid) was additionally performed. An interferon-free regimen of cycloferon + ribavirin led to sustained remission of HCV infection running with its systemic manifestations. The therapy could improve the function of not only the liver, but also the lung. In suspected extrahepatic HCV infections, an investigation of molecular biological markers for viremia (HCV RNA PCR) in the peripheral blood mononuclear cells is an essential diagnostic technique. Interferonogenic inductors, cycloferon in particular, should be used in combination with ribavirin when a chronic hepatitis C patient with the extrahepatic manifestations of HCV infection has contraindications to conventional therapy with recombinant interferon-α. PMID:25715495

  11. Serum Islet Cell Autoantibodies During Interferon α Treatment in Patients With HCV-Genotype 4 Chronic Hepatitis

    Directory of Open Access Journals (Sweden)

    Gamal Badra

    2006-01-01

    Full Text Available Chronic hepatitis C virus (HCV infection is a leading cause of end-stage liver disease worldwide and HCV genotype 4 (HCV4 is predominant in African and Middle Eastern countries. It is well established that interferon-α (IFNa treatment for HCV may trigger serum autoantibodies against pancreatic islet cells (ICA in a subgroup of patients. Available data on the incidence of ICA during IFNa therapy for chronic HCV4 infection are not conclusive. We investigated the appearance of ICA in 40 naïve Egyptian patients (38 males, 32 ± 6 years with histologically defined chronic HCV4 infection undergoing IFNa treatment at a dose of 9-million U/week for 24 weeks. Serum samples were collected at baseline and following IFNa therapy and ICA were detected using indirect immunofluorescence. Baseline evaluation indicated that 2/40 (5% patients had detectable serum ICA. After the completion of the treatment scheme, 12/38 (32% previously ICA negative patients became ICA positive; however, no patient developed impaired glucose tolerance (IGT or diabetes during follow-up. In conclusion, we submit that IFNa treatment for chronic hepatitis C (CHC may induce serum ICA in one-third of Egyptian patients with HCV4. These autoantibodies, however, do not lead to alterations in glucose metabolism.

  12. Study on the diagnosis value of combination of HCV-cAg and anti-HCV in HCV infection%HCV-cAg和HCV-Ab联合检测对HCV感染诊断价值的研究

    Institute of Scientific and Technical Information of China (English)

    林俊填; 余晋林; 伍伟健; 陈展泽; 龚道元

    2015-01-01

    Objective To explore the clinical value of combination of HCV-cAg and anti-HCV detection in HCV infection. Methods The serum samples from outpatients and inpatients were detected for HCV-cAg,anti-HCV and HCV-RNA. The quanti-tative real-time PCR was applied to detect HCV-RNA,and enzyme-linked immunosorbent assay (ELISA) kits were utilized to test anti-HCV and HCV-cAg). Result The sensitivity and specificity of anti-HCV detection were 90.91% and 99.17% respectively, and that of HCV-cAg were 70.25%and 100%respectively. Notably,the sensitivity(99.17%) and specificity(99.17%) increased sig-nificantly in case of combinational detection method. In addition,no consistency between the results of anti-HCV and HCV-cAg was detected. Conclusion Combination detection of anti-HCV and HCV-cAg was recommended because of its remarkable advan-tage in screening and diagnosis of HIV infection.%目的:探讨HCV-cAg和HCV-Ab两个指标联合检测对HCV感染的临床价值。方法对门诊和住院患者血液标本进行HCV-cAg、HCV-Ab 及HCV-RNA联合检测,采用实时荧光定量 PCR 法检测 HCV-RNA,采用酶联免疫吸附法(ELISA)检测试剂盒检测HCV-Ab和HCV-cAg。结果 HCV-Ab检测的灵敏度和特异度分别为90.91%和99.17%;HCV-cAg检测的灵敏度和特异度分别为70.25%和100%,两者的特异度相近,但是HCV-Ab检测的灵敏度比HCV-cAg的要高。两者联合检测时灵敏度和特异度分别为99.17%和99.17%,灵敏度明显增加。此外,HCV-Ab和HCV-cAg两者之间的检测结果无一致性。结论 HCV-Ab和HCV-cAg检测相互间无法替代,将抗-HCV和HCV-cAg两种指标结合起来检测,对临床上提高HCV感染的筛查和诊断具有重要的价值。

  13. Current and future disease progression of the chronic HCV population in the United States.

    Science.gov (United States)

    Zalesak, Martin; Francis, Kevin; Gedeon, Alex; Gillis, John; Hvidsten, Kyle; Kidder, Phyllis; Li, Hong; Martyn, Derek; Orne, Leslie; Smith, Amanda; Kwong, Ann

    2013-01-01

    Chronic hepatitis C virus (HCV) infection can lead to advanced liver disease (AdvLD), including cirrhosis, decompensated cirrhosis, and liver cancer. The aim of this study was to determine recent historical rates of HCV patient progression to AdvLD and to project AdvLD prevalence through 2015. We first determined total 2008 US chronic HCV prevalence from the National Health and Nutrition Evaluation Surveys. Next, we examined disease progression and associated non-pharmacological costs of diagnosed chronic HCV-infected patients between 2007-2009 in the IMS LifeLink and CMS Medicare claims databases. A projection model was developed to estimate AdvLD population growth through 2015 in patients diagnosed and undiagnosed as of 2008, using the 2007-2009 progression rates to generate a "worst case" projection of the HCV-related AdvLD population (i.e., scenario where HCV treatment is the same in the forecasted period as it was before 2009). We found that the total diagnosed chronic HCV population grew from 983,000 to 1.19 million in 2007-2009, with patients born from 1945-1964 accounting for 75.0% of all patients, 83.7% of AdvLD patients, and 79.2% of costs in 2009, indicating that HCV is primarily a disease of the "baby boomer" population. Non-pharmacological costs grew from $7.22 billion to $8.63 billion, with the majority of growth derived from the 60,000 new patients that developed AdvLD in 2007-2009, 91.5% of whom were born between 1945 and 1964. The projection model estimated the total AdvLD population would grow from 195,000 in 2008 to 601,000 in 2015, with 73.5% of new AdvLD cases from patients undiagnosed as of 2008. AdvLD prevalence in patients diagnosed as of 2008 was projected to grow 6.5% annually to 303,000 patients in 2015. These findings suggest that strategies to diagnose and treat HCV-infected patients are urgently needed to increase the likelihood that progression is interrupted, particularly for patients born from 1945-1964.

  14. Safety and antiviral activity of JTK-652: a novel HCV infection inhibitor

    NARCIS (Netherlands)

    J. de Bruijne; J.F. Bergmann; C.J. Weegink; C.M.J. van Nieuwkerk; R.J. de Knegt; Y. Komoda; J.J. van de Wetering de Rooij; A. van Vliet; P.L.M. Jansen; R. Molenkamp; J. Schinkel; H. Reesink; H.L.A. Janssen

    2010-01-01

    Standard treatment of chronic hepatitis C with pegylated interferon and ribavirin is associated with suboptimal virological response rates and substantial side effects. This study describes the in vitro and in vivo development of JTK-652, a novel pyrrolopyridazin-derived HCV infection inhibitor. JTK

  15. Analysis of hepatitis non-treatment causes in a cohort of HCV and HCV/HIV infected patients

    Directory of Open Access Journals (Sweden)

    Karen Pereira

    2014-11-01

    Full Text Available Introduction: The decision to start hepatitis C virus (HCV treatment and its timing remains controversial. As new treatment regimens are approved, it is essential to identify patients eligible for each regimen in a timed and tailored approach. This study aims to identify the reasons to defer treatment of chronic hepatitis C infection in both HCV and HCV/HIV infected patients. Materials and Methods: Retrospective observational study of a cohort of HCV chronically infected patients with or without HIV infection, followed in an infectious disease clinic in Lisbon. Demographic, epidemiological, clinical, immunologic and virologic data were collected. Statistical analysis was performed with Microsoft Office®- Excel 2012. Kolmogorov-Smirnov, t-test, Chi-square and correlation analysis were performed for a significant p value<0.05. Results: The study included 669 patients, 225 patients infected with HCV (group A and 444 patients co-infected with HCV/HIV (group B. The comparative analysis of those groups (A vs. B showed: mean age was 49.4 years versus 46.9 (p<0.01, mean time since HCV diagnosis was 9.5 versus 14.6 years (p=0.558 both groups shared a male predominance and HCV acquisition due to intravenous drug use. Regarding genotype characterization, the predominant was 1a in both groups (p<0.01. Evaluation of IL28B polymorphism revealed CC 15.5% (A versus 9.45% (B (p<0.01. Group B mean TCD4 count was 585 cells/µL (mean percentage 27.1%. There was spontaneous viral clearance in 10.7% (A versus 4.1% (B (p<0.01. There were treated 52.0% (A versus 32.2% (B patients (p<0.01. For the untreated ones (107 – group A vs 270 – group B, no reason was identified for treatment deferral in 32.5% (A versus 48.0% (B patients. The most frequent reasons for deferring treatment were: withdrawal to follow-up (33.7%, active staging of disease (7.2%, alcohol abuse (6.0% and advanced age (6.0% in group A versus low TCD4 cell count (17.1%, loss to follow-up (7.5%, poor

  16. IL28B Polymorphism Is Not Associated With HCV Protease Diversity in Patients Co-Infected With HIV and HCV Treated With Pegylated Interferon and Ribavirin

    Science.gov (United States)

    Osinusi, Anu; Chary, Aarthi; Winters, Mark A.; Naggie, Susanna; Masur, Henry; Polis, Michael A.; Kottilil, Shyam; Holodniy, Mark

    2013-01-01

    Recent studies have demonstrated that IL28B polymorphisms predict therapeutic responses in chronic hepatitis C virus (HCV)-treated patients; however, the effect on HCV viral diversity, particularly on the HCV protease gene, is not clear. This study sought to evaluate the effect of IL28B polymorphisms on HCV diversity at NS3/4 protease region, which may influence therapeutic response to an HCV protease inhibitor based regimen. Twenty-two patients co-infected with HIV and HCV genotype 1, treatment-naïve on stable HIV antiretroviral therapy initiating interferon-based treatment were evaluated. Plasma HCV NS3 gene diversity was analyzed by clonal analysis at baseline and end of treatment. IL28B (rs12979860) genotypes were tested for associations with virologic outcomes and diversity parameters. There was similar baseline NS3 diversity in patients with CC (favorable) genotype compared to those with CT/TT (unfavorable) genotypes. There was no significant association between IL28B genotype and baseline NS3 nucleotide p-distance, dS-dN, amino acid p-distance, or nucleotide changes. Among patients without a sustained virologic response, between baseline and follow-up there was a significant trend towards decreased diversity after treatment among patients with favorable genotype, which was not observed in unfavorable genotypes. In patients treated with peginterferon/ribavirin therapy, IL28B polymorphism was not associated with enhanced NS3 diversity at baseline. Among non-SVR patients with the less favorable genotype, there was no change in diversity after treatment. This suggests that IL28B genotype is unlikely to have a negative impact on subsequent HCV PI efficacy in patients co-infected with HIV and HCV patients who have previously failed HCV therapy. PMID:22930497

  17. Comprehensive longitudinal analysis of hepatitis C virus (HCV)-specific T cell responses during acute HCV infection in the presence of existing HIV-1 infection

    NARCIS (Netherlands)

    C.H.S.B. van den Berg; T.A. Ruys; N.M. Nanlohy; S.E. Geerlings; J.T. van der Meer; J.W. Mulder; J.A. Lange; D. van Baarle

    2009-01-01

    The aim of this study was to study the development of HCV-specific T cell immunity during acute HCV infection in the presence of an existing HIV-1 infection in four HIV-1 infected men having sex with men. A comprehensive analysis of HCV-specific T cell responses was performed at two time points duri

  18. SKI-1/S1P inhibitor PF-429242 impairs the onset of HCV infection.

    Science.gov (United States)

    Blanchet, Matthieu; Sureau, Camille; Guévin, Carl; Seidah, Nabil G; Labonté, Patrick

    2015-03-01

    Worldwide, approximately 170 million individuals are afflicted with chronic hepatitis C virus (HCV) infection. To prevent the development of inherent diseases such as cirrhosis and hepatocellular carcinoma, tremendous efforts have been made, leading to the development of promising new treatments. However, their efficiency is still dependent on the viral genotype. Additionally, these treatments that target the virus directly can trigger the emergence of resistant variants. In a previous study, we have demonstrated that a long-term (72h) inhibition of SKI-1/S1P, a master lipogenic pathway regulator through activation of SREBP, resulted in impaired HCV genome replication and infectious virion secretion. In the present study, we sought to investigate the antiviral effect of the SKI-1/S1P small molecule inhibitor PF-429242 at the early steps of the HCV lifecycle. Our results indicate a very potent antiviral effect of the inhibitor early in the viral lifecycle and that the overall action of the compound relies on two different contributions. The first one is SREBP/SKI-1/S1P dependent and involves LDLR and NPC1L1 proteins, while the second one is SREBP independent. Overall, our study confirms that SKI-1/S1P is a relevant target to impair HCV infection and that PF-429242 could be a promising candidate in the field of HCV infection treatment.

  19. Hepatocyte Turnover in Chronic HCV-Induced Liver Injury and Cirrhosis

    Directory of Open Access Journals (Sweden)

    Nikolaos P. Karidis

    2015-01-01

    Full Text Available Chronic hepatitis C virus (HCV infection may eventually lead to progressive liver fibrosis and cirrhosis through a complex, multistep process involving hepatocyte death and regeneration. Despite common pathogenetic pathways present in all forms of liver cirrhosis irrespective of etiology, hepatocyte turnover and related molecular events in HCV-induced cirrhosis are increasingly being distinguished from even “similar” causes, such as hepatitis B virus- (HBV- related cirrhosis. New insights in HCV-induced hepatocellular injury, differential gene expression, and regenerative pathways have recently revealed a different pattern of progression to irreversible parenchymal liver damage. A shift to the significant role of the host immune response rather than the direct effect of HCV on hepatocytes and the imbalance between antiapoptotic and proapoptotic signals have been investigated in several studies but need to be further elucidated. The present review aims to comprehensively summarize the current evidence on HCV-induced hepatocellular turnover with a view to outline the significant trends of ongoing research.

  20. Association of CMV, HBV, or HCV co-infection with vaccine response in adults with well-controlled HIV infection.

    Science.gov (United States)

    Troy, S B; Rossheim, A E B; Siik, J; Cunningham, T D; Kerry, J A

    2016-05-01

    Even after CD4 count recovery on antiretroviral therapy, HIV infection is associated with decreased response to most vaccines compared to the general population. Chronic infections with viruses such as cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV), which are more prevalent in HIV-infected populations, have been linked to immune dysfunction and decreased vaccine response in the general population. However, whether co-infection with these other viruses contributes to the decreased vaccine response seen in adults with well-controlled HIV infection is unknown. We conducted a secondary analysis of data and serum from adults with well-controlled HIV infection from an inactivated polio vaccine trial (224 subjects) and a pneumococcal conjugate vaccine study (128 subjects). We evaluated the association of CMV, HBV, or HCV co-infection with post-vaccination antibody levels using both univariate and multivariate analyses, controlling for factors such as age, race, CD4 count, comorbidities, smoking status, and baseline antibody levels. Ninety-three percent, 7%, and 14% of subjects were co-infected with CMV, HBV, and HCV respectively. On both univariate and multivariate analysis, neither CMV nor HCV co-infection were significantly associated with post-vaccination antibody levels to either vaccine. HBV co-infection was significantly associated with post-vaccination antibody concentrations for pneumococcal serotype 7F on univariate analysis and 6A on multivariate analysis, but the association was with higher antibody concentrations. In conclusion, co-infection with CMV, HBV, or HCV does not appear to contribute to the decreased vaccine response seen in adults with well-controlled HIV infection. PMID:26751638

  1. Mortality in patients with chronic and cleared hepatitis C viral infection: a nationwide cohort study

    DEFF Research Database (Denmark)

    Omland, Lars Haukali; Krarup, Henrik; Jepsen, Peter;

    2010-01-01

    It is unknown whether mortality differs between patients with chronic hepatitis C virus (HCV) replication and those who cleared the virus after infection. We examined the impact of chronic HCV replication on mortality among Danish patients testing positive for HCV antibodies....

  2. Lack of TNF-α Gene Polymorphism (rs1799724) Association with Sustained Virological Response in Iranian Patients with Chronic HCV Infection.

    Science.gov (United States)

    Larijani, Mona Sadat; Bahiraei, Narges; Nikbin, Mehri; Mohajel, Nasir; Rad, Leila Naghizadeh; Baghbani, Fahimeh; Mapar, Maryam; Sadat, Seyed Mehdi

    2016-01-01

    Infection with the hepatitis C virus is a major public health concern which can lead to carcinoma and liver failure. It has been shown that single nucleotide polymorphisms can affect the level of gene activity of tumor necrosis factor (TNF) which has an important role, especially in viral infections which can lead to apaptosis of infected hepatocellular cells. We investigated the impact of three possible genotypes for rs1800629 or A/G single nucleotide polymorphism located downstream of TNFα gene promoter in groups of control (n=76) and chronic hepatitis C patients (n=89) focusing on the response to treatment among sensitive and resistant groups. Genomic DNA was extracted from 500 μl prepheral whole blood and PCR and RFLP were used to amplify the region of interest and genotyping. With statistical analyzes a p-value <0.05 was considered meaningful. There was no significant difference in distribution of the possible three genotypes among healthy individuals and patients (P=0.906, OR=1.194, CI=0.063-22.790). However, the frequency of the G allele was higher in patients whereas A allele was more common among healthy individuals (p<0.0001). Further studies with more samples appears to be necessary. PMID:27644640

  3. Systemic Cytokine and Interferon Responsiveness Patterns in HIV and HCV Mono and Co-Infections

    OpenAIRE

    Fernandez-Botran, Rafael; Joshi-Barve, Swati; Ghare, Smita; Barve, Shirish; Young, Mary; Plankey, Michael; Bordon, Jose

    2014-01-01

    The role of host response-related factors in the fast progression of liver disease in individuals co-infected with HIV and HCV viruses remains poorly understood. This study compared patterns of cytokines, caspase-1 activation, endotoxin exposure in plasma as well as interferon signaling in peripheral blood mononuclear cells from HIV/HCV co-infected (HIV+/HCV+), HCV mono-infected (HIV−/HCV+), HIV mono-infected (HIV+/HCV−) female patients and HIV- and HCV-uninfected women (HIV−/HCV−) who had en...

  4. Transcriptional Dysregulation of Upstream Signaling of IFN Pathway in Chronic HCV Type 4 Induced Liver Fibrosis

    Science.gov (United States)

    Ibrahim, Marwa K.; Salum, Ghada Maher; Bader El Din, Noha G.; Dawood, Reham M.; Barakat, Ahmed; Khairy, Ahmed; El Awady, Mostafa K.

    2016-01-01

    IFN orchestrates the expression of various genes to halt hepatitis C virus (HCV) replication with the possibility of either reduced or increased liver fibrosis; due to controlled viral replication or overproduction of inflammatory mediators, repectively. In this study, we examined the transcriptional profiling of type I IFN related genes in HCV-chronically infected patients with varying degrees of liver fibrosis. PCR array was used to examine the expression of 84 type I IFN related genes in peripheral blood mononuclear cells (PBMCs) RNA from 12 treatment-naïve chronic HCV patients (5 F0-F1 and 7 F2-F4) and 5 healthy subjects. We further validated our results by quantitative real time PCR (qRT-PCR) in 103 treatment-naïve chronic HCV patients (43 F0-F1 and 60 F2-F4) and 15 controls. PCR array data revealed dysregulation in TLR7 pathway. The expression of TLR7 was decreased by 4 folds and MyD88 was increased by 3 folds in PBMCs of F2-F4 patients when compared to the healthy volunteers (p = 0.03 and 0.002, respectively). In addition, IRF7 and TLR7 showed dramatic downregulation (6 and 8 folds, respectively) in F2-F4 patients when compared to F0-F1 ones. qRT-PCR confirmed the altered expression patterns of TLR7 and MyD88 in F2-F4 patients when compared to either controls or F0-F1 patients. However, by qRT-PCR, IRF7 and NF-κB1 (TLR7 pathway transcription factors) exhibited similar mRNA abundance among F2-F4 and F0-F1 patients. These results suggest that TLR7 and MyD88 are possible candidates as biomarkers for the progression of HCV-induced liver fibrosis and/ or targets for therapeutic intervention. PMID:27135246

  5. HBV vaccination of HCV-infected patients with occult HBV infection and anti-HBc-positive blood donors

    Directory of Open Access Journals (Sweden)

    J.S.F. Pereira

    2006-04-01

    Full Text Available Anti-HBc positivity is a frequent cause of donation rejection at blood banks. Hepatitis B virus (HBV infection may also occur in HBsAg-negative patients, a situation denoted occult infection. Similarly, very low levels of HBV-DNA have also been found in the sera of patients with chronic hepatitis C virus (HCV infection, even in the absence of serum HBsAg. Initially we searched for HBV-DNA in serum of 100 blood donors and 50 HCV-infected patients who were HBsAg negative/anti-HBc positive by nested-PCR and by an HBV monitor commercial test for HBV-DNA. Anti-HBs seroconversion rates were measured in 100 blood donors and in 22 patients with chronic HCV infection after HBV vaccination to determine if the HBV vaccination could eliminate an occult HBV infection in these individuals. Occult HBV infection was detected in proportionally fewer blood donors (6/100 = 6% than chronic hepatitis C patients (12/50 = 24% (P 0.05. All subjects who were HBV-DNA(+ before the first dose of HBV vaccine (D1, became HBV-DNA(- after D1, D2, and D3. Among 22 HCV-positive patients, 10 HBV-DNA(+ and 12 HBV-DNA(-, seroconversion was observed in 9/10 (90% HBV-DNA(+ and in 9/12 (75% HBV-DNA(- subjects (P > 0.05. The disappearance of HBV-DNA in the majority of vaccinated patients suggests that residual HBV can be eliminated in patients with occult infection.

  6. Insulin resistance and steatosis in HBV-HCV co-infected patients: Role of PNPLA3 polymorphisms and impact on liver fibrosis progression

    Institute of Scientific and Technical Information of China (English)

    Rosa; Zampino; Adriana; Boemio; Aldo; Marrone; Luciano; Restivo; Maria; Chiara; Fascione; Riccardo; Nevola; Luigi; Elio; Adinolfi; Nicola; Coppola; Carmine; Minichini; Mario; Starace; Evangelista; Sagnelli; Grazia; Cirillo; Emanuele; Miraglia; del; Giudice; Maria; Stanzione; Emanuele; Durante-Mangoni; Giovanna; Salzillo

    2014-01-01

    AIM:To evaluate steatosis,insulin resistance(IR)and patatin-like phospholipase domain-containing 3(PNPLA3) and their relation to disease progression in hepatitis B and C viruses(HCV-HBV) coinfected patients.METHODS:Three hundred and thirty patients with biopsy proven chronic hepatitis were enrolled:66 had HBV-HCV,66 HBV and 198 HCV infection.Prevalence of steatosis,IR and PNPLA3 polymorphisms and their relation to anthropometric,biochemical,virological and histological parameters were evaluated.RESULTS:Prevalence of steatosis in group HBV-HCV was similar to that in HCV(47.0% vs 49.5%,respec-tively);group HBV showed the lowest steatosis(33.3%).Group HBV-HCV had a lesser degree of steatosis than HCV(P = 0.016),lower HCV RNA levels(P = 0.025) and lower prevalence and degree of IR(P = 0.01).PNPLA3 polymorphisms were associated with steatosis.Group HBV-HCV showed higher levels of liver fibrosis than group HCV(P = 0.001),but similar to that ob-served in HBV group.In HBV-HCV group,liver fibrosis was not associated with steatosis,IR or PNPLA3.HBV infection was the independent predictor of advanced liver fibrosis.CONCLUSION:HBV-HCV co-infected patients have lower degree of hepatic steatosis,IR and HCV RNA than HCV mono-infected;co-infected patients showed a more rapid liver fibrosis progression that seems to be due to the double infection and/or HBV dominance.

  7. Evidence for Protection against Chronic Hepatitis C Virus Infection in Chimpanzees by Immunization with Replicating Recombinant Vaccinia Virus▿

    OpenAIRE

    Youn, Jin-Won; Hu, Yu-Wen; Tricoche, Nancy; Pfahler, Wolfram; Shata, Mohamed Tarek; Dreux, Marlene; Cosset, François-Loic; Folgori, Antonella; Lee, Dong-Hun; Brotman, Betsy; Prince, Alfred M.

    2008-01-01

    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...

  8. Management of Antiviral Induced Anemia in HCV Infected Patients

    Directory of Open Access Journals (Sweden)

    Mitra Ranjbar

    2005-03-01

    Full Text Available IntroductionHepatitis C virus (HCV infection affects more than 170 million people worldwide(1,2. Approximately 80% of patients with acute infection will subsequently develop chronic disease, and an estimated 20% to 30% will develop cirrhosis and hepatocellular carcinoma(3. The maost effective therapeutic regimen for chronic hepatitis C is the combination of pegylated interferon alpha and ribavirin, which yields a sustained virologic response (SVR in up to 56% of patients(4, 5. However, combination therapy is also associated with significant adverse events and is contraindicated in certain patient populations. Development of side effects, particularly hematologic ones, may result in suboptimal dosing or discontinuation of therapy that can reduce the likelihood of SVR.IncidenceIn clinical trials, significant anemia (hemoglobin 10.6 mg/kg/d is 65% compared with a rate of 50% for those receiving peginterferon alfa-2b plus ribavirin at dosages of 10.6 mg/kg/d or less.It has been shown that SVR rates are significantly higher in patients who receive more than 80% of their full interferon alfa-2b plus ribavirin doses for more than 80% of the time for more than 80% of the intended duration of therapy(14. In the Hepatitis C Long-term Treatment Against Cirrhosis (HALT-C trial, a trial involving patients who were previous nonresponders to or relapsers after therapy, reduction of ribavirin dose from> 80% to 10.6 mg/kg/d. The standard-of-care management of ribavirin induced anemia has been dose reduction to 600 mg/d when the hemoglobin level decreases to =2g/dL decrease inhemoglobinduring any 4-weektreatment period 12g/dL despite 4weeks at reduceddose Recombinant human erythropoietin therapy in the HCV-infected patient who becomes anemic during antiviral therapy represents an alternative to ribavirin dose reduction or discontinuation. Erythropoietin is mainly produced by the kidney in adults in response to tissue hypoxia, and it increases the number of

  9. [Investigation of the correlation between anti-HCV levels (S/Co) with HCV-RNA in the diagnosis of hepatitis C virus (HCV) infection].

    Science.gov (United States)

    Şanlıdağ, Tamer; Akçalı, Sinem; Ecemiş, Talat; Süer, Kaya; Erbay Dündar, Pınar; Arıkan, Ayşe; Güvenir, Meryem; Güler, Emrah

    2016-07-01

    Detection of borderline and/or low positive anti-HCV results by enzyme immunoassay (EIA) leads to severe problems in routine laboratories and needs confirmation with nucleic acid amplification tests which can increase the cost. In EIA tests, if the ratio of sample to cut-off (S/Co) is ≥ 1, the sample is accepted as positive according to the manufacturers' instructions. Although over the last decade the application of S/Co values have also applied to HCV-RNA readings, the current study aims to determine whether the S/Co value is adequate and applicable for the anti-HCV EIA test, and to determine whether a correlation exists between HCV-RNA and HCV infections. A total of 658 cases (402 female, 256 male; mean age: 49.4 ± 17.0 years) who were found anti-HCV positive between January 2011-July 2013 were included in the study. Anti-HCV tests were performed by chemiluminescent EIA (Architect i2000SR, Abbott, USA and LiaisonXL Murex, DiaSorin, Italy) and HCV-RNA by real-time PCR (Cobas Ampliprep/Cobas TaqMan HCV, Roche, USA). The mean S/Co value of the cases was 7.3 ± 4.8 (range: 1.00-17.59) and mean HCV-RNA value was 2.3x105 ± 2.1x106 copies/ml. When the anti-HCV S/Co value of varying ranges was compared with HCV-RNA readings a particular trend was noted. In the anti-HCV S/Co values of 1.0-4.0; 4.1-7.0; 7.1-10.0; 10.1-13.0; 13.1-16.0 and ³16.1, HCV-RNA positivity rates were detected as 1.9%, 24.7%,37.1%, 46.7%, 56.4% and 75%, respectively. Statistical analysis indicated an intermediate positive correlation (r= 0.454) between anti-HCV ve HCV-RNA readings (p= 0.000). An adequate S/Co value was accepted as 5.0 based on the ROC analysis, and this value gave a performance confidence level of 95.6% when determining whether a patient is HCV positive. Based on the data of this study it became evident that further EIA testing is not required if the S/Co value is ≥ 5.0, however if the S/Co value is less than 5.0, then further clinical analysis and revaluation of the patient

  10. Managing HCV infection in pediatric age group: Suggested recommendations

    Directory of Open Access Journals (Sweden)

    Danish Fazal

    2010-01-01

    Full Text Available Hepatitis C virus (HCV infection in children is different from the adult infection in many ways, like natural course of the disease; duration, therapeutic response and side effects profile of the drug therapy; and prognosis. Special considerations include consideration on what could be the appropriate time to investigate a suspected child, when to institute drug therapy and how to prevent vertical transmission. Although over the past one decade many landmark studies have greatly increased our insight on this subject, yet we are far from developing a consensus statement. In this article, a concise yet comprehensive review of HCV infection in children - diagnosis and treatment - is given, followed by suggested recommendations at the end. It is hoped that these recommendations will help develop local guidelines on this subject.

  11. Stability of hepatitis C virus (HCV) RNA levels among interferon-naïve HIV/HCV-coinfected individuals treated with combination antiretroviral therapy

    DEFF Research Database (Denmark)

    Grint, D; Peters, L; Reekie, J;

    2013-01-01

    Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. High HCV RNA levels have been associated with poor treatment response. This study aimed to examine the natural history of HCV RNA in chronically HCV/HIV-coinfected individuals.......Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. High HCV RNA levels have been associated with poor treatment response. This study aimed to examine the natural history of HCV RNA in chronically HCV/HIV-coinfected individuals....

  12. HCV genotyping from NGS short reads and its application in genotype detection from HCV mixed infected plasma.

    Science.gov (United States)

    Qiu, Ping; Stevens, Richard; Wei, Bo; Lahser, Fred; Howe, Anita Y M; Klappenbach, Joel A; Marton, Matthew J

    2015-01-01

    Genotyping of hepatitis C virus (HCV) plays an important role in the treatment of HCV. As new genotype-specific treatment options become available, it has become increasingly important to have accurate HCV genotype and subtype information to ensure that the most appropriate treatment regimen is selected. Most current genotyping methods are unable to detect mixed genotypes from two or more HCV infections. Next generation sequencing (NGS) allows for rapid and low cost mass sequencing of viral genomes and provides an opportunity to probe the viral population from a single host. In this paper, the possibility of using short NGS reads for direct HCV genotyping without genome assembly was evaluated. We surveyed the publicly-available genetic content of three HCV drug target regions (NS3, NS5A, NS5B) in terms of whether these genes contained genotype-specific regions that could predict genotype. Six genotypes and 38 subtypes were included in this study. An automated phylogenetic analysis based HCV genotyping method was implemented and used to assess different HCV target gene regions. Candidate regions of 250-bp each were found for all three genes that have enough genetic information to predict HCV genotypes/subtypes. Validation using public datasets shows 100% genotyping accuracy. To test whether these 250-bp regions were sufficient to identify mixed genotypes, we developed a random primer-based method to sequence HCV plasma samples containing mixtures of two HCV genotypes in different ratios. We were able to determine the genotypes without ambiguity and to quantify the ratio of the abundances of the mixed genotypes in the samples. These data provide a proof-of-concept that this random primed, NGS-based short-read genotyping approach does not need prior information about the viral population and is capable of detecting mixed viral infection.

  13. Spontaneous viral clearance, viral load, and genotype distribution of hepatitis C virus (HCV) in HIV-infected patients with anti-HCV antibodies in Europe

    DEFF Research Database (Denmark)

    Soriano, Vincent; Mocroft, Amanda; Rockstroh, Juergen;

    2008-01-01

    BACKGROUND: Variables influencing serum hepatitis C virus (HCV) RNA levels and genotype distribution in individuals with human immunodeficiency virus (HIV) infection are not well known, nor are factors determining spontaneous clearance after exposure to HCV in this population. METHODS: All HCV...... antibody (Ab)-positive patients with HIV infection in the EuroSIDA cohort who had stored samples were tested for serum HCV RNA, and HCV genotyping was done for subjects with viremia. Logistic regression was used to identify variables associated with spontaneous HCV clearance and HCV genotype 1. RESULTS......: Of 1940 HCV Ab-positive patients, 1496 (77%) were serum HCV RNA positive. Injection drug users (IDUs) were less likely to have spontaneously cleared HCV than were homosexual men (20% vs. 39%; adjusted odds ratio [aOR], 0.36 [95% confidence interval {CI}, 0.24-0.53]), whereas patients positive...

  14. Expression of core antigen of HCV genotype 3a and its evaluation as screening agent for HCV infection in Pakistan

    Directory of Open Access Journals (Sweden)

    Rehman Irshad U

    2011-07-01

    Full Text Available Abstract Background Pakistan is facing a threat from hepatitis C infection which is increasing at an alarming rate throughout the country. More specific and sensitive screening assays are needed to timely and correctly diagnose this infection. Methods After RNA extraction from specimen (HCV-3a, cDNA was synthesized that was used to amplify full length core gene of HCV 3a. After verification through PCR, DNA sequencing and BLAST, a properly oriented positive recombinant plasmid for core gene was digested with proper restriction enzymes to release the target gene which was then inserted downstream of GST encoding DNA in the same open reading frame at proper restriction sites in multiple cloning site of pGEX4t2 expression vector. Recombinant expression vector for each gene was transformed in E. coli BL21 (DE3 and induced with IPTG for recombinant fusion protein production that was then purified through affinity chromatography. Western blot and Enzyme Linked Immunosorbant Assay (ELISA were used to detect immuno-reactivity of the recombinant protein. Results The HCV core antigen produced in prokaryotic expression system was reactive and used to develop a screening assay. After validating the positivity (100% and negativity (100% of in-house anti-HCV screening assay through a standardized panel of 200 HCV positive and 200 HCV negative sera, a group of 120 serum specimens of suspected HCV infection were subjected to comparative analysis of our method with commercially available assay. The comparison confirmed that our method is more specific than the commercially available assays for HCV strains circulating in this specific geographical region of the world and could thus be used for HCV screening in Pakistan. Conclusion In this study, we devised a screening assay after successful PCR amplification, isolation, sequencing, expression and purification of core antigen of HCV genotype 3a. Our developed screening assay is more sensitive, specific and

  15. The Association between Female Genital Cutting and Spousal HCV Infection in Egypt

    OpenAIRE

    Chris R. Kenyon; Robert Colebunders

    2014-01-01

    Objective. To identify the risk factors for HCV infection within married couples in Egypt. Methods. In 2008 Egypt conducted its first nationally representative survey of HCV prevalence. 11126 of the 12780 individuals aged 15–59 year who were sampled agreed to participate and provided information via a questionnaire about demographic and behavioural characteristics and blood for HCV antibody and RNA analysis. We assessed the risk factors for HCV infection in a subsample of 5182 married individ...

  16. Transcriptomic assay of CD8+ T cells in treatment-naive HIV, HCV-mono-infected and HIV/HCV-co-infected Chinese.

    Directory of Open Access Journals (Sweden)

    Jin Zhao

    Full Text Available BACKGROUND: Co-infection with HIV and HCV is very common. It is estimated that over 5 million people are co-infected with HIV and HCV worldwide. Accumulated evidence shows that each virus alters the course of infection of the other one. CD8+ T cells play a crucial role in the eradication of viruses and infected target cells. To the best of our knowledge, no one has investigated the gene expression profiles in HIV/HCV-co-infected individuals. METHODOLOGY: Genome-wide transcriptomes of CD8+ T cells from HIV/HCV-co-infected or mono-infected treatment-naïve individuals were analyzed by microarray assays. Pairwise comparisons were performed and differentially expressed genes were identified followed by quantitative real-time PCR (qRT-PCR validation. Directed Acyclic Graphs (DAG from Web-based Gene SeT AnaLysis Toolkit (WebGestalt and DAVID bioinformatics resources 6.7 (the Database for Annotation, Visualization, and Integrated Discovery were used to discover the Gene Ontology (GO categories with significantly enriched gene numbers. The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG pathways were also obtained by using WebGestalt software. RESULTS AND CONCLUSIONS: A total of 110, 24 and 72 transcript IDs were shown to be differentially expressed (> 2-fold and p<0.05 in comparisons between HCV- and HIV-mono-infected groups, HIV/HCV-co-infected and HIV-mono-infected groups, and HIV/HCV-co-infected and HCV-mono-infected groups, respectively. In qRT-PCR assay, most of the genes showed similar expressing profiles with the observation in microarray assays. Further analysis revealed that genes involved in cell proliferation, differentiation, transcriptional regulation and cytokine responses were significantly altered. These data offer new insights into HIV/HCV co-infections, and may help to identify new markers for the management and treatment of HIV/HCV co-infections.

  17. Geographical variations of risk factors associated with HCV infection in drug users in southwestern China.

    Science.gov (United States)

    Zhou, Y B; Wang, Q X; Yang, M X; Gong, Y H; Yang, Y; Nie, S J; Liang, S; Nan, L; Coatsworth, A; Yang, A H; Liao, Q; Song, X X; Jiang, Q W

    2016-04-01

    Hepatitis C virus (HCV) has become a global public health problem. Many studies have been conducted to identify risk factors for HCV infection. However, some of these studies reported inconsistent results. Using data collected from 11 methadone clinics, we fit both a non-spatial logistical regression and a geographically weighted logistic regression to analyse the association between HCV infection and some factors at the individual level. This study enrolled 5401 patients with 30·0% HCV infection prevalence. The non-spatial logistical regression found that injection history, drug rehabilitation history and senior high-school education or above were related to HCV infection; and being married was negatively associated with HCV infection. Using the spatial model, we found that Yi ethnicity was negatively related to HCV infection in 62·0% of townships, and being married was negatively associated with HCV infection in 81·0% of townships. Senior high-school education or above was positively associated with HCV infection in 55·2% of townships of the Yi Autonomous Prefecture. The spatial model offers better understanding of the geographical variations of the risk factors associated with HCV infection. The geographical variations may be useful for customizing intervention strategies for local regions for more efficient allocation of limited resources to control transmission of HCV. PMID:26542331

  18. The association of syringe type and syringe cleaning with HCV infection among IDUs in Budapest, Hungary.

    Science.gov (United States)

    Gyarmathy, V Anna; Neaigus, Alan; Mitchell, Mary M; Ujhelyi, Eszter

    2009-03-01

    We assessed whether syringe type, syringe cleaning and distributive syringe sharing were associated with self-reported and laboratory-confirmed HCV infection among Hungarian IDUs. Injecting drug users (N=215) were recruited from non-treatment settings in Budapest, Hungary between October 2005 and December 2006. Multivariate logistic regression models identified correlates of self-report of being HCV infected and testing positive for HCV. While 37% tested positive for HCV, 14% of the total (39% of those who tested positive) self-reported being HCV infected. Using any two-piece syringes was significantly associated with self-reported HCV infection, while distributive syringe sharing was not associated with self-report of being HCV infected. Engaging in receptive sharing of only one-piece syringes but always cleaning before reuse was not associated with testing HCV positive, while any receptive sharing of only one-piece syringes and not always cleaning before reuse was significantly associated with testing HCV positive. Sharing cookers and squirting drugs from one syringe into another syringe were not associated with testing HCV positive. The high percent of those HCV infected who did not know they were infected highlights the need to provide better access to confidential testing and counseling services. Counseling should emphasize secondary prevention of HCV among HCV infected IDUs. Our findings also indicate that syringe type and syringe cleaning practices may play a role in HCV transmission. Ethnographic research should identify the reasons why IDUs may use two-piece syringes and suggest means to reduce their use. Thorough cleaning of one-piece syringes when sterile syringes are unavailable may be an efficient way to reduce the risk of HCV infection. PMID:19058925

  19. Management of HCV Infection and Liver Transplantation

    Directory of Open Access Journals (Sweden)

    2006-04-01

    Full Text Available A major challenge facing liver transplant recipients and their physicians is recurrence of hepatitis C virus infection following otherwise technically successful liver transplantation. Recurrent infection leads to diminished graft and patient survival. Although a number or predictors of severe recurrence have been identified, no definitive strategy has been developed to prevent recurrence. Generally the tempo of hepatitis C recurrence is gauged by serial liver biopsies with the decision to intervene with antiviral therapy based on local philosophy and expertise. Treating hepatitis C in this population has a number of major challenges including diminished patient tolerance for side-effects as well as managing the patient's immunesuppression. However sustained viral responses are possible with the potential to reduce the impact of recurrent hepatitis on the graft. However recurrent hepatitis C virus infection will remain the most frequent form of recurrent disease in liver transplant programs for the foreseeable future.

  20. Validity of Autotaxin as a Novel Diagnostic Marker for Liver Fibrosis in Egyptian Chronic HCV Patients

    OpenAIRE

    Ezzat, Wafaa M.; Halla M. Ragab; Nabila Abd El Maksoud; Nour A. Abdulla; Yasser A. Elhosary

    2013-01-01

    We aimed to detect the validity of serum ATX as a diagnostic marker for liver fibrosis. Forty-eight males and 16 females were enrolled in the current study. Their ages ranged from 29-57 years with mean of 45.09, all were chronically HCV infected. Laboratory assessment was done for all subjects in form of complete blood picture; liver function test; lipid profile and serum detection of ATX. Patients were grouped according to the stage of fibrosis into group 1: fibrosis score 0, 1, 2, 3; group ...

  1. The Association between Female Genital Cutting and Spousal HCV Infection in Egypt

    Directory of Open Access Journals (Sweden)

    Chris R. Kenyon

    2014-01-01

    Full Text Available Objective. To identify the risk factors for HCV infection within married couples in Egypt. Methods. In 2008 Egypt conducted its first nationally representative survey of HCV prevalence. 11126 of the 12780 individuals aged 15–59 year who were sampled agreed to participate and provided information via a questionnaire about demographic and behavioural characteristics and blood for HCV antibody and RNA analysis. We assessed the risk factors for HCV infection in a subsample of 5182 married individuals via multivariate logistic regression. Results. Overall HCV antibody prevalence in the married couples was 18.2% (95% CI, 16.8–19.6. HCV antibody prevalence was higher in the husbands (23.7% than the wives (12.1%; P<0.001. Having a spouse who was infected with HCV was an independent risk factor for HCV infection with odds ratios of 2.1 (95% CI, 1.6–2.9 and 2.2 (95% CI, 1.6–3.1 for women and men, respectively. Husbands whose wives had experienced female genital cutting (FGC had a higher prevalence of HCV and this relationship was driven by a strong association in urban areas. Amongst the women there was no association between FGC and HCV overall but in urban areas only women who had experienced FGC were HCV infected. Conclusions. This study provides additional evidence of the importance of intrafamilial transmission of HCV in Egypt.

  2. Dental problems delaying the initiation of interferon therapy for HCV-infected patients

    Directory of Open Access Journals (Sweden)

    Nagao Yumiko

    2010-08-01

    Full Text Available Abstract Background There has been little discussion about the importance of oral management and interferon (IFN therapy, although management of the side effects of therapy for chronic hepatitis C has been documented. This study determined whether dental problems delayed the initiation of IFN therapy for hepatitis C virus (HCV-infected patients. Results We analyzed 570 HCV-infected patients who were admitted to our hospital from December 2003 to June 2010 for treatment consisting of pegylated IFN (Peg-IFN monotherapy or Peg-IFN/ribavirin combination therapy. The group comprised 274 men and 296 women with a mean age 57.2 years. Of the 570 patients, six could not commence Peg-IFN therapy, despite their admission, because of dental problems such as periodontitis, pupitis, and pericoronitis. The ages of six whose dental problems delayed the initiation of Peg-IFN ranged from 25 to 67 years, with a mean age of 47.3 ± 15.2 years. IFN therapy was deferred for 61.3 ± 47.7 days. Among the six subjects for whom IFN treatment was delayed, only one had a salivary flow that was lower than the normal value. Conclusions Treatment of dental infections is required before IFN therapy for HCV infection can be started. To increase the depth of understanding of oral health care, it is hoped that dentists and medical specialists in all areas will hold discussions to generate cooperation.

  3. Hepatitis C virus (HCV) genotypes in 373 Italian children with HCV infection: changing distribution and correlation with clinical features and outcome

    OpenAIRE

    Bortolotti, F; Resti, M; Marcellini, M; Giacchino, R.; Verucchi, G.; Nebbia, G; Zancan, L; Marazzi, M G; Barbera, C; Maccabruni, A; Zuin, G.; Maggiore, G; Balli, F.; Vajro, P; Lepore, L

    2005-01-01

    Background and aim: Little is known of hepatitis C virus (HCV) genotypes in HCV infected children. This retrospective, multicentre study investigated genotype distribution and correlation with clinical features and outcome in a large series of Italian children.

  4. Occult HCV infection: an unexpected finding in a population unselected for hepatic disease.

    Directory of Open Access Journals (Sweden)

    Laura De Marco

    Full Text Available BACKGROUND: Occult Hepatitis C virus (HCV infection is a new pathological entity characterized by presence of liver disease and absence or very low levels of detectable HCV-RNA in serum. Abnormal values of liver enzymes and presence of replicative HCV-RNA in peripheral blood mononuclear cells are also observed. Aim of the study was to evaluate occult HCV occurrence in a population unselected for hepatic disease. METHODOLOGY/PRINCIPAL FINDINGS: We chose from previous epidemiological studies three series of subjects (n = 276, age range 40-65 years unselected for hepatic disease. These subjects were tested for the presence of HCV antibodies and HCV-RNA in plasma and in the peripheral blood mononuclear cells (PBMCs by using commercial systems. All subjects tested negative for HCV antibodies and plasma HCV-RNA and showed normal levels of liver enzymes; 9/276 patients (3.3% were positive for HCV-RNA in PBMCs, identifying a subset of subjects with potential occult HCV infection. We could determine the HCV type for 8 of the 9 patients finding type 1a (3 patients, type 1b (2 patients, and type 2a (3 patients. CONCLUSIONS: The results of this study show evidence that occult HCV infection may occur in a population unselected for hepatic disease. A potential risk of HCV infection spread by subjects harbouring occult HCV infection should be considered. Design of prospective studies focusing on the frequency of infection in the general population and on the clinical evolution of occult HCV infection will be needed to verify this unexpected finding.

  5. Systemic cytokine and interferon responsiveness Patterns in HIV and HCV mono and co-infections.

    Science.gov (United States)

    Fernandez-Botran, Rafael; Joshi-Barve, Swati; Ghare, Smita; Barve, Shirish; Young, Mary; Plankey, Michael; Bordon, Jose

    2014-11-01

    The role of host response-related factors in the fast progression of liver disease in individuals co-infected with HIV and HCV viruses remains poorly understood. This study compared patterns of cytokines, caspase-1 activation, endotoxin exposure in plasma as well as interferon signaling in peripheral blood mononuclear cells from HIV/HCV co-infected (HIV(+)/HCV(+)), HCV mono-infected (HIV(-)/HCV(+)), HIV mono-infected (HIV(+)/HCV(-)) female patients and HIV- and HCV-uninfected women (HIV(-)/HCV(-)) who had enrolled in the Women's Interagency HIV Study (WIHS). HIV(+)/HCV(+) women had higher plasma levels of pro-inflammatory cytokines as well as caspase-1 compared with other groups. Both HIV(+)/HCV(+) and HIV(+)/HCV(-) women had significantly higher sCD14 levels compared with other groups. Peripheral blood mononuclear cells from HCV mono-infected patients had reduced levels of phosphorylation of STAT1 compared with other groups as well as lower basal levels of expression of the IFN-stimulated genes, OAS1, ISG15, and USP18 (UBP43). Basal expression of USP18, a functional antagonist of ISG15, as well as USP18/ISG15 ratios were increased in the HIV(+)/HCV(+) group compared with HIV(-)/HCV(+) and HIV(+)/HCV(-) groups. A more pronounced systemic inflammatory profile as well as increased expression ratios of USP18 to ISG15 may contribute to the more rapid progression of liver disease in HIV(+)/HCV(+) individuals. PMID:24955730

  6. Phenotypic characterization of lymphocytes in HCV/HIV co-infected patients.

    LENUS (Irish Health Repository)

    Roe, Barbara

    2009-02-01

    While hepatitis C virus (HCV)-specific immune responses are attenuated in HCV\\/HIV co-infected patients compared to those infected with HCV alone, the reasons for this remain unclear. In this study, the proportions of regulatory, naïve, and memory T cells, along with chemokine receptor expression, were measured in co-infected and mono-infected patients to determine if there is an alteration in the phenotypic profile of lymphocytes in these patients. HCV\\/HIV co-infected patients had increased proportions of CD4(+) naïve cells and decreased proportions of CD4(+) effector cells when compared to HCV mono-infected patients. The proportions of CD4(+) Tregs and CD4(+) CXCR3(+) T cells were also significantly lower in co-infected patients. A decrease in CD4(+) Tregs and subsequent loss of immunosuppressive function may contribute to the accelerated progression to liver disease in co-infected individuals. Dysregulation of immune responses following reduction in the proportions of CD4(+) CXCR3(+) Th-1 cells may contribute to the reduced functional capacity of HCV-specific immune responses in co-infected patients. The findings of this study provide new information on the T-cell immunophenotype in HCV\\/HIV co-infected patients when compared to those infected with HCV alone, and may provide insight into why cell-mediated immune responses are diminished during HCV infection.

  7. Proteasome- and Ethanol-Dependent Regulation of HCV-Infection Pathogenesis

    Directory of Open Access Journals (Sweden)

    Natalia A. Osna

    2014-09-01

    Full Text Available This paper reviews the role of the catabolism of HCV and signaling proteins in HCV protection and the involvement of ethanol in HCV-proteasome interactions. HCV specifically infects hepatocytes, and intracellularly expressed HCV proteins generate oxidative stress, which is further exacerbated by heavy drinking. The proteasome is the principal proteolytic system in cells, and its activity is sensitive to the level of cellular oxidative stress. Not only host proteins, but some HCV proteins are degraded by the proteasome, which, in turn, controls HCV propagation and is crucial for the elimination of the virus. Ubiquitylation of HCV proteins usually leads to the prevention of HCV propagation, while accumulation of undegraded viral proteins in the nuclear compartment exacerbates infection pathogenesis. Proteasome activity also regulates both innate and adaptive immunity in HCV-infected cells. In addition, the proteasome/immunoproteasome is activated by interferons, which also induce “early” and “late” interferon-sensitive genes (ISGs with anti-viral properties. Cleaving viral proteins to peptides in professional immune antigen presenting cells and infected (“target” hepatocytes that express the MHC class I-antigenic peptide complex, the proteasome regulates the clearance of infected hepatocytes by the immune system. Alcohol exposure prevents peptide cleavage by generating metabolites that impair proteasome activity, thereby providing escape mechanisms that interfere with efficient viral clearance to promote the persistence of HCV-infection.

  8. Risk Factors for Hepatitis C Virus (HCV) Infection in Areas with a High Prevalence of HCV in the Republic of Korea in 2013

    OpenAIRE

    Sohn, Hae-Sook; Kim, Jang Rak; Ryu, So Yeon; Lee, Youn-Jae; Lee, Myeong Jin; Min, Hyun Ju; Lee, Jun; Choi, Hwa Young; Song, Yeong Jun; Ki, Moran

    2016-01-01

    Background/Aims The prevalence of hepatitis C virus (HCV) infection in Busan, Gyeongnam, and Jeonnam Provinces in Korea is more than twice the national average. This study aimed to examine whether demographic and lifestyle characteristics are associated with HCV infection in these areas. Methods A case control study was performed at three study hospitals. HCV cases were matched with two controls for sex and age. Patient controls were selected from non-HCV patients at the same hospital. Health...

  9. Chronic hepatitis C virus infection and post-liver transplantation diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Yun Ma; Wen-Wei Yan

    2005-01-01

    Patients with chronic hepatitis C virus (HCV) infection have a significantly increased prevalence of type 2 diabetes mellitus compared to controls or HBV-infected patients.Moreover, the incidence rate of post-liver transplantation diabetes mellitus (PTDM) also appears to be higher among patients with HCV infection. PTDM is often associated with direct viral infection, autoimmune disorders, and immunosuppressive regimen. Activation of tumor necrosis factor-α may be the link between HCV infection and diabetes. In this article, we reviewed the epidemiologic association between HCV infection and PTDM, highlighting the most recent pathophysiologic insights into the mechanisms underlying this association.

  10. Ways and intensity of vertical transfer of the HCV from infected mothers to children

    Directory of Open Access Journals (Sweden)

    Idelbay Shuratov

    2011-03-01

    Full Text Available Ways and intensity of vertical transfer HCV have been studied before sorts in 29 lying-in women, positive on HCV-RNA. Among newborns from these mothers in serum of blood of umbilical cord at the moment of birth, HCV-RNA is found in 6.8%. The infection of newborns from HCV-RNA positive mother occurs through a placenta and at the time of delivery.

  11. Sustained virological response after ten days of triple anti-hepatitis C virus (HCV) therapy with telaprevir plus pegylated interferon and ribavirin in an HIV/HCV co-infected cirrhotic woman.

    Science.gov (United States)

    Hasson, Hamid; Messina, Emanuela; Merli, Marco; Della Torre, Liviana; Morsica, Giulia; Bagaglio, Sabrina; Lazzarin, Adriano; Uberti-Foppa, Caterina

    2014-12-01

    The introduction of first-generation protease inhibitors for the treatment of chronic hepatitis C in subjects infected with hepatitis C virus (HCV) genotype 1 has significantly improved the sustained virological response (SVR) rate. As liver cirrhosis reduces the probability of achieving SVR, current guidelines discourage response-guided therapy in cirrhotic patients. We report the first case of a cirrhotic woman with chronic HCV and HIV co-infection achieving virological response after an ultra-short course of therapy. A 40-year-old HIV/HCV co-infected woman with compensated liver cirrhosis was treated with anti-HCV triple therapy containing telaprevir plus pegylated interferon and ribavirin. Baseline plasma HCV RNA was 3.6 log IU/ml and transaminases were within the normal range. She harboured IL28B rs12979860C/C alleles. Ten days after starting therapy, the patient stopped treatment because of mild anorexia and nausea. Virological response was detected at treatment discontinuation and was maintained up to 24 weeks. This case describes an unexpected SVR after a 10-day course of antiviral therapy in a cirrhotic HIV/HCV co-infected woman presenting positive predictive factors for a response (low viral load, IL28B genotype). Nonetheless, there is no evidence to suggest a shorter duration of treatment in this subset of patients.

  12. Sustained virological response after ten days of triple anti-hepatitis C virus (HCV therapy with telaprevir plus pegylated interferon and ribavirin in an HIV/HCV co-infected cirrhotic woman

    Directory of Open Access Journals (Sweden)

    Hamid Hasson

    2014-12-01

    Full Text Available The introduction of first-generation protease inhibitors for the treatment of chronic hepatitis C in subjects infected with hepatitis C virus (HCV genotype 1 has significantly improved the sustained virological response (SVR rate. As liver cirrhosis reduces the probability of achieving SVR, current guidelines discourage response-guided therapy in cirrhotic patients. We report the first case of a cirrhotic woman with chronic HCV and HIV co-infection achieving virological response after an ultra-short course of therapy. A 40-year-old HIV/HCV co-infected woman with compensated liver cirrhosis was treated with anti-HCV triple therapy containing telaprevir plus pegylated interferon and ribavirin. Baseline plasma HCV RNA was 3.6 log IU/ml and transaminases were within the normal range. She harboured IL28B rs12979860 C/C alleles. Ten days after starting therapy, the patient stopped treatment because of mild anorexia and nausea. Virological response was detected at treatment discontinuation and was maintained up to 24 weeks. This case describes an unexpected SVR after a 10-day course of antiviral therapy in a cirrhotic HIV/HCV co-infected woman presenting positive predictive factors for a response (low viral load, IL28B genotype. Nonetheless, there is no evidence to suggest a shorter duration of treatment in this subset of patients.

  13. Socioeconomic status in HCV infected patients – risk and prognosis

    Directory of Open Access Journals (Sweden)

    Oml

    2013-05-01

    Full Text Available Lars Haukali Omland,1 Merete Osler,2 Peter Jepsen,3,4 Henrik Krarup,5 Nina Weis,6 Peer Brehm Christensen,7 Casper Roed,1 Henrik Toft Sørensen,3 Niels Obel1 On behalf of the DANVIR Cohort Study1Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 2Research Center for Prevention and Health, Copenhagen University Hospital, Glostrup Hospital, Glostrup, Denmark; 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Medicine V (Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 5Department of Clinical Biochemistry, Aalborg Hospital, Aalborg, Denmark; 6Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Denmark; 7Department of Infectious Diseases, Odense University Hospital, Odense, DenmarkBackground and aims: It is unknown whether socioeconomic status (SES is a risk factor for hepatitis C virus (HCV infection or a prognostic factor following infection.Methods: From Danish nationwide registries, we obtained information on three markers of SES: employment, income, and education. In a case control design, we examined HCV infected patients and controls; conditional logistic regression was employed to obtain odds ratios (ORs for HCV infection for each of the three SES markers, adjusting for the other two SES markers, comorbidity, and substance abuse. In a cohort design, we used Cox regression analysis to compute mortality rate ratios (MRRs for each of the three SES markers, adjusting for the other two SES markers, comorbidity level, age, substance abuse, and gender.Results: When compared to employed persons, ORs for HCV infection were 2.71 (95% confidence interval [CI]: 2.24–3.26 for disability pensioners and 2.24 (95% CI: 1.83–2.72 for the unemployed. When compared to persons with a high income, ORs were 1.64 (95% CI: 1.34–2.01 for low income persons and 1.19 (95% CI: 1.02–1.40 for

  14. Incidence of recent HCV infection among persons seeking voluntary counselling and testing for HIV and sexually transmitted infections in Taiwan

    Directory of Open Access Journals (Sweden)

    Yi-Ching Su

    2014-11-01

    Full Text Available Introduction: The incidence of recent hepatitis C virus infection (HCV infection has been noted to be increasing among men who have sex with men (MSM, especially those with HIV infection, in several resource-rich settings. In Taiwan, the incidence of recent HCV infection increased from 0 in 1994–2000, 2.29 in 2001–2005 to 10.13 per 1000 person-years of follow-up (PYFU in 2006–2010. In this study, we aimed to estimate the incidence rate of recent HCV infection among those individuals who sought voluntary counselling and testing (VCT service at a University Hospital. Methods: Between May 2006 and December 2013, 18,246 tests for HIV antibody were performed among 12,143 individuals at the VCT services. A total of 2157 clients without HIV or HCV infection at baseline were included for estimation of incidence rate of recent HCV infection. Antibodies to HCV were determined with a third-generation enzyme immunoassay. A nested case-control study with four matched controls without HCV seroconversion for one HCV seroconverter was conducted to investigate the factors associated with recent HCV infection. Phylogenetic analysis was performed among the HCV strains obtained from VCT clients and patients coinfected with HIV and HCV between 2006 and 2013. Results: During the study period, 2157 clients received a total of 8260 tests. The HCV seroprevalence at baseline was 0.3%. Of the 2150 HCV-negative clients who contributed 5074.99 PYFU, 17 developed HCV seroconversion (incidence rate, 3.35 per 1000 PYFU; 95% CI, 1.76–4.94; the rate increased from 2.28 per 1000 PYFU (95% CI, 0.05–4.51 in 2006–2009, to 3.33 per 1000 PYFU (95% CI, 0.86–5.80 in 2010–2011, to 4.94 per 1000 PYFU (95% CI, 0.99–8.99 in 2012–2013. In case-control study, HCV seroconverters were more likely to have HIV-infected partners, recent syphilis and a Rapid Plasma Reagin (RPR titre of 4 or greater. In multivariate analysis, having HIV-infected partners remained as the only

  15. Daclatasvir plus peginterferon and ribavirin is noninferior to peginterferon and ribavirin alone, and reduces the duration of treatment for HCV genotype 2 or 3 infection

    DEFF Research Database (Denmark)

    Dore, Gregory J; Lawitz, Eric; Hézode, Christophe;

    2015-01-01

    BACKGROUND & AIMS: Twenty-four weeks of treatment with peginterferon and ribavirin for chronic hepatitis C virus (HCV) genotype 2 or 3 infection produces a sustained virologic response (SVR) in 70%-80% of patients. We performed a randomized, double-blind, phase 2b study to assess whether adding...... daclatasvir, a nonstructural protein 5A (NS5A) inhibitor that is active against these genotypes, improves efficacy and shortens therapy. METHODS: Patients with HCV genotype 2 or 3 infection (n = 151), enrolled at research centers in North America, Europe, or Australia, were assigned randomly to groups given...... after treatment (SVR24). RESULTS: Baseline characteristics were similar among patients within each HCV genotype group. However, the 80 patients with HCV genotype 3, compared with the 71 patients with HCV genotype 2, were younger (mean age, 45 vs 53 y, respectively), and a larger proportion had cirrhosis...

  16. Sustained Virologic Response at 24 Weeks after the End of Treatment Is a Better Predictor for Treatment Outcome in Real-World HCV-Infected Patients Treated by HCV NS3/4A Protease Inhibitors with Peginterferon plus Ribavirin

    Science.gov (United States)

    Kanda, Tatsuo; Nakamoto, Shingo; Sasaki, Reina; Nakamura, Masato; Yasui, Shin; Haga, Yuki; Ogasawara, Sadahisa; Tawada, Akinobu; Arai, Makoto; Mikami, Shigeru; Imazeki, Fumio; Yokosuka, Osamu

    2016-01-01

    Background. Direct-acting antiviral agents against HCV with or without peginterferon plus ribavirin result in higher eradication rates of HCV and shorter treatment duration. We examined which is better for predicting persistent virologic response, the assessment of serum HCV RNA at 12 or 24 weeks after the end of treatment for predicting sustained virologic response (SVR12 or SVR24, respectively) in patients treated by HCV NS3/4A protease inhibitors with peginterferon plus ribavirin. Methods. In all, 149 Japanese patients infected with HCV genotype 1b treated by peginterferon plus ribavirin with telaprevir or simeprevir were retrospectively analyzed: 59 and 90 patients were treated with telaprevir- and simeprevir-including regimens, respectively. HCV RNA was measured by TaqMan HCV Test, version 2.0, real-time PCR assay. SVR12 or SVR24, respectively, was defined as HCV RNA negativity at 12 or 24 weeks after ending treatment. Results. Total SVR rates were 78.0% and 66.7% in the telaprevir and simeprevir groups, respectively. In the telaprevir group, all 46 patients with SVR12 finally achieved SVR24. In the simeprevir group, 60 (93.8%) of the total 64 patients with SVR12 achieved SVR24, with the other 4 patients all being previous-treatment relapsers. Conclusions. SVR12 was suitable for predicting persistent virologic response in almost all cases. In simeprevir-including regimens, SVR12 could not always predict persistent virologic response. Clinicians should use SVR24 for predicting treatment outcome in the use of HCV NS3/4A protease inhibitors with peginterferon plus ribavirin for any group of real-world patients chronically infected with HCV. PMID:27076789

  17. Safety of cyclosporin A in HCV-infected patients: experience with cyclosporin A in patients affected by rheumatological disorders and concomitant HCV infection.

    Science.gov (United States)

    Galeazzi, Mauro; Bellisai, Francesca; Giannitti, Chiara; Manganelli, Stefania; Morozzi, Gabriella; Sebastiani, Gian Domenico

    2007-09-01

    Because of the relatively high prevalence of both hepatitis C virus (HCV) infection and autoimmune disorders (ADs), it is not rare to encounter in daily clinical practice patients with ADs also carrying HCV. Corticosteroids and/or immunosuppressant drugs are needed to treat ADs, but they place HCV-infected patients at risk of worsening the infection. So, rheumatologists have often refrained from using corticosteroids or immunosuppressants in AD when HCV-RNA is also present. Cyclosporin A (CsA) is an immunosuppressive agent used to treat a wide range of ADs, but there is a large evidences in the literature, both in vitro and in vivo, suggesting that CsA also exerts an inhibitory effect on HCV replication at standard therapeutic dose. Therefore, this evidence has opened new ways to improve the therapy and the prognosis in patients with HCV-related liver diseases, including those with transplants. Recent reports, although limited in number, also suggest the safety of CsA in the treatment of patients with AD and concomitant HCV infection. In this review we also report our personal experience on the combination treatment with CsA and anti-TNF-alpha agents in rheumatoid arthritis.

  18. Prevalence, genotypes and factors associated with HCV infection among prisoners in Northeastern Brazil

    Institute of Scientific and Technical Information of China (English)

    Bruno Fernandes de Oliveira Santos; Nathalie Oliveira de Santana; Alex Vianey Callado Franca

    2011-01-01

    AIM: To determine hepatitis C virus (HCV) seroprevalence and its genotypes, and to identify the factors associated with HCV infection. METHODS: This cross-sectional study, conducted in two prisons (one male and one female) in the State of Sergipe, Brazil, comprised 422 subjects. All of the prisoners underwent a rapid test for the detection of HCV antibodies. Patients with a positive result were tested for anti- HCV by enzyme linked immunosorbent assay and for HCV RNA by qualitative polymerase chain reaction (PCR). The virus genotype was defined in every serum sample that presented positive for PCR-HCV. In order to determine the factors independently associated with positive serology for HCV, multivariate logistic regression was used. RESULTS: HCV seroprevalence was 3.1%. Of the 13 subjects with positive anti-HCV, 11 had viremia confirmed by PCR. Of these, 90.9% had genotype 1. A total of 43 (10.2%) were injecting drug users, and HCV seroprevalence in this subgroup was 20.6%. The variable most strongly associated with positive serology for HCV was use of injecting drugs [odds ratio (OR), 23.3; 95% confidence interval (CI), 6.0-90.8]. Age over 30 years (OR, 5.5; 95%CI, 1.1-29.2), history of syphilis (OR, 9.8; 95%CI, 1.7-55.2) and history of household contact with HCV positive individual (OR, 14.1; 95%CI, 2.3-85.4) were also independently associated with HCV infection. CONCLUSION: Most of the HCV transmissions result from parenteral exposure. However, there is evidence to suggest a role for sex and household contact with an infected subject in virus transmission.

  19. Prevalence of anti HCV infection in patients with beta-thalassemia in Isfahan-Iran

    Directory of Open Access Journals (Sweden)

    Behrooz Ataei

    2012-01-01

    Conclusions: Our findings revealed that blood transfusion was the main risk factors for HCV infection among beta-thalassemic patients. Therefore, more blood donor screening programs and effective screening techniques are needed to prevent transmission of HCV infection among beta-thalassemic patients.

  20. Prevalence and treatment of chronic hepatitis C virus infection in the US Department of Veterans Affairs.

    Science.gov (United States)

    Beste, Lauren A; Ioannou, George N

    2015-01-01

    Chronic hepatitis C virus (HCV) is the most common blood-borne pathogen in the United States. HCV disproportionately affects Veterans Affairs (VA) health-care users: 174,302 HCV-infected veterans were in VA care in 2013, making the VA the world's largest HCV care provider. This systematic review identified 546 articles related to HCV in the VA. After assessment by 2 independent reviewers, 28 articles describing prevalence and treatment of HCV in VA users ultimately met inclusion criteria. Most VA patients currently living with HCV infection were born between 1945 and 1965 and were infected with HCV between 1970 and 1990. To prevent HCV-related complications such as cirrhosis, hepatocellular carcinoma, and death, medical personnel must identify and treat HCV. However, antiviral therapy has historically been limited by medication side effects, contraindications, and patient acceptance. Although treatment initiation rates are higher in the VA than in the general United States, only 23% of VA HCV patients have received treatment and, of those, only a minority were cured. Recent development of more effective and tolerable antiviral agents represents a major pharmacological breakthrough. Eradication of HCV is theoretically possible for the majority of HCV patients for the first time, although new barriers, such as high drug costs, may limit future uptake. PMID:25600415

  1. Knowledge of HBV and HCV and individuals' attitudes toward HBV- and HCV-infected colleagues: a national cross-sectional study among a working population in Japan.

    Directory of Open Access Journals (Sweden)

    Hisashi Eguchi

    Full Text Available Prejudice and discrimination in the workplace regarding the risk of transmission of Hepatitis B virus (HBV and Hepatitis C virus (HCV are increased by excess concerns due to a lack of relevant knowledge. Education to increase knowledge about HBV and HCV and their prevention could be the first step to reduce prejudice and discrimination. This study aimed to determine the association between the level of knowledge and negative attitudes toward HBV- and HCV-infected colleagues among the Japanese working population. An online anonymous nationwide survey involving about 3,000 individuals was conducted in Japan. The questionnaire consisted of knowledge of HBV and HCV, and attitudes toward HBV- and HCV-infected colleagues in the workplace. Knowledge was divided into three categories: "ensuring daily activities not to be infected"; "risk of infection"; and "characteristics of HBV/HCV hepatitis", based on the result of factor analysis. Multiple logistic regression analysis was applied. A total of 3,129 persons responded to the survey: 36.0% reported they worried about the possibility of transmission of HBV and HCV from infected colleagues; 32.1% avoided contact with infected colleagues; and 23.7% had prejudiced opinions about HBV and HCV infection. The participants were classified into tertiles. A higher level of knowledge of HBV and HCV was significantly associated with these three negative attitudes (P for trend < 0.005. This study suggests that increasing knowledge may decrease individuals' negative attitudes towards HBV- and HCV-infected colleagues. Thus, we should promote increased knowledge of HBV and HCV in stages to reduce negative attitudes toward HBV- and HCV-infected colleagues.

  2. Association between Celiac Disease and Chronic Hepatitis C Virus Infection

    OpenAIRE

    Garg, Ashish; Reddy, Chandrasekhar; Duseja, Ajay; Chawla, Yogesh; Radha K. Dhiman

    2011-01-01

    Celiac disease affects the proximal small intestine and is caused by a local immune response to dietary gluten. Celiac disease usually presents with chronic diarrhea; however, presentations with elevated hepatic transaminase levels in blood or with iron-deficiency anemia have been described. Celiac disease has been reported to be associated with autoimmune liver diseases. Hepatitis C virus (HCV) can also initiate autoimmune disease process. Therefore, HCV infection and celiac disease may occu...

  3. Liver stiffness measurements in patients with HBV vs HCV chronic hepatitis:A comparative study

    Institute of Scientific and Technical Information of China (English)

    Ioan; Sporea; Roxana; Sirli; Alexandra; Deleanu; Adriana; Tudora; Alina; Popescu; Manuela; Curescu; Simona; Bota

    2010-01-01

    AIM:To assess the values of liver stiffness (LS) in pa-tients with hepatitis B virus (HBV) chronic hepatitis and to compare them with those in patients with hepatitis C virus (HCV) chronic hepatitis. METHODS: The study included 140 patients with HBV chronic hepatitis, and 317 patients with HCV chronic hepatitis, in which LS was measured (FibroScan-Echo-sens) and liver biopsy was performed in the same session (assessed according to the Metavir score). RESULTS:According to the Metavir score of the 140 HBV p...

  4. Proteome-wide Anti-HCV and Anti-HIV Antibody Profiling for Predicting and Monitoring Response to HCV Treatment in HIV Co-infected Patients

    Science.gov (United States)

    Burbelo, Peter D.; Kovacs, Joseph A.; Ching, Kathryn H.; Issa, Alexandra T.; Iadarola, Michael J.; Murphy, Alison A; Schlaak, Joerg F.; Masur, Henry; Polis, Michael A.; Kottilil, Shyam

    2010-01-01

    We quantified antibody responses to the HCV proteome that are associated with sustained virologic response (SVR) in HIV/HCV co-infected patients treated with pegylated interferon and ribavirin. Analysis of pre- and post-treatment samples revealed significant decreases in the combined anti-core, anti-E1 and anti-NS4 HCV antibody titers in those with SVR, but not in the relapsers or non-responders. Furthermore, anti-p24 HIV antibody titers inversely correlated with treatment response. These results suggest that profiling anti-HCV antibody is useful for monitoring HCV therapy especially in discriminating between relapsers and SVRs at 48 weeks. PMID:20684729

  5. Nursing Problems in Care of a Patient with Very Early HCV Infection Recurrence After Liver Transplantation: A Case Report.

    Science.gov (United States)

    Hreńczuk, Marta; Sowińska, Renata; Tronina, Olga; Małkowski, Piotr; Durlik, Magdalena; Pacholczyk, Marek; Kosieradzki, Maciej

    2016-01-01

    BACKGROUND Recurrent HCV infection following liver transplantation is a common problem, and usually has a more aggressive course than primary infection. The aim of the paper was to present nursing problems in the care of a 22-year-old female patient after liver transplantation (Ltx) with a rapid recurrence of HCV infection shortly after Ltx. CASE REPORT Ltx was performed 22 July 2012 due to chronic cirrhosis secondary to HCV infection with viremia (HCV PCR 3.5×107 IU/mL). Graft function worsened 14 days following transplantation. Acute cholestatic hepatitis related to HCV reinfection was diagnosed based on biopsy. During a period of 20 months the patient received 3 different antiviral treatment regimens, beginning with a dual therapy (Interferon and Ribavirin), followed by the inclusion of Telaprevir, then Daclatasvir; however, these treatments were not successful. The fourth-line regimen with sofosbuvir (EU medical experiment) led to viremia elimination (HCV PCR) after 5 weeks of treatment. However, hepatic failure stabilization was unsuccessful, there was an increase in encephalopathy, and the MELD score was 25. Therefore, the patient underwent liver retransplantation. In the post-transplantation period, the patient was in good condition, with no viremia. CONCLUSIONS The most common nursing problems in the care of the patient were associated with the diagnostic process, therapies used (including experimental treatment), and progressive liver failure. The therapeutic success should be attributed to the intensive supervision and monitoring of viremia, immediate inclusion of adequate treatment methods, adequate patient preparation for diagnostic tests, and careful care after diagnostics, as well as psychological support and education. PMID:27357745

  6. Role of interferon gamma and tumor necrosis factor-related apoptosis-inducing ligand receptor 1 single nucleotide polymorphism in natural clearance and treatment response of HCV infection.

    Science.gov (United States)

    Azam, Sikandar; Manzoor, Sobia; Imran, Muhammad; Ashraf, Javed; Ashraf, Sarah; Resham, Saleha; Ghani, Eijaz

    2015-05-01

    Hepatitis C virus (HCV) pathogenesis and treatment outcomes are multifactorial phenomena involving both viral and host factors. This study was designed to determine the role of tumor necrosis factor-related apoptosis-inducing ligand receptor 1(TRAIL-R1) and interferon gamma (IFN-γ) genetic mutations in susceptibility and response to interferon-based therapy of hepatitis C virus (HCV) infection. The detection of TRAIL-R1 rs4242392 and IFN-γ rs2069707 single nucleotide polymorphisms was completed in 118 chronic HCV patients and 96 healthy controls by allele-specific polymerase chain reaction and restriction fragment length polymorphisms polymerase chain reaction. Patients were further categorized into sustained virological responder (SVR) and nonresponder (NR) groups on the basis of their response to interferon-based therapy for HCV infection. Real-time PCR was used for HCV quantification. HCV genotyping was performed by Ohno's method. The results demonstrated that the distribution of the TRAIL-R1 rs4242392TT genotype was significantly higher in the SVR group (78%) compared to the NR group (36%). It showed that chronic HCV patients possessing the TRAIL-R1 rs4242392TT genotype are better responders to interferon-based therapy (p0.05). The distribution of IFN-γ rs2069707 was the opposite to TRAIL-R1 rs4242392 prevalence, that is, there was high distribution of the IFN-γ rs2069707GG genotype in patients and healthy controls (p0.05). In conclusion, genetic variation of TRAIL-R1 rs4242392 is linked with response to interferon-based therapy for HCV infection, and genetic variation IFN-γ rs2069707 is associated with natural clearance of HCV infection.

  7. Impact of Helicobacter pylori eradication on refractory thrombocytopenia in patients with chronic HCV awaiting antiviral therapy.

    Science.gov (United States)

    Hanafy, A S; El Hawary, A T; Hamed, E F; Hassaneen, A M

    2016-07-01

    The possibility of delaying treatment of HCV due to severe thrombocytopenia is challenging. This study aimed to detect the prevalence of active helicobacter infection as a claimed cause of thrombocytopenia in a cohort of Egyptian patients with chronic active HCV awaiting combined anti-viral therapy. The study included 400 chronic HCV patients with thrombocytopenia. Laboratory investigations included liver function tests, real time quantitative PCR, reticulocytic count, ESR, ANA, bone marrow aspiration, measurement of anti-helicobacter antibodies, and helicobacter stool antigen. Positive cases for active H. pylori were given the standard triple therapy for 2 weeks. Helicobacter stool antigen was detected 4 weeks after termination of therapy and the change in platelet count was detected 1 month after eradication. A total of 248 out of 281 seropositive patients for H. pylori (88.3 %) showed positive stool antigen (p = 0.01). Eradication was achieved in 169 (68.1 %) patients with platelet mean count 114.9 ± 18.8 × 10(3)/μl with highly significant statistical difference from pretreatment value (49.7 ± 9.2 × 10(3)/μl, p = 0.000). Seventy-nine patients were resistant to conventional triple therapy and given a 7-day course of moxifloxacin-based therapy; 61 patients responded (77.1 %) with mean platelet improvement from 76.4 ± 17.4 × 10(3)/μl to 104.2 ± 15.2 × 10(3)/μl (p = 0.000). The non-responders showed no improvement in their platelet count (74.6 ± 20.5 vs. 73.6 ± 15.3 × 10(3)/ul, P = 0.5). Eradication of active H. pylori in HCV augments platelet count and enhances the early start of antiviral therapy. PMID:27180243

  8. Active hepatitis C infection and HCV genotypes prevalent among the IDUs of Khyber Pakhtunkhwa

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    Uz Zaman Khaleeq

    2011-06-01

    Full Text Available Abstract Injection drug users (IDUs are considered as a high risk group to develop hepatitis C due to needle sharing. In this study we have examined 200 injection drug users from various regions of the Khyber Pakhtunkhwa province for the prevalence of active HCV infection and HCV genotypes by Immunochromatographic assays, RT-PCR and Type-specific PCR. Our results indicated that 24% of the IDUs were actively infected with HCV while anti HCV was detected among 31.5% cases. Prevalent HCV genotypes were HCV 2a, 3a, 4 and 1a. Majority of the IDUs were married and had attained primary or middle school education. 95% of the IDUs had a previous history of needle sharing. Our study indicates that the rate of active HCV infection among the IDUs is higher with comparatively more prevalence of the rarely found HCV types in KPK. The predominant mode of HCV transmission turned out to be needle sharing among the IDUs.

  9. Correlation between pre-treatment quasispecies complexity and treatment outcome in chronic HCV genotype 3a.

    LENUS (Irish Health Repository)

    Moreau, Isabelle

    2012-02-03

    Pre-treatment HCV quasispecies complexity and diversity may predict response to interferon based anti-viral therapy. The objective of this study was to retrospectively (1) examine temporal changes in quasispecies prior to the start of therapy and (2) investigate extensively quasispecies evolution in a group of 10 chronically infected patients with genotype 3a, treated with pegylated alpha2a-Interferon and ribavirin. The degree of sequence heterogeneity within the hypervariable region 1 was assessed by analyzing 20-30 individual clones in serial serum samples. Genetic parameters, including amino acid Shannon entropy, Hamming distance and genetic distance were calculated for each sample. Treatment outcome was divided into (1) sustained virological responders (SVR) and (2) treatment failure (TF). Our results indicate, (1) quasispecies complexity and diversity are lower in the SVR group, (2) quasispecies vary temporally and (3) genetic heterogeneity at baseline can be use to predict treatment outcome. We discuss the results from the perspective of replicative homeostasis.

  10. Extrahepatic manifestations of chronic hepatitis C virus infection.

    Science.gov (United States)

    Cacoub, Patrice; Comarmond, Cloe; Domont, Fanny; Savey, Léa; Desbois, Anne C; Saadoun, David

    2016-02-01

    During hepatitis C virus (HCV) chronic infection, extrahepatic manifestations are frequent and polymorphous. This article reports on a large cohort of patients with HCV-related autoimmune or lymphoproliferative disorders, from mixed cryoglobulinemia vasculitis to frank lymphomas. The relationship between HCV infection and such immune-related diseases has been formally demonstrated by epidemiological, clinical, immunological and pathological data, and results of therapeutic trials. More recently, other nonliver-related HCV disorders have been reported, including cardiovascular (i.e. stroke, ischemic heart disease), renal, metabolic and central nervous system diseases. For these manifestations, most evidence comes from large epidemiological studies; there is a need for mechanistic studies and therapeutic trials for confirmation. Beyond the risk of developing liver complications, that is, cirrhosis and liver cancer, patients with HCV infection have an increased risk of morbidity and mortality related to nonliver diseases. HCV chronic infection should be analyzed as a systemic disease in which extrahepatic consequences increase the weight of its pathological burden. The need for effective viral eradication measures is underlined. PMID:26862398

  11. Metabolic Manifestations and Complications Associated With Chronic Hepatitis C Virus Infection.

    Science.gov (United States)

    Wong, Robert J; Gish, Robert G

    2016-05-01

    Chronic hepatitis C virus (HCV) infection is associated with many extrahepatic manifestations that contribute to morbidity and mortality. It is especially important to be aware of metabolic manifestations and serious complications that affect other organs and cancer risks. Chronic HCV infection itself contributes to de novo development of insulin resistance and hepatic steatosis, both of which increase the risk of cardiovascular diseases. Through these metabolic pathways (as well as through other hypothesized mechanisms that involve lipid metabolism, systemic inflammatory signals, and endothelial dysfunction), chronic HCV infection also contributes to significant systemic cardiovascular morbidity and mortality. While chronic HCV infection contributes to incident development of metabolic complications, the presence of concurrent metabolic diseases also contributes to disease progression, such as higher risks of hepatocellular carcinoma and progression to advanced fibrosis, among patients with chronic HCV infection. The implications of these observations are particularly important given the rising prevalence of obesity and metabolic syndrome in the United States and worldwide. Furthermore, concurrent nonalcoholic fatty liver disease, either as a result of underlying metabolic syndrome or as a direct result of HCV-induced fatty liver disease, further complicates the management of chronic HCV-infected patients. Greater awareness is needed toward the systemic manifestations of chronic HCV infection, with focused attention on the associated metabolic manifestations and complications. Successful treatment and cure of chronic HCV infection with the currently available, highly effective antiviral therapies will significantly improve long-term outcomes among these patients. It is also important to recognize and address the associated metabolic manifestations and complications to reduce cardiovascular-related morbidity and mortality. PMID:27499712

  12. Incidence of recent HCV infection among persons seeking voluntary counselling and testing for HIV and sexually transmitted infections in Taiwan

    OpenAIRE

    Yi-Ching Su; Wen-Chun Liu; Lan-Hsin Chang; Pei-Ying Wu; Yu-Zhen Luo; Cheng-Hsin Wu; Hsin-Yun Sun; Sui-Yuan Chang; Chien-Ching Hung

    2014-01-01

    Introduction: The incidence of recent hepatitis C virus infection (HCV) infection has been noted to be increasing among men who have sex with men (MSM), especially those with HIV infection, in several resource-rich settings. In Taiwan, the incidence of recent HCV infection increased from 0 in 1994–2000, 2.29 in 2001–2005 to 10.13 per 1000 person-years of follow-up (PYFU) in 2006–2010. In this study, we aimed to estimate the incidence rate of recent HCV infection among those individuals who so...

  13. The Emerging Extrahepatic Manifestations of Hepatitis C Virus Infection in Chronic Hepatitis and Mixed Cryoglobulinemia

    Directory of Open Access Journals (Sweden)

    Poupak Fallahi

    2008-08-01

    Full Text Available Hepatitis C virus (HCV is known to be responsible for both hepatic and extrahepatic diseases. Mixed cryoglobulinemia, Sjögren syndrome, and chronic polyarthritis are the most documented rheumatologic extrahepatic manifestations of HCV infection. The most frequent and clinically important extrahepatic endocrine manifestations of chronic HCV infection are thyroid disorders and type 2 diabetes mellitus. From a meta-analysis of the literature, a significant association between HCV infection and thyroid autoimmunity and/or hypothyroidism as well as a high prevalence of thyroid cancer have been reported. The pattern of thyroid disorders observed in HCV infected patients is characterized by the presence of elevated circulating anti-thyroid peroxidase antibodies with increased risk of hypothyroidism. Several clinical epidemiologic studies have reported that HCV infection is a risk factor for type 2 diabetes. The type of diabetes manifested by subjects with chronic HCV infection is not of the classical type 2 diabetes; in fact, HCV-related diabetic patients are leaner than the classical diabetic patients, and have a significantly lower LDL-cholesterol, and both systolic and diastolic blood pressure. Furthermore, patients with mixed cryoglobulinemia (mixed cryoglobulinemia and chronic HCV infection with type 2 diabetes have more frequently non-organ-specific-autoantibodies than non-diabetic patients with mixed cryoglobulinemia and those with chronic HCV infection. Based on the above-mentioned findings, it has been hypothesized that diabetes in HCV infection may have an immune-mediated pathogenesis. In patients with chronic HCV infection, we found an increased risk of carotid artery plaque and carotid intima-media thickening. These findings suggested a possible role for chronic hepatitis C in the pathogenesis of carotid artery remodelling. Recently, high prevalence rates of anti-HCV antibodies were shown in patients with hypertrophic cardiomyopathy or

  14. Different Responses of Two Highly Permissive Cell Lines Upon HCV Infection

    Institute of Scientific and Technical Information of China (English)

    Honghe Chen; Rongjuan Pei; Xinwen Chen

    2013-01-01

    The construction of the first infectious clone JFH-1 speeds up the research on hepatitis C virus (HCV).However,Huh7 cell line was the only highly permissive cell line for HCV infection and only a few clones were fully permissive.In this study,two different fully permissive clones of Huh7 cells,Huh7.5.1 and Huh7-Lunet-CD81 (Lunet-CD81) cells were compared for their responses upon HCV infection.The virus replication level was found slightly higher in Huh7.5.1 cells than that in Lunet-CD81 cells.Viability of Huh7.5.1 cells but not of Lunet-CD81 cells was reduced significantly after HCV infection.Further analysis showed that the cell cycle of infected Huh7.5.1 cells was arrested at G1 phase.The G1/S transition was blocked by HCV infection in Huh7.5.1 cells as shown by the cell cycle synchronization analysis.Genes related to cell cycle regulation was modified by HCV infection and gene interaction analysis in GeneSpring GX in Direct Interactions mode highlighted 31 genes.In conclusion,the responses of those two cell lines were different upon HCV infection.HCV infection blocked G1/S transition and cell cycle progress,thus reduced the cell viability in Huh7.5.1 cells but not in Lunet-CD81 cells.Lunet-CD81 cells might be suitable for long term infection studies of HCV.

  15. Discovery of cellular proteins required for the early steps of HCV infection using integrative genomics.

    Directory of Open Access Journals (Sweden)

    Ji Hoon Park

    Full Text Available Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early steps of hepatitis C virus (HCV infection. By integrating HCV and human protein associations, co-expression data, and tight junction-tetraspanin web specific networks, we identified host proteins required for the early steps in HCV infection. Moreover, we validated the roles of newly identified proteins in HCV infection by knocking down their expression using small interfering RNAs. Specifically, a novel host factor CD63 was shown to directly interact with HCV E2 protein. We further demonstrated that an antibody against CD63 blocked HCV infection, indicating that CD63 may serve as a new therapeutic target for HCV-related diseases. The candidate gene list provides a source for identification of new therapeutic targets.

  16. Liver histology in co-infection of hepatitis C virus (HCV and Hepatitis G virus (HGV

    Directory of Open Access Journals (Sweden)

    STRAUSS Edna

    2002-01-01

    Full Text Available As little is known about liver histology in the co-infection of hepatitis C virus (HCV and hepatitis G virus (HGV, HGV RNA was investigated in 46 blood donors with hepatitis C, 22 of them with liver biopsy: co-infection HCV / HGV (n = 6 and HCV isolated infection (n = 16. Besides staging and grading of inflammation at portal, peri-portal and lobular areas (Brazilian Consensus, the fibrosis progression index was also calculated. All patients had no symptoms or signs of liver disease and prevalence of HGV / HCV co-infection was 15.2%. Most patients had mild liver disease and fibrosis progression index, calculated only in patients with known duration of infection, was 0.110 for co-infection and 0.130 for isolated HCV infection, characterizing these patients as "slow fibrosers". No statistical differences could be found between the groups, although a lesser degree of inflammation was always present in co-infection. In conclusion co-infection HCV / HGV does not induce a more aggressive liver disease, supporting the hypothesis that HGV is not pathogenic.

  17. HCV Specific IL-21 Producing T Cells but Not IL-17A Producing T Cells Are Associated with HCV Viral Control in HIV/HCV Coinfection

    Science.gov (United States)

    MacParland, Sonya A.; Fadel, Saleh M.; Mihajlovic, Vesna; Fawaz, Ali; Kim, Connie; Rahman, A. K. M. Nur-ur; Liu, Jun; Kaul, Rupert; Kovacs, Colin; Grebely, Jason; Dore, Gregory J.; Wong, David K.; Ostrowski, Mario A.

    2016-01-01

    Background Decreased hepatitis C virus (HCV) clearance, faster cirrhosis progression and higher HCV RNA levels are associated with Human Immunodeficiency virus (HIV) coinfection. The CD4+ T helper cytokines interleukin (IL)-21 and IL-17A are associated with virus control and inflammation, respectively, both important in HCV and HIV disease progression. Here, we examined how antigen-specific production of these cytokines during HCV mono and HIV/HCV coinfection was associated with HCV virus control. Methods We measured HCV-specific IL-21 and IL-17A production by transwell cytokine secretion assay in PBMCs from monoinfected and coinfected individuals. Viral control was determined by plasma HCV RNA levels. Results In acutely infected individuals, those able to establish transient/complete HCV viral control tended to have stronger HCV-specific IL-21-production than non-controllers. HCV-specific IL-21 production also correlated with HCV viral decline in acute infection. Significantly stronger HCV-specific IL-21 production was detected in HAART-treated coinfected individuals. HCV-specific IL-17A production was not associated with lower plasma HCV RNA levels in acute or chronic HCV infection and responses were stronger in HIV coinfection. HCV-specific IL-21/ IL-17A responses did not correlate with microbial translocation or fibrosis. Exogenous IL-21 treatment of HCV-specific CD8+ T cells from monoinfected individuals enhanced their function although CD8+ T cells from coinfected individuals were somewhat refractory to the effects of IL-21. Conclusions These data show that HCV-specific IL-21 and IL-17A-producing T cells are induced in HIV/HCV coinfection. In early HIV/HCV coinfection, IL-21 may contribute to viral control, and may represent a novel tool to enhance acute HCV clearance in HIV/HCV coinfected individuals. PMID:27124305

  18. Metabolic Disturbances in Liver {sup 1}H MR Spectroscopy in HIV and HCV Co-infected Patients as a Potential Marker of Hepatocyte Activation

    Energy Technology Data Exchange (ETDEWEB)

    Tarasow, E.; Wierciska-Drapao, A.; Jaroszewicz, J.; Siergiejczyk, L.; Orzechowska-Bobkiewicz, A.; Prokopowicz, D.; Walecki, J. [Medical Academy Hospital, Bialystok (Poland). Dept. of Radiology

    2004-12-01

    Purpose : To evaluate proton magnetic resonance spectroscopy ({sup 1}H MRS) features in order to assess hepatocellular activation in chronic hepatitis C and human immunodeficiency virus/hepatitis C (HIV/HCV) co-infected patients. Material and Methods : Liver in vivo {sup 1}H MR spectra were obtained in 14 patients with hepatitis C virus infection (HCV), 20 HIV/HCV co-infected individuals, and 24 healthy volunteers. Resonances of lipids, glutamine/glutamate (Glx), phosphomonoesters (PME), glycogen/glucose (Glc) were assessed and metabolite ratios to total lipids (TL) were calculated. Results : A significant increase in Glx/TL and PME/TL was observed in the HCV group as compared to healthy individuals. Patients with HIV and HCV co-infection had a further increase of all metabolite ratios. Changes in metabolite ratios were due to both the increase in particular metabolite contents and to the decrease in lipid levels. HIV/HCV-infected patients treated with highly active anti-retroviral therapy (HAART) showed elevated PME and Glx levels and significantly decreased TL compared to patients not undergoing anti-retroviral treatment. Conclusions : Our findings suggest clinical usefulness of liver {sup 1}H MR spectroscopy in detecting even slight disturbances in liver metabolism.

  19. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm

    DEFF Research Database (Denmark)

    Razavi, H; Waked, I; Sarrazin, C;

    2014-01-01

    The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total...... number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries...... studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep...

  20. Predictors of psychopathological outcome during peg-interferon and ribavirin therapy in patients with chronic HCV-correlated hepatitis.

    Science.gov (United States)

    Dell'Osso, Bernardo; Prati, Gianmaria; Palazzo, M Carlotta; Rumi, Maria Grazia; Cavallaro, Flaminia; Aghemo, Alessio; Colombo, Massimo; Altamura, A Carlo

    2013-01-01

    Peg-interferon (Peg-IFN) and ribavirin (RBV) therapy is reported to induce psychiatric symptoms and syndromes in 20% of patients treated for Hepatitis C Virus (HCV) infection. Present study was aimed to quantify the phenomenon and assess the influence of psychiatric counseling over antiviral completion rate and the use of psychometric tools, in terms of prediction of psychopathological outcome. Ninety-six HCV patients were assessed, before antiviral treatment, by means of the Sheehan Disability Scale (SDS), Mood Disorder Questionnaire (MDQ), Symptom Checklist-90, and Internal State Scale (ISS). Sociodemographic and clinical variables and completion rate were collected. Binary logistic regression was performed to evaluate whether scores were predictive of psychiatric visit, development of psychiatric disorders, and need for treatment. Ninety-five patients (99%) completed antiviral treatment; 27 subjects (29%) needed psychiatric visit: among them, mood disorder was diagnosed in 15 (16%) and were pharmacologically treated. Baseline SDS and MDQ higher scores were found to be predictive of psychiatric visit [odds ratio (OR)=1.258, Pcounseling may be needed in almost 30% of HCV patients on antiviral treatment, with positive influence over the completion rate. Baseline higher scores at psychometric questionnaires-MDQ-in particular, predictors of psychopathological outcome during Peg-IFN and RBV therapy in patients with chronic HCV-correlated hepatitis reflecting individual functioning before starting antiviral therapy and positive history for mood disorders, seem to predict psychiatric visit, onset of mood episodes, and need for psychopharmacological treatment. Further investigation is warranted to confirm results. PMID:23276143

  1. Test of IL28B polymorphisms in chronic hepatitis C patients treated with PegIFN and ribavirin depends on HCV genotypes: results from a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Zhifang Jia

    Full Text Available BACKGROUND: Many studies have been published on the association between single nucleotide polymorphisms (SNP near the IL28B gene and response to the combined treatments of pegylated-interferon (PegIFN and ribavirin (RBV in chronic HCV-infected patients, but without identical conclusions. The aim of this study was to assess impact of the IL28B polymorphisms on the effect of HCV standard treatment using meta-analysis based method. METHODS: Association studies between polymorphisms of rs12979860 or rs8099917 and response to PegIFN/RBV treatment in chronic HCV patients were retrieved from PubMed. Data of qualified studies on sustained virological response (SVR in different genotypes were extracted and analyzed using meta-analysis method in Stata 10 software. RESULTS: Thirty-four papers, containing 46 independent studies, were included in the analysis. In the HCV G1/4 patients without treatment history, individuals carrying rs12979860 CC genotype were more likely to achieve SVR (OR 3.97, 95%CI 3.29-4.80 compared to those carrying CT/TT genotypes. Similar results were observed in the HCV G1/4 patients with unsuccessful or unknown treatment history (OR 3.76, 95%CI 2.67-5.28 or in the patients co-infected with human immunodeficiency virus (OR 5.20, 95%CI 3.04-8.90. However, associations could not be observed in HCV G2/3 patients. For rs8099917, similar results were obtained for genotype TT compared to genotypes TG/GG, indicating that TT genotype was significantly associated with better treatment response in patients infected with genotype 1 or 4 HCV, but not genotype 2 or 3 HCV. CONCLUSION: Polymorphisms of rs12979860 and rs8099917 near IL28B only associate with the treatment response to PegIFN/RBV in patients infected with HCV genotype 1 or 4 but not with genotype 2 or 3, irrespective of the previous treatment history or HIV co-infected status. Therefore, identification of IL28B genotypes is necessary only in patients infected with relatively difficult

  2. Constraints on Viral Evolution during Chronic Hepatitis C Virus Infection Arising from a Common-Source Exposure

    OpenAIRE

    Bailey, Justin R.; Laskey, Sarah; Wasilewski, Lisa N.; Munshaw, Supriya; Liam J. Fanning; Kenny-Walsh, Elizabeth; Ray, Stuart C.

    2012-01-01

    Extraordinary viral sequence diversity and rapid viral genetic evolution are hallmarks of hepatitis C virus (HCV) infection. Viral sequence evolution has previously been shown to mediate escape from cytotoxic T-lymphocyte (CTL) and neutralizing antibody responses in acute HCV infection. HCV evolution continues during chronic infection, but the pressures driving these changes are poorly defined. We analyzed plasma virus sequence evolution in 5.2-kb hemigenomes from multiple longitudinal time p...

  3. Exceptional Heterogeneity in Viral Evolutionary Dynamics Characterises Chronic Hepatitis C Virus Infection

    Science.gov (United States)

    Lemey, Philippe; Farci, Patrizia; Pybus, Oliver G.

    2016-01-01

    The treatment of HCV infection has seen significant progress, particularly since the approval of new direct-acting antiviral drugs. However these clinical achievements have been made despite an incomplete understanding of HCV replication and within-host evolution, especially compared with HIV-1. Here, we undertake a comprehensive analysis of HCV within-host evolution during chronic infection by investigating over 4000 viral sequences sampled longitudinally from 15 HCV-infected patients. We compare our HCV results to those from a well-studied HIV-1 cohort, revealing key differences in the evolutionary behaviour of these two chronic-infecting pathogens. Notably, we find an exceptional level of heterogeneity in the molecular evolution of HCV, both within and among infected individuals. Furthermore, these patterns are associated with the long-term maintenance of viral lineages within patients, which fluctuate in relative frequency in peripheral blood. Together, our findings demonstrate that HCV replication behavior is complex and likely comprises multiple viral subpopulations with distinct evolutionary dynamics. The presence of a structured viral population can explain apparent paradoxes in chronic HCV infection, such as rapid fluctuations in viral diversity and the reappearance of viral strains years after their initial detection. PMID:27631086

  4. Chronic Hepatitis C Virus (HCV-associated Cryoglobulinemia and its possible impact on the skin in Egyptian Patients

    Directory of Open Access Journals (Sweden)

    Amin Mohamed Abd El Baki1, Mohamed A.Ezzel Arab2Nabil Abd El Mageed3

    2010-06-01

    Full Text Available Chronic hepatitis C virus (HCV infection may have extremely variable clinical consequences and is more than just a liver disease; it has been associated with numerous extra-hepatic manifestations (EHM. According to various international studies Mixed Cryoglobulinemia (MC was found to be the most common EHM, however its local prevalence in Egyptian HCV patients was not clearly studied. The aim of our study was to investigate the frequency of cryoglobulinaemia in sera of chronic HCV patients and their association with clinical symptoms especially, vasculitis. Method: One hundred patients with chronic HCV infection attending the outpatient clinic of the National Hepatology and Tropical Medicine Research Institute were interviewed. Patients with decompensated liver disease, on interferon therapy, having end-stage renal disease or coexisting viral infection like hepatitis B surface antigen positive patients were all excluded from the research. All patients were subjected to general and dermatological examination for liver affection signs; cryoglobulinemia related clinical manifestations and/or associated dermatoses. Cryoglobulins, CBC, LFT. AFP, ALP, KFT, ANA and RF were assessed. Results: Overall 15% of 100 patients were positive for presence of cryoglobulins in their sera. We found a relatively high incidence of clinical symptoms commonly accompanying cryoglobulinemic cases in the form of Purpura, Arthralgia, Generalized weakness, Peripheral Neuropathy and Reynaud's phenomenon with prevalence of 26.67%, 46.67%, 53.33%, 40% and 6.67% respectively. Our data also demonstrated that 46.67% (7 of our 15 cryopositive patients had concomitant skin manifestations in the form of Pruritus 40% (6 and Vasculitis 26.67% (4 (P=0.004 which was significant in comparison with prevalence of vasculitis in all patients 4.7% (4 patients. Generalized weakness and fatigue, which is the most prevalent symptoms related to Chronic Hepatitis C (CHC patients whether positive

  5. Co-infection rate of HIV, HBV and Syphilis among HCV seropositive identified blood donors in Kathmandu, Nepal

    OpenAIRE

    Shrestha, Ashish Chandra; Ghimire, Prakash; Tiwar, Bishnu Raj; Rajkarnikar, Manita

    2012-01-01

    Background: HIV, HBV, Syphilis and HCV share common modes of transmission. Objective: The study was aimed to determine the co-infection rate of HIV, HBV and Syphilis among HCV seropositive identified blood donors. Methods: The study was conducted on blood samples screened as HCV seropositive at Nepal Red Cross Society, Central Blood Transfusion Service, Kathmandu, Nepal. HCV seropositive samples were further tested for HIV, HBV and Syphilis. Results: Eight co-infections were observed in 139 H...

  6. Hepatitis C virus infection in chronic liver disease in Somalia.

    Science.gov (United States)

    Aceti, A; Taliani, G; Bruni, R; Sharif, O S; Moallin, K A; Celestino, D; Quaranta, G; Sebastiani, A

    1993-04-01

    To assess the role of hepatitis C virus (HCV) in liver disease in Somalia, antibody to HCV (anti-HCV) was studied by enzyme-linked immunosorbent assay (ELISA) and recombinant immunoblot assay (RIBA) in 110 patients with chronic liver diseases, in 309 healthy adults, in 179 institutionalized subjects with a high prevalence of intestinal parasites and Schistosoma haematobium, and in 287 children with diseases other than hepatitis. According to the RIBA test, anti-HCV was present in three healthy adults (0.97%), in four institutionalized individuals (2.2%), but in none of the children. The prevalence of anti-HCV was 4.8% in patients with hepatitis B surface antigen (HBsAg)-positive chronic liver diseases and 20.6% in patients with HBsAg-negative chronic liver diseases. Thus, HCV infection appears to play a minor role in HBsAg-positive liver disease in Somalia but may be an important factor in HBsAg-negative chronic liver disease. The low anti-HCV prevalence in individuals with no hepatic disorders is consistent with the fact that HCV does not spread by nonpercutaneous transfer. We found also a large proportion of both patients with hepatic disease and institutionalized individuals who tested positive by ELISA but not confirmed by RIBA. However, the likelihood of a true positive result increases proportionally with the ELISA value; thus, in most cases a low ELISA value probably represents a false-positive reaction, while a high ELISA value probably represents a true positive reaction. PMID:7683179

  7. Association of interleukin-12 p40 gene 3'-untranslated region polymorphism and outcome of HCV infection

    Institute of Scientific and Technical Information of China (English)

    Li-Min Yin; Qi-Xin Wang; Yan Gao; Hui Zhuang; Wan-Fu Zhu; Lai Wei; Xiao-Yuan Xu; De-Gui Sun; Yan-Bin Wang; Wen-Mei Fan; Min Yu; Xiu-Lan Tian

    2004-01-01

    AIM: To investigate the effect of interleukin-12 p40 gene (IL12B) 3'-untranslated region polymorphism on the outcome of HCV infection.METHODS: A total of 133 patients who had been infected with HCV for 12-25 (18.2±3.8) years, were enrolled in this study. Liver biochemical tests were performed with an automated analyzer and HCV RNA was detected by fiuorogenic quantitative polymerase chain reaction. B-mode ultrasound was used for liver examination. Polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) was used for the detection of IL12B (1188A/C) polymorphism.RESULTS: Self-limited infection was associated with AC genotype (OR = 3.48; P = 0.001) and persistent infection was associated with AA genotype (OR = 0.34; P = 0.014)at site 1188 of IL12B. In patients with persistent HCV infection, no significant differences were found regarding the age, gender, duration of infection and biochemical characteristics (P>0.05). According to B-mode ultrasound imaging and clinical diagnosis, patients with persistent infection were divided into groups based on the severity of infection. No significant differences were found in the frequency of IL-12 genotype (1188A/C) between different groups (P>0.05).CONCLUSION: The polymorphism of IL12B (1188A/C)appears to have some influence on the outcome of HCV infection.

  8. Proteome Analysis of Liver Cells Expressing a Full- Length Hepatitis C Virus (HCV) Replicon and Biopsy Specimens of Posttransplantation Liver from HCV-Infected Patients

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, Jon M.; Diamond, Deborah L.; Chan, Eric Y.; Gritsenko, Marina A.; Qian, Weijun; Stastna, Miroslava; Baas, Tracey; Camp, David G.; Carithers, Jr., Robert L.; Smith, Richard D.; Katze, Michael G.

    2005-06-01

    The development of a reproducible model system for the study of Hepatitis C virus (HCV) infection has the potential to significantly enhance the study of virus-host interactions and provide future direction for modeling the pathogenesis of HCV. While there are studies describing global gene expression changes associated with HCV infection, changes in the proteome have not been characterized. We report the first large scale proteome analysis of the highly permissive Huh-7.5 cell line containing a full length HCV replicon. We detected > 4,400 proteins in this cell line, including HCV replicon proteins, using multidimensional liquid chromatographic (LC) separations coupled to mass spectrometry (MS). The set of Huh-7.5 proteins confidently identified is, to our knowledge, the most comprehensive yet reported for a human cell line. Consistent with the literature, a comparison of Huh-7.5 cells (+) and (-) the HCV replicon identified expression changes of proteins involved in lipid metabolism. We extended these analyses to liver biopsy material from HCV-infected patients where > 1,500 proteins were detected from 2 {micro}g protein lysate using the Huh-7.5 protein database and the accurate mass and time (AMT) tag strategy. These findings demonstrate the utility of multidimensional proteome analysis of the HCV replicon model system for assisting the determination of proteins/pathways affected by HCV infection. Our ability to extend these analyses to the highly complex proteome of small liver biopsies with limiting protein yields offers the unique opportunity to begin evaluating the clinical significance of protein expression changes associated with HCV infection.

  9. Toward a simple risk assessment screening tool for HCV infection in Egypt.

    Science.gov (United States)

    El-Ghitany, Engy M; Farghaly, Azza G; Abdel Wahab, Moataza M; Farag, Shehata; Abd El-Wahab, Ekram W

    2016-10-01

    Asymptomatic patients with HCV infection identified through screening program could benefit not only from treatment but also from other interventions such as counseling to maintain health and avoid risk behaviors. This might prevent the spread of infection and result in significant public health benefits. However, mass screening would quickly deplete resources. This work aims to develop a brief HCV risk assessment questionnaire that inquires initially about a wide range of risk factors found to be potentially associated with HCV infection in order to identify the few most significant questions that could be quickly used to facilitate cost-effective HCV case-finding in the general population in Egypt. An exhaustive literature search was done to include all reported HCV risk factors that were pooled in a 65 item questionnaire. After an initial pilot study, a case-control study was performed that included 1,024 cases and 1,046 controls. In a multivariable model, a list of independent risk factors were found to be significant predictors for being HCV seropositive among two age strata (45 years) for each gender. A simplified model that assigned values of the odds ratio as a weight for each factor present predicted HCV infection with high diagnostic accuracy. Attaining the defined cut-off value of the total risk score enhances the effectiveness of screening. HCV risk factors in the Egyptian population vary by age and gender. An accurate prediction screening tool can be used to identify those at high risk who may benefit most from HCV serologic testing. These results are to be further validated in a large scale cross-sectional study to assess the wider use of this tool. J. Med. Virol. 88:1767-1775, 2016. © 2016 Wiley Periodicals, Inc.

  10. Toward a simple risk assessment screening tool for HCV infection in Egypt.

    Science.gov (United States)

    El-Ghitany, Engy M; Farghaly, Azza G; Abdel Wahab, Moataza M; Farag, Shehata; Abd El-Wahab, Ekram W

    2016-10-01

    Asymptomatic patients with HCV infection identified through screening program could benefit not only from treatment but also from other interventions such as counseling to maintain health and avoid risk behaviors. This might prevent the spread of infection and result in significant public health benefits. However, mass screening would quickly deplete resources. This work aims to develop a brief HCV risk assessment questionnaire that inquires initially about a wide range of risk factors found to be potentially associated with HCV infection in order to identify the few most significant questions that could be quickly used to facilitate cost-effective HCV case-finding in the general population in Egypt. An exhaustive literature search was done to include all reported HCV risk factors that were pooled in a 65 item questionnaire. After an initial pilot study, a case-control study was performed that included 1,024 cases and 1,046 controls. In a multivariable model, a list of independent risk factors were found to be significant predictors for being HCV seropositive among two age strata (45 years) for each gender. A simplified model that assigned values of the odds ratio as a weight for each factor present predicted HCV infection with high diagnostic accuracy. Attaining the defined cut-off value of the total risk score enhances the effectiveness of screening. HCV risk factors in the Egyptian population vary by age and gender. An accurate prediction screening tool can be used to identify those at high risk who may benefit most from HCV serologic testing. These results are to be further validated in a large scale cross-sectional study to assess the wider use of this tool. J. Med. Virol. 88:1767-1775, 2016. © 2016 Wiley Periodicals, Inc. PMID:26970264

  11. Seroprevalence of HBV, HCV & HIV co-infection and risk factors analysis in Tripoli-Libya.

    Directory of Open Access Journals (Sweden)

    Mohamed A Daw

    Full Text Available BACKGROUND: In 1998 Libya experienced a major outbreak of multiple blood borne viral hepatitis and HIV infections. Since then, no studies have been done on the epidemic features and risk factors of HBV, HCV, HIV and co-infection among the general population. METHODS: A prospective study was carried out using a multi-centre clustering method to collect samples from the general population. The participants were interviewed, and relevant information was collected, including socio-demographic, ethnic, and geographic variables. This information was correlated with the risk factors involved in the transmission of HBV, HCV and HIV. Blood samples were collected and the sera were tested for HBsAg, anti-HCV and anti-HIV using enzyme immunoassay. RESULTS: A total of 9,170 participants from the nine districts of Tripoli were enrolled. The average prevalence of HBsAg was 3.7%, anti-HCV 0.9%, anti-HIV 0.15% and co-infection 0.02%. The prevalence varied from one district to another. HBV was more prevalent among those aged over 50 years and was associated with family history. Anti-HCV and anti-HIV were more prevalent among those aged 20-40 years. Intravenous drug use and blood transfusion were the main risk factors for HCV and HIV infection. CONCLUSION: HBV, HCV, HIV and co-infection are relatively common in Libya. High prevalence was associated with geographic, ethnic and socioeconomic variability within the community. HCV and HIV infections among the younger age groups are becoming an alarming issue. Regulations and health care education need to be implemented and longer term follow-up should be planned.

  12. Patient concerns regarding chronic hepatitis C infections.

    Science.gov (United States)

    Minuk, G Y; Gutkin, A; Wong, S G; Kaita, K D E

    2005-01-01

    Counselling of patients with chronic hepatitis C infections is often limited to discussions regarding how the virus is transmitted and what can be done to decrease the risk of transmission to others. The purpose of the present study was to document the principal concerns of newly diagnosed and follow-up patients with chronic hepatitis C, and thereby enhance counselling strategies and content. Seventy newly diagnosed and 115 follow-up patients with chronic hepatitis C virus (HCV) infection were initially asked in an open-ended manner (volunteered concerns) and then to prioritize from a prepared list of seven potential concerns (prioritized concerns), to identify those concerns that were of utmost importance to them. The most common volunteered concerns of newly diagnosed patients in decreasing order were: disease progression (27%), premature death (19%), infecting family members (13%), side-effects of treatment (11%) and miscellaneous others. In decreasing order, prioritized concerns included: infecting family members, development of liver cancer, infecting others, development of cirrhosis, social stigma of having liver disease, need for liver transplant and loss of employment. The principal volunteered and prioritized concerns of follow-up patients were similar to those of newly diagnosed patients. Volunteered and prioritized concerns were relatively consistent across the different genders, age groups, ethnic backgrounds, education level, marital status, employment, modes of viral acquisition and in the case of follow-up patients, duration of follow-up. These results indicate that health care providers who focus counselling efforts exclusively on viral transmission are unlikely to address other important concerns of newly diagnosed and follow-up patients with chronic HCV infection. PMID:15655048

  13. NAFLD and NASH in HCV Infection: Prevalence and Significance in Hepatic and Extrahepatic Manifestations.

    Science.gov (United States)

    Adinolfi, Luigi Elio; Rinaldi, Luca; Guerrera, Barbara; Restivo, Luciano; Marrone, Aldo; Giordano, Mauro; Zampino, Rosa

    2016-01-01

    The aim of this paper is to review and up to date the prevalence of hepatitis C virus (HCV)-associated non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) and their significance in both accelerating progression of HCV-related liver disease and development of HCV-associated extrahepatic diseases. The reported mean prevalence of HCV-related NAFLD was 55%, whereas NASH was reported in 4%-10% of cases. HCV genotype 3 directly induces fatty liver deposition, namely "viral steatosis" and it is associated with the highest prevalence and degree of severity, whereas, HCV non-3 genotype infection showed lower prevalence of steatosis, which is associated with metabolic factors and insulin resistance. The host's genetic background predisposes him or her to the development of steatosis. HCV's impairment of lipid and glucose metabolism causes fatty liver accumulation; this seems to be a viral strategy to optimize its life cycle. Irrespective of insulin resistance, HCV-associated NAFLD, in a degree-dependent manner, contributes towards accelerating the liver fibrosis progression and development of hepatocellular carcinoma by inducing liver inflammation and oxidative stress. Furthermore, NAFLD is associated with the presence of metabolic syndrome, type 2 diabetes, and atherosclerosis. In addition, HCV-related "metabolic steatosis" impairs the response rate to interferon-based treatment, whereas it seems that "viral steatosis" may harm the response rate to new oral direct antiviral agents. In conclusion, a high prevalence of NAFLD occurs in HCV infections, which is, at least in part, induced by the virus, and that NAFLD significantly impacts progression of the liver disease, therapeutic response, and some extrahepatic diseases. PMID:27231906

  14. Studies on the allostimulatory function of dendritic cells from HCV-HIV-1 co-infected patients

    Institute of Scientific and Technical Information of China (English)

    Justin STEBBING; Brian GAZZARD; Steve PATTERSON; Simon PORTSMOUTH; Claire THOMAS; Robert GLASSMAN; Adrian WILDFIRE; Frances GOTCH; Mark BOWER; Mark NELSON

    2004-01-01

    There is increasing recognition of the potential morbidity and mortality associated with HIV-1 and hepatitis C (HCV)co-infection. HIV appears to adversely affect HCV disease while the reciprocal effect of HCV on HIV remains controversial.We therefore studied the effect of co-infection on dendritic cell function versus HIV infection alone, as previous work has shown that HCV impairs dendritic cell (DC) function. HIV-1 positive individuals with HCV were matched for CD4count, HIV- 1 RNA viral load and therapy, to HIV- 1 positive patients without HCV. Monocyte-derived DC were generated and mixed leukocyte reactions were performed. We assessed allostimulatory capacity with and without administration of exogenous Thl cytokines, using thymidine uptake and cell division analyses with the vital dye CFSE. We found that monocyte-derived DC from co-infected individuals showed no significant differences in allostimulatory capacity to ex vivo generated DC from HIV-1 infected individuals without HCV. Unlike the situation with HCV infection alone, this impairment was not reversed by increasing concentrations of either interleukin-2 or -12. Monocyte-derived DC from HIV-1 and HCV co-infected individuals have a similar allostimulatory capacity to DC from matched patients with HIV-1alone. These findings are compatible with results of prior clinical studies that found no evidence that HCV co-infection altered HIV disease progression and has implications for immunotherapeutic approaches in co-infected individuals.

  15. The Distribution of Hepatitis C Virus Genotypes in Patients with Chronic Hepatitis C Infection

    Directory of Open Access Journals (Sweden)

    Sevin Kırdar

    2015-12-01

    Full Text Available Objective: Hepatitis C virus (HCV infection represents a major public health problem worldwide. HCV can cause chronic hepatitis infection which may ultimately result in cirrhosis and hepatocellular carcinoma. Seven major genotypes and more than 100 subtypes of HCV are shown by sequence analysis. Genotype 1 is associated with more severity of liver disease than genotypes 2 and 3 and sustained response totreatment is known to be less. In this study, we aimed to determine the HCV genotype distribution in chronic hepatitis C patients. Materials and Methods: A total of 50 patients with chronic HCV infection who attended the Microbiology Laboratory at Adnan Menderes University Hospital between August 2007 and December 2010 found to be positive for anti-HCV and HCV-RNA were included in the study. Anti-HCV testing was performed using microparticle Enzyme-Linked immunosorbent assay test kit (Murex Anti-HCV version 4, UK with autoanalyser (Grifols Triturus, Spain. The quantification of serum HCV-RNA was carried out by a realtime polymerase chain reaction method with two different systems (Cobas TaqMan HCV, Roche Diagnostics, Germany and RotorGene 6000,Corbett Research, USA. HCV genotype analysis was performed by using a kit (HCV-TS; AB Analitica, Italy based on the reverse hybridization of 5’-untranslated region and amplified products with genotype-specific probes. Results: The mean age of the 50 chronic hepatitis C patients [27 (54% female, and 23 (46% male] was 57.1±14.3 years. Genotype 1b was found in 36 (72% subjects, genotype 1a in nine (18%, genotype 2b in one (2%, genotype 3 in one (2%, and genotype 1a/1b was found in three (6% patients. No statistically significant difference was detected in HCV-RNA quantities and anti-HCV index between HCV genotypes (p>0.05. Conclusion: Compatible with the previous data obtained in Turkey, genotype 1b was found to be the most common HCV genotype in patients with chronic hepatitis C followed in our hospital.

  16. Risk Factors for Hepatitis C Virus Infection in Canadian Patients with Chronic Type C Hepatitis

    Directory of Open Access Journals (Sweden)

    GY Minuk

    1995-01-01

    Full Text Available Previous reports from the United States indicate that as many as 40% of patients with chronic hepatitis C virus (HCV have no identifiable risk factor for HCV infection. To determine whether the same is true of Canadian patients with chronic HCV the records of 89 anti-HCV positive patients referred to the authors' tertiary care centre for evaluation of liver disease were reviewed. Each patient had been specifically asked about the following risk factors: previous blood transfusions; intravenous drug abuse; homosexual activity; sexual promiscuity (multiple sexual partners or a history of sexually transmitted diseases; tattoos made with nonsterile techniques; and ear piercing using nonsterile techniques. The results of the study revealed that 76 of 89 patients (85% had at least one risk factor for HCV exposure, 38 (43% had only one risk factor, 19 (21% had two, 12 (14% had three and the remaining three patients (3% had four. The most common risk factor was a history of intravenous drug abuse (30 of 89 patients, 34% followed by sexual promiscuity (28, 32%, previous blood transfusions (21, 24%, tattoos (17, 19%, homosexual contacts (seven, 8% and ear piercing (five, 6%. Contrary to a recent report identifying sexual contact as an independent risk factor for HCV infection, only four cases (5% were found where sexual promiscuity was identified as the only risk factor. In conclusion, these findings indicate that a possible source of HCV infection can be identified in a large majority of Canadians referred to an urban centre with chronic HCV infection.

  17. Treatment for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection - Danish national guidelines 2011

    DEFF Research Database (Denmark)

    Christensen, Peer Brehm; Clausen, Mette Rye; Krarup, Henrik Bygum;

    2012-01-01

    countries, probably infected at birth or early childhood in their country of origin, while the majority of patients with HCV infection have been infected by drug use. For both groups it is estimated that only half of the patients have been diagnosed, of whom only 20% attends specialized care...

  18. Clinical and epidemiological features of patients with chronic hepatitis C co-infected with HIV

    Directory of Open Access Journals (Sweden)

    Braga Eduardo Lorens

    2006-02-01

    Full Text Available Co-infection with hepatitis C virus (HCV and human immunodeficiency virus (HIV is increasingly common and affects the clinical course of chronic hepatitis C. Highly active antiretroviral therapy has improved the life expectancy of HIV infected patients, but, by extending survival, it permits the development of HCV cirrhosis. This study tried to evaluate clinical and epidemiological features of patients with chronic hepatitis C co-infected with HIV. We evaluated 134 HCV-infected patients: i group A - 65 co-infected HCV/HIV patients, ii group B - 69 mono-infected HCV patients. The impact of HIV infection on HCV liver disease was analyzed using Child's score, ultrasound findings and liver histology. Patients were subjected to HCV genotyping and anti-HBs dosage. Patients mean age was 42.4 years (±9.1 and 97 (72.4% were males. Injected drug use and homo/bisexual practice were more frequently encountered in the co-infected group: 68.3% and 78.0%, respectively. Antibodies against hepatitis B virus (anti-HBs were found in only 38.1% of the patients (66.7% group A x 33.3% group B. Ten out of 14 individuals (71.4% who had liver disease (Child B or C and 25 out of 34 (73.5% who showed ultrasound evidence of chronic liver disease were in the co-infection group. HCV genotype-2/3 was more frequently encountered in co-infected patients (36.9% group A vs. 21.8% group B. Conclusions: a HIV infection seems to adversely affect the clinical course of chronic hepatitis C, b injected drug use, bi/homosexual practice and genotype-2/3 were more frequently encountered in co-infected patients, c immunization against HBV should be encouraged in these patients.

  19. Apoptosis and clinical severity in patients with psoriasis and HCV infection

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    Sami A Gabr

    2014-01-01

    Full Text Available Background: It has been proposed that hepatitis C virus (HCV antigens are involved in the pathogenesis of psoriasis and may contribute to severity of the disease. Increased expression of the apoptosis-regulating proteins p53 and tTG and decreased levels of bcl-2 in the keratinocytes of the skin of psoriatic patients have been reported. Aim: This study aims to identify the serum levels of apoptosis-regulating proteins in patients with psoriasis and without HCV infection and to study the relation between clinical severity of psoriasis and the presence of HCV infection. Materials and Methods: Disease severity was assessed by psoriasis area severity index score (PASI of 90 patients with psoriasis grouped as mild (n = 30, moderate (n = 30 and severe (n = 30; 20 healthy individuals were used as controls. All groups were subjected for complete history taking, clinical examination, and tests for liver function and HCV infection. The serum levels of apoptosis related proteins: p53, tTG and bcl-2 were estimated by enzyme linked immune sorbent assay (ELISA. Results: There was a statistically significant (P < 0.001 correlation between clinical severity of psoriasis and presence of HCV antibodies and HCV-mRNA. In addition, significantly (P < 0.001 raised serum p53 and tTG, and reduced bcl-2 were observed among HCV-positive patients as compared to HCV-negative patients and control patients. Conclusion: These results conclude that clinical severity of psoriasis is affected by the presence of HCV antibodies and overexpression of apoptotic related proteins. In addition, altered serum levels of apoptosis-regulating proteins could be useful prognostic markers and therapeutic targets of psoriatic disease.

  20. Comparative Proteomics Reveals Important Viral-Host Interactions in HCV-Infected Human Liver Cells.

    Directory of Open Access Journals (Sweden)

    Shufeng Liu

    Full Text Available Hepatitis C virus (HCV poses a global threat to public health. HCV envelop protein E2 is the major component on the virus envelope, which plays an important role in virus entry and morphogenesis. Here, for the first time, we affinity purified E2 complex formed in HCV-infected human hepatoma cells and conducted comparative mass spectrometric analyses. 85 cellular proteins and three viral proteins were successfully identified in three independent trials, among which alphafetoprotein (AFP, UDP-glucose: glycoprotein glucosyltransferase 1 (UGT1 and HCV NS4B were further validated as novel E2 binding partners. Subsequent functional characterization demonstrated that gene silencing of UGT1 in human hepatoma cell line Huh7.5.1 markedly decreased the production of infectious HCV, indicating a regulatory role of UGT1 in viral lifecycle. Domain mapping experiments showed that HCV E2-NS4B interaction requires the transmembrane domains of the two proteins. Altogether, our proteomics study has uncovered key viral and cellular factors that interact with E2 and provided new insights into our understanding of HCV infection.

  1. Comparative Proteomics Reveals Important Viral-Host Interactions in HCV-Infected Human Liver Cells.

    Science.gov (United States)

    Liu, Shufeng; Zhao, Ting; Song, BenBen; Zhou, Jianhua; Wang, Tony T

    2016-01-01

    Hepatitis C virus (HCV) poses a global threat to public health. HCV envelop protein E2 is the major component on the virus envelope, which plays an important role in virus entry and morphogenesis. Here, for the first time, we affinity purified E2 complex formed in HCV-infected human hepatoma cells and conducted comparative mass spectrometric analyses. 85 cellular proteins and three viral proteins were successfully identified in three independent trials, among which alphafetoprotein (AFP), UDP-glucose: glycoprotein glucosyltransferase 1 (UGT1) and HCV NS4B were further validated as novel E2 binding partners. Subsequent functional characterization demonstrated that gene silencing of UGT1 in human hepatoma cell line Huh7.5.1 markedly decreased the production of infectious HCV, indicating a regulatory role of UGT1 in viral lifecycle. Domain mapping experiments showed that HCV E2-NS4B interaction requires the transmembrane domains of the two proteins. Altogether, our proteomics study has uncovered key viral and cellular factors that interact with E2 and provided new insights into our understanding of HCV infection. PMID:26808496

  2. Prevalence and correlates of HCV, HVB, and HIV infection among prison inmates and staff, Hungary.

    Science.gov (United States)

    Tresó, Bálint; Barcsay, Erzsébet; Tarján, Anna; Horváth, Gergely; Dencs, Agnes; Hettmann, Andrea; Csépai, Mária Magdolna; Gyori, Zoltán; Rusvai, Erzsébet; Takács, Mária

    2012-02-01

    The aim of this national, multicenter, cross-sectional study was to assess the prevalence of hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency viruses (HIV) among prisoners, and to identify related risk behaviors including injection drug use. Overall, 4,894 inmates from 20 prisons were enrolled. To have a comparison group, prison staff were also asked to take part. Altogether, 1,553 of the 4,894 inmates from seven prisons completed a questionnaire on risk behaviors. According to the survey, 1.5%, 4.9%, and 0.04% of the prisoners were tested positive for HBsAg, anti-HCV and anti-HIV, respectively. These prevalence data are among the lowest reported from prisons worldwide, although comparable to the Central European data. The prevalence of HBV, HCV, and HIV in the Hungarian prison staff was low (0.38%, 0.47%, and 0%, respectively). The rate of HCV infection was significantly higher among inmates who have ever injected drugs (22.5%) than among inmates who reported they had never injected drugs (1.1%). This first prevalence study of illegal drug injection-related viral infections among Hungarian prisoners points out that ever injecting drugs is the main reason for HCV infection among inmates. The opportunity to reach drug users infected with HCV for treatment underlines the importance of screening programs for blood-borne viruses in prisons. PMID:22143408

  3. Seroprevalence of anti-HCV and hepatitis B surface antigen in HIV infected patients

    Directory of Open Access Journals (Sweden)

    Tankhiwale S

    2003-01-01

    Full Text Available Human immunodeficiency virus (HIV is known to influence the natural history of infections with certain hepatitis viruses and interactions between HIV and hepatitis viruses may potentiate HIV replication. There is high degree of epidemiological similarity between hepatitis B virus and HIV as regard to high-risk group and route of transmission. Transmission of hepatitis C virus (HCV through blood transfusion and intravenous drug abuse is well documented. Present study deals with the study of concurrent infection of HBV and HCV with HIV infection. In the study of 110 HIV seropositive patients, 34(30.4% were positive for HBV and 8(7.27% for HCV. The difference of concomitant infection was highly significant compared to controls. (p value < 0.0001. Heterosexual high risk behaviour was observed in 89(80.91% of 110 HIV positive patients, out of which 23(25.8% and 5(5.62% were HBsAg and anti-HCV positive respectively. History of transmission was unclear in remaining patients. Concomitant infection of HIV and HBV was found to be significantly more in the symptomatic group (40.68% compared to asymptomatic group (19.6%. As HIV infection is known to affect the natural history of both HBV and HCV infection, screening of their concurrent association is necessary.

  4. Extrahepatic manifestations of chronic hepatitis C virus infection:297 cases from a tertiary medical center in Beijing, China

    Institute of Scientific and Technical Information of China (English)

    Cheng Zhaojing; Zhou Baotong; Shi Xiaochun; Zhang Yao; Zhang Lifan; Chen Limeng; Liu Xiaoqing

    2014-01-01

    Background Chronic hepatitis C virus (HCV) infection can affect multiple organ systems and cause a variety of extrahepatic manifestations (EMs).We sought to assess the constituent ratio of EMs in Chinese patients with chronic HCV infection and identify the clinical and biological factors associated with EM.Methods The medical records of 297 patients with chronic HCV infection were analyzed and demographic and epidemiological information was collected.The diagnosis of chronic HCV infection was based on positive anti-HCV combined with a positive HCV-RNA or at least two times of elevated aminotransferases attributable to HCV infection.Patients with HBV and/or HIV coinfection,autoimmune hepatitis,and history of alcohol abuse were excluded.Results Sixty-two percent (184/297) of the patients had at least one EM,including fatigue (29.4%),type 2 diabetes mellitus (28.2%),renal involvement (12.5%),lymphadenopathy (9.6%),fever (9.4%),thyroid dysfunction (8.1%),and arthralgia (7.4%).Neuropathy,sicca syndrome,B-cell lymphoma,Raynaud's phenomenon,and lichen planus were rare.The mean age of patients with EM was older compared with those without EM.Conclusions EMs were common in Chinese patients with chronic HCV infection,particularly fatigue,type 2 diabetes,renal impairment,lymphadenophy,fever,and thyroid dysfunction.Older age was associated with EMs.

  5. Treatment of HCV Infection in Multitransfused Thalassemic Patients: Does Liver Iron Status Affect the Outcome of Response?

    Directory of Open Access Journals (Sweden)

    Shahram Mirmomen

    2005-03-01

    Full Text Available IntroductionPatients with transfusion dependent thalassemia (TDT require blood transfusion program throughout their life to sustain their growth and development during childhood. Transfusion not only exposes these patients to increased risk of blood borne viruses (the most important one is HCV infection(1, but also causes an inevitable accumulation in body iron(2. Regular chelating program can delay the secondary iron overload but not completely avert the development of hepatic fibrosis. The secondary Iron overload and HCV infection are the two main causes of chronic liver fibrosis in patients with TDT(3, which is a common cause of death after the age of 15 in TDT patients(4. Notably in the last 3 decades we have witnessed profound changes in the management of patients with thalassemia major. Regular red blood cell transfusions and iron chelating permit a normal development throughout childhood, and extend survival. So treatment of HCV infection would have a great influence in the survival of a great number of TDT patients who pass their second decade of life.Iran is located in thalassemia belt with more than 25,000 registered TDT. Epidemiologic studies have shown that around 20 to 40% of Iranian TDT patients are infected with HCV virus(5,6,7. It should be mentioned that after initiation of donor screening for HCV in 1995 and exclusion of high risk groups from donation pool, the prevalence of HCV infection in thalassemic patients had decreased significantly(7a. On the other hand, similar rate of HCV infection has been shown in TDT patients worldwide(8, which in turn puts another emphasis on the importance of HCV treatment in this group of patients.History of HCV Treatment in ThalassemiaInterferon-alpha (IFN-a monotherapy is currently approved as the first line treatment for HCV infection in TDT patients. Because of hemolytic complications of ribavirin, currently combination of IFN and ribavirin is preserved for IFN non-responders and only under

  6. Venue-Based Networks May Underpin HCV Transmissions amongst HIV-Infected Gay and Bisexual Men

    Science.gov (United States)

    Bradshaw, Daniel; Raghwani, Jayna; Jacka, Brendan; Sacks-Davis, Rachel; Lamoury, Francois; Down, Ian; Prestage, Garrett; Applegate, Tanya L.; Hellard, Margaret; Sasadeusz, Joe; Dore, Gregory J.; Pybus, Oliver G.; Matthews, Gail V.; Danta, Mark

    2016-01-01

    Background This study aimed to investigate the potential influence of venue-based networks on HCV transmission in HIV-positive gay and bisexual men (GBM). Methods This was a prospectively recruited cohort of HIV-infected GBM with recently-acquired HCV infection resident in Melbourne and Sydney. Clinical and demographic data were collected together with blood samples for HCV sequencing. Phylogenies were inferred and clusters of individuals infected with HCV with genetic sequence homology were identified. Venues used for sourcing sexual partners were identified; sourcing partners from the same venue was considered a potential social link. Using the Jaccard similarity coefficient, associations were identified between the network of sites where men sourced sex partners and transmission relationships as defined by phylogenetic clustering. Results Forty individuals were recruited, of whom 62.5% were considered to have sexually- and 37.5% IDU-acquired HCV. Venue use was consistent with men being members of a more sexually adventurous gay community subculture. Six phylogenetically-determined pairs or clusters were identified, comprising fifteen (15/28, 53.6%) individuals. Participants belonging to phylogenetic clusters were observed within the same networks. There was a significant correlation between the network and phylogenetic clustering when both cities were considered simultaneously (p = 0.005), raising the possibility that social connections may be important for HCV transmissions. Conclusions Venue-based network elicitation is a promising approach for elucidating HCV transmissions amongst HIV-infected GBM. Public health approaches targeting individuals and venues prominent within networks may reduce onward HCV transmission. PMID:27584149

  7. Immunization with Recombinant Adenoviral Vectors Expressing HCV Core or F Proteins Leads to T Cells with Reduced Effector Molecules Granzyme B and IFN-γ: A Potential New Strategy for Immune Evasion in HCV Infection.

    Science.gov (United States)

    Samrat, Subodh Kumar; Vedi, Satish; Singh, Shakti; Li, Wen; Kumar, Rakesh; Agrawal, Babita

    2015-01-01

    Multispecific, broad, and potent T cell responses have been correlated with viral clearance in hepatitis C virus (HCV) infection. However, the majority of infected patients develop chronic infection, suggesting that natural infection mostly leads to development of inefficient T cell immunity. Multiple mechanisms of immune modulation and evasion have been shown in HCV infection through various investigations. This study examined the generation and modulation of T cell responses against core and frameshift (F) proteins of HCV. A single immunization of mice with replication incompetent recombinant adenovirus vectors encoding for F or core antigens induces poor T cell responses and leads to generation of CD4+ and CD8+ T cells with low granzyme B (GrB) expression. These T cells have impaired GrB enzyme activity and are unable to kill peptide loaded target cells. The low intracellular expression of GrB is not due to degranulation of cytotoxic granules containing cytotoxic T cells. Addition of exogenous IL-2 in in vitro cultures leads to partial recovery of GrB production, whereas immunization with the Toll-like receptor (TLR) agonist poly I:C leads to complete restoration of GrB expression in both CD4+ and CD8+ T cells. Thus, a possible new strategy of T cell modulation is recognized wherein effector T cells are caused to be dysfunctional by HCV-derived antigens F or core, and strategies are also delineated to overcome this dysfunction. These studies are important in the investigation of prophylactic vaccine and immunotherapy strategies for HCV infection. PMID:26133045

  8. HCV-related liver cancer in people with haemophilia

    NARCIS (Netherlands)

    Meijer, K.; Haagsma, E. B.

    2012-01-01

    . The topic of this monograph is liver cancer associated with chronic HCV infection. We start with some background information on chronic HCV infection and its long-term sequelae, one of which is liver cancer. The rest of the article is concerned with liver cancer or hepatocellular carcinoma (HCC).

  9. NAFLD and NASH in HCV Infection: Prevalence and Significance in Hepatic and Extrahepatic Manifestations

    Science.gov (United States)

    Adinolfi, Luigi Elio; Rinaldi, Luca; Guerrera, Barbara; Restivo, Luciano; Marrone, Aldo; Giordano, Mauro; Zampino, Rosa

    2016-01-01

    The aim of this paper is to review and up to date the prevalence of hepatitis C virus (HCV)-associated non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) and their significance in both accelerating progression of HCV-related liver disease and development of HCV-associated extrahepatic diseases. The reported mean prevalence of HCV-related NAFLD was 55%, whereas NASH was reported in 4%–10% of cases. HCV genotype 3 directly induces fatty liver deposition, namely “viral steatosis” and it is associated with the highest prevalence and degree of severity, whereas, HCV non-3 genotype infection showed lower prevalence of steatosis, which is associated with metabolic factors and insulin resistance. The host’s genetic background predisposes him or her to the development of steatosis. HCV’s impairment of lipid and glucose metabolism causes fatty liver accumulation; this seems to be a viral strategy to optimize its life cycle. Irrespective of insulin resistance, HCV-associated NAFLD, in a degree-dependent manner, contributes towards accelerating the liver fibrosis progression and development of hepatocellular carcinoma by inducing liver inflammation and oxidative stress. Furthermore, NAFLD is associated with the presence of metabolic syndrome, type 2 diabetes, and atherosclerosis. In addition, HCV-related “metabolic steatosis” impairs the response rate to interferon-based treatment, whereas it seems that “viral steatosis” may harm the response rate to new oral direct antiviral agents. In conclusion, a high prevalence of NAFLD occurs in HCV infections, which is, at least in part, induced by the virus, and that NAFLD significantly impacts progression of the liver disease, therapeutic response, and some extrahepatic diseases. PMID:27231906

  10. NAFLD and NASH in HCV Infection: Prevalence and Significance in Hepatic and Extrahepatic Manifestations

    Directory of Open Access Journals (Sweden)

    Luigi Elio Adinolfi

    2016-05-01

    Full Text Available The aim of this paper is to review and up to date the prevalence of hepatitis C virus (HCV-associated non-alcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH and their significance in both accelerating progression of HCV-related liver disease and development of HCV-associated extrahepatic diseases. The reported mean prevalence of HCV-related NAFLD was 55%, whereas NASH was reported in 4%–10% of cases. HCV genotype 3 directly induces fatty liver deposition, namely “viral steatosis” and it is associated with the highest prevalence and degree of severity, whereas, HCV non-3 genotype infection showed lower prevalence of steatosis, which is associated with metabolic factors and insulin resistance. The host’s genetic background predisposes him or her to the development of steatosis. HCV’s impairment of lipid and glucose metabolism causes fatty liver accumulation; this seems to be a viral strategy to optimize its life cycle. Irrespective of insulin resistance, HCV-associated NAFLD, in a degree-dependent manner, contributes towards accelerating the liver fibrosis progression and development of hepatocellular carcinoma by inducing liver inflammation and oxidative stress. Furthermore, NAFLD is associated with the presence of metabolic syndrome, type 2 diabetes, and atherosclerosis. In addition, HCV-related “metabolic steatosis” impairs the response rate to interferon-based treatment, whereas it seems that “viral steatosis” may harm the response rate to new oral direct antiviral agents. In conclusion, a high prevalence of NAFLD occurs in HCV infections, which is, at least in part, induced by the virus, and that NAFLD significantly impacts progression of the liver disease, therapeutic response, and some extrahepatic diseases.

  11. Evaluation of viral load in saliva from patients with chronic hepatitis C infection.

    Science.gov (United States)

    Xavier Santos, Renata L; de Deus, Dayse M V; de Almeida Lopes, Edmundo P; Duarte Coêlho, Maria R C; de Castro, Jurema F L

    2015-01-01

    Hepatitis C virus can be detected in blood and other bodily fluids, such as saliva. The aim of this study was to detect and quantify the HCV-RNA in saliva and plasma from patients with chronic hepatitis C infections, as well as check the level of viral load in sex groups (age, ethnicity and virus subtypes). Whole saliva and blood from 70 patients with chronic hepatitis C infections attended at the department of gastroenterology from University Hospital. The HCV-RNA load was performed by qRT-PCR using Sybr Green I master mix. HCV-RNA was detected in 80% (56/70) of patients in saliva and 92.85% (65/70) in plasma. The median of the viral load in the plasma was of 4.87 log10, and in saliva, it was 3.32log10, (p = 0.0005). Female patients and black patients exhibited a negative correlation between the HCV-RNA load in saliva vs. the HCV-RNA load in plasma (r = -0.3172, CI95% -0.6240 to -0.03736, p = 0.0491) and (r = -0.3141; IC95% -0.6069 to -0.05926; p = 0.0209), respectively. HCV-RNA was detected and quantified in saliva samples, and according to the quantification levels, saliva may be a possible transmission source of HCV, particularly in women and people of black ethnicity who develop chronic HCV infections.

  12. HCV derived from sera of HCV-infected patients induces pro-fibrotic effects in human primary fibroblasts by activating GLI2

    Science.gov (United States)

    Granato, M.; Zompetta, C.; Vescarelli, E.; Rizzello, C.; Cardi, A.; Valia, S.; Antonelli, G.; Marchese, C.; Torrisi, M. R.; Faggioni, A.; Cirone, M.

    2016-01-01

    Hepatitis C virus (HCV) infection is a leading cause of liver fibrosis, especially in developing countries. The process is characterized by the excess accumulation of ECM that may lead, over time, to hepatic cirrhosis, liver failure and also to hepatocarcinoma. The direct role of HCV in promoting fibroblasts trans-differentiation into myofibroblasts, the major fibrogenic cells, has not been fully clarified. In this study, we found that HCV derived from HCV-infected patients infected and directly induced the trans-differentiation of human primary fibroblasts into myofibroblasts, promoting fibrogenesis. This effect correlated with the activation of GLI2, one of the targets of Hedgehog signaling pathway previously reported to be involved in myofibroblast generation. Moreover, GLI2 activation by HCV correlated with a reduction of autophagy in fibroblasts, that may further promoted fibrosis. GLI2 inhibition by Gant 61 counteracted the pro-fibrotic effects and autophagy inhibition mediated by HCV, suggesting that targeting HH/GLI2 pathway might represent a promising strategy to reduce the HCV-induced fibrosis. PMID:27476557

  13. Loss of immune escape mutations during persistent HCV infection in pregnancy enhances replication of vertically transmitted viruses

    OpenAIRE

    Honegger, Jonathan R; Kim, Seungtaek; Price, Aryn A.; Kohout, Jennifer A.; McKnight, Kevin L.; Prasad, Mona R.; Lemon, Stanley M.; Grakoui, Arash; Walker, Christopher M

    2013-01-01

    Globally, about 1% of pregnant women are persistently infected with the hepatitis C virus (HCV) 1 . Vertical transmission occurs in 3–5% of cases 2 and accounts for most new childhood HCV infections 1,3 . HCV-specific CD8+ cytotoxic T-lymphocytes (CTLs) play a vital role in the clearance of acute infections 4–6 , but in the 60–80% of infections that persist these cells become functionally exhausted or select mutant viruses that escape T-cell recognition 7–9 . Increased HCV replication during ...

  14. Occult hepatitis B infection and its possible impact on chronic hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Habibollahi Peiman

    2009-01-01

    Full Text Available As a well-recognized clinical phenomenon, persistent detectable viral genome in liver or sera in the absence of other serological markers for active hepatitis B virus (HBV replication is called occult HBV infection. The main mechanism through which occult infection occurs is not completely understood and several possible explanations, such as integration into human genome and maintenance in peripheral mononuclear cells, exist. Occult HBV infection has been reported in different populations, especially among patients with Hepatitis C (HCV related liver disease. The probable impact of occult HBV in patients with chronic HCV infection has been previously investigated and the evidence suggests a possible correlation with lower response to anti-viral treatment, higher grades of liver histological changes, and also developing hepatocellular carcinoma. However, in the absence of conclusive results, further studies should be conducted to absolutely assess the impact of occult HBV contamination on the HCV related liver disease.

  15. Effect of combined siRNA of HCV E2 gene and HCV receptors against HCV

    Directory of Open Access Journals (Sweden)

    Ashfaq Usman Alli A

    2011-06-01

    Full Text Available Abstract Background/Aim Hepatitis C virus (HCV is a major threat as almost 3% of the world's population (350 million individual and 10% of the Pakistani population is chronically infected with this virus. RNA interference (RNAi, a sequence-specific degradation process of RNA, has potential to be used as a powerful alternative molecular therapeutic approach in spite of the current therapy of interferon-α and ribavirin against HCV which has limited efficiency. HCV structural gene E2 is mainly involved in viral cell entry via attachment with the host cell surface receptors i.e., CD81 tetraspanin, low density lipoprotein receptor (LDLR, scavenger receptor class B type 1 (SR-B1, and Claudin1 (CLDN1. Considering the importance of HCV E2 gene and cellular receptors in virus infection and silencing effects of RNAi, the current study was designed to target the cellular and viral factors as new therapeutic options in limiting HCV infection. Results In this study the potential of siRNAs to inhibit HCV-3a replication in serum-infected Huh-7 cells was investigated by combined treatment of siRNAs against the HCV E2 gene and HCV cellular receptors (CD81 and LDLR, which resulted in a significant decrease in HCV viral copy number. Conclusion From the current study it is concluded that the combined RNAi-mediated silencing of HCV E2 and HCV receptors is important for the development of effective siRNA-based therapeutic option against HCV-3a.

  16. Prevalence of active HCV infection among the blood donors of Khyber Pakhtunkwa and FATA region of Pakistan and evaluation of the screening tests for anti-HCV

    Directory of Open Access Journals (Sweden)

    Khan Sanaullah

    2011-04-01

    Full Text Available Abstract Hepatitis C is a fatal liver disease caused by the hepatitis C virus. In this study, blood donors, from various districts of the KPK province and the federally administered tribal area (FATA of Pakistan were tested for anti-HCV antibodies and HCV RNA by ICT (Immuno-chromatographic test, ELISA and RT-PCR. Out of the 7148 blood donors, 224 (3.13% were positive for anti-HCV antibodies by ICT, 135 (1.89% by ELISA while 118 (1.65% blood donors had active HCV infection as detected by RT-PCR. We suggest that ELISA should be used for anti-HCV screening in public sector hospitals and health care units.

  17. Dynamic of Mixed HCV Infection in Plasma and PBMC of HIV/HCV Patients Under Treatment With Peg-IFN/Ribavirin.

    Science.gov (United States)

    Bagaglio, Sabrina; Uberti-Foppa, Caterina; Di Serio, Clelia; Trentini, Filippo; Andolina, Andrea; Hasson, Hamid; Messina, Emanuela; Merli, Marco; Porrino, Lucy; Lazzarin, Adriano; Morsica, Giulia

    2015-10-01

    The extent of mixed hepatitis C virus (HCV) genotype in different compartments (plasma and peripheral blood mononuclear cell, PBMC) and possible association with treatment efficacy in HIV/HCV coinfected patients remains to be unknown.The objective of this study was to elucidate the frequency of mixed genotype infection (MG), its profile in different compartments during anti-HCV treatment, and the possible influence of different genotypes on the response rate.The compartmentalization of HCV population was investigated by next-generation sequencing in 19 HIV/HCV coinfected patients under anti-HCV treatment with peginterferon/ribavirin (P-R). Ten individuals were nonresponder (NR) or relapser (RE) to P-R treatment and 9 had a sustained virological response (SVR).Eleven/nineteen (58%) patients had MG in plasma compartment. Ten or 12 patients infected by a difficult to treat genotype (DTG) 1 or 4 as dominant strain, had an MG, whereas only 1/7 individuals infected by easy to treat genotype (ETG) harbored a mixed genotype, P = 0.006. HCV-RNA was more frequently detected in PBMC of NR (10/10) than in those of SVR (5/9), P = 0.032. Mixed genotype infection was detected in 6/15 (40%) PBMC-positive cases and was not associated with P-R treatment response. By multivariate analysis, MG in plasma samples was the most important viral factor affecting the treatment response (P = 0.0237).Detection of MG in plasma of HIV/HCV coinfected patients seems to represent the major determinant of response to P-R treatment. This finding may have important clinical implication in light of the new therapeutic approach in HIV/HCV coinfected individuals suggesting that combination treatment with direct acting antivirals could be less effective in MG.

  18. The effect of IFN-based therapies on the short-term dynamics of alt in HCV-infected patients

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, R. M. (Ruy M.); Talal, A. H. (Andrew H.); Layden, J. E. (Jennifer E.); Powers, K. A. (Kimberly A.); Layden, T. J. (Thomas J.); Perelson, Alan S.,

    2002-01-01

    IFN therapy of HCV-infection has been shown to reduce production of virus from infected cells, but its effect on hepatocytes is less well understood. One indicator of liver damage is ALT, which has been used as an associated diagnostic for HCV infection.

  19. Short interferon and ribavirin treatment for HCV genotype 2 or 3 infection

    DEFF Research Database (Denmark)

    Waldenström, Jesper; Färkkilä, Martti; Rembeck, Karolina;

    2016-01-01

    OBJECTIVE: Interferon-free therapy for hepatitis C virus (HCV) infection is costly, and therefore patients with advanced fibrosis are prioritized. Although coupled with considerable side effects, a large proportion of genotype 2/3 infected patients achieve a sustained virological response (SVR...... predictors, e.g. age, ITPA and IL28B genetic variants, IP-10, liver histopathology and early viral kinetics on outcome was evaluated among HCV genotype 2/3 infected patients enrolled in the NORDynamIC trial. Similarly outcome was evaluated among Finnish and Swedish real-life genotype 2/3 infected patients...... treated for 12-16 weeks in accordance with national guidelines. RESULTS: In the NORDynamIC trial, age HCV RNA 

  20. 慢性丙型肝炎初治和复治患者的细胞因子特征与病毒学应答%Cytokine profiles and virological response in treatment-naive and -experienced patients with chronic HCV infection

    Institute of Scientific and Technical Information of China (English)

    柳雅立; 张永宏; 郭丹丹; 鲁俊锋; 于海滨; 画伟; 陈新月

    2012-01-01

    目的分析比较慢性丙型肝炎初治和复治患者细胞因子水平,并探讨其与疗效间的关系.方法选取慢性丙型肝炎初治患者37例和复治患者24例,均接受聚乙二醇干扰素α-2a联合利巴韦林治疗,动态留取标本并检测细胞因子变化,分析其与疗效的关系.11例健康者作为对照组.结果与初治患者能获得较早的病毒学应答相比,复治组12例(50%)在治疗48周时才获得病毒学应答.初治组白细胞介素-4、干扰素(interferon,IFN) γ、CCL-3(MIP-1a)显著高于复治组(P=0.005);初治组粒细胞集落刺激因子水平则低于复治组(P<0.05).在基线和治疗4周时,初治组较高的IFN γ水平与HCV清除率相关.结论复治患者能否获得治疗成功与宿主免疫应答相关,IFN γ可能是病毒学应答的重要预测因子.%Objective To analyze and compare cytokine levels in treatment-naive and -experienced patients with chronic HCV infection, and to investigate correlation between those immunological factors and antiviral therapy efficacy. Methods Thirty-seven treatment-naive and 24 treatment-experienced patients with chronic HCV infection received combination therapy with pegylated in terferon alfa-2a and ribavirin. Samples was collected dynamically to detect the changes of cytokine levels and the correlation be tween cytokine levels and therapeutic efficacy was analyzed. Eleven healthy donors were recruited as the controls. Results Twelve (50%) treatment-experienced patients with chronic HCV infection achieved a delayed and slow virological response after 48 weeks of combination therapy compared with treatment-naive patients, who had an early and fast virological response. The levels of interleu kin-4, interferon (IFN) γ and CCL-3 (MIP -1a) were significantly higher in treatment-naive patients than those in treatment experienced patients (P=0.005), while the level of granulocyte colony-stimulating factor in treatment-naive patients was lower than that in

  1. Seroprevalence of HCV and HIV Infections by Year of Birth in Spain: Impact of US CDC and USPSTF Recommendations for HCV and HIV Testing

    Science.gov (United States)

    Meijide, Héctor; Cañizares, Angelina; Castro-Iglesias, Ángeles; Delgado, Manuel; Pértega, Sonia; Pedreira, José; Bou, Germán; Poveda, Eva

    2014-01-01

    Background The US Centers for Disease Control and Prevention (CDC) recently add the advice of one-time testing of HCV infection in persons born during 1945–1965. Moreover, the US Preventive Services Task Force (USPSTF) newly recommended one-time HIV testing for persons aged 15–65. Herein, we evaluate the potential impact of these recommendations in a reference medical area of Spain. Methods All assays results entries for HCV and HIV serological markers ordered at a reference lab from primary care and specialized physicians between 2008 and 2012 were recorded in a medical area which covers 501,526 citizens in Northern Spain. The year of birth were also documented. Results A total of 108,159 anti-HCV-Ab results were generated during the study period. The global rate of anti-HCV-Ab+ was 7.7% (95% CI: 7.6%–7.9%), being more prevalent in men than women (8.6% vs. 4.5%). By year of birth, the highest prevalence was found in persons born between 1955 and 1970. HCV genotype 1 was the most prevalent (59.7%) followed by genotype 3 (22.7%). Regard HIV infection, among 65,279 anti-HIV results generated the prevalence of anti-HIV+ was 1.1% (95% CI: 1.0%–1.2%), being more frequent in men (2% vs 0.5%). The years of birth with highest rates of HIV infection exactly match with those for HCV infection. Conclusions The highest rates of HCV and HIV infections are found between 1960 and 1965. Different historical and social circumstances such as the huge intravenous drug use epidemic in the eighties in Spain, might explain it. Therefore, each country needs to determine its own HCV and HIV seroprevalences by year of birth to establish the proper recommendations for the screening of both infections. PMID:25436642

  2. Patterns of Healthcare Utilization Among Veterans Infected With Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) and Coinfected With HIV/HCV: Unique Burdens of Disease

    Science.gov (United States)

    Katrak, Shereen; Park, Lawrence P.; Woods, Christopher; Muir, Andrew; Hicks, Charles; Naggie, Susanna

    2016-01-01

    Background. Hepatitis C virus (HCV) infection is a leading cause of cirrhosis and the primary cause of liver transplantation in the United States, and coinfection with human immunodeficiency virus (HIV) increases the risk of comorbidities. However, healthcare utilization (HCU) patterns among HIV/HCV-coinfected patients are poorly understood. This study compared the rates of HCU and reasons for hospital admission among HCV-infected, HIV-infected, and HIV/HCV-coinfected veterans. Methods. Hepatitis C virus- and HIV-infected and HIV/HCV-coinfected veterans in care with the Department of Veterans Affairs (VA) from 1998 to 2009 (n = 335 371, n = 28 179, n = 13 471, respectively) were identified by HIV- and HCV-associated International Classification of Diseases, Ninth Revision codes from the clinical case registry. We assessed rates of HCU using emergency department (ED) visits, outpatient visits, and hospitalization and primary diagnoses associated with hospitalization. Independent risk factors associated with hospitalization were also examined. Results. Rates of outpatient and ED visits increased over the 11-year study period for all groups, with inpatient admission rates remaining stable. The HCU rates were consistently higher for the coinfected than other cohorts. The primary reason for hospital admission for all groups was psychiatric disease/substance use, accounting for 44% of all admissions. Nadir CD4 500 cells/mm3. Conclusions. As the current population of HCV-infected, HIV-infected, and HIV/HCV-coinfected veterans age, they will continue to place a substantial and increasing demand on the US healthcare system, particularly in their utilization of ED and outpatient services. These data suggest the need for an ongoing investment in mental health and primary care within the VA healthcare system. PMID:27704025

  3. Seroprevalence and risk factors for hepatitis C virus (HCV) infection in pregnant women attending public sector tertiary care hospital in Hyderabad Sindh

    OpenAIRE

    Bibi, Seema; Dars, Saira; Ashfaq, Sanober; Ara Qazi, Roshan; Akhund, Sadaf

    2013-01-01

    Background and Objectives: Pakistan is among the countries having high prevalence of HCV infection in the population but there is dearth of proper epidemiological data regarding acquisition of HCV infection in the pregnant population. Our objective was to determine the seroprevalence of HCV antibodies in healthy pregnant women and to assess the potential risk factors for HCV infection in HCV positive subjects and in the control group. Methodology: This cross sectional and comparative study wa...

  4. Management of chronic hepatitis C virus infection in patients with end-stage renal disease: a review

    Directory of Open Access Journals (Sweden)

    Aguirre Valadez J

    2015-02-01

    Full Text Available Jonathan Aguirre Valadez,1 Ignacio García Juárez,1 Rodolfo Rincón Pedrero,2 Aldo Torre11Department of Gastroenterology, 2Department of Nephrology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico Abstract: Infection with hepatitis C virus (HCV is highly prevalent in chronic kidney disease (CKD patients, mainly in those on hemodialysis (HD. The seroprevalence of HCV in developing countries ranges between 7% and 40%. Risk factors for this infection in the CKD population include the number of blood transfusions, duration of end-stage renal disease (ESRD, and prevalence of HCV in HD. Chronic HCV infection in patients with ESRD is associated with an increase in morbidity and mortality in the pre and post kidney transplant periods. The increase in mortality is directly associated with liver complications and an elevated cardiovascular risk in HCV-infected patients on hemodialysis. Antiviral treatment may improve the prognosis of patients with HCV, and standard interferon remains the cornerstone of treatment. Treatment of HCV in patients with CKD is complex, but achieving a sustained viral response may decrease the frequency of complications after transplantation. It appears that HCV-infected patients who remain on maintenance dialysis are at increased risk of death compared with HCV patients undergoing renal transplantation.Keywords: hepatitis C virus, chronic kidney disease, hemodialysis, interferon

  5. Alterations of seminal and hormonal parameters: An extrahepatic manifestation of HCV infection?

    Institute of Scientific and Technical Information of China (English)

    Marilena Durazzo; Alberto Premoli; Cataldo Di Bisceglie; Angela Bertagna; Emanuela Fagà; Giampaolo Biroli; Chiara Manieri; Simona Bo; Gianfranco Pagano

    2006-01-01

    AIM: To evaluate the possible influences of HCV infection and relative antiviral treatment on seminal parameters and reproductive hormonal serum levels.METHODS: Ten male patients with HCV-related chronic hepatitis and 16 healthy male volunteers were studied.In all subjects seminal parameters (nemaspermic concentration, progressive motility, morphology) and hormonal levels were determined. Seminal parameters and inhibin B, follicle-stimulating hormone, luteinizing hormone, total and free testosterone, estradiol, prolactine in patients were measured after six and twelve months of antiviral combined (interferon + ribavirin) treatment.RESULTS: Patients before treatment showed a significantly lower nemaspermic motility and morphology as well as lower inhibin B and free testosterone levels than controls. Inhibin B levels in cases were improved six and 12 mo after treatment in five responders (161.9 ± 52.8 pg/mL versus 101.7 ± 47.0 pg/mL and 143.4 ± 46.1 pg/mL versus 95.4 ± 55.6 pg/mL, respectively). Hormonal pattern of patients did not significantly change after treatment, with the exception of estradiol levels with an initial reduction and an overall subsequent increment (19.7 ± 6.4 pg/mL versus 13.6 ± 5.0 pg/mL versus 17.3 ± 5.7 pg/mL). However in 1-year responders a significant increment of free testosterone (14.2 ± 2.54 pg/mL versus 17.1 ± 2.58 pg/mL) occurred. An impairment of nemaspermic morphology occurred, while other seminal parameters did not change significantly during antiviral treatment.CONCLUSION: Patients with HCV infection show worse spermatic parameters than controls, suggesting a possible negative influence of virus on spermatogenesis, with further mild impairment during antiviral treatment. However therapy could improve the spermatic function, as suggested by the increased inhibin B levels and improved hormonal pattern in responders. Further studies are needed to confirm these preliminary intriguing results.

  6. Co-infection rate of HIV, HBV and Syphilis among HCV seropositive identified blood donors in Kathmandu, Nepal

    Directory of Open Access Journals (Sweden)

    Ashish Chandra Shrestha

    2012-02-01

    Full Text Available Background: HIV, HBV, Syphilis and HCV share common modes of transmission. Objective: The study was aimed to determine the co-infection rate of HIV, HBV and Syphilis among HCV seropositive identified blood donors. Methods: The study was conducted on blood samples screened as HCV seropositive at Nepal Red Cross Society, Central Blood Transfusion Service, Kathmandu, Nepal. HCV seropositive samples were further tested for HIV, HBV and Syphilis. Results: Eight co-infections were observed in 139 HCV seropositives with total co-infection rate of 5.75% (95% CI = 2.52-11.03. Conclusion: Co-infection of HIV, HBV and Syphilis with HCV is prevalent in the healthy looking blood donors of Kathmandu, Nepal.

  7. Interferon (IFN) and Cellular Immune Response Evoked in RNA-Pattern Sensing During Infection with Hepatitis C Virus (HCV).

    Science.gov (United States)

    Nakai, Masato; Oshiumi, Hiroyuki; Funami, Kenji; Okamoto, Masaaki; Matsumoto, Misako; Seya, Tsukasa; Sakamoto, Naoya

    2015-01-01

    Hepatitis C virus (HCV) infects hepatocytes but not dendritic cells (DCs), but DCs effectively mature in response to HCV-infected hepatocytes. Using gene-disrupted mice and hydrodynamic injection strategy, we found the MAVS pathway to be crucial for induction of type III interferons (IFNs) in response to HCV in mouse. Human hepatocytes barely express TLR3 under non-infectious states, but frequently express it in HCV infection. Type I and III IFNs are induced upon stimulation with polyI:C, an analog of double-stranded (ds)RNA. Activation of TLR3 and the TICAM-1 pathway, followed by DC-mediated activation of cellular immunity, is augmented during exposure to viral RNA. Although type III IFNs are released from replication-competent human hepatocytes, DC-mediated CTL proliferation and NK cell activation hardly occur in response to the released type III IFNs. Yet, type I IFNs and HCV-infected hepatocytes can induce maturation of DCs in either human or mouse origin. In addition, mouse CD8+ DCs mature in response to HCV-infected hepatocytes unless the TLR3/TICAM-1 pathway is blocked. We found the exosomes containing HCV RNA in the supernatant of the HCV-infected hepatocytes act as a source of TLR3-mediated DC maturation. Here we summarize our view on the mechanism by which DCs mature to induce NK and CTL in a status of HCV infection.

  8. IFN‐λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV infection

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    Depla, Marion; Pelletier, Sandy; Bédard, Nathalie; Brunaud, Camille; Bruneau, Julie

    2016-01-01

    Abstract Introduction Polymorphisms in the type III interferon IFN‐λ3 and the killer cell immunoglobulin‐like receptor (KIR) genes controlling the activity of natural killer (NK) cells can predict spontaneous resolution of acute hepatitis C virus (HCV) infection. We hypothesized that IFN‐λ3 polymorphism may modulate NK cell function during acute HCV. Methods We monitored the plasma levels of type III IFNs in relation to the phenotype and the function of NK cells in a cohort of people who inject drugs (PWID) during acute HCV infection with different outcomes. Results Early acute HCV was associated with high variability in type III IFNs plasma levels and the favorable IFN‐λ3 CC genotype was associated with higher viral loads. Reduced expression of Natural Killer Group Protein 2A (NKG2A) was associated with lower IFN‐λ3 plasma levels and the CC genotype. IFN‐γ production by NK cells was higher in individuals with the CC genotype during acute infection but this did not prevent viral persistence. IFN‐λ3 plasma levels did not correlate with function of NK cells and IFN‐λ3 prestimulation did not affect NK cell activation and function. Conclusions These results suggest that IFN‐λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV but other factors may act in concert to determine the outcome of the infection. PMID:27621819

  9. Quantitation of HCV RNA in liver of patients with chronic hepatitis C Quantificação do RNA-HCV no fígado de pacientes com hepatite C crônica

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    Ana de Lôurdes Candolo MARTINELLI

    2000-10-01

    Full Text Available Background/Aims - Liver HCV RNA has been quantitated in few studies and the feasibility and the role of this parameter in the evaluation of patients with chronic HCV hepatitis still warrant study. Our aim was to determine the concentrations of HCV RNA in the liver of chronic HCV patients and to correlate the results with serum viral load. We also studied the relation of levels of HCV RNA in the liver with serum aminotransferases levels and with the presence of cirrhosis. Methods - Twenty patients (14 males, aged 28 to 61 years were studied. Twelve were infected by HCV type 1, six by type 3 and one by type 5. Percutaneous liver biopsy samples were obtained from 14 patients, and the remainder from liver explant in patients undergoing OLT. Twelve had chronic hepatitis and eight cirrhosis. HCV RNA levels were determined by bDNA. Results - HCV RNA levels below the detection limit were found in one liver and in five serum samples. HCV RNA (mean ± SD was 2.1 x 10(8 ± 2.2 x 10(8Eq/gm in the liver and 94 x 10(5 ± 93 x 10(5Eq/mL in serum, with a significant correlation between these values (r = 0.89; P Introdução/Objetivos - Poucos estudos avaliam a quantificação do RNA-HCV no fígado, portanto a praticabilidade e a aplicação desse parâmetro na avaliação de pacientes com hepatite C crônica ainda não estão definidas. O objetivo foi determinar as concentrações do RNA-HCV no fígado de pacientes com infecção crônica pelo vírus C da hepatite e correlacionar os resultados com a carga viral do soro. Foram também estudadas a relação dos níveis de RNA-HCV no fígado com os de aminotransferases no soro e com a presença de cirrose. Métodos - Foram estudados 20 pacientes (14 homens, 28 a 61 anos. A genotipagem do vírus da hepatite C revelou: tipo 1 (12 pacientes, tipo 3 (6 pacientes , tipo 5 (1 paciente. Amostras de fígado foram obtidas por via percutânea em 14 pacientes e de explantes de fígado de pacientes submetidos a transplante em

  10. Natural Polymorphisms Conferring Resistance to HCV Protease and Polymerase Inhibitors in Treatment-Naive HIV/HCV Co-Infected Patients in China.

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    Kali Zhou

    Full Text Available The advent of direct-acting agents (DAAs has improved treatment of HCV in HIV co-infection, but may be limited by primary drug resistance. This study reports the prevalence of natural polymorphisms conferring resistance to NS3/4A protease inhibitors and NS5B polymerase inhibitors in treatment-naïve HIV/HCV co-infected individuals in China.Population based NS3/4A sequencing was completed for 778 treatment-naïve HIV/HCV co-infected patients from twelve provinces. NS3 sequences were amplified by nested PCR using in-house primers for genotypes 1-6. NS5B sequencing was completed for genotyping in 350 sequences. Resistance-associated variants (RAVs were identified in positions associated with HCV resistance.Overall, 72.8% (566/778 of all HCV sequences had at least one RAV associated with HCV NS3/4A protease inhibitor resistance. Variants were found in 3.6% (7/193 of genotype 1, 100% (23/23 of genotype 2, 100% (237/237 of genotype 3 and 92% (299/325 of genotype 6 sequences. The Q80K variant was present in 98.4% of genotype 6a sequences. High-level RAVs were rare, occurring in only 0.8% of patients. 93% (64/69 patients with genotype 1b also carried the C316N variant associated with NS5B low-level resistance.The low frequency of high-level RAVs associated with primary HCV DAA resistance among all genotypes in HIV/HCV co-infected patients is encouraging. Further phenotypic studies and clinical research are needed.

  11. Natural Polymorphisms Conferring Resistance to HCV Protease and Polymerase Inhibitors in Treatment-Naïve HIV/HCV Co-Infected Patients in China

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    Wang, Charles; Hu, Fengyu; Ning, Chuanyi; Lan, Yun; Tang, Xiaoping; Tucker, Joseph D.; Cai, Weiping

    2016-01-01

    Background The advent of direct-acting agents (DAAs) has improved treatment of HCV in HIV co-infection, but may be limited by primary drug resistance. This study reports the prevalence of natural polymorphisms conferring resistance to NS3/4A protease inhibitors and NS5B polymerase inhibitors in treatment-naïve HIV/HCV co-infected individuals in China. Methods Population based NS3/4A sequencing was completed for 778 treatment-naïve HIV/HCV co-infected patients from twelve provinces. NS3 sequences were amplified by nested PCR using in-house primers for genotypes 1–6. NS5B sequencing was completed for genotyping in 350 sequences. Resistance-associated variants (RAVs) were identified in positions associated with HCV resistance. Results Overall, 72.8% (566/778) of all HCV sequences had at least one RAV associated with HCV NS3/4A protease inhibitor resistance. Variants were found in 3.6% (7/193) of genotype 1, 100% (23/23) of genotype 2, 100% (237/237) of genotype 3 and 92% (299/325) of genotype 6 sequences. The Q80K variant was present in 98.4% of genotype 6a sequences. High-level RAVs were rare, occurring in only 0.8% of patients. 93% (64/69) patients with genotype 1b also carried the C316N variant associated with NS5B low-level resistance. Conclusions The low frequency of high-level RAVs associated with primary HCV DAA resistance among all genotypes in HIV/HCV co-infected patients is encouraging. Further phenotypic studies and clinical research are needed. PMID:27341031

  12. Protective KIR-HLA interactions for HCV infection in intravenous drug users

    Science.gov (United States)

    Zúñiga, Joaquin; Romero, Viviana; Azocar, José; Terreros, Daniel; Vargas-Rojas, María Inés; Torres-García, Diana; Jimenez-Alvarez, Luis; Vargas-Alarcón, Gilberto; Granados-Montiel, Julio; Husain, Zaheed; Chung, Raymond T.; Alper, Chester A.; Yunis, Edmond J.

    2009-01-01

    Intravenous drug use has become the principal route of hepatitis C virus (HCV) transmission due to the sharing of infected needles. In this study, we analyzed the distribution of HLA-KIR genotypes among 160 Puerto Rican intravenous drug users (IDUs) with HCV infection and 92 HCV-negative Puerto Rican IDUs. We found a significant association between the presence of different combinations of KIR inhibitory receptor genes (KIR2DL2 and/or KIR2DL3, pC = 0.01, OR = 0.07; KIR2DL2 and/or KIR2DL3+KIR2DS4, pC = 0.01, OR = 0.39) and HLA-C1 homozygous genotypes (HLA-C1+KIR2DS4, pC = 0.02, OR = 0.43; HLA-C1+KIR2DL2+KIR2DS4, pC = 0.02, OR = 0.40) together with the activating receptor KIR2DS4 (HLA-C1+KIR2DS4+KIR2DL3 and/or KIR2DL2, pC = 0.004, OR = 0.38) with protection from HCV infection. Our findings in HCV-infected and non-infected IDUs suggest an important role for KIRs (KIR2DL2 and KIR2DL3) with group HLA-C1 molecules, in the presence of activating KIR2DS4, in protection from HCV infection. These results support the hypothesis that activator signaling, mediated by KIR2DS4, is a determinant in the regulation of NK cell antiviral-activity. PMID:19552960

  13. 男性HIV和HCV并发感染者HCV抗体的表达%Study on the HCV Antibody Response in Men HIV and HCV Concurrent Infections

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    贺美荣; 焦东丽; 贾艳春; 严震

    2012-01-01

    目的 观察人免疫缺陷病毒(HIV)男性患者并发丙型肝炎病毒(HCV)感染后HCV抗体的表达情况,探讨影响HCV抗体表达的因素.方法 选取经筛选检测最终确诊的HIV/HCV并发感染男性患者23例,每隔3个月随访一次共随访6个月.检测HIV及HCV病毒载量、CD4+T细胞计数及HCV抗体.结果 首次HCV RNA检测阳性时78.3%的患者HCV抗体阴性;3个月后,34.8%的患者为HCV抗体阴性;6个月后,17.4%的患者HCV抗体为阴性.结论 HIV 并发HCV的男性感染者,HCV抗体阳性率表达较低,应早期联合核酸检测.%Objective To estimated the positive rates of antibodies and the influencing factors of antibodies expansion in Human immunoddficiency virus(HIV) men infected with hepatitis C virus(HCV). Methods 23 HIV-positive patients with early HCV infection were identified. Plasma samples obtained at 3 monthly intervals( total 6 month) for routine monitoring of HIV and HCV viral load,CD4 cell counts,HCV antibodies. Results On first amplification of HCV,78. 3% of patients were serologically negative. Antibody detection remain seronegative 34. 8% by 3 months to 17. 4% at 6 months. Conclusion The lower of HCV antibodies positive rates in HIV men with HCV should early combination of nucleic acid testing.

  14. Anti-HCV prevalence in firstyear students, that will practise professions of high risk of infection with the HCV

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    Penelope Siourda

    2007-07-01

    Full Text Available Aim: We have studied the prevalence of Hepatitis C on the first‐year students of the Paramedical Schools (Medical Lab Department, Nursing Department, Baby Nursing Department and Obstetrics Department of the Health and Foresight Professions School of Technological Educational School of Thessaloniki. Materials and Methods: The sample consists of 502 students of the Paramedical Schools. The students at first filled a questionnaire form (25 questions about the knowledge and the information in point of the infectious diseases in the Immunological – Hormonological Health Center. Then they gave blood sample and at the end, they were given a "Basic Guidebook for Preventing and Handling Hospital Infections". The samples were checked with ELISA method for anti‐HCV antibodies. Results: All the tests were negative for anti-HCV antibodies. Conclusions: It was ascertained that the prevalence of Hepatitis C on our target group is similar to the literature's known data (low in Greece. However since there is not a vaccine yet, anyone must be careful with Hepatitis C, specially the students of paramedical schools. Radical solution will be given inr the development of an appropriate vaccine.

  15. Prevalence of HCV infection and associated factors among illicit drug users in Breves, State of Pará, northern Brazil

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    Suzy Danielly Barbosa Pacheco

    2014-06-01

    Full Text Available Introduction: Illicit drug users (DUs are vulnerable to hepatitis C virus (HCV infection. The shared use of illicit drugs is the main method of HCV transmission. Methods: A cross-sectional study was conducted in Breves, in northern Brazil. We surveyed 187 DUs to determine the prevalence of and factors associated with HCV infection. Results: The prevalence of anti-HCV antibodies was 36.9%, and the prevalence of hepatitis C virus-ribonucleic acid (HCV-RNA was 31%. Hepatitis C virus infection was associated with tattoos, intravenous drug use, shared use of equipment for drug use, drug use for longer than 3 years, and daily drug use. Conclusions: Strategies for preventing and controlling HCV transmission should be implemented among DUs.

  16. Characterization of the specific CD4+ T cell response against the F protein during chronic hepatitis C virus infection.

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    De-Yong Gao

    Full Text Available BACKGROUND: The hepatitis C virus (HCV Alternate Reading Frame Protein (ARFP or F protein presents a double-frame shift product of the HCV core gene. We and others have previously reported that the specific antibodies against the F protein could be raised in the sera of HCV chronically infected patients. However, the specific CD4(+ T cell responses against the F protein during HCV infection and the pathological implications remained unclear. In the current study, we screened the MHC class II-presenting epitopes of the F protein through HLA-transgenic mouse models and eventually validated the specific CD4(+ T cell responses in HCV chronically infected patients. METHODOLOGY: DNA vaccination in HLA-DR1 and-DP4 transgenic mouse models, proliferation assay to test the F protein specific T cell response, genotyping of Chronic HCV patients and testing the F-peptide stimulated T cell response in the peripheral blood mononuclear cell (PBMC by in vitro expansion and interferon (IFN- γ intracellular staining. PRINCIPAL FINDINGS: At least three peptides within HCV F protein were identified as HLA-DR or HLA-DP4 presenting epitopes by the proliferation assays in mouse models. Further study with human PBMCs evidenced the specific CD4(+ T cell responses against HCV F protein as well in patients chronically infected with HCV. CONCLUSION: The current study provided the evidence for the first time that HCV F protein could elicit specific CD4(+ T cell response, which may provide an insight into the immunopathogenesis during HCV chronic infection.

  17. Injection drug use is a risk factor for HCV infection in urban Egypt.

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    Adela Paez Jimenez

    Full Text Available OBJECTIVE: To identify current risk factors for hepatitis C virus (HCV transmission in Greater Cairo. DESIGN AND SETTING: A 1:1 matched case-control study was conducted comparing incident acute symptomatic hepatitis C patients in two "fever" hospitals of Greater Cairo with two control groups: household members of the cases and acute hepatitis A patients diagnosed at the same hospitals. Controls were matched on the same age and sex to cases and were all anti-HCV antibody negative. Iatrogenic, community and household exposures to HCV in the one to six months before symptoms onset for cases, and date of interview for controls, were exhaustively assessed. RESULTS: From 2002 to 2007, 94 definite acute symptomatic HCV cases and 188 controls were enrolled in the study. In multivariate analysis, intravenous injections (OR = 5.0; 95% CI = 1.2-20.2, medical stitches (OR = 4.2; 95% CI = 1.6-11.3, injection drug use (IDU (OR = 7.9; 95% CI = 1.4-43.5, recent marriage (OR = 3.3; 95% CI = 1.1-9.9 and illiteracy (OR = 3.9; 95% CI = 1.8-8.5 were independently associated with an increased HCV risk. CONCLUSION: In urban Cairo, invasive health care procedures remain a source of HCV transmission and IDU is an emerging risk factor. Strict application of standard precautions during health care is a priority. Implementation of comprehensive infection prevention programs for IDU should be considered.

  18. Impact of Chronic Hepatitis C Virus Genotype 1b Infection on Triglyceride Concentration in Serum Lipoprotein Fractions

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    Tomohisa Nagano

    2015-08-01

    Full Text Available Reduced low-density lipoprotein (LDL cholesterol level is a characteristic feature of dyslipidemia in chronic hepatitis C virus (HCV infection. However, abnormality in serum triglyceride (TG has not been fully investigated. To clarify the impact of HCV genotype 1b (G1b infection and advanced fibrosis on serum TG profiles, TG concentrations in lipoprotein fractions were examined in fasting sera from 185 subjects with active or cleared HCV infection by high-performance liquid chromatography. Serum lipoproteins were fractionated into four classes: chylomicron, very low-density lipoprotein (VLDL, LDL, and high-density lipoprotein (HDL. Then, the significance of HCV G1b infection on TG levels in each lipoprotein fraction was determined using multiple regression models. We found that active HCV G1b infection was positively associated with high HDL-TG levels and low VLDL-TG levels, independent of other factors included in the regression model. In VLDL sub-fractions, active HCV infection was only found to be associated with low levels of large VLDL-TG. Similarly, advanced liver fibrosis in chronic HCV G1b infection was associated with high levels of LDL-TG, HDL-TG, and small VLDL-TG, independent of other clinical factors. These findings indicate that active HCV G1b infection and advanced fibrosis are closely associated with abnormal serum TG profiles.

  19. Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals.

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    Ferns, R Bridget; Tarr, Alexander W; Hue, Stephane; Urbanowicz, Richard A; McClure, C Patrick; Gilson, Richard; Ball, Jonathan K; Nastouli, Eleni; Garson, Jeremy A; Pillay, Deenan

    2016-05-01

    HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization.

  20. HCV INFECTION THROUGH PERFORATING AND CUTTING MATERIAL AMONG CANDIDATES FOR BLOOD DONATION IN BELÉM, BRAZILIAN AMAZON

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    Rubenilson Caldas Valois

    2014-12-01

    Full Text Available This study evaluated epidemiological factors for HCV infection associated with sharing perforating and cutting instruments among candidates for blood donation (CBD in the city of Belém, Pará, Brazilian Amazon. Two definitions of HCV infection cases were used: anti-HCV positivity shown by EIA, and HCV-RNA detection by PCR. Infected and uninfected CBD completed a questionnaire about possible risk factors associated with sharing perforating and cutting instruments. The information was evaluated using simple and multiple logistic regressions. Between May and November 2010, 146 (1.1% persons with anti-HCV antibodies and 106 (0.8% with HCV-RNA were detected among 13,772 CBD in Belém. Risk factors associated with HCV infection based on the EIA (model 1 and PCR (model 2 results were: use of needles and syringes sterilized at home; shared use of razors at home, sharing of disposable razors in barbershops, beauty salons etc.; and sharing manicure and pedicure material. The models of HCV infection associated with sharing perforating and cutting instruments should be taken into account by local and regional health authorities and by those of other countries with similar cultural practices, in order to provide useful information to guide political and public strategies to control HCV transmission.

  1. Persistence of HCV in Acutely-Infected Patients Depletes C24-Ceramide and Upregulates Sphingosine and Sphinganine Serum Levels

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    Grammatikos, Georgios; Dietz, Julia; Ferreiros, Nerea; Koch, Alexander; Dultz, Georg; Bon, Dimitra; Karakasiliotis, Ioannis; Lutz, Thomas; Knecht, Gaby; Gute, Peter; Herrmann, Eva; Zeuzem, Stefan; Mavromara, Penelope; Sarrazin, Christoph; Pfeilschifter, Josef

    2016-01-01

    Hepatitis C virus (HCV) substantially affects lipid metabolism, and remodeling of sphingolipids appears to be essential for HCV persistence in vitro. The aim of the current study is the evaluation of serum sphingolipid variations during acute HCV infection. We enrolled prospectively 60 consecutive patients with acute HCV infection, most of them already infected with human immunodeficiency virus (HIV), and serum was collected at the time of diagnosis and longitudinally over a six-month period until initiation of antiviral therapy or confirmed spontaneous clearance. Quantification of serum sphingolipids was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Spontaneous clearance was observed in 11 out of 60 patients (18.3%), a sustained viral response (SVR) in 43 out of 45 patients (95.5%) receiving an antiviral treatment after follow-up, whereas persistence of HCV occurred in six out of 60 patients (10%). C24-ceramide (C24-Cer)-levels increased at follow-up in patients with spontaneous HCV eradication (p < 0.01), as compared to baseline. Sphingosine and sphinganine values were significantly upregulated in patients unable to clear HCV over time compared to patients with spontaneous clearance of HCV infection on follow-up (p = 0.013 and 0.006, respectively). In summary, the persistence of HCV after acute infection induces a downregulation of C24Cer and a simultaneous elevation of serum sphingosine and sphinganine concentrations. PMID:27304952

  2. Contribution of donor age to the recent decrease in patient survival among HCV-infected liver transplant recipients.

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    Berenguer, Marina; Prieto, Martín; San Juan, Fernando; Rayón, José M; Martinez, Fernando; Carrasco, Domingo; Moya, Angel; Orbis, Francisco; Mir, José; Berenguer, Joaquín

    2002-07-01

    Recurrent hepatitis occurs in the majority of patients undergoing liver transplantation for hepatitis C virus (HCV) cirrhosis, with progression to cirrhosis in up to 30% after 5 years. Based on these data, a decrease in survival can be anticipated with prolonged follow-up. Furthermore, posttransplantation HCV-fibrosis progression has been shown in recent years to increase. Our aims were (1) to describe the natural history of HCV-infected recipients, particularly to determine whether survival has decreased in recent years; (2) to compare this outcome with that observed in non-HCV-infected cirrhosis controls; and (3) to determine the factors associated with disease severity and survival. Among 522 cirrhotic patients undergoing transplantation between 1991 and 2000, 283 (54%) were infected with HCV. Yearly biopsies were performed in these recipients and at 1 and 5 years in the remainder. With similar follow-up, the percentage of deaths in the HCV(+) group was significantly higher than in the HCV- group (37% vs. 22%, P <.001), and patient survival was lower (77%, 61%, 55% vs. 87%, 76%, 70% at 1, 5, and 7 years, respectively; P =.0001). Although survival has increased in the HCV- group in recent years, it has significantly decreased in HCV recipients (P <.0001). The main cause of death among the latter was decompensated graft cirrhosis (n = 23/105, 22%), whereas that of HCV- patients was infections (n = 10/52, 19%). Reasons for the recent worse outcome in HCV+ recipients include the increased donor age and stronger immunosuppression. In conclusion, patient survival is lower among HCV+ recipients than among HCV- ones and has been decreasing in recent years. The aging of donors is a major contributor to this worse outcome.

  3. Characteristics of HCV co-infection among HIV infected individuals from an area with high risk of blood-borne infections in central China.

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    Tiejun Zhang

    Full Text Available OBJECTIVE: Hepatitis C virus (HCV and human immunodeficiency virus (HIV co-infection has been proved to be a growing public health concern. The prevalence and genotypic pattern vary with geographic locations. Limited information is available to date with regard to HCV genotype and its clinical implications among those former commercial blood donor communities. The aims of this study were to genetically define the HCV genotype and associated clinical characteristics of HIV/HCV co-infected patients from a region with commercial blood donation history in central China. METHODS: A cross sectional study, including 164 HIV infected subjects, was conducted in Shanxi province central China. Serum samples were collected and HCV antibody testing, AST and ALT testing were performed. Seropositive samples were further subjected to RT-PCR followed by direct sequence coupled with phylogenetic analysis of Core-E1 and NS5B regions performed in comparison with known reference genotypes. FINDINGS: A total of 139 subjects were HCV antibody positive. Genotype could be determined for 88 isolates. Phylogenetic analysis revealed that the predominant circulating subtype was HCV 1b (65.9%, followed by HCV 2a (34.1%. The HCV viral load in the subjects infected with HIV1b was significantly higher than those infected with HCV 2a (P = 0.006. No significant difference for HCV RNA level was detected between ART status, CD4+ cell count level and HIV RNA level. Serum AST and ALT level were likely to increase with HCV RNA level, although no significance was observed. Those who had conducted commercial donation later than 1991 (OR 3.43, 95% CI: 1.12-10.48 and had a short duration of donation (OR 0.35, 95% CI: 0.13-0.96 were more likely to be infected with HCV 1b. CONCLUSION: These results suggest that HCV subtype 1b predominates in this population, and the impact of HIV status and ART on HCV disease progression is not significantly correlated.

  4. Evolution of the Humoral Response during HCV Infection: Theories on the Origin of Broadly Neutralizing Antibodies and Implications for Vaccine Design.

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    Murira, Armstrong; Lapierre, Pascal; Lamarre, Alain

    2016-01-01

    Similar to human immunodeficiency virus (HIV)-1, vaccine-induced elicitation of broadly neutralizing (bNt) antibodies (Abs) is gaining traction as a key goal toward the eradication of the hepatitis C virus (HCV) pandemic. Previously, the significance of the Ab response against HCV was underappreciated given the prevailing evidence advancing the role of the cellular immune response in clearance and overall control of the infection. However, recent findings have driven growing interest in the humoral arm of the immune response and in particular the role of bNt responses due to their ability to confer protective immunity upon passive transfer in animal models. Nevertheless, the origin and development of bNt Abs is poorly understood and their occurrence is rare as well as delayed with emergence only observed in the chronic phase of infection. In this review, we characterize the interplay between the host immune response and HCV as it progresses from the acute to chronic phase of infection. In addition, we place these events in the context of current hypotheses on the origin of bNt Abs against the HIV-1, whose humoral immune response is better characterized. Based on the increasing significance of the humoral immune response against HCV, characterization of these events may be critical in understanding the development of the bNt responses and, thus, provide strategies toward effective vaccine design.

  5. Risk-taking behavior and impulsivity among HCV-infected patients.

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    Dantas-Duarte, Adriana; Morais-de-Jesus, Mychelle; Nunes, Ana Paula; Miranda-Pettersen, Karine; Araújo-de-Freitas, Lucas; Netto, Liana R; Santos, Carlos Teles; Codes, Liana; Quarantini, Lucas C

    2016-09-30

    The association between risk behaviors and hepatitis C virus (HCV) has been extensively studied. It is also proved that impulsivity is associated with risk behaviors. However, there is a lack of studies investigating the association between HCV and impulsivity, a characteristic that can contribute directly to these risk behaviors. This study aimed to investigate HCV-infected individuals' impulsivity and whether this feature mediates risk behavior. Adult patients with liver diseases (n=269) were divided into two groups: viral group (n=157) - patients with HCV and nonviral group (n=112). Risk behaviors were evaluated by a sociodemographic questionnaire. Impulsivity was assessed through Barratt Impulsiveness Scale - BIS-11. Psychiatric comorbidities were investigated by the Mini International Neuropsychiatric Interview 5.0.0. The viral group patients had higher impulsivity than the nonviral group in all domains: attentional impulsivity, motor impulsivity, and nonplanning. Risk behaviors were also shown to be associated with impulsivity levels. Our results suggest that HCV-infected patients are more impulsive than individuals with other liver diseases, even when analyses are controlled for the presence of comorbid mental disorders. In addition, at-risk behavior was significantly mediated by impulsivity.

  6. Is chronic hepatitis C virus infection a risk factor for breast cancer?

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    Dominique; Larrey; Marie-Cécile; Bozonnat; Ihab; Kain; Georges-Philippe; Pageaux; Eric; Assenat

    2010-01-01

    AIM:To evaluate the prevalence of breast tumors in adult females with chronic hepatitis C virus(HCV) infection.METHODS:Prospective,single-center study,based on female outpatients consulting in a liver unit,for 1 year.The study group included females with present and/or past history of chronic infection by HCV.Patients with spontaneous recovery were excluded.Chronic hepatitis had been proved by liver biopsy in the majority of cases and/or biological markers of inflammation and fibrosis.The control group incl...

  7. Urban-Rural Comparison of HBV and HCV Infection Prevalence in Eastern China

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The present study was initiated to make an urban-rural comparison of the prevalence of cases positive to hepatitis B and C virus (HBV and HCV, respectively) infection markers in densely populated eastern half of China. For this purpose, 10 survey sites were selected, i.e., six sites in urban areas (the city group; Beijing, Shanghai and four provincial capitals) and four sites in rural areas (the village group ; one village each in Jilin and Shandong Provinces, and two villages in Shaanxi Province). About 50 adult women per site volunteered to participate, from whom 494 valid blood samples were collected. Positivities to HBsAg (HBsAg+), anti-HBs (anti-HBs+) and anti-HBc (anti-HBc+) were examined by RIA methods, and that to anti-HCV (anti-HCV+) by either EIA or RIA. Those positive to any one of the three HBV infection markers were taken as HBV infection-positive (HBV+). The prevalence of HBsAg+, HBV+ and anti-HBc+ was 8%, 70% and 2.7% in the city group, and 8%, 65% and 2.0% in the village group, and no significant difference was found between the two groups. The overall prevalence was 8% for HBsAg+, 68% for HBV+, and 2.4% for anti-HCV+. The results were discussed in reference to some 20 papers each on HBV+ and anti-HCV+ prevalence in China published since 1991. The reviewing of these papers confirmed that the prevalence of HBV was high (i.e., in excess of 50%), whereas the prevalence of anti-HCV was low (well below 5%), and that no substantial difference was found between the rural and urban populations.

  8. Hepatitis virus infection and chronic liver disease among atomic-bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Saeko; Cologne, John; Akahoshi, Masazumi [Radiation Effects Research Foundation, Hiroshima (Japan); Kusumi, Shizuyo [Institute of Radiation Epidemiology, Radiation Effects Association, Tokyo (Japan); Kodama, Kazunori; Yoshizawa, Hiroshi [Hiroshima University School of Medicine, Hiroshima (Japan)

    2000-05-01

    Hepatitis C and B virus (HCV, HBV) infection plays a crucial role in the etiology of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, which have been reported to increase with radiation dose among the atomic bomb survivors. The purpose of this study is to investigate whether radiation exposure altered the prevalence of hepatitis virus infection or accelerated the progress toward chronic hepatitis after hepatitis virus infection. Levels of serum antibody to hepatitis C virus (anti-HCV), HBs antigen (HBsAg), and anti-HBs antibody (anti-HBs) were measured for 6,121 participants in the Adult Health Study of atomic bomb survivors in Hiroshima and Nagasaki. No relationship was found between anti-HCV prevalence and radiation dose, after adjusting for age, sex, city, history of blood transfusion, acupuncture, and family history, but prevalence of anti-HCV was significantly lower overall among the radiation-exposed people (relative prevalence 0.84, p=0.022) compared to people with estimated radiation dose 0 Gy. No significant interaction was found between any of the above mentioned risk factors and radiation dose. People with anti-HCV positive had 13 times higher prevalence of chronic liver disease than those without anti-HCV. However, the radiation dose response for chronic liver disease among anti-HCV positive survivors may be greater than that among anti-HCV negative survivors (slope ratio 20), but the difference was marginally significant (p=0.097). Prevalence of HBsAg increased with whole-body kerma. However, no trend with radiation dose was found in the anti-HBs prevalence. In the background, prevalence of chronic liver disease in people with HBsAg-positive was approximately three times higher that in those without HBsAg. No difference in slope of the dose was found among HBsAg positive and negative individuals (slope: HBsAg positive 0.91/Gy, HBsAg negative 0.11/Gy, difference p=0.66). In conclusion, no dose-response relationship was found between

  9. Dendritic cells: The warriors upfront-turned defunct in chronic hepatitis C infection

    Institute of Scientific and Technical Information of China (English)

    Meenakshi; Sachdeva; Yogesh; K; Chawla; Sunil; K; Arora

    2015-01-01

    Hepatitis C virus(HCV) infection causes tremendousmorbidity and mortality with over 170 million people infected worldwide. HCV gives rise to a sustained, chronic disease in the majority of infected individuals owing to a failure of the host immune system to clear the virus. In general, an adequate immune response is elicited by an efficient antigen presentation by dendritic cells(DCs), the cells that connect innate and adaptive immune system to generate a specific immune response against a pathogen. However, HCV seems to dysregulate the activity of DCs, making them less proficient antigen presenting cells for the optimal stimulation of virusspecific T cells, hence interfering with an optimal antiviral immune response. There are discordant reports on the functional status of DCs in chronic HCV infection(CHC), from no phenotypic or functional defects to abnormal functions of DCs. Furthermore, the molecular mechanisms behind the impairment of DC function are even so not completely elucidated during CHC. Understanding the mechanisms of immune dysfunction would help in devising strategies for better management of the disease at the immunological level and help to predict the prognosis of the disease in the patients receiving antiviral therapy. In this review, we have discussed the outcomes of the interaction of DCs with HCV and the mechanisms of DC impairment during HCV infection with its adverse effects on the immune response in the infected host.

  10. Impact of Il28b-related single nucleotide polymorphisms on liver transient elastography in chronic hepatitis C infection.

    Directory of Open Access Journals (Sweden)

    Magdalena Ydreborg

    Full Text Available BACKGROUND AND AIMS: Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs in proximity to IL28B predict spontaneous clearance of hepatitis C virus (HCV infection as well as outcome following pegylated interferon and ribavirin therapy among genotype 1 infected patients. Additionally the presence of the otherwise favorable IL28B genetic variants in the context of HCV genotype 3 infection reportedly entail more pronounced liver fibrosis and steatosis. The present study aimed to evaluate the impact of IL28B SNP variability on liver stiffness as accessed by transient elastography. METHODS: Seven hundred and seventy-one Swedish HCV infected patients sequentially undergoing liver stiffness measurement by means of Fibroscan® in the context of a real-life trial had samples available for IL28B genotyping (rs12979860 and HCV genotyping. RESULTS: CC(rs12979860 was more common among HCV genotype 2 or 3 infected treatment-naïve patients than among those infected with genotype 1 (P<0.0001. Additionally CC(rs12979860 among HCV genotype 3 infected patients was associated with higher liver stiffness values (P = 0.004, and higher AST to platelet ratio index (APRI; p = 0.02 as compared to carriers of the T allele. Among HCV genotype 1 infected patients, CC(rs12979860 was significantly associated with higher viral load (P = 0.001, with a similar non-significant trend noted among HCV genotype 3 infected patients. CONCLUSION: This study confirms previous reports that the CC(rs12979860 SNP is associated with more pronounced liver pathology in patients chronically infected with HCV genotype 3 as compared to genotype 1, suggesting that IL28B genetic variants differently regulates the course of HCV infection across HCV genotypes.

  11. New pandemics: HIV and AIDS, HCV and chronic hepatitis, Influenza virus and flu

    Science.gov (United States)

    Gatignol, Anne; Dubuisson, Jean; Wainberg, Mark A; Cohen, Éric A; Darlix, Jean-Luc

    2007-01-01

    New pandemics are a serious threat to the health of the entire world. They are essentially of viral origin and spread at large speed. A meeting on this topic was held in Lyon, France, within the XIXth Jacques Cartier Symposia, a series of France-Québec meetings held every year. New findings on HIV and AIDS, on HCV and chronic hepatitis, and an update on influenza virus and flu were covered during this meeting on December 4 and 5, 2006. Aspects of viral structure, virus-host interactions, antiviral defenses, drugs and vaccinations, and epidemiological aspects were discussed for HIV and HCV. Old and recent data on the flu epidemics ended this meeting. PMID:17270043

  12. New pandemics: HIV and AIDS, HCV and chronic hepatitis, Influenza virus and flu

    Directory of Open Access Journals (Sweden)

    Cohen Éric A

    2007-02-01

    Full Text Available Abstract New pandemics are a serious threat to the health of the entire world. They are essentially of viral origin and spread at large speed. A meeting on this topic was held in Lyon, France, within the XIXth Jacques Cartier Symposia, a series of France-Québec meetings held every year. New findings on HIV and AIDS, on HCV and chronic hepatitis, and an update on influenza virus and flu were covered during this meeting on December 4 and 5, 2006. Aspects of viral structure, virus-host interactions, antiviral defenses, drugs and vaccinations, and epidemiological aspects were discussed for HIV and HCV. Old and recent data on the flu epidemics ended this meeting.

  13. Acute hepatitis C in a chronically HIV-infected patient: Evolution of different viral genomic regions

    Institute of Scientific and Technical Information of China (English)

    Diego Flichman; Veronica Kott; Silvia Sookoian; Rodolfo Campos

    2003-01-01

    AIM: To analyze the molecular evolution of different viral genomic regions of HCV in an acute HCV infected patient chronically infected with HIV through a 42-month follow-up.METHODS: Serum samples of a chronically HIV infected patient that seroconverted to anti HCV antibodies were sequenced, from the event of superinfection through a period of 17 months and in a late sample (42nd month). Hypervariable genomic regions of HIV (V3 loop of the gp120) and HCV (HVR-1 on the E2 glycoprotein gene) were studied. In order to analyze genomic regions involved in different biological functions and with the cellular immune response, HCV core and NS5A were also chosen to be sequenced. Amplification of the different regions was done by RT-PCR and directly sequenced. Confirmation of sequences was done on reamplified material. Nucleotide sequences of the different time points were aligned with CLUSTAL W 1.5, and the corresponding amino acid ones were deduced.RESULTS: Hypervariable genomic regions of both viruses (HVR1 and gp120 V3 loop) presented several nonsynonymous changes but, while in the gp120 V3 loop mutations were detected in the sample obtained right after HCV superinfection and maintained throughout, they occurred following a sequential and cumulative pattern in the HVR1. In the NS5A region of HCV, two amino acid changes were detected during the follow-up period, whereas the core region presented several amino acid replacements, once the HCV chronic infection had been established.CONCLUSION: During the HIV-HCV superinfection, each genomic region analyzed shows a different evolutionary pattem.Most of the nucleotide substitutions observed are nonsynonymous and clustered in previously described epitopes,thus suggesting an immune-driven evolutionary process.

  14. The Association of Il28b Genotype with the Histological Features of Chronic Hepatitis C Is HCV Genotype Dependent

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    Roberta D'Ambrosio

    2014-04-01

    Full Text Available The interleukin 28B (IL28B rs12979860 polymorphism is associated with treatment outcome in hepatitis C virus (HCV genotype 1 and 4 patients. Its association with the histological features of chronic hepatitis C and disease severity needs further clarifications. To assess the correlation between IL28B genotype, HCV genotype and liver biopsy findings in untreated patients. Materials and Methods: Pre-treatment liver biopsies from 335 HCV Caucasian patients (59% males, age 50 years enrolled in the MIST study were staged for fibrosis and inflammation according to the METAVIR and the Ishak scoring systems; steatosis was dichotomized as <5% or ≥5%. IL28B was typed by Taqman Single Nucleotide Polymorphism (SNP genotyping assay. HCV genotype was 1 in 151 (45%, 2 in 99 (30%, 3 in 50 (15% and 4 in 35 (10% patients. IL28B genotype was CC in 117 (34%, CT in 166 (49% and TT in 52 (15%. At univariate analysis, the IL28B CC genotype was associated with severe portal inflammation in HCV-1 patients (CC vs. CT/TT: 86% vs. 63%, p = 0.005, severe lobular inflammation in HCV-2 patients (CC vs. CT/TT: 44% vs. 23%, p = 0.03, and less fatty infiltration in HCV-1 patients (CC vs. CT/TT: 72% vs. 51%, p = 0.02. Despite the lack of any association between IL28B and fibrosis stage, in HCV-3 patients IL28B CC correlated with METAVIR F3-F4 (CC vs. CT/TT: 74% vs. 26%, p = 0.05. At multivariate analysis, the genotype CC remained associated with severe portal inflammation in HCV-1, only (Odds Ratio (OR: 95% Confidence Interval (CI: 3.24 (1.23–8.51. IL28B genotype is associated with the histological features of chronic hepatitis C in a HCV genotype dependent manner, with CC genotype being independently associated with severe portal inflammation.

  15. Effect of hcv infection on hepatic fibrosis in patients of thalassaemia major

    International Nuclear Information System (INIS)

    Objective: To investigate the effect of HCV infection on hepatic fibrosis in patients of thalassaemia major with iron overload in order to modify Pesaro criteria for classification into prognostic groups for allogenic haemopoietic stem cell transplant in these patients. Design: Cross-sectional comparative study. Place and Duration of Study: Armed Forces Institute of Pathology, Armed Forces Bone Marrow Transplant Center and Departments of Pediatrics of Military Hospital and Combined Military Hospital, Rawalpindi, from July 2003 to June 2004. Subjects and Methods: Twenty eight HCV- and 18 HCV+ patients of thalassaemia major, who were prospective recipients of allogeneic bone marrow transplant, were included in the study. Serum ferritin was estimated by chemiluminescent immunoassay. Degree of fibrosis in liver biopsy was scored using Knodell's scoring system. Correlation between the two was evaluated statistically through Pearson's correlation coefficient. Results: Mean serum ferritin was lower and degree of hepatic fibrosis was less in hepatitis C negative patients of TM. The correlation between serum ferritin and the degree of hepatic fibrosis was much stronger in hepatitis C negative patients with 'r' value of 0.507 and 'p' value of 0.006, which was statistically significant. Conclusion: A strong correlation between serum ferritin and degree of hepatic fibrosis was observed in patients of thalassaemia major not infected with hepatitis C infection. Serum ferritin levels alone are, therefore, not sufficient to assess degree of fibrosis in HCV positive patients of TM. (author)

  16. Identification and Clinical Management of Persons with Chronic Hepatitis C Virus Infection - Cherokee Nation, 2012-2015.

    Science.gov (United States)

    Mera, Jorge; Vellozzi, Claudia; Hariri, Susan; Carabin, Hélène; Drevets, Douglas A; Miller, Anna; Reilley, Brigg; Essex, Whitney; Gahn, David; Lyons, Lisa; Leston, Jessica; Ward, John W

    2016-01-01

    An estimated 3.5 million persons in the United States are living with hepatitis C virus (HCV) infection, resulting in approximately 20,000 deaths each year, primarily from cirrhosis or hepatocellular carcinoma (1,2). American Indian/Alaska Native (AI/AN) populations have the highest incidence of acute HCV infection among all U.S. racial/ethnic groups and are at greater risk for HCV-related mortality compared with the general population (3). In 2013, new antiviral drugs became available that make possible 8-12 week treatment regimens with fewer adverse events and are able to achieve sustained virologic response (SVR) in >90% of treated patients (4), equivalent to a cure of HCV infection. Also of note, HCV testing recommendations were expanded in 2012 by CDC and in 2013 by the U.S. Preventive Services Task Force to include one-time testing of persons born during 1945-1965 (the "baby boomer" cohort) in addition to anyone at increased risk for HCV infection (5,6). Given the availability of new HCV drugs, expanded testing recommendations, and high incidence of HCV infection in AI/AN populations, in October 2012, Cherokee Nation Health Services (CNHS) implemented a tribal HCV testing policy.* As part of the policy, CNHS added a reminder in the electronic health record (EHR) for clinical decision support and provided HCV education to primary care clinicians. From October 2012 to July 2015, among 92,012 persons with at least one CNHS clinic encounter, the cumulative number who received HCV screening for the first time increased from 3,337 (3.6%) to 16,772 (18.2%). The largest percentage of HCV screening was among persons born during 1945-1965. Of 715 persons who tested positive for HCV antibodies, 488 (68.3%) were tested for HCV RNA; among those 488 persons, 388 (79.5%) were RNA positive and were thus confirmed to have chronic HCV infection. Treatment was initiated for 223 (57.5%) of the 388 with chronic infection; 201 (90.1%) completed treatment, of whom 180 (89

  17. TRAIL receptor I (DR4 polymorphisms C626G and A683C are associated with an increased risk for hepatocellular carcinoma (HCC in HCV-infected patients

    Directory of Open Access Journals (Sweden)

    Körner Christian

    2012-03-01

    Full Text Available Abstract Background Tumour surveillance via induction of TRAIL-mediated apoptosis is a key mechanism, how the immune system prevents malignancy. To determine if gene variants in the TRAIL receptor I (DR4 gene affect the risk of hepatitis C virus (HCV-induced liver cancer (HCC, we analysed DR4 mutations C626G (rs20575 and A683C (rs20576 in HCV-infected patients with and without HCC. Methods Frequencies of DR4 gene polymorphisms were determined by LightSNiP assays in 159 and 234 HCV-infected patients with HCC and without HCC, respectively. 359 healthy controls served as reference population. Results Distribution of C626G and A683C genotypes were not significantly different between healthy controls and HCV-positive patients without HCC. DR4 variants 626C and 683A occurred at increased frequencies in patients with HCC. The risk of HCC was linked to carriage of the 626C allele and the homozygous 683AA genotype, and the simultaneous presence of the two risk variants was confirmed as independent HCC risk factor by Cox regression analysis (Odds ratio 1.975, 95% CI 1.205-3.236; p = 0.007. Furthermore HCV viral loads were significantly increased in patients who simultaneously carried both genetic risk factors (2.69 ± 0.36 × 106 IU/ml vs. 1.81 ± 0.23 × 106 IU/ml, p = 0.049. Conclusions The increased prevalence of patients with a 626C allele and the homozygous 683AA genotype in HCV-infected patients with HCC suggests that these genetic variants are a risk factor for HCC in chronic hepatitis C.

  18. Combination of "low-dose" ribavirin and interferon alfa-2a therapy followed by interferon alfa-2a monotherapy in chronic HCV-infected non-responders and relapsers after interferon alfa-2a monotherapy

    Institute of Scientific and Technical Information of China (English)

    Perdita Wietzke-Braun; Volker Meier; Felix Braun; Giuliano Ramadori

    2001-01-01

    AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon monotherapy.METHODS Thirty-four chronic hepatitis C virus-infected non-responders to interferon alfa2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa 2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10 mg/ kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as monotherapy.RESULTS Seven (20.6%) of 34 non-responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%)non-responders, the combined therapy was stopped after three months because of non-response. Ten of the 27 non-responders completed the 1;2-month treatment course. At a mean follow up of 28 months (16- 37 months)after the treatment, 4/10 (15%) previous non-responders still remained complete responders,All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22months (9 - 36 months) after treatment, 6/13(46%) the previous relapsers were stillsustained complete responders.CONCLUSION Our treatment schedule of the combined therapy for 6 months of interferon alfa2a with a low dose of ribavirin (10 mg/kg/day)followed by 6 months of interferon alfa-2amonotherapy is able to induce a sustainedcomplete response rate in 15% of non-responders and 46% of relapsers with chronic hepatitis C virus-related liver diseases comparable to those obtained with the standarddoses of ribavirin 1000 - 1200 mg/day.Randomized prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be

  19. Using phosphazide in regimes of ART in patients co-infected with HIV and HCV receiving treatment of hepatitis

    Directory of Open Access Journals (Sweden)

    A Kravchenko

    2012-11-01

    Full Text Available Purpose: Comparing of the efficacy and safety of treatment of chronic hepatitis C PegIFN and RBV in HIV-infected patients receiving HAART with phosphazide (PhAZT or abacavir (ABC. Methods: 81 co-infected with HIV/HCV patients with ART>3 months, treated by PegIFN and RBV (1000–1200 mg/day by weight during 24–48 weeks. 50 patients (group 1 received PhAZT+3TC+EFV or PIs, and 31 patients (group 2 -ABC+3TC+EFV or PIs. Patients in both groups did not differ by sex, age, stage of HIV infection, body mass index, HCV genotype, HCV RNA levels, the degree of hepatic fibrosis. Results: Virologic response EOT in 1st group was 74% (genotype 1–56%, genotype 3–92%, in 2nd group-75.9% (genotype 1–61.5%; genotype 3–87.5%. Sustained virological response (SVR in 1st group was 62% (genotype 1–44%, genotype 3–80%, and in 2nd group −53.3% (genotype 1–46.7%, genotype 3–60%. Relapse of HCV replication within 24 wks after therapy was observed in 12% of pts with 1st group and 22.6%-2nd group (p<0.05. The frequency of relapse in pts with G1 was 12% and 14.8%, with G3-12% and 27.5% (in 1st and 2nd groups, p<0.05. If the duration of HCV therapy was <48 wks, SVR rates in pts of both groups was 50% and 41.1%, and if 48 wks and more−73.1% and 71.4%, respectively (p<0.05. When using PIs-SVR was 52% and 57% in 1st and 2nd groups. In appointing EFV SVR in 1st group − 76.2% (genotype 1–70%, genotype 3–81.8%, in 2nd group−50% (genotype 1–44.4%, genotype 3–57.1%, p<0.05. Inclusion in the regime of HAART PhAZT had no significant effect on the performance of peripheral blood. Decreased hemoglobin, neutrophil and platelet counts were similar in both groups and no more than 1–2 degrees of toxicity. Reducing the CD4+count during HCV treatment has been less pronounced when using PhAZT (compared with ABC in combination with EFV, and with PI. Conclusions: PegIFN and RBV therapy in pts with HIV/HCV co-infection receiving HAART, is effective in 44–47

  20. 皖南地区 HIV 感染者中 HCV 感染状况的调查%Investigation of HCV co-infection among HIV-1 infected patients in the South of Anhui

    Institute of Scientific and Technical Information of China (English)

    肖敏敏; 王毅; 邵慧; 张艳; 李萍

    2014-01-01

    Objective To investigate the ratio of hepatitis C virus (HCV ) co-infected with human immunodeficiency virus (HIV)-1 and the impact of HCV co-infection on CD4 + T cell counts in HIV-1 infected patients. Methods HCV-Ab was detected by enzyme-linked immunosorbent assay (ELISA),and HCV-RNA was determined by polymerase chain reaction (PCR)with serum and peripheral blood mononuclear cell (PBMC).Results Among 234 HIV-1 infected patients,the infection through sex accounted for 83.7% (male gay sex for 48.7% and heterosexual contact for 35.0%),drug addiction for 4.2%,inpatient for 2.6% and maternal-neonatal transmission for 2.1%.The percentage of HCV-Ab positive was 12.8% (30 /234),that of serum HCV-RNA was 11.5% (27 /234),which 26 cases were HCV-Ab positive and 1 case was HCV-Ab negative,while the serum HCV-RNA content was 3.60 × 103 copies/mL,and 14 cases were HCV-RNA positive in PBMC accounting for 6.0%,thus the ratio of HCV co-infection was 13.2% as a total.The average counts of CD4 + T cell among HIV-1 HCV infection and single HIV-1 infection were 322 cells/mL and 477 cells/mL.Conclusions The ratio of HIV-1 HCV co-infection was 13.2% in the South of Anhui,and the determination of HCV during screening HIV-1 infection may help with the early diagnosis and treatment of HCV,and the detection of HCV-RNA with PBMC should be taken attention.%目的:调查皖南地区人类免疫缺陷病毒(HIV)-1感染者中丙型肝炎病毒(HCV)的混合感染率,探讨HCV 对 HIV-1感染者 CD4+T 细胞计数的影响。方法对皖南地区234例 HIV-1感染者,分别采用酶联免疫吸附试验(ELISA)检测血清中 HCV-Ab、聚合酶链反应(PCR)检测血清和外周血单个核细胞(PBMC)中的 HCV-RNA 含量;同时采用流式细胞技术检测外周血 CD4+T 细胞亚群数量。结果234例 HIV-1感染者中,性途径感染占83.7%(男男途径占48.7%;异性途径占35.0%);吸毒者占4.2%;住院患者占2.6

  1. Treatment of rheumatic diseases in patients with HCV and HIV infection.

    Science.gov (United States)

    Galeazzi, Mauro; Giannitti, Chiara; Manganelli, Stefania; Benucci, Maurizio; Scarpato, Salvatore; Bazzani, Chiara; Caporali, Roberto; Sebastiani, Gian Domenico

    2008-12-01

    A wide variety of rheumatic diseases has been documented in the presence of hepatitis C virus (HCV) infection and in human immunodeficiency virus (HIV) infection. In this conditions, physicians are refrained from using corticosteroids and/or immunosuppressants agents because of the risk of favouring viral replication and the progression of the underlying viral disease. In the present review we have focused our attention on the possible role of cyclosporine A (CsA), anti-Tumour Necrosis Factor (TNF) alpha agents in the treatment of HIV or HCV infected autoimmune patients. The results drown from the literature and from our personal experience confirm the safety of CsA and anti-TNF alpha agents, in terms of viral load and liver toxicity. A limited experience also suggest that both therapies can be given in combination in rheumatoid arthritis patients without increasing the risk of adverse events.

  2. Biomarkers of inflammation, coagulation and microbial translocation in HIV/HCV co-infected patients in the SMART study

    DEFF Research Database (Denmark)

    Peters, Lars; Neuhaus, Jacqueline; Duprez, Daniel;

    2014-01-01

    on levels of biomarkers of inflammation, coagulation and microbial translocation in HIV/HCV co-infected persons in the SMART study. STUDY DESIGN: All HIV/HCV co-infected persons with stored plasma at study entry and at six months of follow-up were included (N=362). D-dimer, IL-6, sCD14 and hepatic......-coagulation markers but the overall coagulation profile was not affected. Interruption of ART lead to a particularly pronounced increase in IL-6 levels in persons with elevated HA levels (p=0.01 for interaction between randomization group and continuous HA level). CONCLUSIONS: HIV/HCV co-infected persons...

  3. Inhibition of HCV 3a genotype entry through Host CD81 and HCV E2 antibodies

    Directory of Open Access Journals (Sweden)

    Ashfaq Usman A

    2011-11-01

    Full Text Available Abstract Background HCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage hepatocellular carcinoma and death. HCV glycoproteins play an important role in HCV entry by binding with CD81 receptors. Hence inhibition of virus at entry step is an important target to identify antiviral drugs against HCV. Methods and result The present study elaborated the role of CD81 and HCV glycoprotein E2 in HCV entry using retroviral pseudo-particles of 3a local genotype. Our results demonstrated that HCV specific antibody E2 and host antibody CD81 showed dose- dependent inhibition of HCV entry. HCV E2 antibody showed 50% reduction at a concentration of 1.5 ± 1 μg while CD81 exhibited 50% reduction at a concentration of 0.8 ± 1 μg. In addition, data obtained with HCVpp were also confirmed with the infection of whole virus of HCV genotype 3a in liver cells. Conclusion Our data suggest that HCV specific E2 and host CD81 antibodies reduce HCVpp entry and full length viral particle and combination of host and HCV specific antibodies showed synergistic effect in reducing the viral titer.

  4. Are the Real HCV Infection Features in Iranian Patients the Same As What Is Expected?

    Directory of Open Access Journals (Sweden)

    Seyed-Moayed Alavian

    2005-03-01

    Full Text Available Hepatitis Monthly issue 7 contained four clinical trials of pegylated interferon (Peg- IFN plus ribavirin for Iranian patients with chronic hepatitis C infection conducted in four various centers(1-4. Apart from one trial(2, which enrolled only patients with inherited bleeding disorders, three others enrolled heterogeneous HCV infected populations. However, reported sustained virologic response (SVR rate was varied from 50% to 78% in these studies. This wide SVR range might make difficulties for the readers to gain clear data regarding efficacy of this therapeutic regimen on Iranian patients.Almost analogous inclusion and exclusion criteria as well as the details of these four studies allow us to intervene and join the cases and reanalyze the datafrom a single pool. However, the slight differences among these studies will obviously diminish the accuracy and make us discuss the results conservatively. For instance, in the study by Merat et al. none of the patients underwent liver biopsy(2 or Zali et al. excluded cirrhotic patients from the study(4. Moreover, the sensitivities of RT-PCR tests applied to define response to treatment were varied from 100 copies/ml to 600 copies/ml in various studies. In spite of these inevitable biases, our intervention is able to provide useful information.To analyze the data, we applied intention to treat analysis (ITT. ITT analysis is generally interpreted as including all patients who received at least one dose of medication(s, regardless of whether they actually satisfied the entry criteria, the treatment actually received, and subsequent withdrawal or deviation from the protocol(5. Therefore, all patients who do not complete the study are considered to have failure to treatment. It is a strategy to avoid the problems created by omitting dropouts and noncompliant patients, which can introduce bias in the trial, and overestimate clinical effectiveness. Although there is a debate about the validity of excluding

  5. New pandemics: HIV and AIDS, HCV and chronic hepatitis, Influenza virus and flu

    OpenAIRE

    Cohen Éric A; Wainberg Mark A; Dubuisson Jean; Gatignol Anne; Darlix Jean-Luc

    2007-01-01

    Abstract New pandemics are a serious threat to the health of the entire world. They are essentially of viral origin and spread at large speed. A meeting on this topic was held in Lyon, France, within the XIXth Jacques Cartier Symposia, a series of France-Québec meetings held every year. New findings on HIV and AIDS, on HCV and chronic hepatitis, and an update on influenza virus and flu were covered during this meeting on December 4 and 5, 2006. Aspects of viral structure, virus-host interacti...

  6. Coinfecciones por HBV y HCV en pacientes HIV positivos en la "era HAART": nuevos desafíos Hbv and hcv co-infections in hiv positive patients in the "HAART era": new challenges

    Directory of Open Access Journals (Sweden)

    Natalia L. Laufer

    2007-02-01

    Full Text Available Las coinfecciones con virus de la hepatitis C (HCV y/o virus de la hepatitis B (HBV en pacientes infectados por el virus de la inmunodeficiencia humana (HIV son un hallazgo frecuente en virtud de las similares vías de transmisión que estos agentes presentan (sexual, parenteral y vertical. Desde el advenimiento del tratamiento antirretroviral de alta eficiencia (TARV se evidenció una marcada disminución en la morbi-mortalidad de los pacientes; sin embargo, ante la prolongación de su sobrevida, las complicaciones crónicas debidas a las coinfecciones con estos virus hepatotropos han cobrado importancia, convirtiéndose la enfermedad hepática en una de las primeras causas de morbi-mortalidad de los pacientes HIV positivos en los países desarrollados. Se disponen en la actualidad de nuevas terapias y métodos de diagnóstico y seguimiento para HBV y HCV, lo cual permite un mejor control de ambas coinfecciones.Co-infections with HIV and HCV/HBV are frequently found due to the similar routes of transmission (sexual, parenteral and vertical. Since the introduction of highly active antiretroviral therapy (HAART there has been a notably decrease in patients morbidity and mortality, nevertheless with the prolonged survival, many of these patients are at risk of developing chronic complication, secondary to the infection of hepatotropic viruses. End stage liver disease is one of the main causes of morbid-mortality among HIV patients in developed countries. Nowadays there are new available therapies, diagnostic and follow up techniques for HBV and HCV, what provides a better control of both co-infections.

  7. Progress in the development of experimental animal models of HCV infection%HCV实验动物模型研究进展

    Institute of Scientific and Technical Information of China (English)

    陶万银; 张岩; 钟劲

    2012-01-01

    HCV是威胁人类健康的重要病原体之一,可在人体肝脏形成持续性感染,导致慢性肝炎、肝纤维化、肝硬化和肝癌.HCV的实验动物模型不仅是HCV免疫学、病理学和病毒学等基础科学的重要研究手段,还为HCV疫苗和药物的研发提供了关键的工具和平台.黑猩猩是除了人类以外唯一可以被HCV感染的灵长类动物,为HCV的研究做出了重要贡献,但其使用受到了成本及伦理上的限制.近年在利用树鼩和人源化小鼠建立HCV小动物模型的研究上取得良好的进展.本文将总结常用HCV实验动物模型的现状和挑战.%HCV is one of the major pathogens that pose threats to human public health. It can establish persistent infection in human liver, leading to chronic hepatitis, liver fibrosis/cirrhosis and hepatocellular carcinoma. The experimental animal models for HCV infection are not only important research means for investigating immunology, pathology and virology of HCV infection, but also serve as the means and platform for the development of HCV vaccines and novel agents. Chimpanzees, the sole primate except hu man beings who can be infected by HCV, have made significant contributions to HCV research. However, their application has been hampered due to their cost and ethical issues. A big progress has been made in developing small animal models for HCV research using tupaia and humanized mice in recent years. This review summarizes the current status and challenges of the development of HCV animal models.

  8. Rapid Virological Response Represents the Highest Prediction Factor of Response to Antiviral Treatment in HCV-Related Chronic Hepatitis: a Multicenter Retrospective Study

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    Federico

    2015-06-01

    Full Text Available Background Standard [i.e. pegylated interferon (Peg-IFN + ribavirin] treatment of hepatitis C virus (HCV-related chronic hepatitis is associated with a sustained virological response (SVR in 50 - 90% of patients. A rapid virological response (RVR (i.e. negative HCV-RNA after 4 weeks of treatment predicts SVR in almost 90% of patients. Objectives The main aim of this study was to assess the strength of RVR, as a predictive factor of antiviral treatment response. Patients and Methods Using univariate and multivariate analysis, we retrospectively evaluated biochemical, metabolic, genetic and viral variables that might affect both RVR and SVR to Peg-IFN plus ribavirin, in 315 consecutive outpatients affected by HCV-related chronic hepatitis. Results At univariate analysis, staging, body mass index, RVR, genotype and viral load were significantly related to SVR (P < 0.001. At multivariate analysis, RVR and genotype remained significant (P < 0.00001. The RVR had a predictive value of 83%. At univariate and multivariate analyses, diabetes (P = 0.003, genotype 2 (P = 0.000 and HCV-RNA values (P = 0.016 were independent predictors of RVR, even though at multivariate analyses, only genotype 2 was significantly related to RVR. When we stratified patients, according to genotype, no laboratory or clinical factors were predictive of RVR in genotype 1 patients at either univariate or multivariate analysis. In genotype 2 patients, staging (P = 0.029 and diabetes (P = 0.001 were the only significant predictors of RVR at univariate analyses, whereas no factor was independently related to RVR, at multivariate analysis. Conclusions The RVR is the strongest factor of SVR and infection with HCV genotype 2 is significantly associated with RVR. Neither biochemical and/or metabolic factors seem to exert influence on RVR.

  9. Characteristics of co-infections by HCV and HBV among Brazilian patients infected by HIV-1 and/or HTLV-1

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    Marcia Moreira

    2013-12-01

    Full Text Available BACKGROUND: The human retroviruses HIV-1 and HTLV-1 share the routes of infection with hepatitis viruses B and C. Co-infection by these agents are a common event, but we have scarce knowledge on co-infection by two or more of these agents. OBJECTIVE: To evaluate the characteristics and risk factors for co-infections by HBV and HCV in patients infected by HIV-1 or/and HTLV-1, in Salvador, Brazil. METHODS: In a case-control study we evaluated patients followed in the AIDS and HTLV clinics of Federal University of Bahia Hospital. Clinical and epidemiological characteristics were reviewed, and patients were tested for the presence of serological markers of HBV and HCV infections. HCV-infected patients were tested by PCR to evaluate the presence of viremia. RESULTS: A total of 200 HIV-1, 213 HTLV-1-infected, and 38 HIV-HTLV-co-infected individuals were included. HIV-infected patients were more likely to have had more sexual partners in the lifetime than other patients' groups. HIV-HTLV-co-infected subjects were predominantly male. Patients infected by HTLV or co-infected had a significantly higher frequency of previous syphilis or gonorrhea, while HIV infection was mainly associated with HPV infection. Co-infection was significantly associated to intravenous drug use (IVDU. HBV and/or HCV markers were more frequently found among co-infected patients. HBV markers were more frequently detected among HIV-infected patients, while HCV was clearly associated with IVDU across all groups. AgHBs was strongly associated with co-infection by HIV-HTLV (OR = 22.03, 95% CI: 2.69-469.7, as well as confirmed HCV infection (p = 0.001. Concomitant HCV and HBV infection was also associated with retroviral co-infection. Patients infected by HTLV-1 had a lower chance of detectable HCV viremia (OR = 0.04, 95% CI: 0.002-0.85. CONCLUSIONS: Infection by HCV and/or HBV is frequent among patients presenting retroviral infection, but risk factors and prevalence for each

  10. High interferon-stimulated gene ISG-15 expression affects HCV treatment outcome in patients co-infected with HIV and HCV.

    Science.gov (United States)

    Katsounas, Antonios; Hubbard, Jonathan J; Wang, Crystal H; Zhang, Xiaozhen; Dou, Diana; Shivakumar, Bhavana; Winter, Sophie; Schlaak, Joerg F; Lempicki, Richard A; Masur, Henry; Polis, Michael; Kottilil, Shyam; Osinusi, Anu

    2013-06-01

    Increased baseline expression and lack of induction of interferon-stimulated genes (ISG) are strong negative predictors of therapeutic response to PegIFN/RBV in patients co-infected with HIV and hepatitis C virus (HCV). This study specifically addressed whether ISG-15 expression influences therapeutic responses in 20 HIV/HCV genotype-1 subjects undergoing HCV treatment. Non-responders had significantly higher baseline expression and selective induction of ISG-15 after IFN-α treatment relative to participants with sustained virological response. High baseline levels of ISG-15 were also associated with less induction of ISG with treatment. These results support a role for ISG-15 as a prognostic indicator and resistance factor to IFN-α.

  11. Tumor Necrosis Factor Receptor 1 Expression Is Upregulated in Dendritic Cells in Patients with Chronic HCV Who Respond to Therapy

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    Raul Cubillas

    2010-01-01

    Full Text Available The present studies assessed the level of tumor necrosis factor receptor (TNFR expression in peripheral blood mononuclear cells (PBMCs subsets from patients with chronic HCV undergoing interferon /ribavirin-based therapy (Ifn/R. Methods. TNFR family member mRNA expression was determined using quantitative real-time PCR assays (RTPCRs in PBMC from 39 HCV+ patients and 21 control HCV− patients. Further subset analysis of HCV + patients (untreated (U, sustained virological responders (SVR, and nonresponders (NR/relapsers (Rel PBMC was performed via staining with anti-CD123, anti-CD33, anti-TNFR1 or via RTPCR for TNFR1 mRNA. Results. A similar level of TNFR1 mRNA in PBMC from untreated HCV+ genotype 1 patients and controls was noted. TNFR1 and TNFR2 mRNA levels in PBMC from HCV+ patients with SVR were statistically different than levels in HCV(− patients. A significant difference was noted between the peak values of TNFR1 of the CD123+ PBMC isolated from SVR and the NR/Rel. Conclusion. Upregulation of TNFR1 expression, occurring in a specific subset of CD123+ dendritic cells, appeared in HCV+ patients with SVR.

  12. Neutralizing antibodies in patients with chronic hepatitis C and correlation to liver cirrhosis and estimated duration of infection.

    Science.gov (United States)

    Pedersen, Jannie; Lundbo, Lene Fogt; Krarup, Henrik; Bukh, Jens; Weis, Nina

    2016-10-01

    Although chronic hepatitis C virus (HCV) infection accounts for 30% of individuals with cirrhotic livers worldwide, factors influencing disease progression are far from elucidated. The aim of this study was to determine whether the level of neutralizing antibodies (NAbs) correlated with the development of cirrhosis in patients with chronic HCV infection, genotype 1, when adjusting for estimated duration of infection. Thirty-nine patients with chronic hepatitis C, with either no/mild fibrosis (n = 23) or cirrhosis (n = 16), were enrolled from two university hospitals in Denmark. Duration of HCV infection was estimated based on patient information and/or anti-HCV seroconversion. Serial dilutions of purified serum/plasma derived IgGs were tested for their ability to neutralize six HCV-genotype 1 cell-culture strains. The results were expressed as the lowest IgG concentration yielding ≥50% neutralization (NAb50 -titer). A significant difference in HCV NAb50 -titers among the six genotype 1a/1b recombinants was found. In patients with cirrhosis, a tendency for higher level of NAbs was observed compared to patients with no/mild fibrosis, although not statistical significant. Stratifying the two groups revealed that being infected >25 years resulted in higher levels of NAbs in both. Furthermore, by correlating estimated duration of HCV infection to NAb50 -titers a significant result was found against two recombinants. The NAb titer does not differ significantly between HCV patients with either no/mild fibrosis or cirrhosis but show a tendency for increasing level with increased duration of infection. NAbs might contribute as a biological marker to increase the accuracy of patient based information on duration of HCV infection. J. Med. Virol. 88:1791-1803, 2016. © 2016 Wiley Periodicals, Inc. PMID:27027386

  13. Neutralizing antibodies in patients with chronic hepatitis C and correlation to liver cirrhosis and estimated duration of infection.

    Science.gov (United States)

    Pedersen, Jannie; Lundbo, Lene Fogt; Krarup, Henrik; Bukh, Jens; Weis, Nina

    2016-10-01

    Although chronic hepatitis C virus (HCV) infection accounts for 30% of individuals with cirrhotic livers worldwide, factors influencing disease progression are far from elucidated. The aim of this study was to determine whether the level of neutralizing antibodies (NAbs) correlated with the development of cirrhosis in patients with chronic HCV infection, genotype 1, when adjusting for estimated duration of infection. Thirty-nine patients with chronic hepatitis C, with either no/mild fibrosis (n = 23) or cirrhosis (n = 16), were enrolled from two university hospitals in Denmark. Duration of HCV infection was estimated based on patient information and/or anti-HCV seroconversion. Serial dilutions of purified serum/plasma derived IgGs were tested for their ability to neutralize six HCV-genotype 1 cell-culture strains. The results were expressed as the lowest IgG concentration yielding ≥50% neutralization (NAb50 -titer). A significant difference in HCV NAb50 -titers among the six genotype 1a/1b recombinants was found. In patients with cirrhosis, a tendency for higher level of NAbs was observed compared to patients with no/mild fibrosis, although not statistical significant. Stratifying the two groups revealed that being infected >25 years resulted in higher levels of NAbs in both. Furthermore, by correlating estimated duration of HCV infection to NAb50 -titers a significant result was found against two recombinants. The NAb titer does not differ significantly between HCV patients with either no/mild fibrosis or cirrhosis but show a tendency for increasing level with increased duration of infection. NAbs might contribute as a biological marker to increase the accuracy of patient based information on duration of HCV infection. J. Med. Virol. 88:1791-1803, 2016. © 2016 Wiley Periodicals, Inc.

  14. Molecular genotyping of HCV infection in seropositive blood donor

    Science.gov (United States)

    Zarin, Siti Noraziah Abu; Ibrahim, Nazlina

    2013-11-01

    This study is to investigate the prevalence of hepatitis C virus infection in seropositive blood donor. RNA was extracted from 32 positive samples in National Blood Centre and Melaka Hospital. The core and NS5B sequences were obtained from 23 samples. Genotype 3a is most prevalent in this study followed by genotype 1a. Evidence of mixed-genotypes (3a and 1b) infections was found in 5 subjects.

  15. EBV CHRONIC INFECTIONS

    Directory of Open Access Journals (Sweden)

    Delia Racciatti

    2010-02-01

    Full Text Available

    The infection from Epstein-Barr virus (EBV or virus of infectious mononucleosis, together with other herpesviruses’ infections, represents a prototype of persistent viral infections characterized by the property of the latency. Although the reactivations of the latent infection are associated with the resumption of the viral replication and eventually with the “shedding”, it is still not clear if this virus can determine chronic infectious diseases, more or less evolutive. These diseases could include some pathological conditions actually defined as “idiopathic”and characterized by the “viral persistence” as the more credible pathogenetic factor. Among the so-called idiopathic syndromes, the “chronic fatigue syndrome” (CFS aroused a great interest around the eighties of the last century when, just for its relationship with EBV, it was called “chronic mononucleosis” or “chronic EBV infection”.

    Today CFS, as defined in 1994 by the CDC of Atlanta (USA, really represents a multifactorial syndrome characterized by a chronic course, where reactivation and remission phases

  16. Inflammatory pseudotumor of the liver in a patient with congenital granulocytopenia and HCV infection

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, G. E-mail: ragsne@uniklink-saarland.de; Fries, P.; Samaras, P.; Remberger, K.; Uder, M.; Kramann, B

    2003-12-01

    Inflammatory pseudotumor (IPT) of the liver is a rare pathologic lesion. Although IPTs within the liver shows spontaneous regression, these lesions are frequently misdiagnosed as malignant on the basis of the clinical manifestation and the results of diagnostic imaging. With special regard to magnetic resonance imaging (MRI), differential diagnosis such as hepatocellular or cholangiocellular carcinoma (HCC/CCC) as well as regenerative liver lesions are discussed in a case of IPT with concomitant hepatitis C virus (HCV) infection and congenital granulocytopenia.

  17. Benign and malignant hematological manifestations of chronic Hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Shiksha Kedia

    2014-01-01

    Full Text Available Chronic hepatitis C virus (HCV infection, that affects 3% of world′s population, is associated with several hematological manifestations mainly benign cytopenias, coagulopathy and lymphoproliferative diseases. Immune or non-immune-mediated thrombocytopenia is a major challenge in chronic HCV infected patients especially in the setting of an advanced liver disease, with average prevalence of nearly 24%. Although several treatment modalities such as steroids, intravenous immunoglobulin, splenectomy and immunosuppresants have been tried with some success, their efficacy is not impressive and can result in an increase in viral load or other thrombotic complications. Even though a recent phase 2 study has shown promising role of a platelet growth factor, eltrombopag, in boosting platelets counts prior to antiviral treatment, its use in pre-operative setting had unexpected complications. Unlike thrombocytopenia, anemia and neutropenia are more frequently seen in treated patients and are often the result of antiviral therapy. HCV infection also pre-disposes to lymphoproliferative diseases, mainly non-Hodking′s lymphomas, likely as a result of chronic antigenic stimulation and mutation of several genes involved in carcinogenesis. Understanding of the role of HCV infection in these conditions has therapeutic implications. Whereas antiviral therapy has shown therapeutic role in HCV-associated indolent lymphomas, monitoring of hepatic function and viral load is important in the management of diffuse large B-cell lymphoma in HCV-infected patients. Although our knowledge about the HCV infection and hematological manifestations has substantially grown in last few decades, further studies are important to advance our therapeutic approach.

  18. Resolution of chronic hepatitis C following parasitosis

    Institute of Scientific and Technical Information of China (English)

    Valerie Byrnes; Sanjiv Chopra; Margaret J Koziel

    2007-01-01

    An inefficient cellular immune response likely leads to chronic hepatitis C virus (HCV) infection. Resolution of chronic HCV infection in the absence of treatment is a rare occurrence. We report the case of a 39-year old white male with a 17-year history of chronic HCV infection, who eradicated HCV following a serious illness due to co-infection with Babesia (babesiosis), Borriela Borgdorferi (Lyme disease) and Ehrlichia (human granulocytic ehrlichiosis). We hypothesize that the cellular immune response mounted by this patient in response to his infection with all three agents but in particular Babesia was sufficient to eradicate HCV.

  19. Alterations in microRNA expression profile in HCV-infected hepatoma cells: Involvement of miR-491 in regulation of HCV replication via the PI3 kinase/Akt pathway

    International Nuclear Information System (INIS)

    Highlights: → HCV infection upregulated miR-192, -194, -215, downregulated miR-320, -491. → Transfection of miR-192, -215, and -491 enhanced HCV replication. → Transfection of miR-491 inhibited Akt phosphorylation. → Akt inhibition could be responsible for augmentation of HCV replication by miR-491. -- Abstract: The aim of this study was to investigate the role of microRNA (miRNA) on hepatitis C virus (HCV) replication in hepatoma cells. Using miRNA array analysis, miR-192/miR-215, miR-194, miR-320, and miR-491 were identified as miRNAs whose expression levels were altered by HCV infection. Among them, miR-192/miR-215 and miR-491 were capable of enhancing replication of the HCV replicon as well as HCV itself. HCV IRES activity or cell proliferation was not increased by forced expression of miR-192/miR-215 or miR-491. Investigation of signaling pathways revealed that miR-491 specifically suppressed the phosphoinositol-3 (PI3) kinase/Akt pathway. Under inhibition of PI3 kinase by LY294002, the suppressive effect of miR-491 on HCV replication was abolished, indicating that suppression of HCV replication by miR-491 was dependent on the PI3 kinase/Akt pathway. miRNAs altered by HCV infection would then affect HCV replication, which implies a complicated mechanism for regulating HCV replication. HCV-induced miRNA may be involved in changes in cellular properties including hepatocarcinogenesis.

  20. Alterations in microRNA expression profile in HCV-infected hepatoma cells: Involvement of miR-491 in regulation of HCV replication via the PI3 kinase/Akt pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Hisashi; Tatsumi, Tomohide; Hosui, Atsushi; Nawa, Takatoshi; Kodama, Takahiro; Shimizu, Satoshi; Hikita, Hayato; Hiramatsu, Naoki; Kanto, Tatsuya [Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita 565-0871 (Japan); Hayashi, Norio [Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki 660-8511 (Japan); Takehara, Tetsuo, E-mail: takehara@gh.med.osaka-u.ac.jp [Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita 565-0871 (Japan)

    2011-08-19

    Highlights: {yields} HCV infection upregulated miR-192, -194, -215, downregulated miR-320, -491. {yields} Transfection of miR-192, -215, and -491 enhanced HCV replication. {yields} Transfection of miR-491 inhibited Akt phosphorylation. {yields} Akt inhibition could be responsible for augmentation of HCV replication by miR-491. -- Abstract: The aim of this study was to investigate the role of microRNA (miRNA) on hepatitis C virus (HCV) replication in hepatoma cells. Using miRNA array analysis, miR-192/miR-215, miR-194, miR-320, and miR-491 were identified as miRNAs whose expression levels were altered by HCV infection. Among them, miR-192/miR-215 and miR-491 were capable of enhancing replication of the HCV replicon as well as HCV itself. HCV IRES activity or cell proliferation was not increased by forced expression of miR-192/miR-215 or miR-491. Investigation of signaling pathways revealed that miR-491 specifically suppressed the phosphoinositol-3 (PI3) kinase/Akt pathway. Under inhibition of PI3 kinase by LY294002, the suppressive effect of miR-491 on HCV replication was abolished, indicating that suppression of HCV replication by miR-491 was dependent on the PI3 kinase/Akt pathway. miRNAs altered by HCV infection would then affect HCV replication, which implies a complicated mechanism for regulating HCV replication. HCV-induced miRNA may be involved in changes in cellular properties including hepatocarcinogenesis.

  1. Coinfection with HIV-1 alleviates iron accumulation in patients with chronic hepatitis C virus infection.

    Directory of Open Access Journals (Sweden)

    Yuan Liu

    Full Text Available Most chronically-infected hepatitis C virus (HCV patients have increased levels of iron in the liver. Iron overload reduces sustained responses to antiviral therapy, leading to more rapid progression to liver cirrhosis and the development of hepatocellular carcinoma. However, it is still unclear how HIV-1 infection affects iron status in patients chronically infected with HCV. The present study recruited 227 patients from a village in central China. These patients were either monoinfected with HCV (n = 129 or coinfected with HCV/HIV-1 (n = 98. Healthy controls (n = 84 were also recruited from the same village. Indicators of iron status, such as serum levels of iron, ferritin, and transferrin, total iron-binding capacity (TIBC, transferrin saturation (Tfs, and hepcidin, were analyzed and compared across the three groups. The results showed that serum levels of iron (p = 0.001 and ferritin (p = 0.009 and the Tfs (p = 0.002 were significantly higher in HCV-monoinfected patients than in the healthy controls; however, there were no differences in iron levels and Tfs between HCV/HIV-1 coinfected patients and healthy controls. Additionally, although serum hepcidin levels in HCV-monoinfected and HCV/HIV-1-coinfected patients were lower (p<0.001 than those in health controls, the levels in coinfected patients were higher (p = 0.025 than those in HCV-monoinfected patients. Serum iron and ferritin levels in HCV-monoinfected patients were positively correlated with serum ALT/AST. Serum transferrin levels were negatively correlated with ALT/AST levels. The levels of iron in the serum of coinfected patients with a CD4+T-cell count <500/µl were lower than those in patients with a CD4+T-cell count ≥500/µl, whereas serum hepcidin levels showed the opposite trend. Taken together, these results suggest that coinfection with HIV-1 alleviates iron accumulation caused by chronic HCV infection. Our study indicated that determining the

  2. Mortality in HIV-infected injection drug users with active vs cleared hepatitis C virus-infection: a population-based cohort study

    DEFF Research Database (Denmark)

    Omland, L H; Jepsen, P; Weis, N;

    2010-01-01

    Acute hepatitis C virus (HCV) infection may lead to chronic HCV-infection with detectable HCV RNA or to spontaneous clearance with no HCV RNA, but detectable HCV antibodies. It is unknown whether HCV RNA status is associated with mortality in HIV-infected injection drug users (IDUs). We conducted...... a nationwide population-based cohort study to examine the impact of HCV RNA status on overall and cause-specific mortality in HIV-infected IDUs. We computed cumulative mortality and used Cox Regression to estimate mortality rate ratios (MRR). We identified 392 HIV-infected patients of whom 284 (72%) had...... chronic HCV-infection (HCV RNA positive patients) and 108 (28%) had cleared the HCV-infection (HCV RNA negative patients). During 1286 person-years of observation (PYR), 157 persons died (MR = 122/1000 PYR, 95% CI: 104-143). The estimated 5-year probabilities of survival were 0.58 (95% CI: 0...

  3. HBV or HCV coinfections and risk of myocardial infarction in HIV-infected individuals: the D:A:D Cohort Study

    DEFF Research Database (Denmark)

    Weber, Rainer; Sabin, Caroline; Reiss, Peter;

    2010-01-01

    Data on a link between HCV or HBV infection and the development of cardiovascular disease among HIV-negative and HIV-positive individuals are conflicting. We sought to investigate the association between HBV or HCV infection and myocardial infarction in HIV-infected individuals.......Data on a link between HCV or HBV infection and the development of cardiovascular disease among HIV-negative and HIV-positive individuals are conflicting. We sought to investigate the association between HBV or HCV infection and myocardial infarction in HIV-infected individuals....

  4. Prevalence of HCV Infections and Co-Infection With HBV and HIV and Associated Risk Factors Among Addicts in Drug Treatment Centers, Lorestan Province, Iran

    Science.gov (United States)

    Norouzian, Hossein; Gholami, Mohammadreza; Shakib, Pegah; Goudarzi, Gholamreza; Ghobadian Diali, Hamze; Rezvani, Azam

    2016-01-01

    Background: Hepatitis C is an infectious disease caused by blood-borne pathogen, hepatitis C virus (HCV). Objectives: The purpose of this study was to investigate the prevalence of HCV infection and associated risk factors among addicts in drug treatment centers in Lorestan Province, Iran. Patients and Methods: A cross-sectional sero-behavioral survey was given to drug addicts in the drug treatment centers of Khorramabad, Lorestan Province, Iran during June 2012 - March 2013. Drug addicts were interviewed using a standard questionnaire including demographic, imprisonment history, and HCV-related risk behavior items. Thereafter, the sera drawn from the participants were tested for anti-HCV antibody (Ab), anti-human immunodeficiency virus (HIV) Ab, and hepatitis B surface antigen (HBsAg). Results: The mean age of the cohorts was 31.7. Up to 60.2% of drug users had educational levels less than high school, 67.5% were self-employed, and 32.5% were office workers. The mean duration of drug injection was 6.8 years. Statistical analyses indicated that the prevalence of HCV among drug addicts was positively associated with age, past incarceration, drug injection history, the duration of drug use, and tattooing. In addition, 16.23% of volunteers were HCV-positive. Of those infected with HCV, 1.10% was co-infected with HBV, 2.95% were positive for HIV, and 0.36% of HCV-positive cases were infected with all three viruses. Conclusions: The high prevalence of HCV infection among this group implies a high rate of transmission and exposure to the risk of serious diseases. It is important that the high prevalence of HCV infection be taken into consideration to control further transmission of this infection. PMID:27162762

  5. Risk Factors for Hepatitis C Virus (HCV) Infection in Areas with a High Prevalence of HCV in the Republic of Korea in 2013

    Science.gov (United States)

    Sohn, Hae-Sook; Kim, Jang Rak; Ryu, So Yeon; Lee, Youn-Jae; Lee, Myeong Jin; Min, Hyun Ju; Lee, Jun; Choi, Hwa Young; Song, Yeong Jun; Ki, Moran

    2016-01-01

    Background/Aims The prevalence of hepatitis C virus (HCV) infection in Busan, Gyeongnam, and Jeonnam Provinces in Korea is more than twice the national average. This study aimed to examine whether demographic and lifestyle characteristics are associated with HCV infection in these areas. Methods A case control study was performed at three study hospitals. HCV cases were matched with two controls for sex and age. Patient controls were selected from non-HCV patients at the same hospital. Healthy controls were subjects participating in medical checkups. Conditional logistic regression models were used. Results A total of 234 matched-case and patient- and healthy-control pairs were analyzed. The significant risk factors for both controls were sharing razors (adjusted odds ratio [aOR], 2.39 and 3.29, respectively) and having more than four lifetime sexual partners (aOR, 2.15 and 6.89, respectively). Contact dockworkers (aOR, 1.91) and tattoos (aOR, 2.20) were significant risk factors for the patient controls. Transfusion (aOR, 5.38), a bloody operation (aOR, 5.02), acupuncture (aOR, 2.08), and piercing (aOR, 5.95) were significant risk factors for the healthy controls. Needle stick injuries and intravenous drug abuse were significant in the univariate analysis. Conclusions More education concerning the dangers of sharing razors, tattoos and piercings is required to prevent HCV infection. More attention should be paid to needle stick injuries in hospitals and the community. PMID:26260752

  6. Alarming increase in tuberculosis and hepatitis C virus (HCV among HIV infected intravenous drug users

    Directory of Open Access Journals (Sweden)

    Cristiana Oprea

    2014-11-01

    Full Text Available Introduction: In the last years, we observed an alarming increase in the number of newly diagnosed HIV infected intravenous drug users (IDUs co-infected with hepatitis viruses or with severe bacterial infections. The aim of our study was to assess the incidence, the demographic and clinical characteristics of IDUs diagnosed with HIV, HCV and tuberculosis (TB. Materials and Methods: Prospective study on HIV infected IDUs with HCV and TB admitted in a single centre between January 2009 and April 2014. Data were compared to a group of HIV infected IDUs without TB. Statistical analysis was performed using Graphpad Prism 4.01. Results: Out of 450 HIV infected IDUs, 134 (29.7% were diagnosed with HIV, HCV and TB. TB incidence among IDUs increases from 0% in 2009 to 30.2% in 2013. The TB coinfected patients had a mean age at diagnosis of 30 [15–56] years; were in majority males, 106 (84.4%; from urban areas, 120 (89.5%; and had significantly lower education level (85% vs 68.3%, p<0.0001 and higher rates of unemployment (80% vs 55%, p<0.0001 than those without TB. The median CD4 cell count was lower in the TB versus non TB IDUs (143 vs 472/mm3, p<0.0001. TB infected IDUs tend to be more frequently late presenters (59.7 vs 24.6, p<0.0001 and to have advanced HIV disease (47.7 vs 7.59%, p<0.0001 than those without TB. TB cultures were positive in 64 (47.7% patients, 3 (2.2% had multidrug resistant TB and 2 (1.5% had extended drug resistance. Disseminated and/or extrapulmonary TB was diagnosed in 51 patients (38%. The overall mortality rate was higher in TB compared to non TB IDUs (19.4% vs 8.2%, p=0.0007, disseminated TB being associated with the most severe immunosuppression (median CD4 cell count 42/mm3 and the highest mortality rate (27.4%. Conclusions: The incidence of TB in HIV/HCV coinfected IDUs was high and rose over the time. TB infection was more frequent in patients with severe immunosuppression and the mortality rate was higher in IDUs with

  7. Infection with HIV and HCV enhances the release of fatty acid synthase into circulation: evidence for a novel indicator of viral infection

    Directory of Open Access Journals (Sweden)

    Aragonès Gerard

    2010-08-01

    Full Text Available Abstract Background Fatty acid synthase (FASN is an enzyme synthesized by the liver and plays an important role in lipogenesis. The present study aimed to investigate whether serum FASN concentration may provide a direct link between HIV and/or HCV viral infections and lipid metabolic disorders commonly observed in HIV/HCV-infected patients. Methods We evaluated serum FASN concentration in 191 consecutive HIV-infected patients in the absence or presence of HCV co-infection. For comparison, 102 uninfected controls were included. Metabolic and inflammatory phenotype was also compared with respect to the presence of HCV co-infection. Results Serum FASN concentration was significantly higher in HIV-infected patients than in healthy participants and HCV co-infected patients showed higher levels than those without co-infection. Levels were also affected by treatment regimen, but marginally influenced by virological variables. Insulin concentration was the sole variable among metabolic parameters that demonstrated a significant correlation with serum FASN concentrations. Serum alanine aminotransferase (ALT values correlated significantly with serum FASN concentration and provided the best discrimination with respect to the presence or absence of HCV co-infection. In multivariate analysis, only ALT, monocyte chemoattractant protein-1 (MCP-1 and the presence of antiretroviral treatment regimen significantly contributed to explain serum FASN concentration in HIV/HCV co-infected patients. Conclusion Serum FASN concentration is significantly increased in HIV-infected individuals. The release of FASN into the circulation is further enhanced in patients who are co-infected with HCV. Subsequent studies should explore the usefulness of this indicator to monitor the effect of viral infections on disease progression and survival.

  8. Dual daclatasvir and sofosbuvir for treatment of genotype 3 chronic hepatitis C virus infection.

    Science.gov (United States)

    Sundaram, Vinay; Kowdley, Kris V

    2016-01-01

    Chronic hepatitis C virus (HCV) infection is one of the most common etiologies of liver-related mortality throughout the world. Traditionally, therapy has been focused on pegylated interferon in combination with ribavirin, with clinical trials demonstrating that HCV genotype 1 had the lowest response rate (40-50%), while genotype 3 had an intermediate response rate (60-70%). Recently, significant advances have been made with all-oral direct-acting antiviral (DAA) therapy, which have significantly improved cure rates for HCV genotype 1. Accordingly, HCV genotype 3 is now potentially the most difficult to treat. One of the most potent DAA medications is sofosbuvir, a pan-genotypic nucleotide analogue that inhibits the NS5B polymerase of HCV. Daclatasvir, a pan-genotypic inhibitor of the HCV NS5A replication complex, was recently approved in the United States for treatment of HCV genotype 3 in conjunction with sofosbuvir. This combination may provide a powerful tool in the treatment of HCV genotype 3.

  9. HCV related glomerulonephritis induced by infection of HCV: one case report%HCV感染引起的HCV感染相关性肾炎1例报道

    Institute of Scientific and Technical Information of China (English)

    施理; 符健; 林锋; 贾杰; 陈所贤; 肖芙蓉

    2011-01-01

    One patient was infected with HCV by blood transfusion. The replication of HCV RNA was activated by prednisone accompanied with wores renal function. The membranous glomerulonephritis, mesangial proliferative glomerulonephritis associated with glomeruloscle-rosis, tubulointestinal chronic lesions, and thickening of the vessel wall inlima were observed. The patient was given with IFN combined with ribavirin.%患者因输血而感染HCV,在应用泼尼松治疗肾病同时,HCV复制激活,引起肾功能损害,肾病理检查提示膜型肾小球肾炎、系膜增生性病变伴肾小球硬化、肾小管-间质慢性病变及血管壁内膜增厚、肾组织有HCV抗体;给予IFNα 300万U隔日1次,皮下注射,联合利巴韦林0.3 mg,3次/d,疗程12个月,尿蛋白降低,肾功能改善,浮肿消退.

  10. A Potential Inhibitory Profile of Liver CD68+ Cells during HCV Infection as Observed by an Increased CD80 and PD-L1 but Not CD86 Expression

    Science.gov (United States)

    Said, Elias A.; Al-Reesi, Iman; Al-Riyami, Marwa; Al-Naamani, Khalid; Al-Sinawi, Shadia; Al-Balushi, Mohammed S.; Koh, Crystal Y.; Al-Busaidi, Juma Z.; Idris, Mohamed A.; Al-Jabri, Ali A.

    2016-01-01

    Aim The lack of potent innate immune responses during HCV infection might lead to a delay in initiating adaptive immune responses. Kupffer cells (KCs) and liver-infiltrating monocytes/macrophages (CD68+ cells) are essential to establish effective anti-HCV responses. They express co-stimulatory molecules, CD80 and CD86. CD86 upregulation induces activator responses that are then potentially regulated by CD80. The relative levels of expression of CD80, CD86 and the inhibitory molecule, PD-L1, on CD68+ cells modulate T cell activation. A few studies have explored CD80 and PD-L1 expression on KCs and infiltrating monocytes/macrophages in HCV-infected livers, and none investigated CD86 expression in these cells. These studies have identified these cells based on morphology only. We investigated the stimulatory/inhibitory profile of CD68+ cells in HCV-infected livers based on the balance of CD80, CD86 and PD-L1 expression. Methods CD80, CD86 and PD-L1 expression by CD68+ cells in the lobular and portal areas of the liver of chronic HCV-infected (n = 16) and control (n = 14) individuals was investigated using double staining immunohistochemistry. Results The count of CD68+ KCs in the lobular areas of the HCV-infected livers was lower than that in the control (p = 0.041). The frequencies of CD68+CD80+ cells and CD68+PD-L1+ cells in both lobular and total areas of the liver were higher in HCV-infected patients compared with those in the control group (p = 0.001, 0.031 and 0.007 respectively). Moreover, in the lobular areas of the HCV-infected livers, the frequency of CD68+CD80+ cells was higher than that of CD68+CD86+ and CD68+PD-L1+ cells. In addition, the frequencies of CD68+CD80+ and CD68+CD86+ cells were higher in the lobular areas than the portal areas. Conclusions Our results show that CD68+ cells have an inhibitory profile in the HCV-infected livers. This might help explain the delayed T cell response and viral persistence during HCV infection. PMID:27065104

  11. Is sustained virological response a marker of treatment efficacy in patients with chronic hepatitis C viral infection with no response or relapse to previous antiviral intervention?

    DEFF Research Database (Denmark)

    Gurusamy, Kurinchi S; Wilson, Edward; Koretz, Ronald L;

    2013-01-01

    Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs....

  12. HCV and HCC molecular epidemiology

    Directory of Open Access Journals (Sweden)

    Flor H. Pujol

    2007-02-01

    cirrhotic patients than for HBVinfected ones.

    HCV genotype 1b has also been more frequently associated with a more severe liver disease. However, this association seems to be due to the fact that individuals infected with this genotype have a longer mean duration of infection. An heterogeneity in the IFN sensitivity determining region (ISDR of HCV genotype 1b isolates has been observed in patients presenting with HCC, compared with the isolates of patients presenting with liver cirrhosis without HCC, which exhibit a more homogeneous ISDR region, although an opposite observation has been reported by others. Some nucleotides in the 5' non-coding region and specific amino acid substitutions within the entire HCV genome have been also found in the HCV strains infecting patients with HCC. Hepatic steatosis is a common consequence of HCV infection, particularly HCV genotype 3, and has been recently associated with the development of HCC. Steatosis might be contributing to the progression of fibrosis in HCV-related disease. More studies are needed to evaluate an eventual correlation between HCV genotype 3, the presence of steatosis, and progression to HCC.

    Even if it seems that an effective vaccine against HCV will not be readily obtained in the near future, available therapeutic approaches seem to delay the progression to HCC in infected patients who respond at least transiently to treatment. The evolution to HCC associated with infection by HCV seems to be a multifactor process. Although the role of chronic infection with HCV in the etiology of liver cancer is well established, more studies are needed to assess the individual contribution of specific viral strains in the development of HCC. The limited arsenal available against HCV (improving therapeutic agents is crucial since it might prevent or delay

  13. Frequency of Hepatitis B and C Co-Infection in Chronic Liver Disease Patients in Calabar, Cross River State, Nigeria.

    Science.gov (United States)

    Kooffreh-Ada, M; Okpokam, D C; Okaormhe, Z A; Nna, V U

    2016-01-01

    Hepatitis B (HBsAg) and C (HCV) virus are becoming a significant causative factors in the aetiology of chronic liver disease (CLD) worldwide. However, the information on the frequency of HBsAg and HCV virus co-infection in CLD is sparsely reported in Nigeria. In this study, we assessed the frequency of HBsAg and HCV co-infection in CLD. One hundred and eleven subjects aged 19 - 76 years, comprising of 76 CLD patients and 35 apparently healthy subjects without CLD were tested for both HBsAg and HCV virus antibodies using ELISA test kits. Out of the 111 subjects recruited for this study, 76 (68.5%) were CLD patients tested positive for HBsAg and 35 (31.5%) tested negative for HBsAg and served as control. Out of the 76 CLD patients that tested positive for HBsAg, 34 (44.7%) of them also tested positive for HCV, thus, having co-infection with HBV. Incidence of co-infection was highest in those aged 36 - 45 years, and greater in males than females. Among the control group, 4 (11.4%) of the subjects (3 males and 1 female) tested positive for HCV, while 31 (88.6%) subjects (20 males and 11 females) tested negative. This work has shown that the co-infection with HBV and HCV among chronic liver disease patients and the incidence of HCV is high in our locality. Also, some of the supposed apparently healthy subjects in this study tested positive for HCV, hence the need for improving the awareness of this virus. It is therefore necessary to give immunization and test for HBsAg and HCV in both rural and urban areas. PMID:27574763

  14. Genetic Markers of the Host in Persons Living with HTLV-1, HIV and HCV Infections

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    Tatiane Assone

    2016-02-01

    Full Text Available Human T-cell leukemia virus type 1 (HTLV-1, hepatitis C virus (HCV and human immunodeficiency virus type 1 (HIV-1 are prevalent worldwide, and share similar means of transmission. These infections may influence each other in evolution and outcome, including cancer or immunodeficiency. Many studies have reported the influence of genetic markers on the host immune response against different persistent viral infections, such as HTLV-1 infection, pointing to the importance of the individual genetic background on their outcomes. However, despite recent advances on the knowledge of the pathogenesis of HTLV-1 infection, gaps in the understanding of the role of the individual genetic background on the progress to disease clinically manifested still remain. In this scenario, much less is known regarding the influence of genetic factors in the context of dual or triple infections or their influence on the underlying mechanisms that lead to outcomes that differ from those observed in monoinfection. This review describes the main factors involved in the virus–host balance, especially for some particular human leukocyte antigen (HLA haplotypes, and other important genetic markers in the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP and other persistent viruses, such as HIV and HCV.

  15. PCR-Based Molecular Diagnosis of Hepatitis Virus (HBV and HDV) in HCV Infected Patients and Their Biochemical Study

    Science.gov (United States)

    Anwar, Muhammad Ayaz; Raheel, Ummar; Badshah, Yasmeen; Akhtar, Hashaam; Tamanna, Kosar; Tahir, Muhammad; Sadaf Zaidi, Najam us Sahar

    2016-01-01

    Seroprevalence of HCV indicates that HCV is found in more than 10% of HBV- or HDV-infected patients worldwide leading to liver disease. Here we show HBV and HDV coinfection association with HCV infected Pakistani patients, study of disease severity, and possible interpretation of associated risk factors in coinfected patients. A total of 730 liver diseased patients were included, out of which 501 were found positive for HCV infection via PCR. 5.1% of patients were coinfected with HBV while 1% were coinfected with HBV and HDV both. LFTs were significantly altered in dually and triply infected patients as compared to single HCV infection. Mean bilirubin, AST, and ALT levels were highest (3.25 mg/dL, 174 IU/L, and 348 IU/L) in patients with triple infection while dual infection LFTs (1.6 mg/dL, 61 IU/L, and 74 IU/L) were not high as in single infection (1.9 mg/dL, 76 IU/L, and 91 IU/L). The most prominent risk factor in case of single (22%) and dual infection (27%) group was “reuse of syringes” while in triple infection it was “intravenous drug users” (60%). It is concluded that HBV and HDV coinfections are strongly associated with HCV infected Pakistani patients and in case of severe liver disease the possibility of double and triple coinfection should be kept in consideration. PMID:27366331

  16. Occult HCV in Egyptian volunteer blood donors

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    Mostafa A. Amin 1, Kouka S. E. Abdel-Wahab 2 and Adel A.

    2013-01-01

    Full Text Available Objective: The study aims to investigate the risk of post-transfusion transmission of hepatitis c virus (HCV in the circumstances of occult HCV when anti-HCV is undetectable by ELISA and HCV-RNA is detected by RT-PCR in the plasma and or in peripheral blood mononuclear cells (PBMCs of donor blood and the recipients are immunocompromised. Patients & methods: The study covered 18 chronic renal failure patients (CRF [12 males (66.7% their age ranged from 28 to 65 years and 6 females (33.3 % their age ranged from 15 to 55 years] undergoing hemodialysis in Nile Hospital as part of their therapy have to receive blood transfusions (275 blood units for the first time. Commercial ELISA kits for anti-HCV and nested-RT-PCR (N-RT-PCR kits were used. Results: Anti-HCV was positive in one serum from the eighteen (5.5% poly transfused CRF patients at the end of the study while the seventeen sera were negative. This serum was also positive for HCV RNA by N-RT-PCR. Out of the 20 transfused blood units, one blood unit (three components were tested by blood banking anti-HCV negative by ELISA, were positive for HCV RNA by N-RT-PCR. The collective markers of this blood unit represent an occult HCV. The risk of acquiring post-transfusion HCV infection from an occult HCV blood unit is 5%. Real time PCR showed variation in the viral load of the serum of the infected CRF patient, the plasma of blood unit, the PBMCs of this blood unit whether activated by PHA-M or not.

  17. Losartan may inhibit the progression of liver fibrosis in chronic HCV patients

    Science.gov (United States)

    Salama, Zakaria A.; Sadek, Ahmed; Abdelhady, Ahmed M.; Morsy, Shereif Ahmed; Esmat, Gamal

    2016-01-01

    Background Abundant experimental evidence indicates overproduction of angiotensin II in the injured liver, and a role in stimulation of hepatic stellate cell (HSC) activation and fibrogenesis thereby, representing an attractive antifibrotic target. The aim of this study was to examine the antifibrotic effect of losartan on histopathologic level in chronic HCV patients. Methods A prospective study on fifty patients with chronic HCV and liver fibrosis proved by liver biopsy was conducted. They included patients who did not respond (n=36) or comply (n=2) or receive therapy due to established cirrhosis (n=10), or refused to receive (n=2) combined interferon and ribavirin therapy. They were divided randomly into 2 groups. The 1st group (n=25) was given losartan 50 mg OD for 1 year and the 2nd group (25 patients) was given silymarin, 140 mg t.i.d., (silymarin group). Liver biopsy was done at baseline and 1 year from the onset of treatment (end of study). Results In the second liver biopsy after 1 year, the decrease in fibrosis stage was significantly different between losartan group and silymarin group (a decrease of 1.88±0.96 (50.9%) vs. 0.45±0.93 (11.7%), respectively; P<0.01). In patients treated with losartan, regression in fibrosis stage was observed in 14/16 patients vs. 2/11 in silymarin group (P<0.01). No differences were observed in inflammation grades in both groups. A significant increase in albumin and prothrombin levels and a decrease in systolic blood pressure were found in losartan but not in silymarin group (P=0.009, 0.001 & 0.018 respectively and P=0.158, 0.603 & 0.288, respectively). Conclusions Histopathological scores showed that losartan had an inhibitory effect on progression and even led to regression of fibrosis stage but had no effect on the grade of inflammation. PMID:27275467

  18. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection

    DEFF Research Database (Denmark)

    Lanford, Robert E; Hildebrandt-Eriksen, Elisabeth S; Petri, Andreas;

    2010-01-01

    The liver-expressed microRNA-122 (miR-122) is essential for hepatitis C virus (HCV) RNA accumulation in cultured liver cells, but its potential as a target for antiviral intervention has not been assessed. We found that treatment of chronically infected chimpanzees with a locked nucleic acid (LNA...

  19. Sieroprevalenza di infezione da HBV e HCV tra pazienti in dialisi

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    Rosa Anna Leone

    2003-12-01

    Full Text Available The aim of the present study was to investigate the seroprevalence of HBV and HCV among dialysis patients in the Lamezia Terme (CZ area during the period 1999-2002. Sera from 63 patients in haemodialysis (HD and 10 patients in peritoneal dialysis (PD were analyzed with a follow-up every three months for HBsAg, HBcAb, HBsAb, anti-HCV and anti-HIV (Elisa Test,AxSYM,Abbott;we analyzed reactive sera for anti-HCV by using supplemental test (RIBA Test, Ortho; we also looked for viremia (RT-PCR Amplicor, Roche Diagnostics and HCV genotypes (Inno-Lipa HCV II, Innogenetics.The results show that, among the HD patients, 3 were HBsAg positive (Chronic Infection and 7 HBcAb and HBsAb positive/HBsAg negative (Passed Infection; 14 individuals were anti-HCV positive. No patients in PD were positive for HBV and HCV markers.The prevalence of chronic HBV infection was 4.8% (instead of 3% in other Dialysis Units, that of anti-HCV positive was 22% (in others 24%- 33%; among anti-HCV positive patients, the HCV-RNA prevalence was 79% (instead of 80%; the most recurrent HCV genotype was 2a/2c (instead of 1b in general population.These findings lead us to hypothesize that the environmental transmission in the dialysis setting is tightly correlated to the risk of HBV and HCV infection.

  20. Reduced IFNλ4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes

    DEFF Research Database (Denmark)

    Terczynska-Dyla, Ewa; Bibert, Stephanie; Duong, Francois H T;

    2014-01-01

    Hepatitis C virus (HCV) infections are the major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma worldwide. Both spontaneous and treatment-induced clearance of HCV depend on genetic variation within the interferon-lambda locus, but until now no clear causal relationship has...... of poor HCV clearance....

  1. HCV-Induced Oxidative Stress: Battlefield-Winning Strategy

    Science.gov (United States)

    Rebbani, Khadija; Tsukiyama-Kohara, Kyoko

    2016-01-01

    About 150 million people worldwide are chronically infected with hepatitis C virus (HCV). The persistence of the infection is controlled by several mechanisms including the induction of oxidative stress. HCV relies on this strategy to redirect lipid metabolism machinery and escape immune response. The 3β-hydroxysterol Δ24-reductase (DHCR24) is one of the newly discovered host markers of oxidative stress. This protein, as HCV-induced oxidative stress responsive protein, may play a critical role in the pathogenesis of HCV chronic infection and associated liver diseases, when aberrantly expressed. The sustained expression of DHCR24 in response to HCV-induced oxidative stress results in suppression of nuclear p53 activity by blocking its acetylation and increasing its interaction with MDM2 in the cytoplasm leading to its degradation, which may induce hepatocarcinogenesis. PMID:27293514

  2. Total and high molecular weight adiponectin and hepatocellular carcinoma with HCV infection.

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    Shuji Sumie

    Full Text Available BACKGROUND: Adiponectin is shown to be inversely associated with development and progression of various cancers. We evaluated whether adiponectin level was associated with the prevalence and histological grade of hepatocellular carcinoma (HCC, and liver fibrosis in patients with hepatitis C virus (HCV infection. METHODS: A case-control study was conducted on 97 HCC patients (cases and 97 patients (controls matched for sex, Child-Pugh grade and platelet count in patients with HCV infection. The serum total and high molecular weight (HMW adiponectin levels were measured by enzyme-linked immunosorbent assays and examined in their association with the prevalence of HCC. In addition, the relationship between these adiponectin levels and body mass index (BMI, progression of liver fibrosis, and histological grade of HCC was also evaluated. Liver fibrosis was assessed using the aspartate aminotransferase to platelet ratio index (APRI. RESULTS: There were no significant differences in the serum total and HMW adiponectin levels between cases and controls. Moreover, there were no inverse associations between serum total and HMW adiponectin levels and BMI in both cases and controls. On the other hand, serum total and HMW adiponectin levels are positively correlated with APRI in both cases (r = 0.491, P<0.001 and r = 0.485, P<0.001, respectively and controls (r = 0.482, P<0.001 and r = 0.476, P<0.001, respectively. Interestingly, lower serum total (OR 11.76, 95% CI: 2.97-46.66 [P<0.001] and HMW (OR 10.24, CI: 2.80-37.40 [P<0.001] adiponectin levels were independent risk factors of worse histological grade of HCC. CONCLUSIONS: Our results suggested that serum total and HMW adiponectin levels were predictors of liver fibrosis, but not prevalence of HCC in patients with HCV infection. Moreover, low these adiponectin levels were significantly associated with worse histological grades.

  3. Successful interferon desensitization in a patient with chronic hepatitis C infection

    Institute of Scientific and Technical Information of China (English)

    Seyed Alireza Taghavi; Ahad Eshraghian

    2009-01-01

    Treatment of hepatitis C, even when absolutely necessary, is almost impossible when interferon cannot be administered for any reason. We report a 65-year-old patient with chronic hepatitis C virus (HCV) infection and fibrosis, who was unable to receive interferon because of systemic hypersensitivity. The patient was desensitized successfully through gradual incremental exposure to interferon, and HCV infection was eradicated after a complete course of treatment,with no further allergic reactions. This case report that describes successful eradication of hepatitis C in a patient with advanced liver disease after desensitization to interferon revealed that desensitization may not necessarily damage the therapeutic efficacy of the drug.

  4. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965.

    Science.gov (United States)

    Smith, Bryce D; Morgan, Rebecca L; Beckett, Geoff A; Falck-Ytter, Yngve; Holtzman, Deborah; Teo, Chong-Gee; Jewett, Amy; Baack, Brittney; Rein, David B; Patel, Nita; Alter, Miriam; Yartel, Anthony; Ward, John W

    2012-08-17

    Hepatitis C virus (HCV) is an increasing cause of morbidity and mortality in the United States. Many of the 2.7-3.9 million persons living with HCV infection are unaware they are infected and do not receive care (e.g., education, counseling, and medical monitoring) and treatment. CDC estimates that although persons born during 1945-1965 comprise an estimated 27% of the population, they account for approximately three fourths of all HCV infections in the United States, 73% of HCV-associated mortality, and are at greatest risk for hepatocellular carcinoma and other HCV-related liver disease. With the advent of new therapies that can halt disease progression and provide a virologic cure (i.e., sustained viral clearance following completion of treatment) in most persons, targeted testing and linkage to care for infected persons in this birth cohort is expected to reduce HCV-related morbidity and mortality. CDC is augmenting previous recommendations for HCV testing (CDC. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47[No. RR-19]) to recommend one-time testing without prior ascertainment of HCV risk for persons born during 1945-1965, a population with a disproportionately high prevalence of HCV infection and related disease. Persons identified as having HCV infection should receive a brief screening for alcohol use and intervention as clinically indicated, followed by referral to appropriate care for HCV infection and related conditions. These recommendations do not replace previous guidelines for HCV testing that are based on known risk factors and clinical indications. Rather, they define an additional target population for testing: persons born during 1945-1965. CDC developed these recommendations with the assistance of a work group representing diverse expertise and perspectives. The recommendations are informed by the Grading of Recommendations Assessment, Development, and Evaluation

  5. A CCL5 Haplotype Is Associated with Low Seropositivity Rate of HCV Infection in People Who Inject Drugs.

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    Kristi Huik

    Full Text Available The role of CC chemokine receptor 5 (CCR5 and its ligand CCL5 on the pathogenesis of HIV infection has been well studied but not for HCV infection. Here, we investigated whether CCL5 haplotypes influence HIV and HCV seropositivity among 373 Caucasian people who inject drugs (PWID from Estonia.Study included 373 PWID; 56% were HIV seropositive, 44% HCV seropositive and 47% co-infected. Four CCL5 haplotypes (A-D were derived from three CCL5 polymorphisms (rs2107538/rs2280788/rs2280789 typed by Taqman allelic discrimination assays. The data of CCR5 haplotypes were used from our previous study. The association between CCL5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis.Possessing CCL5 haplotype D (defined by rs2107538A/rs2280788G/rs2280789C decreased the odds of HCV seropositivity compared to those not possessing it (OR = 0.19; 95% CI 0.09-0.40, which remained significant after adjustment to co-variates (OR = 0.08; 95% CI 0.02-0.29. An association of this haplotype with HIV seropositivity was not found. In step-wise logistic regression with backward elimination CCL5 haplotype D and CCR5 HHG*1 had reduced odds for HCV seropositivity (OR = 0.28 95% CI 0.09-0.92; OR = 0.23 95% CI 0.08-0.68, respectively compared to those who did not possess these haplotypes, respectively.Our results suggest that among PWID CCL5 haplotype D and CCR5 HHG*1 independently protects against HCV. Our findings highlight the importance of CCL5 genetic variability and CCL5-CCR5 axis on the susceptibility to HCV.

  6. Genetic diversity of near genome-wide hepatitis C virus sequences during chronic infection: evidence for protein structural conservation over time.

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    Hui Li

    Full Text Available Infection with hepatitis C virus (HCV is one of the leading causes of chronic hepatitis, liver cirrhosis and end-stage liver disease worldwide. The genetics of HCV infection in humans and the disease course of chronic hepatitis C are both remarkably variable. Although the response to interferon treatment is largely dependent on HCV genotypes, whether or not a relationship exists between HCV genome variability and clinical course of hepatitis C disease still remains unknown. To more thoroughly understand HCV genome evolution over time in association with disease course, near genome-wide HCV genomes present in 9 chronically infected participants over 83 total study years were sequenced. Overall, within HCV genomes, the number of synonymous substitutions per synonymous site (d(S significantly exceeded the number of non-synonymous substitutions per site (d(N. Although both d(S and d(N significantly increased with duration of chronic infection, there was a highly significant decrease in d(N/d(S ratio in HCV genomes over time. These results indicate that purifying selection acted to conserve viral protein structure despite persistence of high level of nucleotide mutagenesis inherent to HCV replication. Based on liver biopsy fibrosis scores, HCV genomes from participants with advanced fibrosis had significantly greater d(S values and lower d(N/d(S ratios compared to participants with mild liver disease. Over time, viral genomes from participants with mild disease had significantly greater annual changes in d(N, along with higher d(N/d(S ratios, compared to participants with advanced fibrosis. Yearly amino acid variations in the HCV p7, NS2, NS3 and NS5B genes were all significantly lower in participants with severe versus mild disease, suggesting possible pathogenic importance of protein structural conservation for these viral gene products.

  7. Therapeutic Vaccines for Chronic Infections

    Science.gov (United States)

    Autran, Brigitte; Carcelain, Guislaine; Combadiere, Béhazine; Debre, Patrice

    2004-07-01

    Therapeutic vaccines aim to prevent severe complications of a chronic infection by reinforcing host defenses when some immune control, albeit insufficient, can already be demonstrated and when a conventional antimicrobial therapy either is not available or has limited efficacy. We focus on the rationale and challenges behind this still controversial strategy and provide examples from three major chronic infectious diseases-human immunodeficiency virus, hepatitis B virus, and human papillomavirus-for which the efficacy of therapeutic vaccines is currently being evaluated.

  8. Treatment of Recurrent Hepatocellular Carcinoma with Sorafenib in a HIV/HCV Co-Infected patient in HAART: A Case Report

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    De Nardo Pasquale

    2012-06-01

    Full Text Available Abstract Background Liver disease is the second cause of death among HIV patients receiving highly active antiretroviral therapy (HAART in Europe. HIV patients have a high prevalence of chronic HBV (6–10% and HCV (33% co-infection, and accelerated progression of viral hepatitis. Furthermore, the long duration of both HIV and HCV diseases in the HAART era increases the risk of hepatocellular carcinoma. Findings We report the case of a 49 year -old HIV/HCV co-infected male patient who developed hepatocellular carcinoma. The patient underwent a partial hepatectomy, and a few months later was treated with transcatheter arterial chemoembolisation due to hepatocarcinoma recurrence. Two months later, advanced hepatocellular carcinoma was diagnosed and sorafenib therapy was initiated. The patient achieved partial response of the main lesions, complete regression of the smallest lesions and did not experience clinical progression during the 20-month follow-up period. During therapy with sorafenib, the patient was treated with HAART with good viral and immunological responses. We used the therapeutic drug monitoring to assess antiretroviral concentrations during co-administration of sorafenib. Fosamprenavir Ctrough was found under the minimum level recommended by international guidelines. No grade 3 or 4 toxicities were observed. At month 20 of treatment, new liver lesions with portal vein thrombosis were diagnosed. After 28 months of sorafenib therapy, the patient deceased for severe liver insufficiency. Conclusions Sorafenib monotherapy demonstrated a marked delay in HCC disease progression in an HIV/HCV co-infected patient. Fosamprenavir Ctrough was found under the minimum level recommended by international guidelines, suggesting a possible interaction.

  9. "Assessment of Safety and Efficacy of Transjugular Liver Biopsy As a Diagnostic Method in Adult Patients with Congenital Bleeding Disorders with HCV Infection "

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    "M. Nassiri Toosi

    2004-06-01

    Full Text Available Background/Objectives: Liver biopsy in patients with congenital bleeding disorders (CBD and hepatitis C virus (HCV infection is still a challenge between risk of procedure and effect of biopsy result on management. Materials and Methods: We did transjugular liver biopsy (TJLB on 12 patients with CBD with chronic HCV infection and elevated liver enzymes to determine its safety, efficiency and therapeutic conse-quences. Results: All patients were men, with a median age of 29.5 years (14–54 years. Eleven patients had haemophilia A (10 severe, one moder-ate and one patient had factor XIII deficiency, with no titer of inhibitor. HCV genotyping was carried out with type 1a (7 patients, type 1b (2 patients, type 3 (2 patients and genotype 1a and 1b (1 patient. HIV and HBV co-infection was negative in all patients. We used the modified Ross needle with 100% transjugular access rate to the hepatic veins and 92% success rate in tissue obtaining. The specimen obtained was satisfactory but limited for histopathologic diagnosis in 54.5%. Mild hepatitis was revealed in 4 patients (36.4%, moderate hepatitis in 5 (45.4% and extended fibrosis or cirrhosis in 2 (18.2%. There were 2 procedure-related complications (16.6%. The major limitation of technique was low number of portal area in liver biopsies. Conclusion: TJLB with some limitations is useful in patients with CBD. Transjugular approach to liver biopsy is a safe and effective alternative to the percutaneous approach in patients with CBD and could be requested to determine their liver prognosis and considered for diagnostic liver biopsy prior to anti-HCV therapy.

  10. HCV replication in PBMC and its influence on interferon therapy

    Institute of Scientific and Technical Information of China (English)

    Guo-Zhong Gong; Li-Ying Lai; Yong-Fang Jiang; Yan He; Xian-Shi Su

    2003-01-01

    AIM: To study hepatic virus C (HCV) RNA and HCV proteinexpression in peripheral blood mononuclear cells (PBMCs)of patients with HCV infection, and explore the relationshipbetween the HCV RNA in the PBMCs and response tointerferon (IFN) therapy.METHODS: Type-specific primers were designed and RT-nested PCR was used to detect the plus- and minus- strandsof HCV RNA in PBMCs of 54 patients with HCV infection;Indirect immunofluorescence assay was applied to identifyHCVNS5 protein expression in PBMCs; 6 month-, 3 MU-IFNregiment was administrated to observe the responses toIFN in 35 chronic hepatitis C patients with different HCVRNA status in PBMCs.RESULTS: HCV plus strand RNA was found in 10 of 19(52.6 %) acute hepatitis C patients and 22 of 35 (62.9 %)chronic hepatitis C patients. HCV minus strand RNA wasdetected in 14 of 35 (40.0 %) chronic hepatitis C patients,but only one patient (5.3 %) with acute HCV infection wasfound to be minus HCV RNA positive. Though no HCV NS5protein expression was found in the examined 10 cases ofacute HCV infection, it was positive in 17 of 20 (85.0 %)chronic hepatitis C patients by indirect immunofluoresenceassay. There are significant differences of positive rate of theminus-strand and HCVNS5 protein between acute and chronichepatitis C groups(u=2.07, P<0.05and u=4.43, P<0.01respectively). The patients with minus-strand HCV RNAshowed a significantly lower 6-month sustained response (SR-6) to IFN compared to those without minus-strand HCVRNAin PBMCs (biologically 14.3 % vs 42.8 %, X2=4.12, P<0.05and virologically 7.1% vs23.9 %, X2=4.24, P<0.05).CONCLUSION: HCV is capable of infecting and replicatingin PBMCs, and HCVNS5 protein was expressed in PBMCs.The patients with minus strand HCV RNA in PBMCs showeda significantly lower 6-month sustained response to IFN,suggesting that minus-strand HCV RNA in PBMCs may beone of the factors influencing response to IFN therapy.

  11. Chronic Infection and Severe Asthma.

    Science.gov (United States)

    Carr, Tara F; Kraft, Monica

    2016-08-01

    Chronic bacterial infection is implicated in both the development and severity of asthma. The atypical bacteria Mycoplasma pneumoniae and Chlamydophila pneumoniae have been identified in the airways of asthmatics and correlated with clinical features such as adult onset, exacerbation risks, steroid sensitivity, and symptom control. Asthmatic patients with evidence of bacterial infection may benefit from antibiotic treatment directed towards these atypical organisms. Examination of the airway microbiome may identify microbial communities that confer risk for or protection from severe asthma. PMID:27401621

  12. Unique and differential protein signatures within the mononuclear cells of HIV-1 and HCV mono-infected and co-infected patients

    Directory of Open Access Journals (Sweden)

    Boukli Nawal M

    2012-09-01

    Full Text Available Abstract Background Pathogenesis of liver damage in patients with HIV and HCV co-infection is complex and multifactorial. Although global awareness regarding HIV-1/HCV co-infection is increasing little is known about the pathophysiology that mediates the rapid progression to hepatic disease in the co-infected individuals. Results In this study, we investigated the proteome profiles of peripheral blood mononuclear cells from HIV-1 mono-, HCV mono-, and HIV-1/HCV co-infected patients. The results of high-resolution 2D gel electrophoresis and PD quest software quantitative analysis revealed that several proteins were differentially expressed in HIV-1, HCV, and HIV-1/HCV co-infection. Liquid chromatography-mass spectrometry and Mascot database matching (LC-MS/MS analysis successfully identified 29 unique and differentially expressed proteins. These included cytoskeletal proteins (tropomyosin, gelsolin, DYPLSL3, DYPLSL4 and profilin-1, chaperones and co-chaperones (HSP90-beta and stress-induced phosphoprotein, metabolic and pre-apoptotic proteins (guanosine triphosphate [GTP]-binding nuclear protein Ran, the detoxifying enzyme glutathione S-transferase (GST and Rho GDP-dissociation inhibitor (Rho-GDI, proteins involved in cell prosurvival mechanism, and those involved in matrix synthesis (collagen binding protein 2 [CBP2]. The six most significant and relevant proteins were further validated in a group of mono- and co-infected patients (n = 20 at the transcriptional levels. Conclusions The specific pro- and anti- apoptotic protein signatures revealed in this study could facilitate the understanding of apoptotic and protective immune-mediated mechanisms underlying HIV-1 and HCV co-infection and their implications on liver disease progression in co-infected patients.

  13. HCV RNA decline in the first 24 hours exhibits high negative predictive value of sustained virologic response in HIV/HCV genotype 1 co-infected patients treated with peginterferon and ribavirin

    Science.gov (United States)

    Laufer, N; Bolcic, F; Rolón, MJ; Martinez, A; Reynoso, R; Pérez, H; Salomón, H; Cahn, P; Quarleri, J

    2011-01-01

    Summary Background Treatment with Peg-interferon and ribavirin (PEG-IFN/RBV) for HIV patients co-infected with hepatitis C virus (HCV) genotype 1 has suboptimal rates of response. Viral kinetics has emerged as one of the best prognostic factors of treatment outcome. Methods Twenty HIV/HCV genotype 1 co-infected patients in treatment with PEG-IFN/RBV, had blood drawn at baseline, 24h, 4, 12, 24, 48, and 72 weeks. HCV-RNA levels were evaluated at each time point. ROC curves were used to evaluate the log10 HCV-RNA decay at 24h that exhibits the best predictive value of achieving response. Genomic characterization of HCV NS5A at both interferon sensitivity-determining region (ISDR) and protein-kinase binding (PKRBD) domains were performed in order to evaluate its heterogeneity and association with 24h HCV-RNA decay and SVR. Results Non-responder patients exhibited a mean of 0.7log10 (SD 0.74log10) HCV-RNA decay at 24h, whereas responder-patients presented 1.6log10 (SD 0.28log10), p=0.04. A reduction in HCV viral load from baseline to 24h of 1.4log10, exhibited 3.1(SD 1.5) amino acids substitutions in ISDR and 4.8(SD 2.3) in PKRBD regions and 1.6(SD 0.7) and 2.4(SD1.3), respectively, in those patients presenting lower reduction in HCV-RNA. Conclusions HIV/HCV genotype 1 co-infected patients with a decrease in HCV-VL at 24h >1.4 log10 are more likely to achieve SVR when treated with PEG-IFN/RBV than those with lower levels of HCV-RNA decay. Along with other host-related and viral-related prognostic factors in HIV/HCV co-infected patients, this very early time point of evaluation could be of relevance in the management of HCV-specific treatment. PMID:21376083

  14. The molecular mimicry and its possible role in origin of false-positive results in HCV-infection testing

    Directory of Open Access Journals (Sweden)

    Benkovskaya L. K.

    2013-09-01

    Full Text Available The main reason for the false positive results of the detection of antibodies to HCV is considered the unspecific binding of the blood serum immunoglobulins with the components of the test-systems’ immunosorbent, what is observed in various pathologies. When considering the issues of diagnosis, prevention and treatment of infectious diseases examined the impact of antigenic heterogeneity and molecular mimicry. With regarding to hepatitis C this phenomenon more illustrated in terms of pathogenesis, autoimmune, extrahepatic lesions. This does not exclude the influence of antigenic mimicry on the specificity of serological tests for anti-HCV detection. Aim. Estimation the frequency of false-positive reactions of anti-HCV testing in patients with chronic somatic diseases and assessment of the antigenic mimicry’s role in their occurrence. Methods. Total anti-HCV, antibodies to the single viruses’ protein, and false positive sera antibodies’ interaction with microbial origin combinations (mimicrins were determined by ELISA. Mimicrins were separated from the cultural medium after cultivation Staphylococcus aureus, Micobacterium tuberculosis and Candida albicans. Results. Upon detection of anti-HCV in patients with chronic pathologies detected a significant number of false-positive results are more likely in patients with diabetes and among healthy individuals – in pregnant women.The majorities of false positive sera interacted with mimicrins. Conclusions. The antigenic crossings over between mimicrins and antibodies in the structure of false positive sera must be considered during the evaluation of the specific diagnostics’ results in the persons with different pathologic states.

  15. Interleukin-27 is differentially associated with HIV viral load and CD4+ T cell counts in therapy-naive HIV-mono-infected and HIV/HCV-co-infected Chinese.

    Directory of Open Access Journals (Sweden)

    Lai He

    Full Text Available Human Immunodeficiency Virus (HIV infection and the resultant Acquired Immunodeficiency Syndrome (AIDS epidemic are major global health challenges; hepatitis C virus (HCV co-infection has made the HIV/AIDS epidemic even worse. Interleukin-27 (IL-27, a cytokine which inhibits HIV and HCV replication in vitro, associates with HIV infection and HIV/HCV co-infection in clinical settings. However, the impact of HIV and HCV viral loads on plasma IL-27 expression levels has not been well characterized. In this study, 155 antiretroviral therapy-naïve Chinese were recruited. Among them 80 were HIV- and HCV-negative healthy controls, 45 were HIV-mono-infected and 30 were HIV/HCV-co-infected. Plasma level HIV, HCV, IL-27 and CD4+ number were counted and their correlation, regression relationships were explored. We show that: plasma IL-27 level was significantly upregulated in HIV-mono-infected and HIV/HCV-co-infected Chinese; HIV viral load was negatively correlated with IL-27 titer in HIV-mono-infected subjects whereas the relationship was opposite in HIV/HCV-co-infected subjects; and the relationships between HIV viral loads, IL-27 titers and CD4+ T cell counts in the HIV mono-infection and HIV/HCV co-infection groups were dramatically different. Overall, our results suggest that IL-27 differs in treatment-naïve groups with HIV mono-infections and HIV/HCV co-infections, thereby providing critical information to be considered when caring and treating those with HIV mono-infection and HIV/HCV co-infection.

  16. Monitoring renal function during combination therapy with telaprevir in HIV/HCV co-infected patients with advanced/fibrosis cirrhosis

    Directory of Open Access Journals (Sweden)

    Cinzia Puzzolante

    2014-11-01

    Full Text Available Introduction: Telaprevir (TVR plus peg interferon (PEG-IFN and ribavirin (RBV substantially increase treatment efficacy for genotype 1 chronic hepatitis C virus (HCV infection but data about its safety in HIV patients with cirrhosis are lacking. Our purpose was to evaluate estimated Glomerular Filtration Rates (eGFR variations during combination therapy in a difficult-to-treat HIV/HCV population with advanced fibrosis/cirrhosis through three different scores commonly used in clinical practice: CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease (MDRD scores (that consider gender, ethnicity, age, serum creatinine level [SCL] and MDRD 6 variable (that considers the previous parameters plus blood urea nitrogen and serum albumin. Second objective was to identify any association between creatinin clearance and haemoglobin (Hb variation during combination therapy. Materials and Methods: We conducted an observational retrospective study including 18 HIV/HCV patients attending our clinic who started combination therapy for HCV, including in the analysis the first 16 weeks of therapy. Treatment included TVR 1125 mg BID (twice a day for 12 weeks, PEG-IFN α-2a 180 mcg QW and RBV daily dose according to body weight (800 mg in individuals 75 kg. Advanced fibrosis was defined as Metavir score=F3 or Ishak 3–4 and cirrhosis was defined as Metavir score F4 or Ishak 5–6 assessed by liver biopsy or transient elastography respectively. P per trend were assessed to evaluate any change of SCL and eGFR (according to different formulas. Multilevel linear regression analysis was performed to estimate factors associated with reduction of Hb. Results: Baseline characteristics and HCV virological responses were collected. Figure 1 shows median SCL and eGFR trends across follow-up period: SCR p-per-trend was 0.28, for CKD-EPI was 0.50, for MDRD was 0.48, for MDRD-6 variables was 0.27. Hb trend was also assessed and a

  17. Incidence and predictors of cardiovascular disease, chronic kidney disease, and diabetes in HIV/HCV-coinfected patients who achieved sustained virological response.

    Science.gov (United States)

    Leone, S; Prosperi, M; Costarelli, S; Nasta, P; Maggiolo, F; Di Giambenedetto, S; Saracino, A; Di Pietro, M; Gori, A

    2016-09-01

    Data on the effects of sustained virologic response (SVR) to hepatitis C virus (HCV) therapy on the outcome of extrahepatic complications are scarce. We conducted this study to assess the impact of SVR on the occurrence of chronic kidney disease (CKD), diabetes mellitus (DM), and cardiovascular disease (CVD) in a cohort of human immunodeficiency virus (HIV)-infected patients. We analyzed coinfected HIV/HCV patients in the Management of Standardized Evaluation of Retroviral HIV Infection (MASTER) cohort. Only event-free patients with a serum HCV-RNA determination at baseline were included. Patients were divided into four groups: INF-exposed with SVR; INF-exposed without SVR; spontaneous HCV clearance; untreated viremic patients. We estimated the incidence of extrahepatic complications and employed Kaplan-Meier curves and Cox regression to assess the association of SVR/INF strata adjusted for a series of confounders. Data from 1676 patients were analyzed (20.29 % started an INF-based regimen). Overall, the incidence of CKD, DM, CVD, and death was 5.32 [95 % confidence interval (CI) 3.99-6.98], 10.13 (95 % CI 8.20-12.37), 6.79 (95 % CI 5.26-8.65), and 13.49 (95 % CI 11.29-16.0) per 1000 person-years of follow-up, respectively. In the Cox model for treated patients, SVR was not associated with a lower risk of CKD, DM, CVD, and death compared to non-SVR. Cirrhosis was significantly associated with a higher risk of CKD [hazard ratio (HR) 2.13; 95 % CI 1.06-4.31], DM (HR 3.48; 95 % CI 2.18-5.57), and death (HR 6.18; 95 % CI 4.1-9.31), but not of CVD (HR 1.14; 95 % CI 0.57-2.3). There are still many unknowns regarding the impact of SVR on the occurrence of extrahepatic complications in coinfected HIV/HCV patients. Further investigations are needed in order to elucidate the role of SVR as an independent prognostic factor for extrahepatic events. PMID:27272121

  18. Frequency of HCV infection and its genotypes among patients attending a liver clinic and voluntary blood donors in a rural area of Pakistan

    International Nuclear Information System (INIS)

    Objectives: To determine the frequency of Hepatitis C virus (HCV) infection and its genotypic distribution in a rural area of Sindh, Pakistan. Methodology: Retrospective study of patients attending the Free Liver Clinic (FLC), and investigated for detectable HCV antibodies (n=1638), and those screened for HCV infection prior to voluntary blood donation (n=804) at a teaching hospital, located in rural Sindh. All patients had HCV antibodies tested by ELISA. A total of 1022 patients, who tested 'reactive' to HCV antibodies, and who could financially afford to have HCV RNA tested by PCR, had their results analysed. A total of 200 patients also had their HCV genotyped and analysed. Results: Patients at FLC had a higher chance of being reactive for HCV antibodies, compared to voluntary blood donors (20% VS 14% - p = 0.004). HCV RNA was detectable in 904/1022 (88%) patients. Among type able genotypes, 125/166 (75%) had a single genotype, and 7 patients (4%) were infected with genotype 1, either alone (n=4) or in combination with 3a. Conclusions: One out of every five people tested in our FLC, and 14% of 'healthy' voluntary blood donors were seropositive for HCV antibodies. Genotype 1 is very rare in our region. (author)

  19. Occult HBV infection status among chronic hepatitis C and hemodialysis patients in Northeastern Egypt: regional and national overview

    Directory of Open Access Journals (Sweden)

    Mohamed Mandour

    2015-06-01

    Full Text Available INTRODUCTION: Occult hepatitis B infection (OBI is considered to be one of the major risks for patients suffering from end-stage renal disease (ESRD on regular hemodialysis (HD and patients with chronic hepatitis C virus (HCV infection. This study compared the prevalence of OBI among these two high-risk groups in the Suez Canal region, Northeastern Egypt, to obtain a better national overview of the magnitude of OBI in this region. METHODS: Serum samples were collected from 165 HD patients and 210 chronic HCV-infected patients. Anti-HCV antibody, hepatitis B surface antigen (HBsAg, total hepatitis B core (anti-HBc antibody, and hepatitis B surface antibody (anti-HBs were detected by enzyme-linked immunosorbent assay (ELISA. HCV RNA was detected using a quantitative real-time RT-PCR assay, and HBV was detected using a nested PCR. RESULTS: All patients were negative for HBsAg. A total of 49.1% and 25.2% of the patients in the HD and HCV groups, respectively, were anti-HBc-positive. In addition, more anti-HBs-positive patients were detected in the HD group compared to the HCV group (52.1% and 11.4%, respectively. Three cases were positive for HBV DNA in the HD group, while eighteen positive cases were detected in the HCV group. Both study groups showed significant differences in serum alanine aminotransferase (ALT and aspartate aminotransferase (AST level as well as anti-HBc, anti-HBs and HBV-DNA positivity. CONCLUSIONS: OBI was more prevalent among chronic HCV patients than HD patients in the Suez Canal region, Egypt, with rates of 8.5% and 1.8%, respectively. However, more precise assessment of this infection requires regular patient follow-up using HBV DNA detection methods.

  20. Effect of chronic hepatitis C virus infection on bone disease in postmenopausal women.

    LENUS (Irish Health Repository)

    Nanda, Kavinderjit S

    2012-02-01

    BACKGROUND & AIMS: Limited data are available on the contribution of chronic HCV infection to the development of bone disease in postmenopausal women. We studied whether women who acquired HCV infection through administration of HCV genotype 1b-contaminated anti-D immunoglobulin from a single source had decreased bone mineral density (BMD) or altered levels of bone turnover markers (BTMs), compared with women who spontaneously resolved infection or age-matched healthy controls. METHODS: From a cohort of postmenopausal Irish women, we compared BMD, determined by dual-energy x-ray absorptiometry, and a panel of BTMs in 20 women chronically infected with HCV (PCR(+)), 21 women who had spontaneously resolved infection (PCR(-)), and 23 age-matched healthy controls. RESULTS: Levels of BTMs and BMD were similar in PCR(+) and PCR(-) women and healthy age-matched controls. However, there was an increased frequency of fractures in PCR(+) (n = 6) compared with PCR(-) women (n = 0, P = .007). PCR(+) women with fractures were postmenopausal for a longer time (median, 15.5, range, 5-20 years vs 4.5, range, 1-20 years in PCR(+) women without fractures; P = .033), had lower BMD at the hip (0.79, range, 0.77-0.9 g\\/cm(2) vs 0.96, range, 0.81-1.10 g\\/cm(2); P = .007), and had a lower body mass index (23.7, range 21.2-28.5 kg\\/m(2) vs 25.6, range 22.1-36.6 kg\\/m(2); P = .035). There was no difference in liver disease severity or BTMs in PCR(+) women with or without fractures. CONCLUSIONS: Chronic HCV infection did not lead to discernable metabolic bone disease in postmenopausal women, but it might be a risk factor for bone fractures, so preventive measures should be introduced. To view this article\\'s video abstract, go to the AGA\\'s YouTube Channel.

  1. Antibody V(h repertoire differences between resolving and chronically evolving hepatitis C virus infections.

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    Vito Racanelli

    Full Text Available Despite the production of neutralizing antibodies to hepatitis C virus (HCV, many patients fail to clear the virus and instead develop chronic infection and long-term complications. To understand how HCV infection perturbs the antibody repertoire and to identify molecular features of antibody genes associated with either viral clearance or chronic infection, we sequenced the V(DJ region of naïve and memory B cells of 6 persons who spontaneously resolved an HCV infection (SR, 9 patients with a newly diagnosed chronically evolving infection (CE, and 7 healthy donors. In both naïve and memory B cells, the frequency of use of particular antibody gene subfamilies and segments varied among the three clinical groups, especially between SR and CE. Compared to CE, SR antibody genes used fewer VH, D and JH gene segments in naïve B cells and fewer VH segments in memory B cells. SR and CE groups significantly differed in the frequency of use of 7 gene segments in naïve B cell clones and 3 gene segments in memory clones. The nucleotide mutation rates were similar among groups, but the pattern of replacement and silent mutations in memory B cell clones indicated greater antigen selection in SR than CE. Greater clonal evolution of SR than CE memory B cells was revealed by analysis of phylogenetic trees and CDR3 lengths. Pauciclonality of the peripheral memory B cell population is a distinguishing feature of persons who spontaneously resolved an HCV infection. This finding, previously considered characteristic only of patients with HCV-associated lymphoproliferative disorders, suggests that the B cell clones potentially involved in clearance of the virus may also be those susceptible to abnormal expansion.

  2. Upregulation of SOCS-3 and PIAS-3 impairs IL-12-mediated interferon-gamma response in CD56 T cells in HCV-infected heroin users.

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    Li Ye

    Full Text Available BACKGROUND: CD56(+ T cells are abundant in liver and play an important role in host innate immunity against viral infections, including hepatitis C virus (HCV infection, a common infection among heroin abusers. We thus investigated the in vivo impact of heroin use or heroin use plus HCV infection on the CD56(+ T cell frequency and function. METHODOLOGY/PRINCIPAL FINDINGS: A total of 37 heroin users with (17 or without (20 HCV infection and 17 healthy subjects were included in the study. Although there was no significant difference in CD56(+ T cell frequency in PBMCs among three study groups, CD56(+ T cells isolated from the heroin users had significantly lower levels of constitutive interferon-gamma (IFN-gamma expression than those from the normal subjects. In addition, when stimulated by interleukin (IL-12, CD56(+ natural T cells from HCV-infected heroin users produced significantly lower levels of IFN-gamma than those from the normal subjects. This diminished ability to produce IFN-gamma by CD56(+ T cells was associated with the increased plasma HCV viral loads in the HCV-infected heroin users. Investigation of the mechanisms showed that although heroin use or heroin use plus HCV infection had little impact on the expression of the key positive regulators (IL-12 receptors, STAT-1, 3, 4, 5, JAK-2, and TYK-2 in IL-12 pathway, heroin use or heroin use plus HCV infection induced the expression of suppressor of cytokine signaling protein-3 (SOCS-3 and protein inhibitors of activated STAT-3 (PIAS-3, two key inhibitors of IL-12 pathway. CONCLUSION/SIGNIFICANCE: These findings provide compelling in vivo evidence that heroin use or heroin use plus HCV infection impairs CD56(+ T cell-mediated innate immune function, which may account for HCV infection and persistence in liver.

  3. The Irish paradigm on the natural progression of hepatitis C virus infection: an investigation in a homogeneous patient population infected with HCV 1b (review).

    LENUS (Irish Health Repository)

    Fanning, Liam J

    2012-02-03

    The aetiological agent of chronic hepatitis C is the hepatitis C virus. The hepatitis C virus is spread by parenteral transmission of body fluids, primarily blood or blood products. In 1989, after more than a decade of research, HCV was isolated and characterised. The hepatitis C viral genome is a positive-sense, single-stranded RNA molecule approximately 9.4 kb in length, which encodes a polyprotein of about 3100 amino acids. There are 6 main genotypes of HCV, each further stratified by subtype. In 1994, a cohort of women was identified in Ireland as having been iatrogenically exposed to the hepatitis C virus. The women were all young and exposed as a consequence of the receipt of HCV 1b contaminated anti-D immunoglobulin. The source of the infection was identified as an acutely infected female. As part of a voluntary serological screening programme involving 62,667 people, 704 individuals were identified as seropositive for exposure to the hepatitis C virus; 55.4% were found to be positive for the viral genome 17 years after exposure. Of these women 98% had evidence of inflammation, but surprisingly, a remarkable 49% showed no evidence of fibrosis. Clinicopathology and virological analysis has identified associations between viral load and the histological activity index for inflammation, and, between inflammation and levels of the liver enzyme alanine aminotransferase. Infection at a younger age appears to protect individuals from progression to advanced liver disease. Molecular analyses of host immunogenetic elements shows that particular class II human leukocyte associated antigen alleles are associated with clearance of the hepatitis C virus. Additional class II alleles have been identified that are associated with stable viraemia over an extended period of patient follow-up. Although, investigation of large untreated homogeneous cohorts is likely to become more difficult, as the efficacy of anti-viral therapy improves, further investigation of host and viral

  4. Liver cancer and non-hodgkin lymphoma in hepatitis C virus-infected patients: results from the danvir cohort study

    DEFF Research Database (Denmark)

    Omland, Lars Haukali; Jepsen, Peter; Krarup, Henrik Bygum;

    2012-01-01

    Hepatitis C virus (HCV)-infection can cause hepatocellular carcinoma (HCC) and most likely non-Hodgkin lymphoma (NHL). No studies have compared the risk of these cancers between patients with chronic and cleared HCV-infection. The aim of this study was to estimate the 10-year risk of HCC and NHL...... in HCV-infected patients and to compare the risk of these cancers between HCV-infected patients and the general population in Denmark and between patients with chronic and cleared HCV-infection. Nationwide cohorts were used: 11,975 HCV-infected patients in the DANVIR cohort and 71,850 individuals from...

  5. Association of Sjögrens Syndrome in Patients with Chronic Hepatitis Virus Infection: A Population-Based Analysis

    Science.gov (United States)

    Yeh, Chih-Ching; Wang, Wen-Chang; Wu, Chien-Sheng; Sung, Fung-Chang; Su, Chien-Tien; Shieh, Ying-Hua; Chang, Shih-Ni; Su, Fu-Hsiung

    2016-01-01

    Objective The association between Sjögren’s syndrome (SS) and chronic hepatitis virus infection is inconclusive. Hepatitis B (HBV) and hepatitis C virus (HCV) infections are highly prevalent in Taiwan. We used a population-based case-control study to evaluate the associations between SS and HBV and HCV infections. Materials and Methods We identified 9,629 SS patients without other concomitant autoimmune diseases and 38,516 sex- and age-matched controls without SS from the Taiwan National Health Insurance claims data between 2000 and 2011. We utilized multivariate logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between SS and HBV and HCV infections. Sex- and age-specific (<55 and ≥55 years) risks of SS were evaluated. Results The risk of SS was higher in patients with HCV than in those without chronic viral hepatitis (OR = 2.49, 95% CI = 2.16–2.86). Conversely, HBV infection was not associated with SS (OR = 1.10, 95% CI = 0.98–1.24). Younger HCV patients were at a higher risk for SS (<55 years: OR = 3.37, 95% CI = 2.62–4.35; ≥55 years: OR = 2.20, 95% CI = 1.84–2.62). Men with HCV were at a greater risk for SS (women: OR = 2.26, 95% CI = 1.94–2.63; men: OR = 4.22, 95% CI = 2.90–6.16). Only men with chronic HBV exhibited a higher risk of SS (OR = 1.61, 95% CI = 1.21–2.14). Conclusion HCV infection was associated with SS; however, HBV only associated with SS in men. PMID:27560377

  6. Efficacy of sofosbuvir-based therapies in HIV/HCV infected patients and persons who inject drugs.

    Science.gov (United States)

    Puoti, Massimo; Panzeri, Claudia; Rossotti, Roberto; Baiguera, Chiara

    2014-12-15

    In the era of Directly Acting anti HCV Antivirals treatment of hepatitis C is successful in the majority of persons treated. However, treatment of persons with HIV or who inject drugs remains challenging because of special issues: drug-drug interactions with antiretroviral, psychiatric and drug substitution therapies, treatment adherence, impact of treatment on HIV disease course or on risk of bacterial infections. Sofosbuvir induced sustained virologic response in 91% of 23 HIV/HCV coinfected persons treated in combination with ribavirin and pegylated interferon, in 83% of 497 treated in combination with ribavirin and in all 50 patients infected with HCV GT1 treated in combination with ledipasvir and ribavirin. The rates of efficacy in HCV-HIV coinfected were almost the same as those observed in HCV monoinfected suggesting that the efficacy of sofosbuvir is not reduced by HIV coinfection. There are no data on the efficacy of sofosbuvir in injection drugs users. The pangenotypic activity, the high barrier to resistance, the modest potential for drug-drug interactions makes sofosbuvir a reference drug for the treatment of these two special populations.

  7. High dead-space syringes and the risk of HIV and HCV infection among injecting drug users.

    Science.gov (United States)

    Zule, William A; Bobashev, Georgiy

    2009-03-01

    This study examines the association between using and sharing high dead-space syringes (HDSSs)--which retain over 1000 times more blood after rinsing than low dead-space syringes (LDSSs)--and prevalent HIV and hepatitis C virus (HCV) infections among injecting drug users (IDUs). A sample of 851 out-of-treatment IDUs was recruited in Raleigh-Durham, North Carolina, between 2003 and 2005. Participants were tested for HIV and HCV antibodies. Demographic, drug use, and injection practice data were collected via interviews. Data were analyzed using multiple logistic regression analysis. Participants had a mean age of 40 years and 74% are male, 63% are African American, 29% are non-Hispanic white, and 8% are of other race/ethnicity. Overall, 42% of participants had ever used an HDSS and 12% had shared one. HIV prevalence was 5% among IDUs who had never used an HDSS compared with 16% among IDUs who had shared one. The HIV model used a propensity score approach to adjust for differences between IDUs who had used an HDSS and those who had never used one. The HCV models included all potential confounders as covariates. A history of sharing HDSSs was associated with prevalent HIV (odds ratio=2.50; 95% confidence interval=1.01, 6.15). Use and sharing of HDSSs were also associated with increased odds of HCV infection. Prospective studies are needed to determine if sharing HDSSs is associated with increased HIV and HCV incidence among IDUs.

  8. The preliminary efficacy of interferon-α and ribavirin combination treatment of chronic hepatitis C in HIV-infected patients

    Institute of Scientific and Technical Information of China (English)

    ZHENG Yu-huang; ZHANG Chun-ying; HE Yan; ZHOU Hua-ying; ZOU Wen; DING Pei-pei; HUANG Li; LI Hui

    2005-01-01

    Background It is internationally accepted that in drug-nave individuals with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection, chronic hepatitis C should be treated first if the CD4 cell count does not require the initiation of anti-retroviral therapy. Present paper evaluated the clinical effect and side-effect of interferon-α (IFN-α) and ribavirin (RBV) combination therapy for Chinese patients with HCV-HIV co-infection, and compared with them for HIV infection alone. Methods Ten patients with HCV-HIV and 17 patients with HCV received 5 million unit IFNα-2b every other day intramuscularly, and 300 mg RBV triple daily by oral. Dynamic observations were made for HCV RNA and HIV RNA loads, CD4+ and CD8+ T lymphocyte counts, liver function and blood cell measurement, and the medicine side-effects. Results After 12-week and 24-week treatments of IFN-α and RBV combination therapy, mean HCV RNA levels reduced 1.14 logs and 1.56 logs from the baseline at week 0 in HCV-HIV co-infection, and reduced 1.48 logs and 1.75 logs in HCV infection, respectively. The HIV RNA levels decreased 1.22 logs and 1.32 logs from the base line; however, there were no obvious different changes at T lymphocyte counts of HCV-HIV and HCV patients through 24-week treatments. Whole 27 patients showed satisfactory biochemical response to therapy. There were some mild or mediate influence-like symptoms, intestinal uncomfortable and depressed blood cell counts in early stage of the treatments. No neuropsychiatric and auto-immune disorders were found. Conclusions IFN-α and RBV combination therapy had similar anti-HCV effects during 24-week treatment for HCV-HIV and HCV infected Chinese patients, and some anti-HIV effect. There were no obvious different biochemical responses and side-effects between two groups above.

  9. Insulin resistance is associated with hepatocellular carcinoma in chronic hepatitis C infection

    Institute of Scientific and Technical Information of China (English)

    Chao-Hung; Hung; Jing-Houng; Wang; Tsung-Hui; Hu; Chien-Hung; Chen; Kuo-Chin; Chang; Yi-Hao; Yen; YuanHung; Kuo; Ming-Chao; Tsai; Chuan-Mo; Lee

    2010-01-01

    AIM:To elucidate the role of insulin resistance(IR) and serum adiponectin level in hepatocellular carcinoma(HCC) associated with chronic hepatitis C.METHODS:Clinical and biochemical characteristics were collected from 165 consecutive patients with newly diagnosed HCC.Homeostasis model assessment of IR(HOMA-IR) and serum adiponectin level were investigated in 188 patients with different stages of hepatitis C virus(HCV) infection.RESULTS:Among HCC patients,type 2 diabetics(DM) was more prevalent in HCV subjec...

  10. CD4+ T-lymphocyte telomere length is related to fibrosis stage, clinical outcome and treatment response in chronic hepatitis C virus infection.

    OpenAIRE

    FLETCHER, JEAN

    2010-01-01

    PUBLISHED BACKGROUND & AIMS: Increasing age is associated with impaired immune function and in chronic HCV infection specifically, with progressive fibrosis, liver failure, HCC and impaired responses to antiviral therapy. T-lymphocyte telomere length declines with age. We hypothesised that shorter T-lymphocyte telomere length would be associated with poor clinical outcome in HCV infection. METHODS: Circulating T-lymphocyte telomere length, an objective measure of immune senescence, was...

  11. HCV genotyping using statistical classification approach

    Directory of Open Access Journals (Sweden)

    Norris Ellie D

    2009-07-01

    Full Text Available Abstract The genotype of Hepatitis C Virus (HCV strains is an important determinant of the severity and aggressiveness of liver infection as well as patient response to antiviral therapy. Fast and accurate determination of viral genotype could provide direction in the clinical management of patients with chronic HCV infections. Using publicly available HCV nucleotide sequences, we built a global Position Weight Matrix (PWM for the HCV genome. Based on the PWM, a set of genotype specific nucleotide sequence "signatures" were selected from the 5' NCR, CORE, E1, and NS5B regions of the HCV genome. We evaluated the predictive power of these signatures for predicting the most common HCV genotypes and subtypes. We observed that nucleotide sequence signatures selected from NS5B and E1 regions generally demonstrated stronger discriminant power in differentiating major HCV genotypes and subtypes than that from 5' NCR and CORE regions. Two discriminant methods were used to build predictive models. Through 10 fold cross validation, over 99% prediction accuracy was achieved using both support vector machine (SVM and random forest based classification methods in a dataset of 1134 sequences for NS5B and 947 sequences for E1. Prediction accuracy for each genotype is also reported.

  12. Seven-years follow-up on trial of Interferon alpha in patients with HCV RNA positive chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Bao Zhang Tang; Lin Zhuarg; Jing You; Hong Bing Zhang; Lu Zhang

    2000-01-01

    AIM To study the long-term efficiency of therapy with Interferon alpha (IFN-a) in patients with HCVRNA positive chronic hepatitis C.METHODS Ten patients were enrolled in the study, whose age 31 -62 years (mean 53 years), course 6- 72months (mean 24 months), of whom, 6 patients with mild CHC, 4 moderate CHC. All patients receivedIFN-a 3 MU three times weekly for six to twelve months, and then followed up for seven years after the endof treatment. The results of hepatic functions and HCV RNA at the end of treatment and follow-up period inall patients were observed.RESULTS ( At the end of treatment, clinical symptoms recovered obviously in all patients, virologicalresponse (defined as HCV RNA loss) occurred in 5 of 7 (71.4%) patients (60 years old). At the end of follow-up, the rates of HCV RNA loss were 42.9% (3/7)and 33.3% (1/3), respectively, in these group. Virological sustained response (defined as HCV RNA loss atthe end of treatment and follow-up) occurred in 3 of 6 (50%) patients (6 - 12 month-course) and in 1 of 4(25%) patients (> 12 month-course). A sustained HCV RNA response was observed in 2 of 7 (28.6%)patients with IFN-a therapy for 6m and in 2 of 3 (66.7%) patients with IFN-a therapy for more than 6 m. Ofall patients, 4 patients with sustained HCV RNA response were mild CHC, 4 patients with sustained HCVRNA positive were mild CHC (2 patients), moderate CHC (2 patients), respectively; other 2 patients withHCV RNA loss at the end of treatment but recurred at the end of follow-up, were moderate CHC. ②Biochemically sustained response (defined as ALT normalization at the end of treatment and follow-up) wasobserved in 5 out of 10 (50%) patients, and these 5 patients were mild CHC, of whom, 4 patients with HCVRNA sustained negative, 1 patient with HCV RNA loss and then recurred again. Two patients with ALTnormalization at the end of follow-up were one mild CHC, one moderate CHC, respectively. Other 3patients with no response were moderate CHC, of whom, 2

  13. NS3 Resistance-Associated Variants (RAVs) in Patients Infected with HCV Genotype 1a in Spain

    Science.gov (United States)

    Jimenez-Sousa, María Ángeles; Gutiérrez-Rivas, Mónica; Álvaro-Meca, Alejandro; García-Álvarez, Mónica; Harrigan, P. Richard; Fedele, Cesare Giovanni; Briz, Verónica

    2016-01-01

    Background Resistance-associated variants have been related to treatment failure of hepatitis C virus (HCV) therapy with direct-acting antiviral drugs. The aim of our study was to analyze the prevalence of clinically relevant resistance-associated variants within NS3 in patients infected with HCV genotype 1a (GT1a) in Spain. Methods We performed a cross-sectional study on 2568 patients from 115 hospitals throughout Spain (2014–2015). The viral NS3 protease gene was amplified by nested polymerase chain reaction and sequenced by Sanger sequencing using an ABI PRISM 377 DNA sequencer. Additionally, clade information for genotype 1a was obtained by using the software geno2pheno (http://hcv.geno2pheno.org/). Results In total, 875 out of 2568 samples were from human immunodeficiency virus (HIV)/HCV-coinfected patients. Q80K was the main RAV found in our patients (11.1%) and the rest of the resistance-associated variants had a lower frequency, including S122G (6.23%), T54S (3.47%), V55A (2.61%), and V55I (2.15%), which were among the most frequent after Q80K. Overall, 286 samples had the Q80K polymorphism (11.1%) and 614 (23.9%) were GT1a clade I. HIV/HCV-coinfected patients had a higher frequency of Q80K and GT1a clade I than HCV-monoinfected patients (12.9% vs. 9.6% [p = 0.012] and 28.5% vs. 21.4% [p<0.001], respectively). Both the prevalence of Q80K and GT1a clade I were not uniform throughout the country (p<0.001), which ranged from 7.3%-22.2% and 15.7%-42.5%, respectively. The frequency of the Q80K polymorphism was far higher in patients infected with GT1a clade I than in patients infected with GT1a clade II (41.5% vs. 1.6%; p<0.001). Conclusions The prevalence of most resistance-associated variants in NS3 was low in patients infected with HCV GT1a in Spain, except for Q80K (11.1%), which was also notably higher in HIV/HCV-coinfected patients. The vast majority of Q80K polymorphisms were detected in GT1a clade I. PMID:27685471

  14. Chronic hepatitis C: latest treatment options.

    Science.gov (United States)

    Iosue, Kathleen

    2002-04-01

    The most common chronic bloodborne infection in the United States, hepatitis C virus (HCV) is the most frequent reason for liver transplantation. Unfortunately, most infected individuals don't realize they're HCV positive and only discover the disease after severe liver damage has occurred. Here, update your knowledge on the epidemiology, transmission and risk factors, diagnosis, clinical presentation, and management of chronic HCV. Insight on counseling and quality of life issues for infected patients is also included. PMID:11984417

  15. The Novel Cyclophilin Inhibitor CPI-431-32 Concurrently Blocks HCV and HIV-1 Infections via a Similar Mechanism of Action.

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    Philippe A Gallay

    Full Text Available HCV-related liver disease is the main cause of morbidity and mortality of HCV/HIV-1 co-infected patients. Despite the recent advent of anti-HCV direct acting antivirals (DAAs, the treatment of HCV/HIV-1 co-infected patients remains a challenge, as these patients are refractory to most therapies and develop liver fibrosis, cirrhosis and liver cancer more often than HCV mono-infected patients. Until the present study, there was no suitable in vitro assay to test the inhibitory activity of drugs on HCV/HIV-1 co-infection. Here we developed a novel in vitro "co-infection" model where HCV and HIV-1 concurrently replicate in their respective main host target cells--human hepatocytes and CD4+ T-lymphocytes. Using this co-culture model, we demonstrate that cyclophilin inhibitors (CypI, including a novel cyclosporin A (CsA analog, CPI-431-32, simultaneously inhibits replication of both HCV and HIV-1 when added pre- and post-infection. In contrast, the HIV-1 protease inhibitor nelfinavir or the HCV NS5A inhibitor daclatasvir only blocks the replication of a single virus in the "co-infection" system. CPI-431-32 efficiently inhibits HCV and HIV-1 variants, which are normally resistant to DAAs. CPI-431-32 is slightly, but consistently more efficacious than the most advanced clinically tested CypI--alisporivir (ALV--at interrupting an established HCV/HIV-1 co-infection. The superior antiviral efficacy of CPI-431-32 over ALV correlates with its higher potency inhibition of cyclophilin A (CypA isomerase activity and at preventing HCV NS5A-CypA and HIV-1 capsid-CypA interactions known to be vital for replication of the respective viruses. Moreover, we obtained evidence that CPI-431-32 prevents the cloaking of both the HIV-1 and HCV genomes from cellular sensors. Based on these results, CPI-431-32 has the potential, as a single agent or in combination with DAAs, to inhibit both HCV and HIV-1 infections.

  16. Hepatitis C virus infection and apoptosis

    Institute of Scientific and Technical Information of China (English)

    Richard Fischer; Thomas Baumert; Hubert E Blum

    2007-01-01

    Apoptosis is central for the control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection,enhanced hepatocyte apoptosis and upregulation of the death inducing ligands CD95/Fas, TRAIL and TNFα occur.Nevertheless, HCV infection persists in the majority of patients. The impact of apoptosis in chronic HCV infection is not well understood. It may be harmful by triggering liver fibrosis, or essential in interferon (IFN)induced HCV elimination. For virtually all HCV proteins,pro- and anti-apoptotic effects have been described,especially for the core and NS5A protein. To date, it is not known which HCV protein affects apoptosis in vivo and whether the infectious virions act pro- or antiapoptotic. With the availability of an infectious tissue culture system, we now can address pathophysiologically relevant issues. This review focuses on the effect of HCV infection and different HCV proteins on apoptosis and of the corresponding signaling cascades.

  17. Tumour Necrosis Factor-Alpha Gene Expression in Chronic Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Saadia Farid, Laila Rashid, Samya Swelam

    2013-04-01

    Full Text Available Objective: Tumour necrosis factor (TNF-alpha, a prototype proinflammatory cytokine, has been implicated as an important pathogenic mediator in a variety of liver conditions. Some genetic polymorphisms in the human TNF-alpha promoter region, such as the G-A transitions -308 and – 238, have been shown to influence TNF-alpha expression in chronic hepatitis C virus infection.Aim of the work: The present study was to investigate the influence that the – 308 and – 238 TNF- alpha promoter polymorphisms have on the response to interferon and ribavirin therapy in chronic hepatitis C virus infection.Patients and methods: One hundred forty patients with chronic hepatitis C virus infection, their age ranges between (20-56 years, selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, during interferon and ribavirin therapy and thirty five healthy individuals were included to serve as controls, the patients and controls were divided into two groups the first group forty patients and fifteen controls for the detection of TNF-alpha -308, -238 genotypes polymorphisms, the second group were one hundred patients and twenty healthy controls for the detection of serum levels of TNF-α. All the patients and controls were subjected to the following history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigation, CBCs and serological assay, genotyping of 308, 238 TNF-alpha promoter polymorphism and serum levels of TNF-α.Results: There was no statistically significant difference between chronic HCV patients and healthy controls as regarding TNF-alpha -238 different alleles.The frequencies of TNF-alpha gene polymorphism with A/G and G/G mutation at – 308 were significantly higher in chronic HCV patients than those in the controls. The serum level of TNF-alpha was markedly higher in the chronic HCV patients than in the healthy controls. There were

  18. Bioinformatics e Biostatistics applied to research in pediatric genetic disease. Clinical evidence in IFNλ4 polymorphisms associated with HCV infection in patients with beta thalassemia and WGCNA analysis weighted for IFNλ4 genotype rs12979860 to detect RPL9P18 as hub in HCV infected cell.

    OpenAIRE

    Marceddu, Giuseppe

    2015-01-01

    Genome-wide association studies have identified host genetic variation to be critical for spontaneous clearance and treatment response in patients infected with hepatitis C virus (HCV). We demonstrated the same in patients with thalassemia major infected by genotype 1b of HCV. In the present first part study we retrospectively analyzed 368 anti-HCV positive patients with beta-thalassemia in two Italian major thalassemic centers (Cagliari and Turin). The strongest IFNλ4 SN...

  19. PREVALENCE OF DIABETES MELLITUS TYPE 2 IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION

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    Ranjeet

    2015-01-01

    Full Text Available BACKGROUND: There is a growing body of literature on the relationship of Hepatitis C Virus (HCV infection and diabetes mellitus type 2 as its unique extrahepatic manifestation. This association was for the first time made by Allison et al. in 1994 . [1] Since then a number of observational studies have been published on the prevalence of diabetes in HCV infection and also the link between association of cirrhosis with diabetes mellitus. AIMS : To study the prevalence of diabetes mellitus type 2 in patients diagnosed to have chronic hepatitis C virus infection. To compare it with the prevalence of diabetes mellitus type 2 in general population. SETTINGS AND DESIGN : A case control study. Participants were the subjects attending the OPD / indoor of Sri Guru Ramdas Institute of Medical Sciences and Research, Amritsar. PATIENTS AND METHODS : 50 patients older than 18 years, with chronic HCV infection confirmed by ELISA, were investigated for their blood counts, LFTs, prothrombin time , serum proteins, glycosylated hemoglobin levels and abdominal ultrasonography after applying the exclusion criteria. Detailed clinical examination was done to assess for signs of encephalopathy and ascites. An equal number of age and sex matched , HCV seronegative patients with normal liver function tests were taken as controls. The prevalence of diabetes mellitus was then determined among the two groups. A relationship between HCV and Diabetes mellitus type 2 was then established. STATISTICAL ANALYSIS USED: Data was expressed as mean + SD. For categorical variables a chi square test was applied and p value was calculated. For the comparison of continuous data, the student t – test was used. Probability levels less than 0.05 were considered significant. RESULTS : 50% ( 25 out of 50 patients with chronic hepatitis C infection were diabetic while 30% (15 out of 50 of the controls were diabetic. The difference was statistically significant ( p=0.041 . Further , of the

  20. Evaluation of the Abbott Real Time HCV genotype II assay for Hepatitis C virus genotyping

    Science.gov (United States)

    Sariguzel, Fatma Mutlu; Berk, Elife; Gokahmetoglu, Selma; Ercal, Baris Derya; Celik, Ilhami

    2015-01-01

    Objective: The determination of HCV genotypes and subtypes is very important for the selection of antiviral therapy and epidemiological studies. The aim of this study was to evaluate the performance of Abbott Real Time HCV Genotype II assay in HCV genotyping of HCV infected patients in Kayseri, Turkey. Methods: One hundred patients with chronic hepatitis C admitted to our hospital were evaluated between June 2012 and December 2012, HCV RNA levels were determined by the COBAS® AmpliPrep/COBAS® TaqMan® 48 HCV test. HCV genotyping was investigated by the Abbott Real Time HCV Genotype II assay. With the exception of genotype 1, subtypes of HCV genotypes could not be determined by Abbott assay. Sequencing analysis was used as the reference method. Results: Genotypes 1, 2, 3 and 4 were observed in 70, 4, 2 and 24 of the 100 patients, respectively, by two methods. The concordance between the two systems to determine HCV major genotypes was 100%. Of 70 patients with genotype 1, 66 showed infection with subtype 1b and 4 with subtype 1a by Abbott Real Time HCV Genotype II assay. Using sequence analysis, 61 showed infection with subtype 1b and 9 with subtype 1a. In determining of HCV genotype 1 subtypes, the difference between the two methods was not statistically significant (P>0.05). HCV genotype 4 and 3 samples were found to be subtype 4d and 3a, respectively, by sequence analysis. There were four patients with genotype 2. Sequence analysis revealed that two of these patients had type 2a and the other two had type 2b. Conclusion: The Abbott Real Time HCV Genotype II assay yielded results consistent with sequence analysis. However, further optimization of the Abbott Real Time HCV Genotype II assay for subtype identification of HCV is required. PMID:26649001

  1. Pegylated interferon, ribavirin, and frequent supportive therapy with growth factors. Which pathogenesis for a severe psoriasis complicating the treatment of chronic HCV hepatitis?

    Directory of Open Access Journals (Sweden)

    Roberto Manfredi

    2009-12-01

    Full Text Available One of the most effective treatments for HCV and HBV infection is the combination of pegylated IFN-alpha and ribavirin. However, both IFN-alpha and ribavirin can induce hematologic toxicity, which can compromise treatment adherence and dose maintenance and could, therefore, influence outcomes. Hematopoietic growth factors (e.g. filgrastim can provide significant benefits in the treatment of this toxicity, but they can also exacerbate cutaneous psoriasis. We report a case of a 54-year-old woman with chronic, progressive hepatitis C, treated with long-term pegylated interferon plus ribavirin, associated with multiple cycles of filgrastim for a severe, recurring granulocytopenia. The patient developed an extensive and severe psoriasis, which improved only after specific treatment with cyclosporin. The case highlights the importance of treatment adherence and dose maintenance to obtain a sustained virologic response, and underlines the difficulties of the management of this disease when side effects, such as hematologic toxicity and psoriasis, are present.

  2. Historical epidemiology of hepatitis C virus (HCV) in selected countries

    DEFF Research Database (Denmark)

    Bruggmann, P; Berg, T; Øvrehus, A L H;

    2014-01-01

    Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained...... through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic...... countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity...

  3. Hepatic compartmentalization of exhausted and regulatory cells in HIV/HCV-coinfected patients.

    Science.gov (United States)

    Barrett, L; Trehanpati, N; Poonia, S; Daigh, L; Sarin, S Kumar; Masur, H; Kottilil, S

    2015-03-01

    Accelerated intrahepatic hepatitis C virus (HCV) pathogenesis is likely the result of dysregulation within both the innate and adaptive immune compartments, but the exact contribution of peripheral blood and liver lymphocyte subsets remains unclear. Prolonged activation and expansion of immunoregulatory cells have been thought to play a role. We determined immune cell subset frequency in contemporaneous liver and peripheral blood samples from chronic HCV-infected and HIV/HCV-coinfected individuals. Peripheral blood mononuclear cells (PBMC) and biopsy-derived liver-infiltrating lymphocytes from 26 HIV/HCV-coinfected, 10 chronic HCV-infected and 10 HIV-infected individuals were assessed for various subsets of T and B lymphocytes, dendritic cell, natural killer (NK) cell and NK T-cell frequency by flow cytometry. CD8(+) T cells expressing the exhaustion marker PD-1 were increased in HCV-infected individuals compared with uninfected individuals (P = 0.02), and HIV coinfection enhanced this effect (P = 0.005). In the liver, regulatory CD4(+) CD25(+) Foxp3(+) T cells, as well as CD4(+) CD25(+) PD1(+) T cells, were more frequent in HIV/HCV-coinfected than in HCV-monoinfected samples (P HIV infection (P ≤ 0.005 for all). Low CD8(+) expression was observed only in PD-1(+) CD8(+) T cells from HCV-infected individuals and healthy controls (P = 0.002) and was associated with enhanced expansion of exhausted CD8(+) T cells when exposed in vitro to PHA or CMV peptides. In conclusion, in HIV/HCV coinfection, ongoing HCV replication is associated with increased regulatory and exhausted T cells in the periphery and liver that may impact control of HCV. Simultaneous characterization of liver and peripheral blood highlights the disproportionate intrahepatic compartmentalization of immunoregulatory T cells, which may contribute to establishment of chronicity and hepatic fibrogenesis in HIV coinfection.

  4. Chronic hepatitis C virus infection: Prevalence of extrahepatic manifestations and association with cryoglobulinemia in Bulgarian patients

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To assess the prevalence of extrahepatic manifestations in Bulgarian patients with chronic hepatitis C virus (HCV) infection and identify the clinical and biological manifestations associated with cryoglobulinemia.METHODS: The medical records of 136 chronically infected HCV patients were reviewed to assess the prevalence of extrahepatic manifestations. Association between cryoglobulin-positivity and other manifestations were identified using χ2 and Fisher's exact test. Risk factors for the presence of extrahepatic manifestations were assessed by logistic regression analysis.RESULTS: Seventy six percent (104/136) of the patients had at least one extrahepatic manifestation.Clinical manifestations included fatigue (59.6%),kidney impairment (25.0%), type 2 diabetes (22.8%),paresthesia (19.9%), arthralgia (18.4%), palpable purpura (17.6%), lymphadenopathy (16.2%), pulmonary fibrosis (15.4%), thyroid dysfunction (14.7%), Raynaud's phenomenon (11.8%), B-cell lymphoma (8.8%),sicca syndrome (6.6%), and lichen planus (5.9%).The biological manifestations included cryoglobulin production (37.5%), thrombocytopenia (31.6%), and autoantibodies: anti-nuclear (18.4%), anti-smooth muscle (16.9%), anti-neutrophil cytoplasm (13.2%) and anti-cardiolipin (8.8%). All extrahepatic manifestations showed an association with cryoglobulin-positivity, with the exception of thyroid dysfunction, sicca syndrome,and lichen planus. Risks factors for the presence of extrahepatic manifestations (univariate analysis) were:age ≥ 60 years, female gender, virus transmission by blood transfusions, longstanding infection (≥ 20 years), and extensive liver fibrosis. The most significant risks factors (multivariate analysis) were longstanding infection and extensive liver fibrosis.CONCLUSION: We observed a high prevalence of extrahepatic manifestations in patients with chronic HCV infection. Most of these manifestations were associated with impaired lymphoproliferation and cryoglobulin production

  5. 不同HCV相关疾病患者血清抗HCV和HCV RNA检测的比较研究%Comparative Study on Detection of Serum anti-HCV and HCV RNA in HCV Related Diseases

    Institute of Scientific and Technical Information of China (English)

    刘伟平; 殷明刚

    2013-01-01

    目的::探讨不同HCV感染疾病患者血清抗HCV和HCV RNA的阳性率,以指导临床诊治相应疾病。方法:收集我院HCV感染患者血清标本共165例,采用ELISA法检测血清抗HCV,利用实时荧光定量PCR技术检测HCV RNA。结果:165例HCV感染患者血清抗HCV总阳性率为97.6%,高于HCV RNA阳性率(72.7%)(P<0.05)。肝硬化组和肝癌组HCV RNA阳性率分别为80.9%和82.9%,高于慢性丙型肝炎组阳性率(63.9%)(P<0.05)。结论:联合检测抗HCV和HCV RNA,有助于HCV感染相关疾病的临床诊断、疗效观察及预后判断。%Objective:The significance of testing serum anti-HCV and HCV RNA in HCV infection patients was discussed for guiding diagnosis and treatment of diseases.Methods:165 cases were collected from HCV infection patients.ELISA was used for assaying anti-HCV and real-time quantitative PCR was employed for determination of HCV RNA.Results:The total positive rate of serum anti-HCV(n=165) was 97.6%,which was higher than that of HCV RNA(72.7%).The positive rate of HCV RNA in liver cirrhosis and liver cancer group were 80.9%and 82.9%,respectively,higher than the one in chronic hepatitis C group 63.9%(P<0.05).Conclusion:The combination testing of anti-HCV and HCV RNA is helpful to the clinical diagnosis,observation of curative effect and prognosis judgment of HCV related diseases.

  6. Generalized Liver- and Blood-Derived CD8+ T-Cell Impairment in Response to Cytokines in Chronic Hepatitis C Virus Infection.

    Directory of Open Access Journals (Sweden)

    Stephanie C Burke Schinkel

    Full Text Available Generalized CD8+ T-cell impairment in chronic hepatitis C virus (HCV infection and the contribution of liver-infiltrating CD8+ T-cells to the immunopathogenesis of this infection remain poorly understood. It is hypothesized that this impairment is partially due to reduced CD8+ T-cell activity in response to cytokines such as IL-7, particularly within the liver. To investigate this, the phenotype and cytokine responsiveness of blood- and liver-derived CD8+ T-cells from healthy controls and individuals with HCV infection were compared. In blood, IL-7 receptor α (CD127 expression on bulk CD8+ T-cells in HCV infection was no different than controls yet was lower on central memory T-cells, and there were fewer naïve cells. IL-7-induced signalling through phosphorylated STAT5 was lower in HCV infection than in controls, and differed between CD8+ T-cell subsets. Production of Bcl-2 following IL-7 stimulation was also lower in HCV infection and inversely related to the degree of liver fibrosis. In liver-derived CD8+ T-cells, STAT5 activation could not be increased with cytokine stimulation and basal Bcl-2 levels of liver-derived CD8+ T-cells were lower than blood-derived counterparts in HCV infection. Therefore, generalized CD8+ T-cell impairment in HCV infection is characterized, in part, by impaired IL-7-mediated signalling and survival, independent of CD127 expression. This impairment is more pronounced in the liver and may be associated with an increased potential for apoptosis. This generalized CD8+ T-cell impairment represents an important immune dysfunction in chronic HCV infection that may alter patient health.

  7. Burden of disease and cost of chronic hepatitis C virus infection in Canada

    Science.gov (United States)

    Myers, Robert P; Krajden, Mel; Bilodeau, Marc; Kaita, Kelly; Marotta, Paul; Peltekian, Kevork; Ramji, Alnoor; Estes, Chris; Razavi, Homie; Sherman, Morris

    2014-01-01

    BACKGROUND: Chronic infection with hepatitis C virus (HCV) is a major cause of cirrhosis, hepatocellular carcinoma and liver transplantation. OBJECTIVE: To estimate the burden of HCV-related disease and costs from a Canadian perspective. METHODS: Using a system dynamic framework, the authors quantified the HCV-infected population, disease progression and costs in Canada between 1950 and 2035. Specifically, 36 hypothetical, ageand sex-defined cohorts were tracked to define HCV prevalence, complications and direct medical costs (excluding the cost of antivirals). Model assumptions and costs were extracted from the literature with an emphasis on Canadian data. No incremental increase in antiviral treatment over current levels was assumed, despite the future availability of potent antivirals. RESULTS: The estimated prevalence of viremic hepatitis C cases peaked in 2003 at 260,000 individuals (uncertainty interval 192,460 to 319,880), reached 251,990 (uncertainty interval 177,890 to 314,800) by 2013 and is expected to decline to 188,190 (uncertainty interval 124,330 to 247,200) in 2035. However, the prevalence of advanced liver disease is increasing. The peak annual number of patients with compensated cirrhosis (n=36,210), decompensated cirrhosis (n=3380), hepatocellular carcinoma (n=2220) and liver-related deaths (n=1880) are expected to occur between 2031 and 2035. During this interval, an estimated 32,460 HCV-infected individuals will die of liver-related causes. Total health care costs associated with HCV (excluding treatment) are expected to increase by 60% from 2013 until the peak in 2032, with the majority attributable to cirrhosis and its complications (81% in 2032 versus 56% in 2013). The lifetime cost for an individual with HCV infection in 2013 was estimated to be $64,694. CONCLUSIONS: Although the prevalence of HCV in Canada is decreasing, cases of advanced liver disease and health care costs continue to rise. These results will facilitate disease

  8. Hepatitis C Virus Serologic and Virologic Tests and Clinical Diagnosis of HCV-Related Liver Disease

    Directory of Open Access Journals (Sweden)

    2006-04-01

    Full Text Available The use of serological and virological tests has become essential in the management of hepatitis C virus (HCV infection in order to diagnose infection, guide treatment decisions and assess the virological response to antiviral therapy. Virological tools include serological assays for anti-HCV antibody detection and serological determination of the HCV genotype, and molecular assays that detect and quantify HCV RNA and determine the HCV genotype. Anti-HCV antibody testing and HCV RNA testing are used to diagnose acute and chronic hepatitis C. Only patients with detectable HCV RNA should be considered for pegylated interferon alfa and ribavirin therapy and the HCV genotype should be systematically determined before treatment, as it determines the indication, the duration of treatment, the dose of ribavirin and the virological monitoring procedure. HCV RNA monitoring during therapy is used to tailor treatment duration in HCV genotype 1 infection, and molecular assays are used to assess the end-of-treatment and, most importantly the sustained virological response, i.e. the endpoint of therapy.

  9. Is laparoscopy an advantage in the diagnosis of cirrhosis in chronic hepatitis C virus infection?

    Institute of Scientific and Technical Information of China (English)

    Perdita Wietzke-Braun; Felix Braun; Peter Schott; Giuliano Ramadori

    2003-01-01

    AIM: To evaluate the potential of laparoscopy in the diagnosis of cirrhosis and outcome of interferon treatment in HCV-infected patients.METHODS: In this retrospective study, diagnostic laparoscopy with laparoscopic liver biopsy was performed in 72 consecutive patients with chronic HCV infection. The presence or absence of cirrhosis was analyzed macroscopically by laparoscopy and microscopically by liver biopsy specimens. Clinical and laboratory data and outcome of interferon-alfa treatment were compared between cirrhotic and noncirrhotic patients.RESULTS: Laparoscopically, cirrhosis was seen in 29.2%(21/72) and non-cirrhosis in 70.8% (51/72) of patients.Cirrhotic patients were significantly older with a significant longer duration of HCV infection than noncirrhotic patients.Laboratory parameters (AST, y-GT, y-globulin fraction) were measured significantly higher as well as significantly lower (prothrombin index, platelet count) in cirrhotic patients than in non-cirrhotic patients. Histologically, cirrhosis was confirmed in 11.1% (8/72) and non cirrhosis in 88.9% (64/72). Patients with macroscopically confirmed cirrhosis (n=21) showed histologically cirrhosis in 38.1% (8/21) and histologically noncirrhosis in 61.9% (13/21). In contrast, patients with macroscopically non-cirrhosis (n=51) showed histologically non cirrhosis in all cases (51/51). Thirty-nine of 72 patients were treated with interferon-alfa, resulting in 35.9% (14/39)patients with sustained response and 64.1% (25/39) with non response. Non-responders showed significantly more macroscopically cirrhosis than sustained responders. In contrast, there were no significant histological differences between non-responders and sustained responders.CONCLUSION: Diagnostic laparoscopy is more accurate than liver biopsy in recognizing cirrhosis in patients with chronic HCV infection. Liver biopsy is the best way to assess inflammatory grade and fibrotic stage. The invasive marker for staging, prognosis and

  10. PNPLA 3 I148M genetic variant associates with insulin resistance and baseline viral load in HCV genotype 2 but not in genotype 3 infection

    Directory of Open Access Journals (Sweden)

    Rembeck Karolina

    2012-09-01

    Full Text Available Abstract Background Hepatic steatosis in HCV patients has been postulated as a risk factor associated with a higher frequency of fibrosis and cirrhosis. A single genetic variant, PNPLA3 I148M, has been widely associated with increased hepatic steatosis. Previous studies of the PNPLA3 I148M sequence variant in HCV infected individuals have reported an association between this variant and prevalence of steatosis, fibrosis, and cirrhosis. To evaluate the impact of PNPLA3 I148M variant on metabolic traits and treatment response in HCV genotype 2 and 3 infected patients. Methods Three hundred and eighty-two treatment naïve HCV genotype 2 or 3 infected patients were included in a phase III, open label, randomized, multicenter, investigator-initiated trial (the NORDynamIC study, in which pretreatment liver biopsies were mandatory. PNPLA3I148M genotyping was performed in a total of 359 Caucasian patients. Results In HCV genotype 2 infected patients carrying the PNPLA3 148M allele, there was significantly increased insulin resistance (P = 0.023 and lower viral load (P = 0.005 at baseline as well as the first seven days of antiviral treatment. These results were not observed in HCV genotype 3 infected patients. Conclusions Our results suggest a possible association between the PNPLA3 148M allele and insulin resistance as well as baseline viral load in HCV genotype 2, but not in genotype 3.

  11. Effect of alpha 2b interferon on inducement of mIL-2R and treatment of HCV in PBMC from patients with chronic viral hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Jian Wang; Gui-Ju Xiang; Bing-Xiang Liu

    2003-01-01

    AIM: To study the level of membrane interleukin-2 receptor (mIL-2R) on surface of peripheral blood mononuclear cells (PBMC) and the therapeutic efficacy of alpha 2b interferon on the treatment of HCV-RNA in PBMC of patients with chronic hepatitis C and to compare the negative rates of HCV-RNA in PBMC, HCV-RNA and anti-HCV in serum.METHODS: Before and after treatment of alpha 2b interferon, the level of mIL-2R of patients with chronic hepatitis C was detected by biotin-streptavidin (BSA). The therapeutic group (26 cases) was treated with alpha 2b interferon (3 MU/d) and control therapeutic group (22 cases)was treated with routine drugs (VitC, aspartic acid). The total course of treatment with alpha 2b interferon and routine drug was six months and per course of the treatment was three months. The levels of HCV-RNA in PBMC, HCV-RNA and anti-HCV in serum were detected before and after a course of the treatment.RESULTS: Before and after treatment of alpha 2b interferon and routine drugs, the levels of mIL-2R in silence stage were (3.44±0.77)% and (2.95±0.72)%, the levels of mIL-2R in inducement stage were (33.62±3.95)% and (30.04±3.73)%. There was a significant difference between two groups (P<0.01-P<0.05). After treatment of alpha 2b interferon with 3 MU/d for two courses of the treatment,the total negative rates of HCV-RNA in the PBMC and HCVRNA, anti-HCV in serum were 42.31% (11/26), 57.69%(15/26), 65.38%(17/26) respectively. After the treatment of routine drug, the negative rates of HCV-RNA in PBMC and HCV-RNA, anti-HCV in serum were 13.64% (3/22),22.73% (5/22), 27.27% (6/22) respectively. There was high significant difference in the group treated with alpha 2b interferon and the group treated with routine drugs (P<0.01-P<0.05).CONCLUSION: The mIL-2R can be induced by alpha 2b interferon during the treatment. The alpha 2b interferon has a definite effect on the treatment of HCV-RNA in PBMC.The curative effect of alpha 2b interferon is better than that

  12. Toxoplasma gondii infection among chronic hepatitis C patients:A case-control study

    Institute of Scientific and Technical Information of China (English)

    Hala A El-Nahas; Nora L El-Tantawy; Raghda E Farag; Argaya MA Alsalem

    2014-01-01

    Objective:To determine the detection rate of anti-Toxoplasma gondii(T. gondii)IgG and IgM in chronicHCV patients attending theDepartment ofTropicalMedicineMansoura University hospital inEgypt.Methods:This study included120 adult chronicHCV patients,81 decompensate cirrhosis(late-stage) and39 chronicHCV non cirrhotic patients(early-stage) and 40 healthy blood donors as controls.Serum samples were examined for anti-ToxoplasmaIgM and anti-ToxoplasmaIgG antibodies byELISA.Real-timeRT-polymerase chain reaction assay was done for quantitation of hepatitisC virus.Results:Anti-T. gondiiIgG antibodies were detected in75(92.6%) of81 late-stage cirrhotic patients,30(76.9%) of the39 chronicHCV non cirrhotic patients(early-stage) and in6(15%) of40 controls with statistically significant difference(P<0.001). Anti-T. gondiiIgM antibodies were found in11(13.6%) in late stage patients,5(12.8%) in early stage and in3(7.5%) of controls with no statistical significant difference(P=0.610).There was no correlation between stage of fibrosis andIgM orIgG antibodies positivity in our studied groups (P=0.526).HighIgG levels significantly correlated with high viral load(P=0.026).Conclusions:Our findings suggest that the serious opportunisticT. gondii infection represent a potential significant risk for chronicHCV patients.So, toxoplasmosis should be considered in their investigations and follow-up.

  13. The pharmacology and activity of non-steroidal anti-inflammatory drugs (NSAIDs: a review of their use as an adjuvant treatment in patients with HBV and HCV chronic hepatitis

    Directory of Open Access Journals (Sweden)

    Sirio Fiorino

    2013-03-01

    Full Text Available Introduction: Different DNA and RNA viruses exploit common strategies to support their persistence and replication in infected individuals. In particular, the hepatitis B virus (HBV and the hepatitis C virus (HCV cause major health problems worldwide. These pathogens exert an immunosuppressive role by inducing the persistent activation of cyclooxygenase-2 (COX-2 and an increased synthesis of prostaglandin E2 (PGE2. The suppression of this proinflammatory network by non-steroidal anti-inflammatory drugs (NSAIDs has been proposed as a therapeutic approach to decrease viral replication. Materials and methods: In this review, the role of inflammation in the support of viral replication and NSAIDs and ketoprofen pharmacology are briefly discussed. In addition, studies that have investigated the use of NSAIDs for the treatment of HBV and HCV chronic hepatitis, which were identified by a systematic literature search of PubMed and MEDLINE, are reported. Results: To date, pegylated-interferon (PEG-IFN and/or nucleot(side analogues and PEG-IFN and ribavirin remain the standard therapy for HBV and HCV chronic hepatitis, respectively. Discussion: The use of NSAIDs in patients with chronic viral hepatitis has only a ‘‘historical’’ interest. Nevertheless, the possible usefulness of ketoprofen with PEG-IFN and ribavirin for HCVinfected patients, non-responders to standard therapy or with genotype 1, should be evaluated in future clinical studies.

  14. Dysregulation of toll-like receptor (TLR) 2 expression on monocytes and upregulation of the frequency of T cells expressing TLR2 in patients with chronic hepatitis C virus infection

    DEFF Research Database (Denmark)

    Ronit, Andreas; Salem, Mohammad; Hartling, Hans J;

    2013-01-01

    Toll-like receptors (TLRs) initiate inflammatory responses that may play a role in disease progression in patients infected with hepatitis C virus (HCV). TLR2 and TLR4 surface expression were assessed on CD14(+) monocytes, CD4(+) and CD8(+) T cells in treatment naïve patients with chronic HCV...... infection with fibrosis, without fibrosis, co-infected with human immunodeficiency virus (HIV), and in healthy controls. Increased expression of TLR2 was found on monocytes in HCV-infected patients with fibrosis (p...

  15. Hepatitis C virus viremia increases the incidence of chronic kidney disease in HIV-infected patients

    DEFF Research Database (Denmark)

    Peters, Lars; Grint, Daniel; Lundgren, Jens;

    2012-01-01

    Several studies have reported on an association between hepatitis C virus (HCV) antibody status and the development of chronic kidney disease (CKD), but the role of HCV viremia and genotype are not well defined.......Several studies have reported on an association between hepatitis C virus (HCV) antibody status and the development of chronic kidney disease (CKD), but the role of HCV viremia and genotype are not well defined....

  16. PRO-C3-levels in patients with HIV/HCV-Co-infection reflect fibrosis stage and degree of portal hypertension

    DEFF Research Database (Denmark)

    Jansen, Christian; Leeming, Diana J; Mandorfer, Mattias;

    2014-01-01

    BACKGROUND: Liver-related deaths represent the leading cause of mortality among patients with HIV/HCV-co-infection, and are mainly related to complications of fibrosis and portal hypertension. In this study, we aimed to evaluate the structural changes by the assessment of extracellular matrix (ECM......) derived degradation fragments in peripheral blood as biomarkers for fibrosis and portal hypertension in patients with HIV/HCV co-infection. METHODS: Fifty-eight patients (67% male, mean age: 36.5 years) with HIV/HCV-co-infection were included in the study. Hepatic venous pressure gradient (HVPG......4M and C5M levels were higher in patients with portal hypertension (HVPG>5 mmHg). CONCLUSION: PRO-C3 levels reflect liver injury, stage of liver fibrosis and degree of portal hypertension in HIV/HCV-co-infected patients. Furthermore, C4M and C5M were associated with increased portal pressure...

  17. HCV and HBV coexist in HBsAg-negative patients with HCV viremia; possibility of coinfection in these patients must be considered in HBV-high endemic area

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong Soon [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1998-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers and is highly associated with HBV infection in Korea. It has been suggested that HCV core protein may impair the polymerase activity of HBV in vitro, potentially lowering HBV titre in coinfected patients. The aim of this study was to confirm the coexistence of HBV viremia in HCV infected patients HCC who have apparent HBsAg seronegativity. The serological profiles of HBV and HCV in 616 patients with HCC were analysed and coinfection rate of HBV and HCV investigated. Sera were obtained from 16 patients who were both anti-HCV and HCV RNA positive but HbsAg negative, and tested for HBV BY PCR. As a control group, sera were obtained from 15 patients with HCC and 30 non-A abd non-B chronic hepatitis patients without HCC; both were anti-HCV, HCV-RNA, and HBsAg negative and tested for HBV PCR. Of 616 patients with HCC, 450 (73.1 %) had current HBV infection, 48 (7.8 %) had anti-HCV antibodies, and nine (1.5 %) had viral markers of both HCV abd HBV by serological profiles. Of 27 the patients with HCV viremia and HBsAg seronegativity, 14 (51.9 %) showed HBV viremia by PCR. In contrast, of the 75 patients in the control group who were both HCV PCR negative and HBsAg negative, five (11.1 %) showed HBV viremia by PCR. The PCR for HBV revealed coexistent HBV viremia in HCV viremia patients, despite HBsAg negativity by EIA. In HBV-endemic areas, the possibility of coinfection of HBV in HBsAg-negative patients with HCV viremia should be considered and molecular analysis for HBV-DNA performed. (author). 18 refs., 4 tabs.

  18. A Comprehensive Analysis of the Impact of HIV on HCV Immune Responses and Its Association with Liver Disease Progression in a Unique Plasma Donor Cohort

    Science.gov (United States)

    Rajapaksa, Ushani S.; Lawrence, Tessa M.; Peng, Yan-Chun; Liu, Jinghua; Xu, Keyi; Hu, Ke; Qin, Ling; Liu, Ning; Sun, Huanqin; Yan, Hui-Ping; Repapi, Emmanouela; Rowland-Jones, Sarah; Thimme, Robert; McKeating, Jane A.; Dong, Tao

    2016-01-01

    Objective Human Immunodeficiency Virus (HIV) and Hepatitis C virus (HCV) co-infection is recognized as a major cause of morbidity and mortality among HIV-1 infected patients. Our understanding of the impact of HIV infection on HCV specific immune responses and liver disease outcome is limited by the heterogeneous study populations with genetically diverse infecting viruses, varying duration of infection and anti-viral treatment. Methods Viral-specific immune responses in a cohort of 151 HCV mono- and HIV co-infected former plasma donors infected with a narrow source of virus were studied. HCV and HIV specific T cell responses were correlated with clinical data. Results HIV-1 accelerated liver disease progression and decreased HCV specific T cell immunity. The magnitude of HCV specific T cell responses inversely correlated with lower HCV RNA load and reduced liver injury as assessed by non-invasive markers of liver fibrosis. HIV co-infection reduced the frequency of HCV specific CD4+ T cells with no detectable effect on CD8+ T cells or neutralizing antibody levels. Conclusion Our study highlights the impact of HIV co-infection on HCV specific CD4+ T cell responses in a unique cohort of patients for both HCV and HIV and suggests a crucial role for these cells in controlling chronic HCV replication and liver disease progression. PMID:27455208

  19. Acute hepatitis C virus (HCV infection in the setting of HIV coinfection: a single-centre 10-year follow-up

    Directory of Open Access Journals (Sweden)

    Patrick Ingiliz

    2014-11-01

    Full Text Available Introduction: Acute hepatitis C virus (HCV infection has emerged as a major cause of morbidity in the HIV-infected population. Most guidelines recommend early treatment with pegylated interferon and ribavirin due to higher cure rates. The impact of acute HCV and its treatment on the outcome of the HIV-infected population is unknown. With new treatment options for HCV, early treatment of acute HCV has to be questioned. Here, we report a long-term analysis on patients with acute HCV. Methods: Retrospective analysis from an outpatient clinic from Berlin. All patients with the diagnosis of acute HCV according to The European AIDS Treatment Network (NEAT criteria were included in the database at their date of HCV diagnosis and followed-up until the last medical contact. Demographic data was taken from the medical file. A fibrosis estimation was performed using transient elastography (Fibroscan(®. A Fibroscan value above 7 kPa was considered as significant fibrosis, above 12.4 kPa as liver cirrhosis. The following outcomes were documented: (a liver-related: hepatic decompensation, cirrhosis, hepatocellular carcinoma. (b non-liver-related: death, myocardial infarction, AIDS-defining event, psychiatric hospitalisation. Results: A total of 207 cases of acute HCV infection in HIV-infected patients were diagnosed between May 2002 and September 2013. All patients were male and declared homosexual contacts as their risk factor for having acquired HIV. The mean age was 39 years, 162 patients (78% were on antiretroviral treatment, and the median CD4 cell count was 593/mm3 (IQR 443–749. At HCV diagnosis, the highest median alanine aminotransferase (ALT level was 408 IU/mL (159–871, the HCV viral load was 800,000 IU/mL (45x103–2.8x106. 22 cases (11% cleared their infection spontaneously, 161 (77% underwent interferon-based treatment. Of those treated, 58% had a sustained virological response. 36 cases of HCV reinfection were documented. All patients were

  20. Liver mortality attributable to chronic hepatitis C virus infection in Denmark and Scotland - using spontaneous resolvers as the benchmark comparator

    DEFF Research Database (Denmark)

    Innes, H; Hutchinson, S J; Obel, N;

    2016-01-01

    Liver mortality among individuals with chronic hepatitis C (CHC) infection is common, but the relative contribution of CHC per se versus adverse health behaviours is uncertain. We explored data on spontaneous resolvers of hepatitis C virus (HCV) as a benchmark group, to uncover the independent...... contribution of CHC on liver mortality. Using national HCV diagnosis and mortality registers from Denmark and Scotland, we calculated the liver mortality rate (LMR) for persons diagnosed with CHC infection (LMRchronic ) and spontaneously resolved infection (LMRresolved ), according to subgroups defined by: age...... (where 0.00=not attributable at all; and 1.00=entirely attributable) of liver mortality attributable to CHC in the diagnosed population. Our cohort comprised 7005, and 21729 persons diagnosed with HCV antibodies in Denmark and Scotland, respectively. The mean follow up duration was 6.3-6.9 years. The TAF...

  1. Molecular profiling of early stage liver fibrosis in patients with chronic hepatitis C virus infection

    International Nuclear Information System (INIS)

    The molecular mechanisms of acute hepatitis C virus (HCV) infection, end-stage hepatitis (cirrhosis), and hepatocellular carcinoma have been extensively studied, but little is known of the changes in liver gene expression during the early stages of liver fibrosis associated with chronic HCV infection, that is, the transition from normal liver (NL) of uninfected patients to the first stage of liver fibrosis (F1-CH-C). To obtain insight into the molecular pathogenesis of F1-CH-C, we used real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to study the mRNA expression of 240 selected genes in liver tissue with F1-CH-C, in comparison with NL. The expression of 54 (22.5%) of the 240 genes was significantly different between F1-CH-C and NL; 46 genes were upregulated and 8 were downregulated in F1-CH-C. The most noteworthy changes in gene expression mainly affected the transcriptional network regulated by interferons (IFNs), including both IFN-α/β-inducible genes (STAT1, STAT2, ISGF3G/IRF9, IFI27, G1P3, G1P2, OAS2, MX1) and IFN-γ-inducible genes (CXCL9, CXCL10, CXCL11). Interesting, upregulation of IFN-α/β-inducible genes (but not IFN-γ-inducible genes) was independent of histological scores (grade and stage of fibrosis) and HCV characteristics (hepatic HCV mRNA levels and the HCV genotype), and was specific to HCV (as compared to hepatitis B virus (HBV)). Other genes dysregulated in F1-CH-C, albeit less markedly than IFN-α/β- and IFN-γ-inducible genes, were mainly involved in the activation of lymphocytes infiltrating the liver (IFNG, TNF, CXCL6, IL6, CCL8, CXCR3, CXCR4, CCR2), cell proliferation (p16/CDKN2A, MKI67, p14/ARF), extracellular matrix remodeling (MMP9, ITGA2), lymphangiogenesis (XLKD1/LYVE), oxidative stress (CYP2E1), and cytoskeleton microtubule organization (STMN2/SCG10). Thus, a limited number of signaling pathways, and particularly the transcriptional network regulated by interferons, are dysregulated in the first

  2. HIV-, HCV-, and co-infections and associated risk factors among drug users in southwestern China: a township-level ecological study incorporating spatial regression.

    Directory of Open Access Journals (Sweden)

    Yi-Biao Zhou

    Full Text Available BACKGROUND: The human immunodeficiency virus (HIV and hepatitis C virus (HCV are major public health problems. Many studies have been performed to investigate the association between demographic and behavioral factors and HIV or HCV infection. However, some of the results of these studies have been in conflict. METHODOLOGY/PRINCIPAL FINDINGS: The data of all entrants in the 11 national methadone clinics in the Yi Autonomous Prefecture from March 2004 to December 2012 were collected from the national database. Several spatial regression models were used to analyze specific community characteristics associated with the prevalence of HIV and HCV infection at the township level. The study enrolled 6,417 adult patients. The prevalence of HIV infection, HCV infection and co-infection was 25.4%, 30.9%, and 11.0%, respectively. Prevalence exhibited stark geographical variations in the area studied. The four regression models showed Yi ethnicity to be associated with both the prevalence of HIV and of HIV/HCV co-infection. The male drug users in some northwestern counties had greater odds of being infected with HIV than female drug users, but the opposite was observed in some eastern counties. The 'being in drug rehabilitation variable was found to be positively associated with prevalence of HCV infection in some southern townships, however, it was found to be negatively associated with it in some northern townships. CONCLUSIONS/SIGNIFICANCE: The spatial modeling creates better representations of data such that public health interventions must focus on areas with high frequency of HIV/HCV to prevent further transmission of both HIV and HCV.

  3. Chronic Hepatitis C in Western Canada: A Survey of Practice Patterns among Gastroenterologists in Alberta and British Columbia

    Directory of Open Access Journals (Sweden)

    Rohit Pai

    2014-01-01

    Full Text Available OBJECTIVE: To survey gastroenterologists in British Columbia and Alberta with regard to awareness of chronic hepatitis C virus (HCV management and practice patterns among physicians who treat and do not treat HCV-infected patients.

  4. Impact of psychiatric disorders on the quality of life of brazilian HCV-infected patients

    Directory of Open Access Journals (Sweden)

    Susana Batista-Neves

    2009-02-01

    Full Text Available The aim of our study was to determine the impact of psychiatric comorbidities on the health-related quality of life of HCV-infected patients. Assessment of clinical, socio-demographic and quality of life data of the patients followed up at a Hepatology unit was performed by using a standard questionnaire and the SF-36 instrument. Psychiatric diagnoses were confirmed by using the Mini International Neuropsychiatric Interview, Brazilian version 5.0.0 (MINI Plus. Evaluation using the MINI plus demonstrated that 46 (51% patients did not have any psychiatric diagnosis, while 44 (49% had at least one psychiatric diagnosis. Among patients with a psychiatric comorbidity, 26 (59.1% had a current mental disorder, out of which 22 (84.6% had not been previously diagnosed. Patients with psychiatric disorders had lower scores in all dimensions of the SF-36 when compared to those who had no psychiatric diagnosis. Scores of physical functioning and bodily pain domains were lower for those suffering from a current psychiatric disorder when compared to those who had had a psychiatric disorder in the past. Females had lower scores of bodily pain and mental health dimensions when compared to males. Scores for mental health dimension were also lower for patients with advanced fibrosis. The presence of a psychiatric comorbidity was the variable that was most associated with the different scores in the SF-36, compared to other variables such as age, gender, aminotransferase levels, and degree of fibrosis.

  5. A GENOTYPIC STUDY OF SEN VIRUS INFECTION IN HEALTHY BLOOD DONORS AND THALASSEMIA PATIENTS: WITH OR WITHOUT HCV INFECTION AND ITS CLINICAL IMPORTANCE

    Directory of Open Access Journals (Sweden)

    BASHAR M. KHAZAAL

    2016-01-01

    Full Text Available Background: SEN-Virus (SEN-V-D and SEN-V-H is a DNA virus which associated with acute post transfusion hepatitis and blood transfusion is the most common mode of transmission of this virus like HCV, HBV and HIV among population. Beta thalassemia is a disease need continuous blood transfusions to manage the patient’s life; so these patients are at increased risk of infection with SEN-V. Aims of this study: This study was designed to search the prevalence of SEN-V among thalassemia patients and blood donors and to evaluate the clinical importance of SEN-Virus in thalassemia patients with or without HCV infection in Iraq and to detect the exact genomic characterization of SEN-V-D and SEN-V-H genotypes in Iraq and study of similarity of these genomes with other countries especially the neighboring countries and the homology between each isolate. Methods: One hundred and fifty eight thalassemia patients (57.6% male, 42.4% female, with mean age of 16.8±8.5 year, and one hundred and fifty healthy blood donors with randomly selected persons (58.7%male, 41.3% female, with mean age of 16.7±8.6 year; all these samples involved in this study. SEN-V and HCV had been identified by nested conventional PCR. Liver transaminases (Aspartate Transaminase and Alanine Transaminase had been determined, in addition of measure of serum ferritin levels by VIDAS. Gene sequencing and phylogenetic analysis had been studied of randomly selected amplified SEN-V D and H DNA samples. Results: SEN-V was detected in 68 from 158 (43% of thalassemia patients and 16 from 150 (10.7% of blood donors. HCV prevalence was (11.4% in thalassemia patients. There was significant increase in prevalence of SEN-V or HCV infection with age but there was no significant difference in prevalence in both with gender. SEN-V and HCV co-infection significantly increases AST level above normal range. SEN-V significantly increases ALT level above normal range and has a great significant ALT level

  6. Hepatitis C Viral Infection in Children: Updated Review

    Science.gov (United States)

    2016-01-01

    Hepatitis C virus (HCV) infection is a major medical challenge affecting around 200 million people worldwide. The main site of HCV replication is the hepatocytes of the liver. HCV is a positive enveloped RNA virus from the flaviviridae family. Six major HCV genotypes are implicated in the human infection. In developed countries the children are infected mainly through vertical transmission during deliveries, while in developing countries it is still due to horizontal transmission from adults. Minimal nonspecific and brief symptoms are initially found in approximately 15% of children. Acute and chronic HCV infection is diagnosed through the recognition of HCV RNA. The main objective for treatment of chronic HCV is to convert detected HCV viremia to below the detection limit. Children with chronic HCV infection are usually asymptomatic and rarely develop severe liver damage. Therefore, the benefits from current therapies, pegylated-Interferon plus ribavirin, must be weighed against their adverse effects. This combined treatment offers a 50-90% chance of clearing HCV infection according to several studies and on different HCV genotype. Recent direct acting antiviral (DAA) drugs which are well established for adults have not yet been approved for children and young adults below 18 years. The most important field for the prevention of HCV infection in children would be the prevention of perinatal and parenteral transmission. There are areas of focus for new lines of research in pediatric HCV-related disease that can be addressed in the near future.

  7. Co-infection of SENV-D among chronic hepatitis C patients treated with combination therapy with high-dose interferon-alfa and ribavirin

    Institute of Scientific and Technical Information of China (English)

    Chia-Yen Dai; Liang-Yen Wang; Ming-Lung Yu; Wan-Long Chuang; Wen-Yu Chang; Shinn-Cherng Chen; Li-Po Lee; Ming-Yen Hsieh; Nei-Jen Hou; Zu-Yau Lin; Ming-Yuh Hsieh

    2005-01-01

    AIM: The clinical significance of co-infection of SENV-D among patients with chronic hepatitis C (CHC) and response of both viruses to combination therapy with high-dose interferon-alfa (IFN) plus ribavirin remain uncertain and are being investigated.METHODS: Total 164 (97 males and 67 females, the mean age 48.1±11.4 years, range: 20-73 years, 128histologically proved) naive CHC patients were enrolled in this study. SENV-D DNA was tested by PCR method.Detection of serum HCV RNA was performed using a standardized automated qualitative RT-PCR assay (COBAS AMPLICOR HCV Test, version 2.0). HCV genotypes 1a,1b, 2a, 2b, and 3a were determined by using genotypespecific primers. Pretreatment HCV RNA levels were determined by using the branched DNA assay (Quantiplex HCV RNA 3.0). There are 156 patients receiving combination therapy with IFN 6 MU plus ribavirin for 24 wk and the response to therapy is determined.RESULTS: Sixty-one (37.2%) patients were positive for SENV-D DNA and had higher mean age than those who were negative (50.7±10.6 years vs46.6±11.6 years,P = 0.026). The rate of sustained viral response (SVR)for HCV and SENV-D were 67.3% (105/156) and 56.3%(27/48), respectively. By univariate analysis, the higher rate of SVR was significantly related to HCV genotype non-1b (P<0.001), younger ages (P = 0.014), lower pretreatment levels of HCV RNA (P = 0.019) and higher histological activity index (HAI) score for intralobular regeneration and focal necrosis (P = 0.037). By multivariate analyses, HCV genotype non-1b, younger age and lower pretreatment HCV RNA levels were significantly associated with HCV SVR (odds ratio (OR)/95% confidence interval (CI): 12.098/0.02-0.19, 0.936/0.890-0.998, and 3.131/1.080-9.077, respectively). The SVR of SENV-D was higher among patients clearing SENV-D than those who had viremia at the end of therapy (P = 0.04).CONCLUSION: Coexistent SENV-D infection, apparently associated with higher ages, is found in more than onethird Taiwanese

  8. Correlates of HIV, HBV, HCV and syphilis infections among prison inmates and officers in Ghana: A national multicenter study

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    Asare Isaac

    2008-03-01

    Full Text Available Abstract Background Prisons are known to be high-risk environments for the spread of bloodborne and sexually transmitted infections. Prison officers are considered to have an intermittent exposure potential to bloodborne infectious diseases on the job, however there has been no studies on the prevalence of these infections in prison officers in Ghana. Methods A national multicenter cross-sectional study was undertaken on correlates of human immunodeficiency virus (HIV, hepatitis B virus (HBV, hepatitis C virus (HCV, and syphilis infections in sample of prison inmates and officers from eight of ten regional central prisons in Ghana. A total of 1366 inmates and 445 officers were enrolled between May 2004 and December 2005. Subjects completed personal risk-factor questionnaire and provided blood specimens for unlinked anonymous testing for presence of antibodies to HIV, HCV and Treponema pallidum; and surface antigen of HBV (HBsAg. These data were analyzed using both univariate and multivariate techniques. Results Almost 18% (1336 of 7652 eligible inmates and 21% (445 of 2139 eligible officers in eight study prisons took part. Median ages of inmates and officers were 36.5 years (range 16–84 and 38.1 years (range 25–59, respectively. Among inmates, HIV seroprevalence was 5.9%, syphilis seroprevalence was 16.5%, and 25.5% had HBsAg. Among officers tested, HIV seroprevalence was 4.9%, HCV seroprevalence was 18.7%, syphilis seroprevalence was 7.9%, and 11.7% had HBsAg. Independent determinants for HIV, HBV and syphilis infections among inmates were age between 17–46, being unmarried, being illiterate, female gender, being incarcerated for longer than median time served of 36 months, history of homosexuality, history of intravenous drug use, history of sharing syringes and drug paraphernalia, history of participation in paid sexual activity, and history of sexually transmitted diseases. Independent determinants for HIV, HBV, HCV and syphilis

  9. Anti-inflammatory/regulatory cytokine microenvironment mediated by IL-4 and IL-10 coordinates the immune response in hemophilia A patients infected chronically with hepatitis C virus.

    Science.gov (United States)

    Pimentel, João Paulo; Chaves, Daniel Gonçalves; Araújo, Ana Ruth Silva; de Araújo, Erbênia Maria Martins; da Silva Fraporti, Liziara; Neves, Walter Luiz Lima; Tarragô, Andrea Monteiro; Torres, Katia Luz; Gentz, Solange Henschke Lima; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Malheiro, Adriana

    2013-06-01

    In the past decades patients with hemophilia were infected commonly by hepatitis C virus (HCV) and a significant number of patients are infected chronically. Focusing on the role of the immune system for controlling and or maintaining HCV infection, the leukocyte and cytokine profiles of peripheral blood from hemophilia A patients and other patients with and without HCV infection were studied. The results demonstrated that hemophilia A is characterized by a general state of circulating leukocytes activation along with an overall increase in the frequency of IL-6 and IL-10 with decrease of IL-8 and IL-12. HCV infection of patients with hemophilia A does not influence further the activation state of circulating leukocytes but is accompanied by lower levels of alanine transaminase (ALT) and a prominent anti-inflammatory/regulatory serum cytokine pattern, mediated by IL-4 and IL-10. Additionally, the results demonstrated that hemophilia A patients infected with HCV displaying No/Low antibody response to C33c and C22 have significant lower viral load and higher serum levels of IL-12 and IL-4. This finding suggests that the differential RIBA reactivity to C33c/C22 HCV core proteins may have a putative value as a prognostic biomarker for the infection in hemophilia A patients.

  10. Effects and Tolerance of Silymarin (Milk Thistle in Chronic Hepatitis C Virus Infection Patients: A Meta-Analysis of Randomized Controlled Trials

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    Zongguo Yang

    2014-01-01

    Full Text Available Objective. This study aimed to evaluate the efficacy and safety of silymarin on chronic hepatitis C virus- (HCV- infected patients. Methods. Randomized controlled trials (RCTs of silymarin in chronic HCV-infected patients up to April 1, 2014 were systematically identified in PubMed, Ovid, Web of Science, and Cochrane Library databases. Results. A total of 222 and 167 patients in five RCTs were randomly treated with silymarin (or intravenous silibinin and placebo, respectively. Serum HCV RNA relatively decreased in patients treated with silymarin compared with those administered with placebo, but no significance was found (P=0.09. Meta-analysis of patients orally treated with silymarin indicated that the changes of HCV RNA are similar in the two groups (P=0.19. The effect on alanine aminotransferase (ALT of oral silymarin is not different from that of placebo (P=0.45. Improvements in quality-of-life (Short Form-36 in both silymarin and placebo recipients were impressive but relatively identical (P=0.09. Conclusion. Silymarin is well tolerated in chronic HCV-infected patients. However, no evidence of salutary effects of oral silymarin has yet been reported based on intermediate endpoints (ALT and HCV RNA in this population. Moreover, intravenous administration of silymarin should be further studied.

  11. Impaired hepatosplenic elimination of circulating cryoglobulins in patients with essential mixed cryoglobulinaemia and hepatitis C virus (HCV) infection

    Science.gov (United States)

    ROCCATELLO, D; MORSICA, G; PICCIOTTO, G; CESANO, G; ROPOLO, R; BERNARDI, M T; CACACE, G; CAVALLI, G; SENA, L M; LAZZARIN, A; PICCOLI, G; RIFAI, A

    1997-01-01

    The pathogenic mechanisms that lead to renal deposition of the cryoprecipitable IgM rheumatoid factor–IgG complexes in essential mixed cryoglobulinaemia (EMC) are unknown. Defective removal of cryoprecipitable complexes from the circulation has been postulated in EMC-associated nephritis. To test this hypothesis, the kinetics and fate of a trace dose of 123I-radiolabelled autologous cryoglobulins were analysed in 13 patients with EMC grouped according to renal involvement. The time course of radioactivity distribution in the blood and organ uptake were measured by gamma camera scintigraphy. In blood sampled 30–300 s after injection, only a minor fraction ( 4 h) biphasic pattern. In patients with quiescent or mild nepthritis, the liver and to a lesser extent the spleen were the major organs that mediated the rapid uptake and processing of the cryoglobulins from the circulation. In contrast, patients with active mesangiocapillary glomerulonephritis showed significantly (P< 0.001) less hepatic uptake, low liver-to-precordium ratio, and slower processing of cryoglobulins, prolonged liver mean transit time, than quiescent patients or mild nephritis patients. To elucidate the role and influence of HCV infection in the pathogenesis of EMC-nephritis, sera and cryoglobulins from all patients were assayed for HCV. None of the control group cases without nephritis showed any evidence of HCV-RNA in serum or cryoglobulin pellet. In contrast, all 10 EMC-nephritis patients' sera, and eight corresponding cryoglobulin pellets contained HCV-RNA. Collectively, these findings suggest an impaired reticuloendothelial system removal of IgM–IgG–HCV complexes may underlie their renal deposition. PMID:9353142

  12. PNPLA 3 I148M genetic variant associates with insulin resistance and baseline viral load in HCV genotype 2 but not in genotype 3 infection

    DEFF Research Database (Denmark)

    Rembeck, Karolina; Maglio, Cristina; Lagging, Martin;

    2012-01-01

    ABSTRACT: BACKGROUND: Hepatic steatosis in HCV patients has been postulated as a risk factor associated with a higher frequency of fibrosis and cirrhosis. A single genetic variant, PNPLA3 I148M, has been widely associated with increased hepatic steatosis. Previous studies of the PNPLA3 I148M...... sequence variant in HCV infected individuals have reported an association between this variant and prevalence of steatosis, fibrosis, and cirrhosis. To evaluate the impact of PNPLA3 I148M variant on metabolic traits and treatment response in HCV genotype 2 and 3 infected patients. METHODS: Three hundred...... and eighty-two treatment naive HCV genotype 2 or 3 infected patients were included in a phase III, open label, randomized, multicenter, investigator-initiated trial (the NORDynamIC study), in which pretreatment liver biopsies were mandatory. PNPLA3I148M genotyping was performed in a total of 359 Caucasian...

  13. IFNL4 and IFNL3 associated polymorphisms strongly influence the spontaneous IFN-alpha receptor-1 expression in HCV-infected patients.

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    Licia Bordi

    Full Text Available Single-nucleotide polymorphism in IFNL3 gene (rs12979860 predicts spontaneous and therapy-induced HCV clearance. In a previous study from our group PBMC from patients with favourable rs12979860 genotype showed higher levels of IFNAR-1 mRNA. Recently, a dinucleotide polymorphism, ss469415590 (TT or ΔG, has been discovered in the region upstream IFNL3 gene, which is in high linkage disequilibrium with rs12979860. ss469415590[ΔG] is a frameshift variant that creates a novel gene, designed IFNL4, encoding the interferon-lambda 4 protein (IFNL4. The aim of the present study was to extend the analysis of IFNAR-1 mRNA levels to the ss469415590 variants. Our results highlight that the difference of IFNAR-1 mRNA levels between favourable and unfavourable genotype combinations, at both rs12979860 and ss469415590 loci, is stronger than that observed for single polymorphisms at each locus. These findings suggest may represent the biological basis for the observed association between IFNL3 CC and IFNL4 TT/TT genotypes and favourable outcome of either natural HCV infection (clearance vs chronic evolution or IFN-based therapy.

  14. Profile of paritaprevir/ritonavir/ombitasvir plus dasabuvir in the treatment of chronic hepatitis C virus genotype 1 infection

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    Smith MA

    2015-11-01

    Full Text Available Michael A Smith, Alice LimDepartment of Pharmacy Practice and Pharmacy Administration, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, USAAbstract: Over the last several years, many advances have been made in the treatment of chronic hepatitis C virus (HCV infection with the development of direct-acting antivirals. Paritaprevir/ritonavir/ombitasvir with dasabuvir (PrOD is a novel combination of a nonstructural (NS 3/4A protein inhibitor boosted by ritonavir, an NS5A protein inhibitor, and an NS5B nonnucleoside polymerase inhibitor. This review aims to discuss the pharmacology, efficacy, safety, drug interactions, and viral drug resistance of PrOD in the treatment of HCV genotype 1 infections. Phase I, II, and III human and animal studies that describe the pharmacology, pharmacokinetics, efficacy, and safety of PrOD for HCV were identified and included. Studies that evaluated patients without cirrhosis (n=2,249 and with cirrhosis (n=422 demonstrated that PrOD for 12 or 24 weeks was effective at achieving sustained virologic response rates (>90% in patients with genotype 1a or 1b HCV infection. Although indicated for the treatment of HCV genotype 1 infection, PrOD is also recommended for the treatment of HCV in patients coinfected with HIV. Additionally, promising data exist for the use of PrOD in liver-transplant recipients. The most common adverse drug events associated with PrOD included nausea, pruritus, insomnia, diarrhea, asthenia, dry skin, vomiting, and anemia. The high efficacy rates seen coupled with a favorable side effect profile seen with PrOD with or without ribavirin have led to its addition as a recommended treatment regimen for HCV genotype 1 infection.Keywords: direct-acting antiviral, interferon-free, ribavirin-free

  15. Profile of paritaprevir/ritonavir/ombitasvir plus dasabuvir in the treatment of chronic hepatitis C virus genotype 1 infection.

    Science.gov (United States)

    Smith, Michael A; Lim, Alice

    2015-01-01

    Over the last several years, many advances have been made in the treatment of chronic hepatitis C virus (HCV) infection with the development of direct-acting antivirals. Paritaprevir/ritonavir/ombitasvir with dasabuvir (PrOD) is a novel combination of a nonstructural (NS) 3/4A protein inhibitor boosted by ritonavir, an NS5A protein inhibitor, and an NS5B nonnucleoside polymerase inhibitor. This review aims to discuss the pharmacology, efficacy, safety, drug interactions, and viral drug resistance of PrOD in the treatment of HCV genotype 1 infections. Phase I, II, and III human and animal studies that describe the pharmacology, pharmacokinetics, efficacy, and safety of PrOD for HCV were identified and included. Studies that evaluated patients without cirrhosis (n=2,249) and with cirrhosis (n=422) demonstrated that PrOD for 12 or 24 weeks was effective at achieving sustained virologic response rates (>90%) in patients with genotype 1a or 1b HCV infection. Although indicated for the treatment of HCV genotype 1 infection, PrOD is also recommended for the treatment of HCV in patients coinfected with HIV. Additionally, promising data exist for the use of PrOD in liver-transplant recipients. The most common adverse drug events associated with PrOD included nausea, pruritus, insomnia, diarrhea, asthenia, dry skin, vomiting, and anemia. The high efficacy rates seen coupled with a favorable side effect profile seen with PrOD with or without ribavirin have led to its addition as a recommended treatment regimen for HCV genotype 1 infection. PMID:26622169

  16. Epidemiological features and specificities of HCV infection: a hospital-based cohort study in a university medical center of Calabria region

    Directory of Open Access Journals (Sweden)

    Liberto MC

    2012-11-01

    Full Text Available Abstract The epidemiological status of HCV in Europe, and in particular in Mediterranean countries, is continuously evolving. The genotype distribution is related to improvement of healthcare conditions, expansion of intravenous drug use and immigration. We review and characterize the epidemiology of the distribution of HCV genotypes within Calabria, an area of Southern Italy. We focus on the pattern of distinct HCV genotype changes over the last 16 years; particularly subtype 1b and genotype 4. We collected data by evaluating a hospital-based cohort of chronic hepatitis C patients; in addition, we report an update including new patients enrolled during last eight months.

  17. Impact of soluble CD26 on treatment outcome and hepatitis C virus-specific T cells in chronic hepatitis C virus genotype 1 infection.

    Directory of Open Access Journals (Sweden)

    Jonas Söderholm

    Full Text Available BACKGROUND: Interferon and ribavirin therapy for chronic hepatitis C virus (HCV infection yields sustained virological response (SVR rates of 50-80%. Several factors such as non-1 genotype, beneficial IL28B genetic variants, low baseline IP-10, and the functionality of HCV-specific T cells predict SVR. With the pending introduction of new therapies for HCV entailing very rapid clearance of plasma HCV RNA, the importance of baseline biomarkers likely will increase in order to tailor therapy. CD26 (DPPIV truncates the chemokine IP-10 into a shorter antagonistic form, and this truncation of IP-10 has been suggested to influence treatment outcome in patients with chronic HCV infection patients. In addition, previous reports have shown CD26 to be a co-stimulator for T cells. The aim of the present study was to assess the utility of CD26 as a biomarker for treatment outcome in chronic hepatitis C and to define its association with HCV-specific T cells. METHODS: Baseline plasma from 153 genotype 1 and 58 genotype 2/3 infected patients enrolled in an international multicenter phase III trial (DITTO-HCV and 36 genotype 1 infected patients participating in a Swedish trial (TTG1 were evaluated regarding baseline soluble CD26 (sCD26 and the functionality of HCV-specific CD8(+ T cells. RESULTS: Genotype 1 infected patients achieving SVR in the DITTO (P = 0.002 and the TTG1 (P = 0.02 studies had lower pretreatment sCD26 concentrations compared with non-SVR patients. Sixty-five percent of patients with sCD26 concentrations below 600 ng/mL achieved SVR compared with 39% of the patients with sCD26 exceeding 600 ng/mL (P = 0.01. Patients with sCD26 concentrations below 600 ng/mL had significantly higher frequencies of HCV-specific CD8(+ T cells (P = 0.02. CONCLUSIONS: Low baseline systemic concentrations of sCD26 predict favorable treatment outcome in chronic HCV infection and may be associated with higher blood counts of HCV-specific CD8(+ T

  18. Lysosomotropic agents as HCV entry inhibitors

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    Nawaz Zafar

    2011-04-01

    Full Text Available Abstract HCV has two envelop proteins named as E1 and E2 which play an important role in cell entry through two main pathways: direct fusion at the plasma membrane and receptor-mediated endocytosis. Fusion of the HCV envelope proteins is triggered by low pH within the endosome. Lysosomotropic agents (LA such as Chloroquine and Ammonium chloride (NH4Cl are the weak bases and penetrate in lysosome as protonated form and increase the intracellular pH. To investigate the antiviral effect of LA (Chloroquine and NH4Cl on pH dependent endocytosis, HCV pseudoparticles (HCVpp of 1a and 3a genotype were produced and used to infect liver cells. The toxicological effects of Chloroquine and NH4Cl were tested in liver cells through MTT cell proliferation assay. For antiviral screening of Chloroquine and NH4Cl, liver cells were infected with HCVpp of 3a and 1a genotype in the presence or absence of different concentrations of Chloroquine and NH4Cl and there luciferase activity was determined by using a luminometer. The results demonstrated that Chloroquine and NH4Cl showed more than 50% reduction of virus infectivity at 50 μM and 10 mM concentrations respectively. These results suggest that inhibition of HCV at fusion step by increasing the lysosomal pH will be better option to treat chronic HCV.

  19. Identification of Novel Markers for Liver Fibrosis in HIV/HCV Co-infected individuals using Genomics-based Approach

    Science.gov (United States)

    Suzman, Daniel L.; McLaughlin, Mary; Hu, Zonghui; Kleiner, David E.; Wood, Brad; Vailati, Mary; Lempicki, Richard A.; Mican, JoAnn M.; Suffredini, Anthony; Masur, Henry; Polis, Michael A.; Kottilil, Shyam

    2009-01-01

    Objective The degree of liver fibrosis is a determinant for initiation of therapy for HCV. Liver biopsy is invasive, risky and costly, but is required to assess fibrosis. This study intended to identify novel non-invasive markers to accurately assess fibrosis in HIV/HCV co-infection. Methods Using 100 biopsies from 68 HIV/HCV co-infected patients, we developed a predictive model consisting of six serum markers along with age and ART experience. DNA microarray analysis of PBMCs associated with a subset of 51 biopsies obtained from 28 patients was performed and incorporated into a second model. Results: The 8-marker model yielded an AUROC of 0.904. Combined analysis of clinical and DNA microarray data in the 51 biopsy subset identified two genes (alanine amino peptidase-N and mitogen-activated protein kinase kinase-3) that predicted fibrosis with high significance. The 4-marker model that included the two genes and two serum markers had an AUROC of 0.852, which did not differ significantly from the 8-marker model on this subset (AUROC = 0.856, p=0.96). Conclusion Both models accurately predicted fibrosis with an accuracy of 87.9%, thereby sparing 83% of patients from obtaining a biopsy. DNA microarray analysis can be invaluable in identifying novel biomarkers of liver fibrosis. PMID:18614866

  20. Analysis on CD4 + CD25 + T cell in HCV infection and HCV/HIV co-infection%HCV感染者和HCV/HIV合并感染者免疫调节

    Institute of Scientific and Technical Information of China (English)

    康辉; 尚红; 刁莹莹; 范霞; 代娣; 姜桐军; 耿文清

    2005-01-01

    目的探讨我国单纯丙型肝炎病毒(HCV)感染者和HCV/HIV合并感染者免疫应答的相关机制.方法分离人外周血单个核细胞;流式细胞仪(FACS)检测CD4+T细胞和CD4+CD25+T细胞表达水平.结果CD4+CD25+T细胞占外周血单个核细胞中CD4+T细胞比例(%CD4+CD25+),HCV感染组明显高于健康对照组(19.2%>13.8%,P<0.05),HCV/HIV合并感染组明显低于对照组(6.9%<13.8%,P<0.001),更明显低于HCV感染组(P<0.001).结论HCV感染者体内CD4+CD25+T细胞增殖明显,提示CD4+CD25+T细胞在HCV慢性感染中发挥免疫调节作用.HCV/HIV合并感染时,CD4+CD25+T细胞受损,从而影响免疫调节功能.

  1. Evaluation of the HIV-HCV co-infection status in a cohort of southeastern of Spain

    Directory of Open Access Journals (Sweden)

    A Moreno Hernández

    2012-11-01

    Full Text Available Purpose of the study: To know the main epidemiological, virological and therapeutic characteristics of HCV infection and the degree of hepatic fibrosis in a cohort of HIV-HCV co-infected patients in a health area of southeastern of Spain. Methods: Prospective cohort of co-infected HIV-HCV patients followed in the University Hospital of Saint Lucia (Spain, which describes the main epidemiological characteristics, degree of liver fibrosis assessed by transient elastography and the level of response to treatment for HCV during the period November 30, 2011–February 28, 2012. Summary of results: The cohort included 109 patients, of whom 27 were females (25% and 82 males (75%, with a mean age of 45.8 (SD: 6.2 years and a mean time of infection of 18.8 (SD: 5.7 years. The main route of transmission was in this order: IDUs in 90 patients (83%, 13 (12% by heterosexual intercourse and 3 (2.8% in MSM. There were no statistically significant differences between the years of evolution of HCV based on the route of transmission (p=0.36. In the genotypic analysis, 55 patients were genotype 1a (51%, 13 genotype 1b (13%, 19 genotype 3 (17% and 9 genotype 4 (8.3%. The median HCV viral load was 868,000 IU/ml (6.15 log10. In this cohort 31 patients (28% received antiviral therapy for HCV: 2 (1.8% Interferon (INF non-pegylated, 3 (2.8% INF non-pegylated with Ribavirin (RBV and 25 (23% INF pegylated with RBV. In 6 cases (19% were achieved sustained viral response (SVR. In the 25 cases without SVR (81%, 9 (36% were partial responders, 7 (28% null responders, 6 (24% relapsers and 3 (12% discontinued treatment due to problems of tolerability. In 108 patients were determined the degree of liver fibrosis by transient elastography: 48 patients (44% had significant fibrosis (F3–F4;>9.5 kpascal and 30 (28% liver cirrhosis (F4;>14.5 kpascal. In patients with F4, 5 (17% had values between 14.5–20 kpascal, 14 (47% values between 21–40 kpascal and 11 (37% values over 40

  2. Infección crónica por el VHC Chronic Hepatitis C virus infection

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    M. Iñarrairaegui

    2004-01-01

    Full Text Available Tras la infección aguda por el virus de la hepatitis C (VHC, un porcentaje importante de pacientes no aclara el virus y desarrollan una hepatitis crónica C. Los síntomas, cuando existen, suelen ser inespecíficos. Aproximadamente un tercio de los pacientes presentan además manifestaciones extrahepáticas de la infección, debidas fundamentalmente al linfotropismo del virus C. De éstas destacan, por su clara asociación con el VHC, la crioglobulinemia mixta y la producción de autoanticuerpos (autoAc. Otras enfermedades como el linfoma no Hodgkin (LNH o la tiroiditis autoinmune no tienen una asociación claramente establecida. Aunque la mayoría de los pacientes con hepatitis crónica C tienen niveles ligeros o moderadamente elevados y fluctuantes de transaminasas, hasta un tercio de los infectados pueden presentar niveles persistentemente normales de transaminasas. El diagnóstico de la infección crónica por el VHC se basa en pruebas serológicas, que detectan la presencia de anticuerpos frente al VHC, y en pruebas virológicas que detectan RNA del VHC, que confirman la existencia de infección activa. Por último, un aspecto importante en la infección crónica por el VHC, tras el diagnóstico, es establecer el estadio de fibrosis y el grado de inflamación, ya que ambas características son muy importantes para predecir la evolución natural y la necesidad de tratamiento. Hoy en día esta información sólo puede obtenerse mediante biopsia hepática, que está indicada en pacientes con infección crónica por el VHC y transaminasas elevadas. Su indicación en pacientes con transaminasas normales permanece todavía controvertida.Following acute hepatitis C virus infection (HCV, a significant percentage of patients do not clear the virus and develop a chronic hepatitis C. The symptoms, when they exist, are usually unspecific. Besides, approximately one third of the patients present extrahepatic manifestations of the infection, basically

  3. Rapid hepatitis C testing among persons at increased risk for infection--Wisconsin, 2012-2013.

    Science.gov (United States)

    Stockman, Lauren J; Guilfoye, Sheila M; Benoit, Andrea L; Vergeront, James M; Davis, Jeffrey P

    2014-04-11

    An estimated 3.2 million persons in the United States have chronic infection with hepatitis C virus (HCV). Most new HCV transmissions occur among persons who inject drugs, often within the first few years of their injection drug use. During 2003-2012, reports of HCV infection increased from 15 to 54 cases per 100,000 among persons aged HCV infection reported injecting drugs (Wisconsin Division of Public Health, unpublished data, 2013). To increase detection of HCV infection, the Wisconsin Division of Public Health (WDPH) piloted a program during October 2012-October 2013 that offered rapid HCV testing to clients of four agencies providing outreach testing for HCV and human immunodeficiency virus infection, syringe exchange, counseling, and other harm reduction services to persons with drug dependence. During that period, 1,255 persons were tested using a rapid HCV test, and 246 (20%) of the results were positive. Most (72%) of the infections had not been reported to WDPH. A blood specimen for further testing was collected from 192 (78%) participants with positive HCV test results; among these participants, 183 were tested for HCV RNA using reverse transcription-polymerase chain reaction (RT-PCR), and these results were positive for 128 (70%) participants, indicating active infection. Use of the rapid HCV test detected previously unreported HCV infections and raised awareness of HCV. Persons identified with active HCV infection should be referred to medical care and counseled on ways to prevent HCV transmission to others. PMID:24717818

  4. Cyclophilin Inhibitors Remodel the Endoplasmic Reticulum of HCV-Infected Cells in a Unique Pattern Rendering Cells Impervious to a Reinfection.

    Directory of Open Access Journals (Sweden)

    Udayan Chatterji

    Full Text Available The mechanisms of action by which cyclophilin inhibitors (CypI interfere with the HCV life cycle remain poorly understood. We reported that CypI and NS5A inhibitors (NS5Ai, but not other classes of anti-HCV agents, prevent assembly of double membrane vesicles (DMVs, which protect replication complexes. We demonstrated that both NS5A and the isomerase cyclophilin A (CypA are required for DMV formation. Here, we examined whether CypI mediate an additional antiviral effect that could further explain the high efficacy of CypI. We identified a unique action of CypI. CypI remodel the organization of the endoplasmic reticulum (ER of HCV-infected cells, but not of uninfected cells. This effect is specific since it was not observed for other classes of anti-HCV agents including NS5Ai, and has no effect on the viability of CypI-treated cells. Since ER serves as platform for the establishment of HCV replication complexes, we asked whether the ER reorganization by CypI would prevent cells from being newly infected. Remarkably, CypI-treated HCV-pre-infected cells remain totally impervious to a reinfection, suggesting that the CypI-mediated ER reorganization prevents a reinfection. This block is not due to residual CypI since CypI-resistant HCV variants also fail to infect these cells. The ER reorganization by CypI is rapid and reversible. This study provides the first evidence that CypI trigger a unique ER reorganization of infected cells, rendering cells transiently impervious to a reinfection. This study further suggests that the HCV-induced ER rearrangement represents a key target for the development of new therapies.

  5. Cyclophilin Inhibitors Remodel the Endoplasmic Reticulum of HCV-Infected Cells in a Unique Pattern Rendering Cells Impervious to a Reinfection

    Science.gov (United States)

    Chatterji, Udayan; Bobardt, Michael; Schaffer, Lana; Wood, Malcolm; Gallay, Philippe A.

    2016-01-01

    The mechanisms of action by which cyclophilin inhibitors (CypI) interfere with the HCV life cycle remain poorly understood. We reported that CypI and NS5A inhibitors (NS5Ai), but not other classes of anti-HCV agents, prevent assembly of double membrane vesicles (DMVs), which protect replication complexes. We demonstrated that both NS5A and the isomerase cyclophilin A (CypA) are required for DMV formation. Here, we examined whether CypI mediate an additional antiviral effect that could further explain the high efficacy of CypI. We identified a unique action of CypI. CypI remodel the organization of the endoplasmic reticulum (ER) of HCV-infected cells, but not of uninfected cells. This effect is specific since it was not observed for other classes of anti-HCV agents including NS5Ai, and has no effect on the viability of CypI-treated cells. Since ER serves as platform for the establishment of HCV replication complexes, we asked whether the ER reorganization by CypI would prevent cells from being newly infected. Remarkably, CypI-treated HCV-pre-infected cells remain totally impervious to a reinfection, suggesting that the CypI-mediated ER reorganization prevents a reinfection. This block is not due to residual CypI since CypI-resistant HCV variants also fail to infect these cells. The ER reorganization by CypI is rapid and reversible. This study provides the first evidence that CypI trigger a unique ER reorganization of infected cells, rendering cells transiently impervious to a reinfection. This study further suggests that the HCV-induced ER rearrangement represents a key target for the development of new therapies. PMID:27442520

  6. Antiviral treatment prioritization in HCV-infected patients with extrahepatic manifestations - An Egyptian perspective.

    Science.gov (United States)

    El-Fishawy, Hussein; Saadi, Gamal; Hassaballa, May; Hussein, Mohamed; Doss, Wahid; Ragab, Gaafar; Barsoum, Rashad

    2016-05-01

    Egypt, the single country with highest incidence of HCV infection in the world, has embarked on a government-sponsored mass treatment program using several combinations of DAAs. Recognizing the importance of extrahepatic manifestations, independently of the hepatic, a subcommittee was assigned to develop national guidelines for respective prioritizing indications and protocols. It evaluated the benefit of treating patients with different extrahepatic manifestations, and reviewed relevant clinical trials and guidelines concerning DAA combinations available in Egypt. The latter included Sofosbuvir plus either peg-interferon, Simeprevir, Ledipasvir or daclatasvir, and the Viekera family comprising paritaprevir/ritonavir + ombitasvir with (GT-1) or without (GT-4) Dasabuvir. Any of these protocols may be used with or without Ribavirin according to indication. A blueprint was subjected to peer debate in dedicated workshops in two national meetings and subsequently to an online professional review, eventually leading to a final report that was adopted by the health authorities. Seven compelling and 10 optional indications were identified for treating patients with predominantly extrahepatic manifestations. The former include kidney disease at different stages, cryoglobulinemic vasculitis and non-Hodgkin lymphoma. Selected treatment protocols, were encoded and their use was prioritized on the basis of evidence of efficacy and safety. We concluded that any of the studied protocols may be used, preferably with ribavirin, for 12-week treatment in all patients with extrahepatic manifestations without cirrhosis and with eGFR above 30 ml/min/1.73 sqm. Ribavirin should be included in protocols for treating patients with compensated cirrhosis. Daclatasvir-based protocols are recommended for decompensated cirrhosis, while the Viekera family is recommended in patients with eGFR sqm, including those on dialysis. In kidney-transplanted patents, caution is due to avoidance of the

  7. Antiviral treatment prioritization in HCV-infected patients with extrahepatic manifestations – An Egyptian perspective

    Science.gov (United States)

    El-Fishawy, Hussein; Saadi, Gamal; Hassaballa, May; Hussein, Mohamed; Doss, Wahid; Ragab, Gaafar; Barsoum, Rashad

    2016-01-01

    Egypt, the single country with highest incidence of HCV infection in the world, has embarked on a government-sponsored mass treatment program using several combinations of DAAs. Recognizing the importance of extrahepatic manifestations, independently of the hepatic, a subcommittee was assigned to develop national guidelines for respective prioritizing indications and protocols. It evaluated the benefit of treating patients with different extrahepatic manifestations, and reviewed relevant clinical trials and guidelines concerning DAA combinations available in Egypt. The latter included Sofosbuvir plus either peg-interferon, Simeprevir, Ledipasvir or daclatasvir, and the Viekera family comprising paritaprevir/ritonavir + ombitasvir with (GT-1) or without (GT-4) Dasabuvir. Any of these protocols may be used with or without Ribavirin according to indication. A blueprint was subjected to peer debate in dedicated workshops in two national meetings and subsequently to an online professional review, eventually leading to a final report that was adopted by the health authorities. Seven compelling and 10 optional indications were identified for treating patients with predominantly extrahepatic manifestations. The former include kidney disease at different stages, cryoglobulinemic vasculitis and non-Hodgkin lymphoma. Selected treatment protocols, were encoded and their use was prioritized on the basis of evidence of efficacy and safety. We concluded that any of the studied protocols may be used, preferably with ribavirin, for 12-week treatment in all patients with extrahepatic manifestations without cirrhosis and with eGFR above 30 ml/min/1.73 sqm. Ribavirin should be included in protocols for treating patients with compensated cirrhosis. Daclatasvir-based protocols are recommended for decompensated cirrhosis, while the Viekera family is recommended in patients with eGFR sqm, including those on dialysis. In kidney-transplanted patents, caution is due to avoidance of the

  8. Determinants of survival among HIV-infected chronic dialysis patients.

    Science.gov (United States)

    Rodriguez, Rudolph A; Mendelson, Michael; O'Hare, Ann M; Hsu, Ling Chin; Schoenfeld, Patricia

    2003-05-01

    Over 100 HIV-infected patients have initiated chronic dialysis at San Francisco General Hospital (SFGH) since 1985. This study employed retrospective analysis to identify determinants of and trends in survival among HIV-infected patients who have initiated chronic dialysis at SFGH from January 1, 1985 to November 1, 2002 (n = 115). Cohort patient survival was compared with survival after an AIDS-opportunistic illness in all HIV-infected patients in San Francisco during the study period. Higher CD4 count (hazard ratio [HR], 0.86 per 50 cells/mm(3) increase; 95% confidence interval [CI], 0.80 to 0.93) and serum albumin (HR, 0.53 per 1 g/dl increase; CI, 0.36 to 0.78) at initiation of dialysis were strongly associated with lower mortality. Survival for those initiating dialysis during the era of highly active antiretroviral therapy (HAART) was 16.1 mo versus 9.4 mo for those initiating dialysis before this time, but this difference was not statistically significant. In adjusted analysis, only a non-statistically significant trend toward improved survival during the HAART era was noted (HR, 0.59; CI, 0.34 to 1.04). By comparison, survival for all HIV-infected patients after an AIDS-opportunistic illness in San Francisco increased from 16 mo in 1994 to 81 mo in 1996. The dramatic improvement in survival that has occurred since the mid-1990s for patients with HIV appears to be greatly attenuated in the sub-group undergoing dialysis. Although this may partly reflect confounding by race, injection drug use and HCV co-infection, future attempts to improve survival among HIV-infected dialysis patients should focus on barriers to the effective use of HAART in this group.

  9. Fracture risk in hepatitis C virus infected persons

    DEFF Research Database (Denmark)

    Hansen, Ann-Brit Eg; Omland, Lars Haukali; Krarup, Henrik;

    2014-01-01

    BACKGROUND & AIMS: The association between Hepatitis C virus (HCV)-infection and fracture risk is not well characterized. We compared fracture risk between HCV-seropositive (HCV-exposed) patients and the general population and between patients with cleared and chronic HCV-infection. METHODS......: Outcome measures were time to first fracture at any site, time to first low-energy and first non-low-energy (other) fracture in 12,013 HCV-exposed patients from the DANVIR cohort compared with a general population control cohort (n=60,065) matched by sex and age. Within DANVIR, 4500 patients with chronic...... HCV-infection and 2656 patients with cleared HCV-infection were studied. RESULTS: Compared with population controls, HCV-exposed patients had increased overall risk of fracture [adjusted incidence rate ratio (aIRR) 2.15, 95% Confidence Interval (CI) 2.03-2.28], increased risk of low-energy fracture (a...

  10. Function of nonstructural 5A protein of genotype 2a in replication and infection of HCV with gene substitution

    Institute of Scientific and Technical Information of China (English)

    Yong-Zhi Wang; Wen-Bo Wang; Ming-Mei Cao; Wen Wang; Lan-Juan Zhao; Gang Xu; Hao Ren; Zhong-Tian Qi

    2011-01-01

    AIM: To explore the function of Nonstructural 5A (NS5A) protein of genotype 2a (JFH1) in the replication and infection of hepatitis C virus (HCV).METHODS: Intergenotypic chimera FL-J6JFH/J4NS5A was constructed by inserting NS5A gene from 1b stain HC-J4 by the overlapping polymerase chain reaction (PPCR) method and the restriction enzyme reaction.In vitro RNA transcripts of chimera, prototype J6JFH and negative control J6JFH1 (GNDD) were prepared and transfected into Huh-7.5 cells with liposomes. Immunofluorescence assay (IFA), fluorescence quantitative PCR and infection assay were performed to determine the protein expression and gene replication in Huh-7.5 cells.RESULTS: The HCV RNA levels in FL-J6JFH/J4NS5A chimera RNA transfected cells were significantly lower than the wild type at any indicated time point (2.58± 5.97×106 vs 4.27 ± 1.72×104, PP = 00.0032). The maximal level of HCV RNA in chimera was 5.6±1.8×104 GE/μg RNA at day 34 after transfection, while the wild type reached a peak level at day 13 which was 126 folds higher (70.65 ± 14.11×105 vs 0.56 ± 0.90×105, = 0.028). HCV proteins could also be detected by IFA in chimera-transfected cells with an obviously low level. Infection assay showed that FL-J6JFH/J4NS5A chimera could produce infectious virus particles, ranging from 10 ± 5 ffu/mL to 78.3 ± 23.6 ffu/mL, while that of FL-J6JFH1 ranged from 5.8 ± 1.5×102 ffu/mL to 2.5 ± 1.4×104 ffu/mL.CONCLUSION: JFH1 NS5A might play an important role in the robust replication of J6JFH1. The establishment of FL-J6JFH/J4NS5A provided a useful platform for studying the function of other proteins of HCV.

  11. Topological analysis of protein co-abundance networks identifies novel host targets important for HCV infection and pathogenesis

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    McDermott Jason E

    2012-04-01

    Full Text Available Abstract Background High-throughput methods for obtaining global measurements of transcript and protein levels in biological samples has provided a large amount of data for identification of 'target' genes and proteins of interest. These targets may be mediators of functional processes involved in disease and therefore represent key points of control for viruses and bacterial pathogens. Genes and proteins that are the most highly differentially regulated are generally considered to be the most important. We present topological analysis of co-abundance networks as an alternative to differential regulation for confident identification of target proteins from two related global proteomics studies of hepatitis C virus (HCV infection. Results We analyzed global proteomics data sets from a cell culture study of HCV infection and from a clinical study of liver biopsies from HCV-positive patients. Using lists of proteins known to be interaction partners with pathogen proteins we show that the most differentially regulated proteins in both data sets are indeed enriched in pathogen interactors. We then use these data sets to generate co-abundance networks that link proteins based on similar abundance patterns in time or across patients. Analysis of these co-abundance networks using a variety of network topology measures revealed that both degree and betweenness could be used to identify pathogen interactors with better accuracy than differential regulation alone, though betweenness provides the best discrimination. We found that though overall differential regulation was not correlated between the cell culture and liver biopsy data, network topology was conserved to an extent. Finally, we identified a set of proteins that has high betweenness topology in both networks including a protein that we have recently shown to be essential for HCV replication in cell culture. Conclusions The results presented show that the network topology of protein co

  12. Predictive Factors for Sustained Virological Response after Treatment with Pegylated Interferon α-2a and Ribavirin in Patients Infected with HCV Genotypes 2 and 3

    Science.gov (United States)

    Niederau, Claus; Mauss, Stefan; Schober, Andreas; Stoehr, Albrecht; Zimmermann, Tim; Waizmann, Michael; Moog, Gero; Pape, Stefan; Weber, Bernd; Isernhagen, Konrad; Sandow, Petra; Bokemeyer, Bernd; Alshuth, Ulrich; Steffens, Hermann; Hüppe, Dietrich

    2014-01-01

    Background Previous trials have often defined genotype 2 and 3 patients as an “easy to treat” group and guidelines recommend similar management. Aims The present study looks for differences between the two genotypes and analyzes predictive factors for SVR. Methods Prospective, community-based cohort study involving 421 physicians throughout Germany. The analysis includes 2,347 patients with untreated chronic HCV genotype 2 (n = 391) and 3 (n = 1,956) infection treated with PEG-IFN α-2a plus ribavirin between August 2007 and July 2012. Results When compared with genotype 2 patients, those with genotype 3 were younger, had a shorter duration of infection, lower values of total cholesterol, LDL cholesterol and BMI, a higher frequency of drug use as infection mode and male gender (p130 mg/dl, a low APRI score, and a γ-GT ≥3-times ULN, RVR, and RBV starting dose were associated with SVR by multivariate analysis. Conclusions The present study corroborates that liver fibrosis is more pronounced in genotype 3 vs. 2. SVR is higher in genotype 2 versus genotype 3 partly because of follow-up problems in genotype 3 patients, in particular in those infected by drug use. Thus, subgroups of genotype 3 patients have adherence problems and need special attention also because they often have significant liver fibrosis. Trial Registration Verband Forschender Arzneimittelhersteller e.V., Berlin, Germany ML21645 ClinicalTrials.gov NCT02106156 PMID:25238535

  13. Correlates of Initiation of Treatment for Chronic Hepatitis C Infection in United States Veterans, 2004-2009.

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    Adi V Gundlapalli

    Full Text Available We describe the rates and predictors of initiation of treatment for chronic hepatitis C (HCV infection in a large cohort of HCV positive Veterans seen in U.S. Department of Veterans Affairs (VA facilities between January 1, 2004 and December 31, 2009. In addition, we identify the relationship between homelessness among these Veterans and treatment initiation. Univariate and multivariable Cox Proportional Hazards regression models with time-varying covariates were used to identify predictors of initiation of treatment with pegylated interferon alpha plus ribavirin. Of the 101,444 HCV treatment-naïve Veterans during the study period, rates of initiation of treatment among homeless and non-homeless Veterans with HCV were low and clinically similar (6.2% vs. 7.4%, p<0.0001. For all U.S. Veterans, being diagnosed with genotype 2 or 3, black or other/unknown race, having Medicare or other insurance increased the risk of treatment. Veterans with age ≥50 years, drug abuse, diabetes, and hemoglobin < 10 g/dL showed lower rates of treatment. Initiation of treatment for HCV in homeless Veterans is low; similar factors predicted initiation of treatment. Additionally, exposure to treatment with medications for diabetes predicted lower rates of treatment. As newer therapies become available for HCV, these results may inform further studies and guide strategies to increase treatment rates in all U.S. Veterans and those who experience homelessness.

  14. [Novel treatments for hepatitis C virus infection in chronic kidney disease].

    Science.gov (United States)

    Fabrizi, Fabrizio; Messa, Piergiorgio

    2016-01-01

    Recent evidence has been accumulated showing a negative impact of chronic hepatitis C virus infection on survival in patients with chronic kidney disease. Moreover, it appears that anti-HCV positive status has been associated with an increased risk of developing chronic kidney disease in the adult general population. These reports have emphasized the need for safe and effective therapies for hepatitis C virus infection in the chronic kidney disease population. Treatment of HCV has made considerable progress with the approval of interferon-free, direct-acting antiviral drug-based combination therapies among patients with intact kidneys; but a paucity of information exists regarding chronic kidney disease patients. The first published report on the antiviral treatment of hepatitis C among patients with chronic kidney disease (stage 4-5) and HCV genotype 1 concerns the combination of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor); excellent safety and efficacy (sustained viral response, 94.3% 115/122) have been reached. In another study, the 3-D regimen (ombitasvir/ paritaprevir/ ritonavir/ dasabuvir with or without ribavirin) has been administered to CKD (stage 4-5) patients with genotype 1 (n=20); the rate of sustained viral response was excellent (90%, 18/20) and no patients discontinued treatment due to adverse events. Preliminary data on the combined treatment of sofosbuvir (NS5B inhibitor) and simeprevir (NS3/4A inhibitor) has given a viral response of 89% (34/38), but the size of the study group (n=38 patients with end-stage renal disease) was small. Thus, the evidence in the medical literature concerning use of DAAs in CKD population is encouraging even if it has a preliminary nature. Also, several points need to be addressed regarding the use of DAAs in CKD population including their impact on survival, costs, and drug-drug interactions. PMID:27545640

  15. Application of functional genomics to the chimeric mouse model of HCV infection: optimization of microarray protocols and genomics analysis

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    Smith Maria W

    2006-05-01

    Full Text Available Abstract Background Many model systems of human viral disease involve human-mouse chimeric tissue. One such system is the recently developed SCID-beige/Alb-uPA mouse model of hepatitis C virus (HCV infection which involves a human-mouse chimeric liver. The use of functional genomics to study HCV infection in these chimeric tissues is complicated by the potential cross-hybridization of mouse mRNA on human oligonucleotide microarrays. To identify genes affected by mouse liver mRNA hybridization, mRNA from identical human liver samples labeled with either Cy3 or Cy5 was compared in the presence and absence of known amounts of mouse liver mRNA labeled in only one dye. Results The results indicate that hybridization of mouse mRNA to the corresponding human gene probe on Agilent Human 22 K oligonucleotide microarray does occur. The number of genes affected by such cross-hybridization was subsequently reduced to approximately 300 genes both by increasing the hybridization temperature and using liver samples which contain at least 80% human tissue. In addition, Real Time quantitative RT-PCR using human specific probes was shown to be a valid method to verify the expression level in human cells of known cross-hybridizing genes. Conclusion The identification of genes affected by cross-hybridization of mouse liver RNA on human oligonucleotide microarrays makes it feasible to use functional genomics approaches to study the chimeric SCID-beige/Alb-uPA mouse model of HCV infection. This approach used to study cross-species hybridization on oligonucleotide microarrays can be adapted to other chimeric systems of viral disease to facilitate selective analysis of human gene expression.

  16. Helicobacter Infection and Chronic Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    Zhao-chun Chi; Xin-juan Yu; Quan-jiang Dong

    2014-01-01

    This paper reviews the recentHelicobacter infection associated with chronic liver disease. The bacteriology, prevalence, pathogenesis and diagnosis were reviewed. Future work should be conducted on the pathogenesis and treatment of this disease.

  17. New perspectives in occult hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Vicente Carre(n)o; Javier Bartolomé; Inmaculada Castillo; Juan Antonio Quiroga

    2012-01-01

    Occult hepatitis C virus (HCV) infection,defined as the presence of HCV RNA in liver and in peripheral blood mononuclear cells (PBMCs) in the absence of detectable viral RNA in serum by standard assays,can be found in anti-HCV positive patients with normal serum levels of liver enzymes and in anti-HCV negative patients with persistently elevated liver enzymes of unknown etiology.Occult HCV infection is distributed worldwide and all HCV genotypes seem to be involved in this infection.Occult hepatitis C has been found not only in anti-HCV positive subjects with normal values of liver enzymes or in chronic hepatitis of unknown origin but also in several groups at risk for HCV infection such as hemodialysis patients or family members of patients with occult HCV.This occult infection has been reported also in healthy populations without evidence of liver disease.Occult HCV infection seems to be less aggressive than chronic hepatitis C although patients affected by occult HCV may develop liver cirrhosis and even hepatocellular carcinoma.Thus,anti-HCV negative patients with occult HCV may benefit from antiviral therapy with pegylatedinterferon plus ribavirin.The persistence of very low levels of HCV RNA in serum and in PBMCs,along with the maintenance of specific T-cell responses against HCV-antigens observed during a long-term follow-up of patients with occult hepatitis C,indicate that occult HCV is a persistent infection that is not spontaneously eradicated.This is an updated report on diagnosis,epidemiology and clinical implications of occult HCV with special emphasis on anti-HCV negative cases.

  18. Prevalence, attitudes and knowledge about HIV HBV and HCV infections among inmates in prisons Prilep and Bitola--a pilot study.

    Science.gov (United States)

    Jovanovska, Tanja; Kocic, Biljana; Stojcevska, Viktorija P

    2014-06-01

    Prisons are associates as facilities liable of high risk of infection disease, as a result of the possibility of transmission of infections in prisons surroundings. Investigations carried out in correctional facilities around the world have shown a high prevalence of blood borne hepatitis viruses and HIV. The study was aimed at confirming prevalence of HIV hepatitis B and hepatitis C among prisoners in Bitola's, and Prilep's prisons, existing of co-infection as well to assess knowledge and attitudes related to HIV, HBV and HCV infections. In this cross-sectional study 200 prisoners have participated, providing answers to structured questionnaire and in order to analyze blood for HIV, HBV and HCV, rapid blood tests in detecting antibodies has been used. Prevalence of HCV is 0.20, HBV 0.17 and HIV prevalence is 0. Co-infection prevalence of HCV/HBV is 0.07 from the total number of examinees. As for the manner of infection with HIV virus 22% are familiar with the fact that persons cannot be infected by HIV if they have only one sexual partner who is not infected and have no other partners, and for the protection of HIV and Hepatitis B by correct use of condoms-58% have given correct answers. PMID:25144968

  19. Variation of transaminases, HCV-RNA levels and Th1/Th2 cytokine production during the post-partum period in pregnant women with chronic hepatitis C.

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    Angeles Ruiz-Extremera

    Full Text Available This study analyses the evolution of liver disease in women with chronic hepatitis C during the third trimester of pregnancy and the post-partum period, as a natural model of immune modulation and reconstitution. Of the 122 mothers recruited to this study, 89 were HCV-RNA+ve/HIV-ve and 33 were HCV-RNA-ve/HIV-ve/HCVantibody+ve and all were tested during the third trimester of pregnancy, at delivery and post-delivery. The HCV-RNA+ve mothers were categorized as either Type-A (66%, with an increase in ALT levels in the post-partum period (>40 U/L; P<0.001 or as Type-B (34%, with no variation in ALT values. The Type-A mothers also presented a significant decrease in serum HCV-RNA levels in the post-delivery period (P<0.001 and this event was concomitant with an increase in Th1 cytokine levels (INFγ, P = 0.04; IL12, P = 0.01 and IL2, P = 0.01. On the other hand, the Type-B mothers and the HCV-RNA-ve women presented no variations in either of these parameters. However, they did present higher Th1 cytokine levels in the partum period (INFγ and IL2, P<0.05 than both the Type-A and the HCV-RNA-ve women. Cytokine levels at the moment of delivery do not constitute a risk factor associated with HCV vertical transmission. It is concluded that differences in the ALT and HCV-RNA values observed in HCV-RNA+ve women in the postpartum period might be due to different ratios of Th1 cytokine production. In the Type-B women, the high partum levels of Th1 cytokines and the absence of post-partum variation in ALT and HCV-RNA levels may be related to permanent Th1 cytokine stimulation.

  20. 河北省HIV-1感染者中HCV和HBV合并感染状况调查%Study on HCV and HBV co-infection among HIV-1 infected people in Hebei Province

    Institute of Scientific and Technical Information of China (English)

    赵翠英; 李巧敏; 赵宏儒; 路新利; 白广义; 李岩; 王莹莹; 王伟

    2012-01-01

    Objective To study the ratios of HCV and HBV co-infection among HIV-1 infected people in Hebei Province. Method Peripheral blood was collected for testing HCV antibody and HBsAg in HIV-1 infected individuals. Results Of the 147 HIV-1 infected individuals receiving blood tests, 17. 7% (26/147) were infected with HCV, 15. 0% (22/147) were infected with HBV,and 3. 4%(5/147) were co-infected with HCV/HBV. The statistical a-nalysis showed a significant difference in the ratios of HCV co-infection among individuals who were infected with HIV through different routes(P<0. 001). The ratios of HCV co-infection were 100. 0%(6/6)in injecting drug users. In those infected via blood transmission and sexual behaviors,the ratios of HCV co-infection were 73. 3%(11/ 15) and 6. 3%(7/lll)respectively. HIV infected females had a higher ratio of HCV co-infection than males (P = 0. 002). Statistically significant difference was found in ratio of HCV co-infection among individuals with various educational backgrounds (P<0. 01). HIV infected individuals with lower education had higher HCV co-infection rati-o. Statistically significant difference was also observed in ratio of HCV co-infection among HIV infected individuals of different ages (P<0. 05). HIV infected individuals of lowe_r age had higher HBV co-infection ratio.' Conclusion There are higher ratios of HCV and HBV co-infection in HIV-1 infected individuals.%目的 了解河北省艾滋病病毒Ⅰ型(HIV-1)感染者中,丙型肝炎病毒(HCV)、乙型肝炎(乙肝)病毒(HBV)的感染状况.方法 采集了HIV-1感染者的抗凝全血样品,进行了HCV抗体和乙肝病毒表面抗原(HBsAg)的检测.结果 147例HIV-1感染者中,HCV感染率为17.7%(26/147),HBV感染率为15.0%(22/147),HCV/HBV混合感染率为3.4%(5/147).在HIV-1感染者中,HCV的感染率在注射吸毒感染者中为100%(6/6),血液途径感染者中为73.3%(11/15),性感染者中为6.3%(7/111),不同感染途径间

  1. HCV-Related Nervous System Disorders

    OpenAIRE

    Salvatore Monaco; Sergio Ferrari; Alberto Gajofatto; Gianluigi Zanusso; Sara Mariotto

    2012-01-01

    Chronic infection with hepatitis C virus (HCV) is associated with a wide spectrum of extrahepatic manifestations, affecting different organ systems. Neurological complications occur in a large number of patients and range from peripheral neuropathy to cognitive impairment. Pathogenetic mechanisms responsible for nervous system dysfunction are mainly related to the upregulation of the host immune response with production of autoantibodies, immune complexes, and cryoglobulins. Alternative mecha...

  2. The Cedar Project: high incidence of HCV infections in a longitudinal study of young Aboriginal people who use drugs in two Canadian cities

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    Spittal Patricia M

    2012-08-01

    Full Text Available Abstract Background Factors associated with HCV incidence among young Aboriginal people in Canada are still not well understood. We sought to estimate time to HCV infection and the relative hazard of risk factors associated HCV infection among young Aboriginal people who use injection drugs in two Canadian cities. Methods The Cedar Project is a prospective cohort study involving young Aboriginal people in Vancouver and Prince George, British Columbia, who use illicit drugs. Participants’ venous blood samples were drawn and tested for HCV antibodies. Analysis was restricted to participants who use used injection drugs at enrolment or any of follow up visit. Cox proportional hazards regression was used to identify independent predictors of time to HCV seroconversion. Results In total, 45 out of 148 participants seroconverted over the study period. Incidence of HCV infection was 26.3 per 100 person-years (95% Confidence Interval [CI]: 16.3, 46.1 among participants who reported using injection drugs for two years or less, 14.4 per 100 person-years (95% CI: 7.7, 28.9 among participants who had been using injection drugs for between two and five years, and 5.1 per 100 person-years (95% CI: 2.6,10.9 among participants who had been using injection drugs for over five years. Independent associations with HCV seroconversion were involvement in sex work in the last six months (Adjusted Hazard Ratio (AHR: 1.59; 95% CI: 1.05, 2.42 compared to no involvement, having been using injection drugs for less than two years (AHR: 4.14; 95% CI: 1.91, 8.94 and for between two and five years (AHR: 2.12; 95%CI: 0.94, 4.77 compared to over five years, daily cocaine injection in the last six months (AHR: 2.47; 95% CI: 1.51, 4.05 compared to less than daily, and sharing intravenous needles in the last six months (AHR: 2.56; 95% CI: 1.47, 4.49 compared to not sharing. Conclusions This study contributes to the limited body of research addressing HCV infection among

  3. Occult Hepatitis C Virus Infection in Haemodialysis Unit: A Single-center Experience

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    Abdel Hamid A. Serwah1, Waleed S. Mohamed1, Mohamed Serwah1, Awateif Edreis2, Ahmad El Zaydi3

    2014-07-01

    Full Text Available Background & Aims: Detection of hepatitis C virus RNA in peripheral blood mononuclear cells (PBMC and/or hepatocytes in the absence of HCV RNA in serum, designated as ‘occult HCV infection’, has been a matter of controversy in the recent years. Occult hepatitis C virus (HCV infection has not been investigated in haemodialysis patients. We investigated for the first time the prevalence of occult HCV infection in large cohorts of chronic hemodialysis (CHD patients in a single heamodialysis center at Al-Taif, KSA. Methods: We enrolled 84 CHD patients, whose sera are negative for HCV markers. HCV RNA was tested in PBMC using a sensitive commercial real time assay. In this study, real-time PCR was used to test for the presence of genomic HCV-RNA in peripheral blood mononuclear cells of all of these patients. For comparison, 20 patients on HD with evidence of chronic hepatitis C virus infection were included as a control group. Results: In CHD patients, occult HCV infection, determined by the presence of genomic HCV-RNA in peripheral blood mononuclear cells (PBMNCs, was found in 13.4 % of the patients; 83 % of these patients had ongoing HCV replication, indicated by the presence of HCV-RNA. Patients with occult HCV infection had spent a significantly longer time on heamodialysis and had significantly higher mean alanine aminotransferase levels during the 3 months before study entry. Compared to CHCV patients, those with occult HCV have less elevated bilirubin, AST and ALT. Conclusions: The prevalence of occult HCV infection was moderate in our CHD patients, and it did not appear to be clinically relevant. Further studies in other geographic populations with high HCV endemicity are required to clarify the significance of occult HCV infection in these patient groups. Abbreviations HCV, Hepatitis C Virus ; antibody against HCV; PBMC, peripheral blood mononuclear cells; rRT-PCR, real time reverse transcriptase polymerase chain reaction; CHD, chronic

  4. TT virus and hepatitis G virus infections in Korean blood donors and patients with chronic liver disease

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    Mee Juhng Jeon; Jong Hee Shin; Soon Pal Suh; Yong Chai Lim; Dong Wook Ryang

    2003-01-01

    AIM: To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea, to investigate the association of TTV and HGV infections with blood transfusion, and to assess the correlation between TTV and HGV viremia and hepatic damage.METHODS: A total of 391 serum samples were examined in this study. Samples were obtained from healthy blood donors (n= 110), hepatitis B surface antigen (HBsAg)-positive donors (n=112), anti-hepatitis C virus (anti-HCV)-positive donors (n=69), patients with type B chronic liver disease (n=81), and patients with type C chronic liver disease (n= 19).TTV DNA was detected using the hemi-nested PCR. HGV RNA was tested using RT-PCR. A history of blood transfusion and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also determined.RESULTS: TTV DNA was detected in 8.2 % of healthy blood donors, 16.1% of HBsAg-positive donors, 20.3 % of antiHCV-positive donors, 21.0 % of patients with type B chronic liver disease, and 21.1% of patients with type C chronic liver disease. HGV RNA was detected in 1.8 % of healthy blood donors, 1.8 % of HBsAg-positive donors, 17.4 % of anti-HCV-positive donors, 13.6% of patients with type B chronic liver disease, and 10.5% of patients with type C chronic liver disease. The prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors (P<0.05),except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy donors. There was a history of transfusion in 66.7% of TTV DNA-positive patients and 76.9% of HGV RNA-positive patients (P<0.05). No significant increase in serum ALT and AST was detected in the TTV- or HGV-positive donors and patients.CONCLUSION: TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood donors. However, there is no significant

  5. Predictive value of liver enzymes and inflammatory biomarkers for the severity of liver fibrosis stage in HIV/HCV co-infected patients.

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    Charlotte Charpentier

    Full Text Available OBJECTIVE: The aim of our study was to assess a possible association between plasma inflammatory biomarkers (CRP, IL-6, soluble CD14 and the extent of fibrosis or cirrhosis using a FibroScan® in HIV/HCV co-infected patients. METHODS: This cross-sectional study assessed 60 HIV/HCV co-infected patients who had paired plasma samples and FibroScan® values available. All included patients were controlled for HIV infection (HIV-1 RNA <50 copies/mL and had detectable HCV RNA levels. Levels of three biomarkers were measured in all samples using commercial ELISA kits. Multivariate logistic regression models identified factors associated with the METAVIR stages of fibrosis (F0-F2 vs. F3-F4. RESULTS: In univariate logistic regression analyses, in addition to sCD14 (odds ratio [OR] = 3.23, 95% confidence interval [95%CI] = 1.30-7.97, P = 0.01, aspartate aminotransferase (AST, alanine aminotransferase, platelet counts, and CD4 cell counts were associated with the stage of liver fibrosis and, thus, were introduced into the model. However, only AST (OR = 1.06, 95%CI = 1.02-1.10, P = 0.0009 was independently associated with F3-F4 stage liver fibrosis. CONCLUSIONS: In our study of HIV/HCV co-infected patients, sCD14 plasma level, a biomarker of monocyte activation, was not independently associated with the F3-F4 stage of liver fibrosis. We hypothesize that the higher levels of inflammation markers observed in HIV/HCV co-infected patients, compared to HCV mono-infected patients, prevent this association being observed within this population.

  6. Chronic Infections and Management Setting in Drug Addicts of MMT Program in Pinang, Malaysia

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    Syed Azhar Syed Sulaiman

    2009-09-01

    Full Text Available Background: The authors sought to identify the prevalence of blood-borne chronic infections and determine the appropriate management therapy setting among the drug addicts of methadone maintenance treatment (MMT program. The purpose to identify such factor is to know the quality of health of respondents active to MMT program and possibly predict the risk reduction of relapse during the treatment. Methodology: As it was known that government of Malaysia allowed MMT on large scale at 2005, so a year retrospective with six months prospective study (from Jan 2007 to May 2008 was conducted in three methadone clinics of Pinang state, Malaysia. All the registered patients were included in the study and data was collected through special design data collection form by reviewing the medical profiles. Results: Findings showed HIV/AIDS was found in 2.3%, HCV 76.3%, HBV 3.3%, while 37.7% respondents were identified impaired liver function. The risk combination was HCV with impaired liver function identified in 39.5% respondents. None of them receives any supportive management treatment for the current chronic infectious condition. Conclusion: This study highly recommends producing necessary resources for the management treatment of Drug addicts for such chronic infection, as further delay can possibly increase the risk to transmit the infection in the society.

  7. Prevalence and Correlates of HCV, HVB, and HIV Infection among Prison Inmates and Staff, Hungary

    OpenAIRE

    Tresó, Bálint; Barcsay, Erzsébet; Tarján, Anna; Horváth, Gergely; Dencs, Ágnes; Hettmann, Andrea; Csépai, Mária Magdolna; Győri, Zoltán; Rusvai, Erzsébet; Takács, Mária

    2011-01-01

    The aim of this national, multicenter, cross-sectional study was to assess the prevalence of hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency viruses (HIV) among prisoners, and to identify related risk behaviors including injection drug use. Overall, 4,894 inmates from 20 prisons were enrolled. To have a comparison group, prison staff were also asked to take part. Altogether, 1,553 of the 4,894 inmates from seven prisons completed a questionnaire on risk behaviors. According t...

  8. Chronic hepatitis virus infection in patients with multiple myeloma: clinical characteristics and outcomes

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    Chung-Jen Teng

    2011-01-01

    Full Text Available OBJECTIVES: Cytotoxic agents and steroids are used to treat lymphoid malignancies, but these compounds may exacerbate chronic viral hepatitis. For patients with multiple myeloma, the impact of preexisting hepatitis virus infection is unclear. The aim of this study is to explore the characteristics and outcomes of myeloma patients with chronic hepatitis virus infection. METHODS: From 2003 to 2008, 155 myeloma patients were examined to determine their chronic hepatitis virus infection statuses using serologic tests for the hepatitis B (HBV and C viruses (HCV. Clinical parameters and outcome variables were retrieved via a medical chart review. RESULTS: The estimated prevalences of chronic HBV and HCV infections were 11.0% (n = 17 and 9.0% (n = 14, respectively. The characteristics of patients who were hepatitis virus carriers and those who were not were similar. However, carrier patients had a higher prevalence of conventional cytogenetic abnormalities (64.3% vs. 25.0%. The cumulative incidences of grade 3-4 elevation of the level of alanine transaminase, 30.0% vs. 12.0%, and hyperbilirubinemia, 20.0% vs. 1.6%, were higher in carriers as well. In a Kaplan-Meier analysis, carrier patients had worse overall survival (median: 16.0 vs. 42.4 months. The prognostic value of carrier status was not statistically significant in the multivariate analysis, but an age of more than 65 years old, the presence of cytogenetic abnormalities, a beta-2-microglobulin level of more than 3.5 mg/L, and a serum creatinine level of more than 2 mg/ dL were independent factors associated with poor prognosis. CONCLUSION: Myeloma patients with chronic hepatitis virus infections might be a distinct subgroup, and close monitoring of hepatic adverse events should be mandatory.

  9. Antiviral Treatment of HCV-Infected Patients with B-Cell Non-Hodgkin Lymphoma: ANRS HC-13 Lympho-C Study

    Science.gov (United States)

    Alric, Laurent; Besson, Caroline; Lapidus, Nathanael; Jeannel, Juliette; Michot, Jean-Marie; Cacoub, Patrice; Canioni, Danielle; Pol, Stanislas; Davi, Frédéric; Rabiega, Pascaline; Ysebaert, Loic; Bonnet, Delphine; Hermine, Olivier

    2016-01-01

    Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral therapies in HCV patients with B-NHL is warranted. Methods: First, we evaluated the sustained virologic response (SVR) and safety of Peg-interferon-alpha (Peg-IFN) + ribavirin +/- first protease inhibitors (PI1s) therapy in 61 HCV patients with B-NHL enrolled in a nationwide observational survey compared with 94 matched HCV-infected controls without B-NHL. In a second series, interferon-free regimens using a newly optimal combination therapy with direct-acting antiviral drugs (DAAs) were evaluated in 10 patients with HCV and B-NHL. Results: The main lymphoma type was diffuse large B-cell lymphoma (38%) followed by marginal zone lymphoma (31%). In the multivariate analysis, patients with B-NHL treated by Peg-IFN-based therapy exhibited a greater SVR rate compared with controls, 50.8% vs 30.8%, respectively, p<0.01, odds ratio (OR) = 11.2 [2.3, 52.8]. B-NHL response was better (p = 0.02) in patients with SVR (69%) than in patients without SVR (31%). Premature discontinuation of Peg-IFN-based therapy was significantly more frequent in the B-NHL group (19.6%) compared with the control group (6.3%), p<0.02. Overall, survival was significantly enhanced in the controls than in the B-NHL group (hazard ratio = 34.4 [3.9, 304.2], p< 0.01). Using DAAs, SVR was achieved in 9/10 patients (90%). DAAs were both well tolerated and markedly efficient. Conclusions: The virologic response of HCV-associated B-NHL is high. Our study provides a comprehensive evaluation of different strategies for the antiviral treatment of B-NHL associated with HCV infection. PMID:27749916

  10. Values of high-resolution computed tomography and pulmonary function tests in managements of patients with chronic hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Oguzhan Okutan; Zafer Kartaloglu; Ahmet Ilvan; Ali Kutlu; Erkan Bozkanat; Emir Silit

    2004-01-01

    function tests (PFT) and high-resolution computed tomography (HRCT) in patients with chronic hepatitis C virus (HCV) infection.METhODS: Thirty-four patients with chronic HCV infection without diagnosis of any pulmonary diseases and 10 healthy cases were enrolled in the study. PFT and HRCT were performed in all cases.RESULTS: A decrease lower than 80% of the predicted value was detected in vital capacity in 9/34 patients, in forced expiatory volume in one second in 8/34 patients, and in forced expiratory flow 25-75 in 15/34 patients, respectively. Carbon monoxide diffusing capacity (DLCO) was decreased in 26/34 patients. Findings of interstitial pulmonary involvement were detected in the HRCT of 16/34 patients. Significant difference was found between controls and patienls with HCV infection in findings of HRCT (X2=4.7, P =0.003). Knodell histological activity index (KHAI) of 28/34 patients in whom liver biopsy was applied was 9.0±4.7. HRCT findings, PFT values and DLCO were not affected by KHAI in patienIs with HCV infection. In these patiente, all the parameters were related with age.CONCLUSION: We suggest that chronic hepatitis C virus infection may cause pulmonary interstitial involvement without evident respiratory symptoms.

  11. Complementary role of HCV and HIV in T-cell activation and exhaustion in HIV/HCV coinfection

    NARCIS (Netherlands)

    Feuth, T.; Arends, J.E.; Fransen, J.H.; Nanlohy, N.M.; Erpecum, K.J. van; Siersema, P.D.; Hoepelman, A.I.; Baarle, D. van

    2013-01-01

    OBJECTIVES: To investigate whether T-cell activation and exhaustion is linked to HCV- and HIV disease parameters in HIV/HCV infected individuals, we studied T-cell characteristics in HIV/HCV coinfected patients and controls. METHODS: 14 HIV/HCV coinfected, 19 HCV monoinfected, 10 HIV monoinfected pa

  12. Prediction of hepatocellular carcinoma risk in chronic hepatitis B and C: review of findings in REVEAL-HBV/HCV study%乙型及丙型肝炎患者发生肝细胞癌的风险预测:REVEAL-HBV/HCV研究的回顾

    Institute of Scientific and Technical Information of China (English)

    杨怀壹; 李美璇; 陈建仁

    2011-01-01

    乙型肝炎病毒(HBV)及丙型肝炎病毒(HCV)的慢性感染是肝细胞癌(HCC)的主要致病原因.全球约有3亿5千万人为HBV的慢性感染者;HCV慢性感染者则有2亿人.全球每年约有50万人死于乙型肝炎引起的HCC,另有25万人死于丙型肝炎引起的HCC.乙型肝炎慢性感染者,其血中HBV DNA及ALT持续处于高水平是HCC最重要的预测因子.其他的危险因子还包括HBV C基因型、HBV基础核心促进子A1762T/G1764A双突变、男性、老年、肝癌家族史、酗酒习惯、以及与HCV或人类免疫不全病毒的合并感染等.根据REVEAL-HBV研究的资料,我们发展出简单易用的列线图,可利用非侵入性的临床特征准确地预测慢性乙型肝炎患者发生HCC的风险.丙型肝炎慢性感染患者发生HCC最重要的预测因子包括高血中HCV RNA水平、高ALT水平、HCV基因型以及老年等.REVEAL-HCV研究案例中,与HCV RNA水平低于检测范围且低ALT水平者相比,HCV RNA可测得、高ALT水平且感染第一型病毒的案例具有最高的HCC发生风险,其多变项调整后的风险比值(95%CI)为21.87(5.09~93.95),这些发现对于慢性丙型肝炎的临床处置具有重要的意义.%Both hepatitis B virus (HBV) and hepatitis C virus (HCV) are major causes of hepatocellular carcinoma (HCC).An estimated 350 million people worldwide are living with chronic HBV infection, and 200 million with chronic HCV infection.Each year, an estimated 500 000 people die of HCC caused by chronic HBV infection, and another 200 000 HCC cases caused by chronic HCV infection.The most important predictors of HCC risk in persons who have chronic HBV infection are persistently elevated serum levels of HBV DNA and alanine aminotransferase (ALT).Other HCC risk predictors for chronic hepatitis B patients include HBV genotype C infection, HBV basal core promoter A1762T/G1764A mutants, male sex, older age, family HCC history, habitual alcohol consumption, and co-infection with

  13. Therapeutic Response to Peg IFN-alpha-2b and Ribavirin in HIV/HCV Co-infected African American and Caucasian Patients as a function of HCV Viral Kinetics and Interferon Pharmacodynamics

    Science.gov (United States)

    Rozenberg, L; Haagmans, BL; Neumann, AU; Chen, G.; McLaughlin, M; Levy-Drummer, RS; Masur, H; Dewar, RL; Ferenci, P; Silva, M.; Viola, MS; Polis, MA; Kottilil, S.

    2010-01-01

    In this study we sought to characterize the relationship between several pharmacokinetic (PK) and pharmacodynamic (PD) parameters and virologic responses among HIV/HCV genotype-1 co-infected patients receiving pegylated interferon-alpha-2b (peg-IFN2b) and ribavirin. We also tried to establish the underlying mechanisms that lead to poor SVR rates observed with African Americans (AA) against Caucasians and compared their results with those observed in a cohort of HCV mono-infected patients. Among our studied population, a viral decline of more than 1.0 log at day 3 combined with viral load of less than 5.0 log IU/ml at day 28 predicted SVR with NPV=100% and PPV=100%. AA had significantly (P<0.01) slower HCV VK as compared to Caucasians. However, peg-IFN2b concentrations and PK parameters, peg-IFN2b max and peg-IFN2b half-life, were similar in both groups and did not predict SVR. Nevertheless, the PD parameter Ec50, estimated from non-linear fitting of the viral kinetics together with peg-IFN2b concentration data, showed that HIV/HCV co-infected AA have lower sensitivity to interferon-alpha thus giving rise to slower viral decline. The combined PK/PD parameter IFNmax/Ec90 was excellent predictor of SVR, thus showing the importance to maintain peg-IFN2b levels above Ec90 to achieve successful treatment. Further studies are needed to evaluate whether these pharmacodynamical predictions are a result of differential host response to peg-IFN2b or other viral factors conferring relative resistance to peg-IFN2b. PMID:19898214

  14. HCV core protein binds to gC1qR to induce A20 expression and inhibit cytokine production through MAPKs and NF-κB signaling pathways.

    Science.gov (United States)

    Song, Xiaotian; Yao, Zhiyan; Yang, Jianling; Zhang, Zhengzheng; Deng, Yuqing; Li, Miao; Ma, Cuiqing; Yang, Lijuan; Gao, Xue; Li, Wenjian; Liu, Jianguo; Wei, Lin

    2016-06-01

    Hepatitis C virus (HCV) infection is characterized by a strong propensity toward chronicity. During chronic HCV infection, HCV core protein is implicated in deregulating cytokine expression that associates with chronic inflammation. A20 is known as a powerful suppressor in cytokine signaling, in this study, we explored the A20 expression in macrophages induced by HCV core protein and the involved signaling pathways. Results demonstrated that HCV core protein induced A20 expression in macrophages. Silencing A20 significantly enhanced the secretion of IL-6, IL-1β and TGF-β1, but not IL-8 and TNF. Additionally, HCV core protein interacted with gC1qR, but not TLR2, TLR3 and TLR4 in pull-down assay. Silencing gC1qR abrogated core-induced A20 expression. Furthermore, HCV core protein activated MAPK, NF-κB and PI3K/AKT pathways in macrophages. Inhibition of P38, JNK and NF-κB but not ERK and AKT activities greatly reduced the A20 expression. In conclusion, the study suggests that HCV core protein ligates gC1qR to induce A20 expression in macrophages via P38, JNK and NF-κB signaling pathways, which leads to a low-grade chronic inflammation during HCV infection. It represents a novel mechanism by which HCV usurps the host for persistence.

  15. Mosaic gene network modelling identified new regulatory mechanisms in HCV infection.

    Science.gov (United States)

    Popik, Olga V; Petrovskiy, Evgeny D; Mishchenko, Elena L; Lavrik, Inna N; Ivanisenko, Vladimir A

    2016-06-15

    Modelling of gene networks is widely used in systems biology to study the functioning of complex biological systems. Most of the existing mathematical modelling techniques are useful for analysis of well-studied biological processes, for which information on rates of reactions is available. However, complex biological processes such as those determining the phenotypic traits of organisms or pathological disease processes, including pathogen-host interactions, involve complicated cross-talk between interacting networks. Furthermore, the intrinsic details of the interactions between these networks are often missing. In this study, we developed an approach, which we call mosaic network modelling, that allows the combination of independent mathematical models of gene regulatory networks and, thereby, description of complex biological systems. The advantage of this approach is that it allows us to generate the integrated model despite the fact that information on molecular interactions between parts of the model (so-called mosaic fragments) might be missing. To generate a mosaic mathematical model, we used control theory and mathematical models, written in the form of a system of ordinary differential equations (ODEs). In the present study, we investigated the efficiency of this method in modelling the dynamics of more than 10,000 simulated mosaic regulatory networks consisting of two pieces. Analysis revealed that this approach was highly efficient, as the mean deviation of the dynamics of mosaic network elements from the behaviour of the initial parts of the model was less than 10%. It turned out that for construction of the control functional, data on perturbation of one or two vertices of the mosaic piece are sufficient. Further, we used the developed method to construct a mosaic gene regulatory network including hepatitis C virus (HCV) as the first piece and the tumour necrosis factor (TNF)-induced apoptosis and NF-κB induction pathways as the second piece. Thus

  16. 丙型肝炎病毒感染实验动物模型的研究进展%Advances in research on experimental animal models of HCV infection

    Institute of Scientific and Technical Information of China (English)

    姜晨晨; 彭宗根

    2014-01-01

    丙型肝炎病毒( HCV)感染是导致人类慢性病毒性肝炎、肝硬化和肝癌的最主要病因之一。由于缺乏合适的HCV感染实验动物模型,使得针对HCV感染更为有效的疗法及疫苗的研发滞后。黑猩猩是HCV感染研究的最佳实验动物,但由于其来源有限、价格昂贵及临床症状等诸多问题,其应用受限,因此发展新的实验动物模型用于HCV感染相关的基础和应用研究迫在眉睫。近年来,以啮齿类等动物为替代模型取得了不少进展,应用转基因等实验技术使替代动物感染了HCV,并成功应用于多个学科领域的研究。本文分析了 HCV自然感染的实验动物、自然感染和非自然感染的替代实验动物在致病机制研究、药物评价和疫苗研发应用中的优缺点及未来研究趋势。%Hepatitis C virus ( HCV) is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcino-ma in humans.Due to the lack of suitable experimental animal models for HCV infection, the development of more effective treatment of HCV infection and vaccines has been delayed.Chimpanzee is the best experimental animal model for the re-search of hepatitis C virus ( HCV) infection.However, because of its limited in resource, expensive in breeding, and difference in clinical symptoms, thus developing new experimental animal models for HCV-related basic and applied re-search is imminent.In recent years, as a surrogate animal model, the development of rodent model and other models has been achieved a lot of progress.Using such as genetically modified experimental techniques, those surrogate animals were infected with HCV in vivo and were successfully applied to research in several areas.In this review, we will focus on the a-chieved progress in naturally infected animal model and transgenic surrogate experimental models, and their advantage and limitation in usage in study on the pathogenetic mechanism of infection, drug

  17. Advances in research on experimental animal models of HCV infection%丙型肝炎病毒感染实验动物模型的研究进展

    Institute of Scientific and Technical Information of China (English)

    姜晨晨; 彭宗根

    2014-01-01

    丙型肝炎病毒( HCV)感染是导致人类慢性病毒性肝炎、肝硬化和肝癌的最主要病因之一。由于缺乏合适的HCV感染实验动物模型,使得针对HCV感染更为有效的疗法及疫苗的研发滞后。黑猩猩是HCV感染研究的最佳实验动物,但由于其来源有限、价格昂贵及临床症状等诸多问题,其应用受限,因此发展新的实验动物模型用于HCV感染相关的基础和应用研究迫在眉睫。近年来,以啮齿类等动物为替代模型取得了不少进展,应用转基因等实验技术使替代动物感染了HCV,并成功应用于多个学科领域的研究。本文分析了 HCV自然感染的实验动物、自然感染和非自然感染的替代实验动物在致病机制研究、药物评价和疫苗研发应用中的优缺点及未来研究趋势。%Hepatitis C virus ( HCV) is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcino-ma in humans.Due to the lack of suitable experimental animal models for HCV infection, the development of more effective treatment of HCV infection and vaccines has been delayed.Chimpanzee is the best experimental animal model for the re-search of hepatitis C virus ( HCV) infection.However, because of its limited in resource, expensive in breeding, and difference in clinical symptoms, thus developing new experimental animal models for HCV-related basic and applied re-search is imminent.In recent years, as a surrogate animal model, the development of rodent model and other models has been achieved a lot of progress.Using such as genetically modified experimental techniques, those surrogate animals were infected with HCV in vivo and were successfully applied to research in several areas.In this review, we will focus on the a-chieved progress in naturally infected animal model and transgenic surrogate experimental models, and their advantage and limitation in usage in study on the pathogenetic mechanism of infection, drug

  18. Epidemiology of hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Miriam J Alter

    2007-01-01

    Globally, hepatitis C virus (HCV) has infected an estimated 130 million people, most of whom are chronically infected. HCV-infected people serve as a reservoir for transmission to others and are at risk for developing chronic liver disease, cirrhosis, and primary hepatocellular carcinoma (HCC). It has been estimated that HCV accounts for 27% of cirrhosis and 25% of HCC worldwide. HCV infection has likely been endemic in many populations for centuries. However, the wave of increased HCV-related morbidity and mortality that we are now facing is the result of an unprecedented increase in the spread of HCV during the 20th century.Two 20th century events appear to be responsible for this increase; the widespread availability of injectable therapies and the illicit use of injectable drugs.

  19. Adiponectin serum level in chronic hepatitis C infection andtherapeutic profile

    Institute of Scientific and Technical Information of China (English)

    Valentina Peta; Carlo Torti; Natasa Milic; Alfredo Focà; Ludovico Abenavoli

    2015-01-01

    Hepatic steatosis is commonly seen in the patients withchronic hepatitis C virus (HCV) infection. HCV is closelyassociated with lipid metabolism, and viral steatosis ismore common in genotype 3 infection owing to a directcytopathic effect of HCV core protein. In non-genotype3 infection, hepatic steatosis is considered largely tobe the result of the alterations in host metabolism;metabolic steatosis is primarily linked with HCV genotype1. Adipose tissue secretes different hormonesinvolved in glucose and lipid metabolisms. It has beendemonstrated that adipocytokines are involved in thepathogenesis of non-alcoholic fatty liver disease, as thedecreased plasma adiponectin levels, a soluble matrixprotein expressed by adipoctyes and hepatocyte, areassociated with liver steatosis. Various studies haveshown that steatosis is strongly correlated negativelywith adiponectin in the patients with HCV infection.The role of adiponectin in hepatitis C virus inducedsteatosis is still not completely understood, but therelationship between adiponectin low levels and liversteatosis is probably due to the ability of adiponectinto protect hepatocytes from triglyceride accumulationby increasing β-oxidation of free fatty acid and thusdecreasing de novo free fatty acid production.

  20. An investigation of HCV HIV and syphilis infection in hemophilia patients in Shandong, 2005-2011%山东省2005-2011年血友病患者HCV HIV和梅毒感染情况

    Institute of Scientific and Technical Information of China (English)

    张雪芹; 张心声; 朱海峰; 曹丹; 唐建华; 滕彬

    2012-01-01

    Objective To better understand the infection status of HCV, HIV and syphilis in hemophilia patients. Methods Serum HCV, HIV and Treponema pallidum, (TP) antibodies were measured by ELISA in 628 hemophilia patients and 2 474 voluntary blood donors. Results The positive rates of HCV, HIV and TP antibodies in 628 hemophilia patients were 9. 6% , 0. 6% and 0. 2% , respectively, and the overall infection rate was 10. 4% (65/628). The positive rates of HCV antibody in different age groups (0 - 19 years, 20 - 39 years and 40 - 77 years) were 3. 3% , 9. 8% and 20. 5%, respectively. The positive rates of HCV, HIV and TP antibodies in 2 474 voluntary blood donors were 0. 4 %, 0.0% and 0.2%, respectively, and the overall infection rate was 0. 6 % (15/2 474). Conclusion The positive rates of HCV and HIV antibodies in hemophilia patients were much higher than those in voluntary blood donors,the rate of HCV infection in hemophilia patients was closely correlated with age.%目的 了解山东省血友病患者丙型肝炎病毒(Hepatitis C virus,HCV)、人类免疫缺陷病毒(Human immunodeficiency virus,HIV)和梅毒螺旋体(Treponema pallidum,TP)的感染情况.方法 对2005-2011年山东省血友病诊疗中心确诊或治疗的628例血友病患者,采用酶联免疫吸附试验检测HCV、HIV和梅毒抗体,并根据年龄段进行分组,随机选择2 474例无偿献血者为正常对照.结果 628例血友病患者抗-HCV、抗-HIV和抗-TP的阳性率分别为9.6%(60/628)、0.6%(4/628)和0.2%(1/628),总感染率为10.4%(65/628).0~19岁、20~39岁、40~77岁年龄段患者抗-HCV阳性率分别为3.3%、9.8%和20.5%.2 474例无偿献血者抗-HCV、抗-HIV和抗-TP的阳性率分别为0.4%(11/2 474)、0和0.2%(4/2 474),总感染率为0.6%(15/2 474).结论 血友病患者抗-HCV和抗-HIV阳性率明显高于无偿献血者,HCV感染与年龄密切相关.

  1. Chimeric antigen receptor (CAR)-engineered T cells redirected against hepatitis C virus (HCV) E2 glycoprotein

    Science.gov (United States)

    Sautto, Giuseppe A; Wisskirchen, Karin; Clementi, Nicola; Castelli, Matteo; Diotti, Roberta A; Graf, Julia; Clementi, Massimo; Burioni, Roberto; Protzer, Ulrike; Mancini, Nicasio

    2016-01-01

    Objective The recent availability of novel antiviral drugs has raised new hope for a more effective treatment of hepatitis C virus (HCV) infection and its severe sequelae. However, in the case of non-responding or relapsing patients, alternative strategies are needed. To this end we have used chimeric antigen receptors (CARs), a very promising approach recently used in several clinical trials to redirect primary human T cells against different tumours. In particular, we designed the first CARs against HCV targeting the HCV/E2 glycoprotein (HCV/E2). Design Anti-HCV/E2 CARs were composed of single-chain variable fragments (scFvs) obtained from a broadly cross-reactive and cross-neutralising human monoclonal antibody (mAb), e137, fused to the intracellular signalling motif of the costimulatory CD28 molecule and the CD3ζ domain. Activity of CAR-grafted T cells was evaluated in vitro against HCV/E2-transfected cells as well as hepatocytes infected with cell culture-derived HCV (HCVcc). Results In this proof-of-concept study, retrovirus-transduced human T cells expressing anti-HCV/E2 CARs were endowed with specific antigen recognition accompanied by degranulation and secretion of proinflammatory and antiviral cytokines, such as interferon γ, interleukin 2 and tumour necrosis factor α. Moreover, CAR-grafted T cells were capable of lysing target cells of both hepatic and non-hepatic origin expressing on their surface the HCV/E2 glycoproteins of the most clinically relevant genotypes, including 1a, 1b, 2a, 3a, 4 and 5. Finally, and more importantly, they were capable of lysing HCVcc-infected hepatocytes. Conclusions Clearance of HCV-infected cells is a major therapeutic goal in chronic HCV infection, and adoptive transfer of anti-HCV/E2 CARs-grafted T cells represents a promising new therapeutic tool. PMID:25661083

  2. Hepatitis C Viral Kinetics During Treatment With Peg IFN-alpha-2b in HIV/HCV Co-Infected Patients as a Function of Baseline CD4+ T Cell Counts

    Science.gov (United States)

    Avidan, Neumann U.; Goldstein, Deborah; Rozenberg, Lynn; McLaughlin, Mary; Ferenci, Peter; Masur, Henry; Buti, Maria; Fauci, Anthony S.; Polis, Michael A.; Kottilil, Shyam

    2009-01-01

    Background HIV/HCV co-infected patients are known to have lower sustained viral response (SVR) rates than HCV mono-infected patients. However, the role of CD4+ T-cell counts on viral kinetics and outcome is not fully understood. Methods HCV-RNA kinetics (bDNA v3, LD=615 IU/ml) was analyzed in 32 HIV/HCV co-infected persons treated with Pegylated interferon-α2b (1.5 μg/kg weekly) and ribavirin (1–1.2 g daily) for 48 weeks and compared with results obtained from 12 HCV monoinfected patients treated with the same regimen. Results Baseline CD4+ T cell counts ≥450cells/mm3 were significantly (P1.0 log) and second-phase viral decline slope (>0.3 log/week) are excellent predictors of SVR for co-infected patients. PMID:19797971

  3. Reliability of immunoassays for anti-HCV antibodies (ELISA and RIBA II) in patients with essential mixed cryoglobulinemia (EMC).

    Science.gov (United States)

    Monteverde, A; Airoldi, G; Ballarè, M; Fortina, G; Quaglia, V; Pigatto, A; Manzini, P

    1993-01-01

    The recent reports of a very high frequency of signs of hepatitis C virus (HCV) infection among patients with essential mixed cryoglobulins (EMC) suggest new hypotheses for the pathogenesis of this disease. However, most of these studies have been seriously criticized. The serologic test designed for detection of anti-HCV antibodies (ELISA, RIBA I and II) may yield a significant rate of false-positive results when performed on cryoglobulinemic sera, and the detection of the HCV genome by PCR is still heavily conditioned by practical problems. Indirect, but possibly more reliable, evidence of HCV infection in cryoglobulinemic patients might come from the demonstration of anti-HCV antibodies by a conventional technique (ELISA or RIBA) in the purified polyclonal non-rheumatoid immunoglobulinemic fraction excreted in the urine by glomerular filtration. Fifty-two patients whose serum had tested positive for HCV antibodies (by ELISA and RIBA) on multiple occasions were enrolled in this study. They were diagnosed as having either EMC or HCV chronic hepatitis without cryoglobulinemia at least one year ago. The urine samples of these patients were tested for anti-HCV antibodies by ELISA and RIBA. In patients with chronic C hepatitis the antibodies most frequently found in the serum were anti-C33c and anti-C22-3. The results of the RIBA were substantially confirmed by ELISA, with a positive test in the urine of 30 of 32 seropositive patients. Similar results were obtained in patients with EMC II. We conclude that the specificity of the RIBA and ELISA tests for HCV antibodies in patients with EMC appears to be as high as in HCV+ patients without serum cryoglobulins. EMC patients have a high incidence of HCV infection and active chronic liver disease. PMID:7507807

  4. A sensitive serodiagnosis of hepatitis C virus (HCV) infection with two non-fused peptides: comparison of antibody responses detected with a newly developed assay and a commercial second-generation test.

    Science.gov (United States)

    Sato, A; Ida, N; Ishikawa, M; Tanahashi, K; Nakamura, H; Sho, Y; Arima, T; Kunitomo, T

    1993-01-01

    An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of anti-HCV antibody. We assayed for antibodies against either oligopeptide (S29-1) deduced from the nucleocapsid gene or the product of nonstructural region (NS3) synthesized in a recombinant Escherichia coli (S4). To reduce false-positive results induced by non-specific binding of antibodies with a carrier protein and to increase the sensitivity of an immunoassay, non-fused S4 peptide was prepared by the recombinant DNA technique and site-specific proteolysis (by factor Xa). In 71 non-A, non-B hepatitis patients with chronic liver disease, 70 (98.5%) were positive by S29-1/S4 ELISA as well as by a second-generation test (Abbott II). On the other hand, of 40 serum samples from blood donors, in which anti-N14 (core) and C100-3 antibodies were not detected but hepatitis C virus (HCV) RNA was detectable by polymerase chain reaction (PCR), 24 (60%) were positive by S29-1/S4 ELISA, whereas only 18 (45%) were diagnosed by Abbott II. In addition, based on results in a small group of 92 blood donors, detection of anti-S29-1/S4 antibody correlated well with HCV viremia as confirmed by PCR. These results indicated that the preparation of nonfused protein (S4) by recombinant DNA technique and a combination of S29-1 and S4 as immobilized antigens in an ELISA provide a sensitive and specific diagnosis for HCV infection with good correlation with the presence of viral RNA as confirmed by PCR. PMID:7688847

  5. Comparative efficacy, pharmacokinetic, pharmacodynamic activity, and interferon stimulated gene expression of different interferon formulations in HIV/HCV genotype-1 infected patients.

    Science.gov (United States)

    Osinusi, Anu; Bon, Dimitra; Nelson, Amy; Lee, Yu-Jin; Poonia, Seerat; Shivakumar, Bhavana; Cai, Shu Yi; Wood, Brad; Haagmans, Bart; Lempicki, Richard; Herrmann, Eva; Sneller, Michael; Polis, Michael; Masur, Henry; Kottilil, Shyam

    2014-02-01

    The effect of different formulations of interferon on therapeutic response in patients coinfected with HIV and HCV is unclear. In this study, the safety, tolerability, viral kinetics (VK) modeling and host responses among HIV/HCV coinfected patients treated with pegylated-IFN or albinterferon alfa-2b (AlbIFN) with weight-based ribavirin were compared. Three trials treated 57 HIV/HCV coinfected genotype-1 patients with PegIFN alfa-2b (1.5 µg/kg/week) (n = 30), PegIFN alfa-2a (180 µg/week) (n = 10), and AlbIFN (900 µg/q2week) (n = 17) in combination with weight-based ribavirin (RBV). HCV RNA, safety labs, and interferon stimulated gene expression (ISG) was evaluated. Adverse events were documented at all study visits. HCV viral kinetics using a full pharmacokinetic/pharmacodynamic model was also evaluated. Baseline patient characteristics were similar across the three studies. All three formulations exhibited comparable safety and tolerability profiles and efficacy. VK/PK/PD parameters for all three studies as measured by mean efficiency and rate of infected cell loss were similar between the three groups. Host responses (ISG expression and immune activation markers) were similar among the three groups. All three regimens induced significant ISG at week 4 (P < 0.05) and ISG expression strongly correlated with therapeutic response (r = 0.65; P < 0.01). In summary, a comprehensive analysis of responses to three different interferon formulations in HIV/HCV coinfected patients demonstrated similar effects. Notably, interferon-based therapy results in a blunted host response followed by modest antiviral effect in HIV/HCV coinfected patients. This suggests that future treatment options that do not rely on host immune responses such as direct antiviral agents would be particularly beneficial in these difficult to treat patients.

  6. Interferon alpha plus ribavirin combination treatment of Japanese chronic hepatitis C patients with HCV genotype 2: A project of the Kyushu University Liver Disease Study Group

    Institute of Scientific and Technical Information of China (English)

    Norihiro Furusyo; Akihide Masumoto; Shinji Shimoda; Kazuhiro Takahashi; Koichi Azuma; Jun Hayashi; Kyushu University Liver Disease Study Group; Masaki Katoh; Yuichi Tanabe; Eiji Kajiwara; Toshihiro Maruyama; Junya Shimono; Hironori Sakai; Makoto Nakamuta; Hideyuki Nomura

    2006-01-01

    AIM: To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus (HCV) of genotype 2,a multi-center study was retrospectively analyzed.METHODS: In total, 173 patients with HCV genotype 2stared to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk.RESULTS: The overall sustained virological response (SVR), defined as undetectable HCV RNA in serum, 24wk after the end of treatment, was remarkably high by 84.4%, (146/173) by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin (46.9%vs 92.9 %), but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment (34.8 % vs 92.0 %).CONCLUSION: The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16weeks.

  7. IFN-α-2a (Interferon) and ribavirin induced suicidal attempt in a patient of chronic HCV: A rare case report

    OpenAIRE

    Deep Inder; Rehan, H. S.; Madhur Yadav; Seema Manak; Pawan Kumar

    2011-01-01

    Interferons (IFNs) are proteins produced by cells, fibroblasts and macrophages, in response to viral invasion, and mediates immune response. IFN-α and ribavirin are the approved treatment for HCV infection, but also carries a risk of neuropsychiatric adverse effects, viz. insomnia, irritability, mood changes, and depression. We present a case report of depression induced by IFN-α and ribavirin, leading to attempted suicide. Following the episode, antidepressant paroxetine (20 mg o.d.) and ...

  8. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis

    NARCIS (Netherlands)

    A.J.P. van der Meer (Adriaan); B.J. Veldt (Bart); S. Feld; H. Wedemeyer (Heiner); J.F. Dufour (Jean-François); F. Lammert (Frank); A. Duarte-Rojo (Andres); E.J. Heathcote (Jenny); M.P. Manns (Michael); L. Kuske (Lorenz); S. Zeuzem (Stefan); W.P. Hofmann (Peter); R.J. de Knegt (Robert); B.E. Hansen (Bettina); H.L.A. Janssen (Harry)

    2012-01-01

    textabstractContext: Chronic hepatitis C virus (HCV) infection outcomes include liver failure, hepatocellular carcinoma (HCC), and liver-related death. Objective: To assess the association between sustained virological response (SVR) and all-cause mortality in patients with chronic HCV infection and

  9. Natural Products as Tools for Defining How Cellular Metabolism Influences Cellular Immune and Inflammatory Function during Chronic Infection

    Directory of Open Access Journals (Sweden)

    Erica S. Lovelace

    2015-11-01

    Full Text Available Chronic viral infections like those caused by hepatitis C virus (HCV and human immunodeficiency virus (HIV cause disease that establishes an ongoing state of chronic inflammation. While there have been tremendous improvements towards curing HCV with directly acting antiviral agents (DAA and keeping HIV viral loads below detection with antiretroviral therapy (ART, there is still a need to control inflammation in these diseases. Recent studies indicate that many natural products like curcumin, resveratrol and silymarin alter cellular metabolism and signal transduction pathways via enzymes such as adenosine monophosphate kinase (AMPK and mechanistic target of rapamycin (mTOR, and these pathways directly influence cellular inflammatory status (such as NF-κB and immune function. Natural products represent a vast toolkit to dissect and define how cellular metabolism controls cellular immune and inflammatory function.

  10. Hepatitis C virus infection in the human immunodeficiency virus infected patient

    DEFF Research Database (Denmark)

    Clausen, Louise Nygaard; Lundbo, Lene Fogt; Benfield, Thomas

    2014-01-01

    Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share the same transmission routes; therefore, coinfection is frequent. An estimated 5-10 million individuals alone in the western world are infected with both viruses. The majority of people acquire HCV by injection drug use and...... HIV-HCV coinfected individuals. Morbidity and mortality rates from chronic HCV infection will increase because the infection incidence peaked in the mid-1980s and because liver disease progresses slowly and is clinically silent to cirrhosis and end-stage-liver disease over a 15-20 year time period...... for 15%-20% of chronically infected individuals. HCV treatment has rapidly changed with the development of new direct-acting antiviral agents; therefore, cure rates have greatly improved because the new treatment regimens target different parts of the HCV life cycle. In this review, we focus...

  11. HCV and HIV infection and co-infection: injecting drug use and sexual behavior, AjUDE-Brasil I Project Infecções e co-infecções pelos vírus HCV e HIV: uso de drogas injetáveis e comportamento sexual, Projeto AjUDE-Brasil I

    Directory of Open Access Journals (Sweden)

    Keli Bahia Felicíssimo Zocratto

    2006-04-01

    Full Text Available This study aimed to characterize sexual and drug-use behaviors in injecting drug users (IDUs in relation to single hepatitis C virus (HCV and human immunodeficiency virus (HIV infection and HCV/HIV co-infection. The sample consisted of 272 IDUs enrolled in the AjUDE-Brasil I Project, a cross-sectional multi-center study conducted in five Brazilian cities in 1998. Data were collected with a structured questionnaire using self-reported risk behavior, and HCV and HIV serological status used ELISA on filter paper. IDUs were clustered in four distinct groups: HCV/HIV seronegative; HCV mono-infected; HIV mono-infected; and HCV/HIV co-infected. Active sharing of injecting equipment was associated with HCV infection (p = 0.001. Sexual behavior variables, especially male same-sex sexual relations, were consistently associated with HIV infection. HCV/HIV co-infection was associated with both sexual and drug use variables. It was possible to distinguish different behavioral indicators for HCV and HIV infection and co-infection in this population.Este estudo objetivou analisar grupos de usuários de drogas injetáveis (UDIs infectados e co-infectados pelos vírus da hepatite C (HCV e da imunodeficiência adquirida (HIV, em relação ao comportamento sexual e uso de drogas. A população de estudo foi composta por 272 UDIs participantes do Projeto AjUDE-Brasil I, estudo transversal multicêntrico realizado em cinco cidades brasileiras, em 1998. Os dados analisados foram coletados através de entrevistas estruturadas e testes sorológicos, utilizando-se papel filtro e a técnica ELISA, para HIV e HCV. Os UDIs foram agrupados em quatro grupos sorológicos distintos, a saber: (1 soronegativos, (2 monoinfectados pelo HCV, (3 monoinfectados pelo HIV e (4 co-infectados. Relato de ter "dado seringa", na vida, apresentou-se significantemente associado à infecção pelo HCV (p = 0,001. Em relação à infecção pelo HIV, variáveis de comportamento sexual, em

  12. Results Analysis of 283 Cases of HIV/HCV Complicated with Infection%283例HIV/HCV合并感染检测结果分析

    Institute of Scientific and Technical Information of China (English)

    杨高峰; 周永玲; 王智龙

    2014-01-01

    Objective Understanding of HIV/HCV co-infection in zhumadian area.Methods Using enzyme-linked immunosorbent assay (ELISA) double antigen testing clamp method.Results HIV/HCV co-infection in 2000~2005 year infection in 213 cases (75%), other years (25%). Sel blood infection in 198 cases (69%), 51 cases (18%), sexual transmission of blood transfusion infection in 26 cases (9.1%), and from mother to child vertical infection in 8 cases (2.8%).Conclusion Zhumadian City HIV/HCV co-infection in recent years is on the decline, but infected with HCV alone showed a trend of rise, this has led to the local government at aches great importance to, is take the necessary testing and prevention measures.%目的了解驻马店地区HIV/HCV合并感染状况。方法采用酶联免疫吸附试验(ELISA)双抗原夹心法进行检测。结果HIV/HCV合并感染年份2000年~2005年感染213例(75%),其他年份(25%)。卖血感染198例(69%),性传播51例(18%),输血感染26例(9.1%),母婴垂直感染8例(2.8%)。结论驻马店市HIV/HCV合并感染最近几年呈下降趋势,但HCV单独感染呈升趋势,这已经引起当地政府高度重视,正采取必要检测和防治措施。

  13. Association of IFNL3 rs12979860 and rs8099917 with biochemical predictors of interferon responsiveness in chronic hepatitis C virus infection.

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    Janett Fischer

    Full Text Available BACKGROUND & AIMS: Genetic variations near the interferon lambda 3 gene (IFNL3, IL28B are the most powerful predictors for sustained virologic response (SVR in patients with chronic hepatitis C virus (HCV infection, compared to other biochemical or histological baseline parameters. We evaluated whether the interplay of both IFNL3 polymorphisms rs12979860 and rs8099917 together with non-genetic clinical factors contributes to the predictive role of these genetic variants. METHODS: The cohort comprised 1,402 patients of European descent with chronic HCV type 1 infection. 1,298 patients received interferon-based antiviral therapy, and 719 (55% achieved SVR. The IFNL3 polymorphisms were genotyped by polymerase chain reaction and melting curve analysis. RESULTS: A significant correlation was found between the IFNL3 polymorphisms and biochemical as well as virologic predictors of treatment outcome such as ALT, GGT, cholesterol, and HCV RNA levels. In multivariate regression analysis, IFLN3 SNPs, HCV RNA levels, and the GGT/ALT ratio were independent predictors of SVR. Dependent on the GGT/ALT ratio and on the HCV RNA concentration, significant variations in the likelihood for achieving SVR were observed in both, carriers of the responder as well as non-responder alleles. CONCLUSIONS: Our data support a clear association between IFNL3 genotypes and baseline parameters known to impact interferon responsiveness. Improved treatment outcome prediction was achieved when these predictors were considered in combination with the IFNL3 genotype.

  14. Association between risk factors, basal viral load, virus genotype and the degree of liver fibrosis with the response to the therapy in patients with chronic hepatitis C virus infection

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    Vuković Vuk R.

    2015-01-01

    Full Text Available Background/Aim. Hepatitis C is an important sociomedical problem worldwide due to frequent progression to chronic disease, occurrence of liver cirrhosis and hepatocellular carcinoma. Standard pegylated interferon alfa 2a plus ribavirin therapy results in resolution of infection only in 50% of patients. The aim of this study was to determine the association of various factors with response to the therapy in patients with chronic hepatitis C virus (HCV infection. Age and sex of patients, inoculation risk factors, histopathological changes in the liver, viral load and HCV genotype were analyzed. Methods. The study included a group of 121 patients with chronic HCV infection. The treatment was carried out 24 weeks for virus genotype 2 and 3, and 48 weeks for genotype 1 and 4. The degree of histopathological changes in the liver was determined by hematoxylin and eosin staining, whereas polimerase chain reaction was used for HCV genotyping. Results. In the group of non-responding patients genotype 1 was represented with 100%, while in the other groups, although predominantly present, its percentage was lower. Unresponsiveness to therapy and relapse of disease were associated with higher viral load and advanced fibrosis. Intravenous use of psychoactive substances, as a risk factor, was present in a high percentage in the group of patients with sustained response, while blood transfusion and dialysis were leading risk factors in the group of relapse responders and non-responders. Conclusion. The results of our study showed that the treatment outcome of chronic HCV infection was associated with baseline HCV ribonucleic acid, HCV genotype, route of infection and the degree of histopathological changes in the liver. [Projekat Ministarstva nauke Republike Srbije, br. III41010

  15. Evaluation of Nitric Oxide (NO Levels in Hepatitis C Virus (HCV Infection: Relationship to Schistosomiasis and Liver Cirrhosis among Egyptian Patients

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    Mahmoud Ismail Hassan

    2002-01-01

    Full Text Available Nitric oxide (NO, a recently discovered free radical, is overproduced in liver cirrhosis. Hepatitis C virus (HCV might increase NO levels via increased inducible NO synthase (iNOS. This work was carried out to study the effect of HCV-induced liver cirrhosis on NO levels among Egyptian patients. The study included 46 patients with liver cirrhosis, and 30 healthy individuals of matched age and sex. NO levels determined as the stable endproduct nitrate, showed a statistically significant increase among patients compared to the control group (P < 0.001. Furthermore, NO levels increased proportionally with the severity of liver cirrhosis as assessed by Child’s classification (P < 0.05. Moreover, schistosomial infection enhanced NO levels in cirrhotic patients with HCV infection compared to non-bilharzial patients (P < 0.001. Polymerase chain reaction (PCR and branched DNA assays were used for detection of HCV RNA positivity, and measurement of the virus load, respectively. Both showed a positive correlation with the NO levels (P < 0.001. At a nitrate cutoff value of 70 μmol/L, the sensitivity and specificity were 83.0% and 37.0% respectively. Chi square analysis showed a significant correlation between ALT levels and both HCV RNA positivity by polymerase chain reaction (PCR (P < 0.02, and virus load (P < 0.05. Interestingly enough, there was a significant positive correlation between HCV RNA and schistosomal antibody titer as measured by hemaglutination inhibition assay (HAI (P < 0.05. The data presented in this report indicated an association between NO levels and the development and progression of liver cirrhosis. Furthermore, the findings obtained from this study demonstrated that schistomiasis is an important risk factor involved in enhancement of NO levels and virus replication. The latter may aggravate liver cell injury and hence the development of cirrhosis.

  16. Evaluation of Nitric Oxide (NO) Levels in Hepatitis C Virus (HCV) Infection: Relationship to Schistosomiasis and Liver Cirrhosis among Egyptian Patients

    Science.gov (United States)

    Hassan, Mahmoud Ismail; Kassim, Samar Kamal; Ali, Hebatalla Said; Sayed, El-Dieb Abd ElSattar; Khalifa, Ali

    2002-01-01

    Nitric oxide (NO), a recently discovered free radical, is overproduced in liver cirrhosis. Hepatitis C virus (HCV) might increase NO levels via increased inducible NO synthase (iNOS). This work was carried out to study the effect of HCV-induced liver cirrhosis on NO levels among Egyptian patients. The study included 46 patients with liver cirrhosis, and 30 healthy individuals of matched age and sex. NO levels determined as the stable endproduct nitrate, showed a statistically significant increase among patients compared to the control group (P < 0.001). Furthermore, NO levels increased proportionally with the severity of liver cirrhosis as assessed by Child’s classification (P < 0.05). Moreover, schistosomial infection enhanced NO levels in cirrhotic patients with HCV infection compared to non-bilharzial patients (P < 0.001). Polymerase chain reaction (PCR) and branched DNA assays were used for detection of HCV RNA positivity, and measurement of the virus load, respectively. Both showed a positive correlation with the NO levels (P < 0.001). At a nitrate cutoff value of 70 μmol/L, the sensitivity and specificity were 83.0% and 37.0% respectively. Chi square analysis showed a significant correlation between ALT levels and both HCV RNA positivity by polymerase chain reaction (PCR) (P < 0.02), and virus load (P < 0.05). Interestingly enough, there was a significant positive correlation between HCV RNA and schistosomal antibody titer as measured by hemaglutination inhibition assay (HAI) (P < 0.05). The data presented in this report indicated an association between NO levels and the development and progression of liver cirrhosis. Furthermore, the findings obtained from this study demonstrated that schistomiasis is an important risk factor involved in enhancement of NO levels and virus replication. The latter may aggravate liver cell injury and hence the development of cirrhosis. PMID:12515909

  17. Evidence of viral adaptation to HLA class I-restricted immune pressure in chronic hepatitis C virus infection.

    Science.gov (United States)

    Gaudieri, Silvana; Rauch, Andri; Park, Lawrence P; Freitas, Elizabeth; Herrmann, Susan; Jeffrey, Gary; Cheng, Wendy; Pfafferott, Katja; Naidoo, Kiloshni; Chapman, Russell; Battegay, Manuel; Weber, Rainer; Telenti, Amalio; Furrer, Hansjakob; James, Ian; Lucas, Michaela; Mallal, Simon A

    2006-11-01

    Cellular immune responses are an important correlate of hepatitis C virus (HCV) infection outcome. These responses are governed by the host's human leukocyte antigen (HLA) type, and HLA-restricted viral escape mutants are a critical aspect of this host-virus interaction. We examined the driving forces of HCV evolution by characterizing the in vivo selective pressure(s) exerted on single amino acid residues within nonstructural protein 3 (NS3) by the HLA types present in two host populations. Associations between polymorphisms within NS3 and HLA class I alleles were assessed in 118 individuals from Western Australia and Switzerland with chronic hepatitis C infection, of whom 82 (69%) were coinfected with human immunodeficiency virus. The levels and locations of amino acid polymorphisms exhibited within NS3 were remarkably similar between the two cohorts and revealed regions under functional constraint and selective pressures. We identified specific HCV mutations within and flanking published epitopes with the correct HLA restriction and predicted escaped amino acid. Additional HLA-restricted mutations were identified that mark putative epitopes targeted by cell-mediated immune responses. This analysis of host-virus interaction reveals evidence of HCV adaptation to HLA class I-restricted immune pressure and identifies in vivo targets of cellular immune responses at the population level. PMID:17071929

  18. Association between chronic viral hepatitis infection and breast cancer risk: a nationwide population-based case-control study

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    Su Fu-Hsiung

    2011-11-01

    Full Text Available Abstract Background In Taiwan, there is a high incidence of breast cancer and a high prevalence of viral hepatitis. In this case-control study, we used a population-based insurance dataset to evaluate whether breast cancer in women is associated with chronic viral hepatitis infection. Methods From the claims data, we identified 1,958 patients with newly diagnosed breast cancer during the period 2000-2008. A randomly selected, age-matched cohort of 7,832 subjects without cancer was selected for comparison. Multivariable logistic regression models were constructed to calculate odds ratios of breast cancer associated with viral hepatitis after adjustment for age, residential area, occupation, urbanization, and income. The age-specific ( Results There were no significant differences in the prevalence of hepatitis C virus (HCV infection, hepatitis B virus (HBV, or the prevalence of combined HBC/HBV infection between breast cancer patients and control subjects (p = 0.48. Multivariable logistic regression analysis, however, revealed that age Conclusions HCV infection, but not HBV infection, appears to be associated with early onset risk of breast cancer in areas endemic for HCV and HBV. This finding needs to be replicated in further studies.

  19. Cloning and expression of NS3 helicase fragment of hepatitis C virus and the study of its immunoreactivity in HCV infected patients

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    Mahrou Sadri

    2015-02-01

    Full Text Available Objective(s: Hepatitis C is a major cause of liver failure worldwide. Current therapies applied for this disease are not fully effective and produce side effects in most cases. Non-structural protein 3 helicase (NS3 of HCV is one of the key enzymes in viral replication and infection. Therefore, this region is a promising target to design new drugs and therapies against HCV infection. The aim of this study was cloning and expression of HCV NS3 helicase fragment in Escherichia coli BL21 (DE3 using pET102/D-TOPO expression vector and studying immunoreactivity of the expressed antigen in Iranian infected with hepatitis C. Materials and Methods: The viral RNA was extracted from the serum of HCV infected patient. The NS3 helicase region was amplified by RT-PCR. The PCR product was directionally cloned into the expression vector pET102/D-TOPO and transformed into the BL21 strain of E. coli (DE3. The transformed bacteria were then induced by adding 1mM isopropyl-β-D-thiogalactopyranoside (IPTG into the culture medium to enhance the protein expression. SDS-PAGE and western blotting were carried out to identify the protein under investigation, and finally purified recombinant fusion protein was used as the antigen for ELISA method. Results: Theinsertion of theDNA fragment of the NS3 regioninto the expression vectorwas further confirmed by PCR and sequencing. SDS-PAGE analysis showed the successful expression of the recombinant protein of interest. Furthermore, immunoreactivity of fusion NS3 helicase was confirmed by ELISA and western blotting. Conclusion: It seems that this recombinant protein could be a useful source of antigen for future studies on HCV diagnosis and therapy.

  20. Most common genotypes and risk factors for HCV in Gaza strip: a cross sectional study

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    Abu-Jadallah Salah Y

    2009-07-01

    Full Text Available Abstract Background The present work aims at determining HCV genotypes in patients with chronic HCV infection, in Gaza strip, Palestine. The most common risk factors for HCV transmission were also evaluated in conjunction with the genotyping data. Results The study shows that there are only two major genotypes of HCV in Gaza Strip: Genotype 1 (subtypes 1a and 1b collectively contribute to 28.3% of the cases, and genotype 4 (subtypes 4a and 4c/d collectively contribute to 64.1% of the cases. Mixed infection with the two genotypes was also present among 7.6% of the cases. In this study a statistically significant relationship was established between the distribution of these genotypes and the patients' living place, traveling history, history of blood transfusion and history of surgical operations. Conclusion The present study is the first to link HCV genotyping in Gaza strip with its possible roots of transmission. Traveling to endemic countries, especially Egypt; blood transfusion and surgical operations are major roots of HCV infection in Gaza strip. The results indicate that iatrogenic and nosocomial procedures may be responsible for the majority of HCV infections in Gaza strip.

  1. HBV And HCV Molecular Evolution

    Directory of Open Access Journals (Sweden)

    Flor H. Pujol

    2007-02-01

    Full Text Available

    Hepatitis B virus (HBV infection is still a significant health concern in in the world, since around 2 billion persons have been infected by this virus (HBV and around 350 millions of them are chronic carriers, in spite of a highly effective vaccine against this virus. Bearing a reverse transcriptase necessary for its replication but with a highly compacted genome, this hepadnavirus exhibits a degree of variability intermediate between DNA and RNA viruses. This plasticiy leads to the generation of several mutants and genotypic variability. HBV mutants develop during the natural course of infection and play an important role in the evasion of the selective pressure applied by the host (immune or chemotherapeutic. Eight HBV genotypes (A-H have been described, based on a minimum divergence of 8% of the complete genome sequences. HBV genotype F is the most divergent of the HBV genotypes, is autochthonous to South America and is highly predominant in the Northen region of South America. The recently described HBV genotype H is closely related to genotype F and seems to be restricted to Central and North America. Recombination among different HBV strains seems to be frequent. Several subgenotypes have also been described inside HBV genotypes, which exhibit a geographic pattern of distribution. The clinical and biologic importance of the genotypic diversity of HBV is of major concern at the present moment and has been studied in Asia and Europe. The origin of HBV is still an open question. Depending on the model used for the phylogenetic analysis, an Asian or an American origin of HBV has been proposed. By revisiting the genotypic diversity of HBV, an alternative explanation is that human HBV genotypes might have emerged by several zoonotic introductions, both in the Old and the New World. Around 170 millions persons in the world are thought to be infected with

  2. Chronic hepatitis C infection in a patient with bone marrow hypoplasia

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Chronic hepatitis C virus (HCV) infection is associated with multifarious extra-hepatic manifestations; the most described and discussed being mixed cryoglob- ulinemia which is strongly related to B-cell lympho- proliferative disorders (LPDs). We present a case of chronic HCV infection and mixed cryoglobulinemia, with minimal liver involvement. The case is a 53-year- old patient who was diagnosed as having bone marrow hypoplasia at the age of three. She received several blood transfusions to normalize her haemoglobin. At the age of 31, she was diagnosed with rheumatoid ar- thritis on account of her diffuse joint pain and inflam- mation, elevated rheumatoid factor (RF) and Raynaud's phenomenon. Twenty years later, monoclonal gam- mopathy of IgG Lambda (one year later, changed to IgM Kappa) was detected during a routine examina- tion. A bone marrow biopsy showed hypoplasia, Kappa positive B-lymphocytes and low-grade malignant lym- phoma cells. PCR of the bone marrow aspirate was not contributory. No treatment was initiated owing to her poor bone marrow function and she is under regular follow-up.

  3. 广州地区吸毒人员HBV、HCV感染流行病学特征%HBV and HCV infection among drug addicts in Guangzhou

    Institute of Scientific and Technical Information of China (English)

    熊华平; 花文峰; 王敏; 廖峭; 戎霞; 黄杰庭; 黄珂; 许茹; 付涌水

    2013-01-01

    Objective To investigate the infection rates and the impact of HBV and HCV infection among drug addicts in Guangzhou.Methods Questionnaire survey was conducted in this study.Blood samples from the drug addicts were collected.HBsAg and HCV antibodies were detected by ELISA assays.The correlation between infection and possible impact factors were analyzed by SPSS16.0 software.Results Of the 1 375 drug addicts,the percentage of HBV and HCV infection was 20.8% and 39.2%,respectively.106 cases (7.7%) were found to have HBV and HCV co-infection.412 cases were intravenous drug users (IDUs),in which the HBV and HCV infection rate was 24.5% and 84.5%,respectively.Elderly and those with a long history of drug addiction had a higher risk of having HBV and HCV infection.Conclusions Drug addiction,especially through the intravenous injection,is the risk factor of HBV and HCV infection.Age,the history of drug addiction,and intravenous drug injection are correlated with HBV and HCV infection.%目的 了解广州地区吸毒人员乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)的感染状况及其影响因素.方法 收集广州地区吸毒人员的血液标本,采用ELISA检测HBsAg及HCV抗体,并对吸毒人员采取统一调查表进行问卷调查,采用统计学方法进行相关性分析.结果 1 375名吸毒者HBV、HCV的感染率分别为20.8%、39.2%,HBV/HCV合并感染率为7.7%(106/1 375).其中采用静脉吸毒者HBV、HCV的感染率分别24.5%、84.5%,均高于非静脉吸毒者的19.2%、19.8%,差异有统计学意义(P<0.05).吸毒者年龄越大、吸毒时间越长越容易发生HBV或HCV感染.结论 吸毒尤其是静脉吸毒是HBV、HCV感染的高危因素.吸毒者年龄、吸毒时间长短及吸毒方式与HBV、HCV感染相关.

  4. Temporal changes in HCV genotype distribution in three different high risk populations in San Francisco, California

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    Evans Jennifer

    2011-08-01

    Full Text Available Abstract Background Hepatitis C virus (HCV genotype (GT has become an important measure in the diagnosis and monitoring of HCV infection treatment. In the United States (U.S. HCV GT 1 is reported as the most common infecting GT among chronically infected patients. In Europe, however, recent studies have suggested that the epidemiology of HCV GTs is changing. Methods We assessed HCV GT distribution in 460 patients from three HCV-infected high risk populations in San Francisco, and examined patterns by birth cohort to assess temporal trends. Multiple logistic regression was used to assess factors independently associated with GT 1 infection compared to other GTs (2, 3, and 4. Results Overall, GT 1 was predominant (72.4%, however younger injection drug users (IDU had a lower proportion of GT 1 infections (54.7% compared to older IDU and HIV-infected patients (80.5% and 76.6%, respectively. Analysis by birth cohort showed increasing proportions of non-GT 1 infections associated with year of birth: birth before 1970 was independently associated with higher adjusted odds of GT 1: AOR 2.03 (95% CI: 1.23, 3.34. African-Americans as compared to whites also had higher adjusted odds of GT 1 infection (AOR: 3.37; 95% CI: 1.89, 5.99. Conclusions Although, HCV GT 1 remains the most prevalent GT, especially among older groups, changes in GT distribution could have significant implications for how HCV might be controlled on a population level and treated on an individual level.

  5. HCV Animal Models: A Journey of More than 30 Years

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    Philip Meuleman

    2009-09-01

    Full Text Available In the 1970s and 1980s it became increasingly clear that blood transfusions could induce a form of chronic hepatitis that could not be ascribed to any of the viruses known to cause liver inflammation. In 1989, the hepatitis C virus (HCV was discovered and found to be the major causative agent of these infections. Because of its narrow ropism, the in vivo study of this virus was, especially in the early days, limited to the chimpanzee. In the past decade, several alternative animal models have been created. In this review we review these novel animal models and their contribution to our current understanding of the biology of HCV.

  6. HCV animal models: a journey of more than 30 years.

    Science.gov (United States)

    Meuleman, Philip; Leroux-Roels, Geert

    2009-09-01

    In the 1970s and 1980s it became increasingly clear that blood transfusions could induce a form of chronic hepatitis that could not be ascribed to any of the viruses known to cause liver inflammation. In 1989, the hepatitis C virus (HCV) was discovered and found to be the major causative agent of these infections. Because of its narrow tropism, the in vivo study of this virus was, especially in the early days, limited to the chimpanzee. In the past decade, several alternative animal models have been created. In this review we review these novel animal models and their contribution to our current understanding of the biology of HCV. PMID:21994547

  7. Safety and efficacy of ombitasvir – 450/r and dasabuvir and ribavirin in HCV/HIV-1 co-infected patients receiving atazanavir or raltegravir ART regimens

    Directory of Open Access Journals (Sweden)

    Joseph J Eron

    2014-11-01

    Full Text Available Objective: Whether concomitant HIV antiretroviral therapy (ART affects the safety and efficacy of interferon-free HCV therapies or whether HCV treatment may negatively affect HIV control is unclear. We assessed the 3 direct-acting antiviral (3D regimen of ombitasvir, ABT-450 (identified by AbbVie and Enanta; co-dosed with ritonavir and dasabuvir with ribavirin (RBV in HCV/HIV-1 co-infected patients with and without cirrhosis, including HCV treatment-experienced, receiving atazanavir (ATV- or raltegravir (RAL-based ART therapy. Methods: HCV genotype 1-positive treatment-naïve or pegIFN/RBV-experienced patients, with or without Child-Pugh A cirrhosis, CD4+ count ≥200 cells/mm3 or CD4 + % ≥14%, and plasma HIV-1 RNA suppressed on stable ART received open-label 3D + RBV for 12 or 24 weeks. Rates of HCV-sustained virologic response at post-treatment weeks 4 and 12 (SVR4 and SVR12, respectively and bilirubin-related adverse events (AEs are reported from post-hoc analyses for subgroups defined by treatment duration and ART regimen. Results: The SVR12 rate for patients receiving 12 weeks of 3D + RBV was 93.5% with comparable rates in patients receiving either ATV (93.8% or RAL therapy (93.3% (Table 1. The SVR4 rate for the 24-week arm was 96.9% with a single virologic breakthrough at treatment week 16 in a patient receiving RAL therapy. Patients receiving concomitant ATV had more AEs related to indirect hyperbilirubinemia including ocular icterus, jaundice and grade 3 or 4 elevations in total bilirubin (predominantly indirect. No patient discontinued the study due to AEs, and no serious AEs were reported during or after treatment. No patient had a confirmed plasma HIV-1 RNA value ≥200 c