WorldWideScience

Sample records for hcv prototipa vakcna

  1. hcv

    African Journals Online (AJOL)

    boaz

    ABSTRACT. Background: Hepatitis C virus (HCV) infection is a major public health concern. The aim of this study was to ascertain the seroprevalence and risk factors of HCV antibodies among pregnant women in Anyigba, Kogi State North Central Nigeria. Materials and methods:Blood samples (5mls) were collected from ...

  2. (HCV) among alcoholics

    African Journals Online (AJOL)

    GREGORY

    2010-12-21

    Dec 21, 2010 ... alcoholics who do not have liver disease (Coelho–Little et al., 1995; Mendenhall et al., 1991; Takase et al., 1993). HCV is transmitted primarily through contaminated blood and less effectively through human bodily secre- tions. HCV has been detected in saliva, urine, semen and ascetic fluid (Campbell et ...

  3. Comparison of HCV core antigen and anti-HCV with HCV RNA results

    African Journals Online (AJOL)

    Background: The measurement of anti-HCV antibodies using immunological methods and the confirmation of viral nuclear acid based on molecular methods is important in diagnosis and follow-up of the HCV infection. Objectives: In this study, we aimed to analyse HCV core Antigen positivity among anti-HCV antibody ...

  4. HCV and Oxidative Stress: Implications for HCV Life Cycle and HCV-Associated Pathogenesis

    Directory of Open Access Journals (Sweden)

    Regina Medvedev

    2016-01-01

    Full Text Available HCV (hepatitis C virus is a member of the Flaviviridae family that contains a single-stranded positive-sense RNA genome of approximately 9600 bases. HCV is a major causative agent for chronic liver diseases such as steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma which are caused by multifactorial processes. Elevated levels of reactive oxygen species (ROS are considered as a major factor contributing to HCV-associated pathogenesis. This review summarizes the mechanisms involved in formation of ROS in HCV replicating cells and describes the interference of HCV with ROS detoxifying systems. The relevance of ROS for HCV-associated pathogenesis is reviewed with a focus on the interference of elevated ROS levels with processes controlling liver regeneration. The overview about the impact of ROS for the viral life cycle is focused on the relevance of autophagy for the HCV life cycle and the crosstalk between HCV, elevated ROS levels, and the induction of autophagy.

  5. HCV and Rheumatic Disease

    Science.gov (United States)

    ... of treating liver disease and your doctors who treat the non-liver symptoms of HCV. Also, make sure you get long-term follow-up care. This is vital, since the liver disease can become worse, leading to liver failure or liver cancer. Support groups also provide helpful support and coping ...

  6. HCV Virus and Lymphoid Neoplasms

    Directory of Open Access Journals (Sweden)

    Yutaka Tsutsumi

    2011-01-01

    Full Text Available Hepatitis C virus (HCV is one of the viruses known to cause hepatic cancer. HCV is also believed to be involved in malignant lymphoma. In this paper, we investigated characteristics of malignant lymphoma cases that were anti-HCV antibody (HCV-Ab positive. We were able to perform pathological examinations on 13 out of 14 HCV-positive cases. Of these, lymphoid tissues of 10 stained positive for HCV-Ab. There was no significant correlation between the degree of HCV staining and the rate of recurrence or resistance to treatment. However, there did appear to be a consistent decrease in the amount of HCV-RNA between pre- and posttreatment among HCV-Ab-positive cases; that is, treatment-resistant cases that exhibited resistance from the first treatment and recurrent cases more frequently had a higher HCV level at treatment termination compared to the pretreatment level. This suggests that the HCV virus either accelerates oncogenesis by direct interaction with B cells or indirectly affects lymphoma prognosis.

  7. Effects of HCV proteins in current HCV transgenic models.

    Science.gov (United States)

    Jiao, Jian; Wang, Jiangbin; Sallberg, Matii

    2010-02-01

    Hepatits C virus (HCV) is an enveloped virus with positive-sense single-stranded RNA genome that causes both acute and persistent infections associated with chronic hepatitis, cirrhosis and hepatocellular carcinoma, which needs fully functional human hepatocytes for its development. Due to the strict human tropism of HCV, only human and higher primates such as chimpanzees have been receptive to HCV infection and development, cognition about pathophysiololgy and host immune responses of HCV infection is limited by lacking of simple laboratory models of infection for a long time. During the past decade, gene transfer approaches have been helpful to the understanding of the molecular basis of human disease. Transgenic cell lines, chimeric and transgenic animal models were developed and had been demonstrated their invaluable benefits. This review focuses on the existing HCV transgenic models and summarize the relative results about probable pathophysical changes induced by HCV proteins.

  8. Hepatitis C virus (HCV) status in newborns born to HCV positive ...

    African Journals Online (AJOL)

    Group one: 30 women HCV antibody (Ab) positive/HCV RNA negative. Group two: 30 women HCV Ab positive/ HCV RNA positive. Newborn sera were subjected to HCV antibody testing, and detection of HCV viral RNA by PCR. Results: None of the newborns born to PCR negative females undergoing ICSI cycles showed ...

  9. Phylogenetics of HCV: Recent advances

    African Journals Online (AJOL)

    ONOS

    2010-09-06

    Sep 6, 2010 ... Tanaka (2006), studied the coalescent analysis indicated that a transition from constant size to rapid exponential growth (spread time) occurred in Japan in the 1920s. (HCV-1b), but not until the 1940s for the same genotype in Spain and other European countries. The spread time of HCV-1a in the United ...

  10. HCV and HCC molecular epidemiology

    Directory of Open Access Journals (Sweden)

    Flor H. Pujol

    2007-02-01

    Full Text Available

    iHepatitis C virus (HCV is a member of the family Flaviviridae, responsible for the majority of the non-A non-B post-transfusion hepatitis before 1990. Around 170 millions persons in the world are thought to be infected with this virus. A high number of HCV-infected people develop cirrhosis and from these, a significant proportion progresses to hepatocellular carcinoma (HCC. Six HCV genotypes and a large number of subtypes in each genotype have been described. Infections with HCV genotype 1 are associated with the lowest therapeutic success. HCV genotypes 1, 2, and 3 have a worldwide distribution. HCV subtypes 1a and 1b are the most common genotypes in the United States and are also are predominant in Europe, while in Japan, subtype 1b is predominant. Although HCV subtypes 2a and 2b are relatively common in America, Europe, and Japan, subtype 2c is found commonly in northern Italy. HCV genotype 3a is frequent in intravenous drug abusers in Europe and the United States. HCV genotype 4 appears to be prevalent in Africa and the Middle East, and genotypes 5 and 6 seem to be confined to South Africa and Asia, respectively. HCC accounts for approximately 6% of all human cancers. Around 500,000 to 1 million cases occur annually worldwide, with HCC being the fifth common malignancy in men and the ninth in women. HCC is frequently a consequence of infection by HBV and HCV. The first line of evidences comes from epidemiologic studies. While HBV is the most frequent cause of HCC in many countries of Asia and South America, both HBV and HCV are found at similar frequencies, and eventually HCV at a higher frequency than HBV, among HCC patients in Europe, North America, and Japan. The cumulative appearance rate of HCC might be higher for HCV

  11. Comparison of Elecsys Anti-HCV II Assay With Other HCV Screening Assays.

    Science.gov (United States)

    Li, Dongdong; Zhu, Siyuan; Wang, Tingting; An, Jingna; Wang, Lanlan; Tao, Chuanmin

    2016-09-01

    Early detection of hepatitis C virus (HCV) is an important step in preventing progression to cirrhosis and hepatocellular carcinoma. Serologic assays for anti-HCV antibody are valuable first-line tests in the screening and diagnosis of HCV infection. This study's aim was to evaluate the sensitivity and specificity of Elecsys Anti-HCV II assay for HCV screening. A total of 1,044 routine sera, 20 known HCV-positive samples, plus 54 preselected weakly positive samples were tested for anti-HCV with Elecsys Anti-HCV II assay, Elecsys Anti-HCV assays, InTec HCV enzymoimmunoassay (EIA), and Livzon Anti-HCV EIA. Interference test was assessed with additional 423 specimens without clinical evidence of HCV infection: preselected HCV weak reactive samples; dialysis samples; anti-HBc (antibody to HBV core antigen) (+), anti-Treponema pallidum (+), and anti-HIV (+) sera; and samples form autoimmune/alcoholic hepatitis or systemic Lupus erythematosus (SLE). Discrepant results were evaluated with recombinant immunoblot assay. The seroconversion panels were evaluated to assess how early each assay could detect HCV infection. The specificity (99.81%) of the Elecsys Anti-HCV II assay was less than that with the two EIA comparison methods. However, false-negative results were easily seen in the EIA assays. When serial bleeds of HCV panels were compared with the above-mentioned methods, the assay detected acute HCV infection only 3.5 days after a positive HCV-RNA nucleic acid test and earlier than the comparator assays. Sensitivities and specificities of the anti-HCV assays were sufficiently high for use in this study. The Elecsys Anti-HCV II assay is suitable for screening and reliable early detection of HCV infection. © 2015 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Pil Soo Sung

    2015-10-01

    Full Text Available 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.

  13. Direct anti-HCV agents

    Directory of Open Access Journals (Sweden)

    Xingquan Zhang

    2016-01-01

    Full Text Available Unlike human immunodeficiency virus (HIV and hepatitis B virus (HBV, hepatitis C virus (HCV infection is a curable disease. Current direct antiviral agent (DAA targets are focused on HCV NS3/4A protein (protease, NS5B protein (polymerase and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir (Sovaldi, simeprevir (Olysio, and fixed combination medicines Harvoni and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the “cure HCV” goal has become a reality. Concerns remain about drug resistance mutations and the high cost of these drugs. The investigation of new HCV drugs is progressing rapidly; fixed dose combination medicines in phase III clinical trials include Viekirax, asunaprevir+daclatasvir+beclabuvir, grazoprevir+elbasvir and others.

  14. Preclinical evaluation of an anti-HCV miRNA cluster for treatment of HCV infection.

    Science.gov (United States)

    Yang, Xiao; Marcucci, Katherine; Anguela, Xavier; Couto, Linda B

    2013-03-01

    We developed a strategy to treat hepatitis C virus (HCV) infection by replacing five endogenous microRNA (miRNA) sequences of a natural miRNA cluster (miR-17-92) with sequences that are complementary to the HCV genome. This miRNA cluster (HCV-miR-Cluster 5) is delivered to cells using adeno-associated virus (AAV) vectors and the miRNAs are expressed in the liver, the site of HCV replication and assembly. AAV-HCV-miR-Cluster 5 inhibited bona fide HCV replication in vitro by up to 95% within 2 days, and the spread of HCV to uninfected cells was prevented by continuous expression of the anti-HCV miRNAs. Furthermore, the number of cells harboring HCV RNA replicons decreased dramatically by sustained expression of the anti-HCV miRNAs, suggesting that the vector is capable of curing cells of HCV. Delivery of AAV-HCV-miR-Cluster 5 to mice resulted in efficient transfer of the miRNA gene cluster and expression of all five miRNAs in liver tissue, at levels up to 1,300 copies/cell. These levels achieved up to 98% gene silencing of cognate HCV sequences, and no liver toxicity was observed, supporting the safety of this approach. Therefore, AAV-HCV-miR-Cluster 5 represents a different paradigm for the treatment of HCV infection.

  15. HCV Infection and B-Cell Lymphomagenesis

    Directory of Open Access Journals (Sweden)

    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.

  16. HBV And HCV Molecular Evolution

    Directory of Open Access Journals (Sweden)

    Flor H. Pujol

    2007-02-01

    hepatitis C virus (HCV. Six genotypes and a large number of subtypes in each genotype have been described for this member of the Flaviviridae family. Infections with HCV genotype 1 are associated with the lowest therapeutic success. 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. HCV genotypes 1, 2, and 3 have a worldwide distribution and display an apidemic pattern of distribution. HCV subtypes 1a and 1b are the most common genotypes in the United States and are also are predominant in Europe, while in Japan, subtype 1b is predominant. Although HCV subtypes 2a and 2b are relatively common in America, Europe, and Japan, subtype 2c is found commonly in northern Italy. HCV genotype 3a is frequent in intravenous drug abusers in Europe and the United States. HCV genotype 4 appears to be prevalent in Africa and theMiddle East, and genotypes 5 and 6 seem to be confined to South Africa and Asia, respectively. These last genotypes display an endemic pattern of distribution. In addition, a change in the frequency of the prevailing genotypes has been described in several countries: in general, HCV genotype 1b is being displaced by genotypes 3a and/or 2. Coalescent studies have allowed to describe the epidemic pattern of dissemination of some HCV subtypes in specific countries, generally around 100 years ago. The origin of this virus is still an open question, but several studies traces it diversification only around 1,000 years ago.

    The replication of HCV is dependent on a RNA-polymerase RNA dependent which lacks proofreading activity, which confers to this virus a high rate of variability. This virus circulates as a quasispecies. This population dynamic inside a single strain confers to this virus the ability to

  17. Physical and Technical Energy Problems: Testing of the Prototype for State Estimation of Large-Scale Power Systems / Lielo Energosistēmu Stāvokļa Novērtēšanas Prototipa Testēšana

    Science.gov (United States)

    Kochukov, O.; Briņķis, K.; Mutule, A.

    2013-08-01

    The paper describes the algorithm for distributed state estimation (SE) and is focused on its testing and validation. For this purpose, different events in the modeled power system of the 330-750 kV electrical ring Latvia - Lithuania - Belarus - Smolensk - Moscow - St. Petersburg - Estonia - Latvia were considered. The methods for testing the Inter-TSO SE prototype and dynamic network monitoring & modeling are based on comparison of the available SCADA data about real events with those of SE calculation. In total, four operational states were studied, including initial, accident and two post-accident operational states Rakstā tiek aprakstīti, testēti un novērtēti izkliedēta stāvokļa novērtēšanas algoritmi. Testēšanas nolūkos tika izmantoti dažādi 330-750 kV elektriskā loka Latvija - Lietuva - Baltkrievija - Smoļenska - Maskava - Pēterburga - Igaunija - Latvija modelēti scenāriji. Prototipa testēšanas metodoloģija balstīta uz pieejamo SCADA datu salīdzināšanu ar stāvokļa novērtēšanas prototipa aprēķina rezultātiem. Kopumā apskatīti sākotnējais, avārijas un divi pēcavārijas režīmi

  18. 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

  19. The history of hepatitis C virus (HCV)

    DEFF Research Database (Denmark)

    Bukh, Jens

    2016-01-01

    The discovery of hepatitis C virus (HCV) in 1989 permitted basic research to unravel critical components of a complex life cycle for this important human pathogen. HCV is a highly divergent group of viruses classified in 7 major genotypes and a great number of subtypes, and circulating in infected...

  20. Hepatitis C virus (HCV) RNA profiles among chronic HIV/HCV-coinfected individuals in ESPRIT; spontaneous HCV RNA clearance observed in nine individuals

    DEFF Research Database (Denmark)

    Grint, D; Tedaldi, Ellen; Peters, L

    2017-01-01

    with the CC interleukin (IL)-28B genotype. This study describes HCV RNA profiles and factors associated with changes over time in HCV RNA levels in the ESPRIT study. METHODS: HIV/HCV-coinfected individuals positive for HCV RNA were included in the study. Follow-up was counted from the first HCV RNA positive...... test and censored at the initiation of interferon-based treatment. HCV RNA and IL-28B measurements were performed in the same reference laboratory. Random effects mixed models were used to analyse changes over time in HCV RNA. RESULTS: A total of 312 ESPRIT patients were included in the study (151...

  1. Sexual Transmission of HCV in Heterologous Monogamous Spouses

    Directory of Open Access Journals (Sweden)

    Mona M. Rafik

    2014-01-01

    Full Text Available We screened for evidence of HCV infection in healthy heterologous monogamous spouses of chronic HCV patients and studied the relation with various risk factors. A cross-sectional study of fifty healthy monogamous heterosexual spouses of HCV-positive index cases was carried out. All participants were HBV and HIV negative. The association with various risk factors was studied. Five spouses (10% showed evidence of HCV infection. Two partners were positive for HCV antibody alone (4% and 3 for antibody and HCV PCR (6%. No association was found between HCV infection and various sociodemographic parameters with the exception of older age categories. Intraspousal transmission of HCV may be an important source of spread of HCV infection. The reservoir of HCV-infected individuals in Egypt is sizable, and sexual transmission of HCV may contribute to the total burden of infection in Egypt.

  2. HCV-induced autophagosomes are generated via homotypic fusion of phagophores that mediate HCV RNA replication.

    Directory of Open Access Journals (Sweden)

    Linya Wang

    2017-09-01

    Full Text Available Hepatitis C virus (HCV induces autophagy to promote its replication, including its RNA replication, which can take place on double-membrane vesicles known as autophagosomes. However, how HCV induces the biogenesis of autophagosomes and how HCV RNA replication complex may be assembled on autophagosomes were largely unknown. During autophagy, crescent membrane structures known as phagophores first appear in the cytoplasm, which then progress to become autophagosomes. By conducting electron microscopy and in vitro membrane fusion assay, we found that phagophores induced by HCV underwent homotypic fusion to generate autophagosomes in a process dependent on the SNARE protein syntaxin 7 (STX7. Further analyses by live-cell imaging and fluorescence microscopy indicated that HCV-induced phagophores originated from the endoplasmic reticulum (ER. Interestingly, comparing with autophagy induced by nutrient starvation, the progression of phagophores to autophagosomes induced by HCV took significantly longer time, indicating fundamental differences in the biogenesis of autophagosomes induced by these two different stimuli. As the knockdown of STX7 to inhibit the formation of autophagosomes did not affect HCV RNA replication, and purified phagophores could mediate HCV RNA replication, the assembly of the HCV RNA replication complex on autophagosomes apparently took place during the formative stage of phagophores. These findings provided important information for understanding how HCV controlled and modified this important cellular pathway for its own replication.

  3. Molecular Epidemiology of Hepatitis C Virus (HCV) in Kadun State ...

    African Journals Online (AJOL)

    Objective: To determine the distribution of hepatitis C virus (HCV) genotypes and subtypes among blood donors and outpatients attendees positive for antibody to HCV (anti-HCV). Justification: Hepatitis C virus (HCV) continues to be a major disease burden on the world and Man is the only known natural host of Hepatitis C ...

  4. Efficient infectious cell culture systems of the hepatitis C virus (HCV) prototype strains HCV-1 and H77

    DEFF Research Database (Denmark)

    Li, Yi-Ping; Ramirez, Santseharay; Mikkelsen, Lotte

    2015-01-01

    UNLABELLED: The first discovered and sequenced hepatitis C virus (HCV) genome and the first in vivo infectious HCV clones originated from the HCV prototype strains HCV-1 and H77, respectively, both widely used in research of this important human pathogen. In the present study, we developed...... efficiently after transfection and subsequent infection of naive Huh7.5 cells, reaching titers of 10(3.5) and 10(4.4) FFU/ml, respectively. IMPORTANCE: Hepatitis C virus (HCV) was discovered in 1989 with the cloning of the prototype strain HCV-1 genome. In 1997, two molecular clones of H77, the other HCV...

  5. HCV core-antigen assay as an alternative to HCV RNA quantification: A correlation study for the assessment of HCV viremia.

    Science.gov (United States)

    Alonso, Roberto; Pérez-García, Felipe; López-Roa, Paula; Alcalá, Luis; Rodeño, Pilar; Bouza, Emilio

    2017-02-25

    Detection of hepatitis C virus (HCV) RNA and the HCV core antigen assay (HCV-Ag) are reliable techniques for the diagnosis of active and chronic HCV infection. Our aim was to evaluate the HCV-Ag assay as an alternative to quantification of HVC RNA. A comparison was made of the sensitivity and specificity of an HCV-Ag assay (204 serum samples) with those of a PCR assay, and the correlation between the two techniques was determined. The sensitivity and specificity of HCV-Ag was 76.6% and 100%, respectively. Both assays were extremely well correlated (Pearson coefficient=0.951). The formula (LogCV=1.15*LogAg+2.26) was obtained to calculate the viral load by PCR from HCV-Ag values. HCV-Ag was unable to detect viral loads below 5000IU/mL. Although the HCV-Ag assay was less sensitive than the PCR assay, the correlation between both assays was excellent. HCV-Ag can be useful as a first step in the diagnosis of acute or chronic HCV infection and in emergency situations. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  6. Liver Fibrosis in HCV Monoinfected and HIV/HCV Coinfected Patients: Dysregulation of Matrix Metalloproteinases (MMPs) and Their Tissue Inhibitors TIMPs and Effect of HCV Protease Inhibitors.

    Science.gov (United States)

    Latronico, Tiziana; Mascia, Claudia; Pati, Ilaria; Zuccala, Paola; Mengoni, Fabio; Marocco, Raffaella; Tieghi, Tiziana; Belvisi, Valeria; Lichtner, Miriam; Vullo, Vincenzo; Mastroianni, Claudio Maria; Liuzzi, Grazia Maria

    2016-03-26

    An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may contribute to liver fibrosis in patients with hepatitis C (HCV) infection. We measured the circulating levels of different MMPs and TIMPs in HCV monoinfected and HIV/HCV coinfected patients and evaluated the potential for anti-HCV therapy to modulate MMP and TIMP levels in HCV subjects. We analyzed 83 plasma samples from 16 HCV monoinfected patients undergoing dual or triple anti-HCV therapy, 15 HIV/HCV coinfected patients with undetectable HIV load, and 10 healthy donors (HD). Levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, TIMP-1, and TIMP-2 were measured by a SearchLight Multiplex Immunoassay Kit. MMP-2 and MMP-9 were the highest expressed MMPs among all the analyzed samples and their levels significantly increased in HCV monoinfected and HIV/HCV coinfected subjects compared to HD. TIMP-1 levels were significantly higher in HCV and HIV/HCV subjects compared to HD and were correlated with liver stiffness. These findings raise the possibility of using circulating TIMP-1 as a non-invasive marker of liver fibrosis in HCV infection. A longitudinal study demonstrated that MMP-9 levels significantly decreased (40% reduction from baseline) in patients receiving dual as well as triple direct-acting antivirals (DAA) anti-HCV therapy, which had no effect on MMP-2, TIMP-1, and TIMP-2. As the dysregulation of MMP-2 and MMP-9 may reflect inflammatory processes in the liver, the decrease of MMP-9 following HCV protease inhibitor treatment suggests a positive effect on the reduction of liver inflammation.

  7. The neuropsychiatric aspect of the HCV infection.

    Science.gov (United States)

    Więdłocha, Magdalena; Marcinowicz, Piotr; Sokalla, Dorota; Stańczykiewicz, Bartłomiej

    2017-01-01

    HCV infection is significantly more prevalent in the population of psychiatric patients, drug addicts and people tending to undertake risky sexual behaviors than in the general population. This article presents a spectrum of psychopathological symptoms and psychological dysfunctions, an outline of current theories on the neuropathology and psychiatric aspects of HCV infection treatment. The unspecific character of the psychopathological symptoms in the HCV infection makes the process of thorough diagnostics and adequate treatment difficult, thus the specific and characteristic features have been emphasized. The aim of this review is to shed light not only on the basic information concerning CNS pathology but also on the conclusions emerging from the studies of different authors, of various methodology, in diverse study groups and also to investigate current topics of research. The results of neuroimaging studies have been presented as well. Attention has also been dedicated separately to specific issues, like psychiatric aspects of co-infection with HCV and HIV viruses, the chronic fatigue in the course of HCV infection, the influence of substance use disorders and difficulties encountered during treatment with interferon. Undiagnosed psychiatric disorders, not only inevitably decrease the already rather low quality of life but also cause non-adherence with recommendations and medications regimes, contributing to a worse treatment outcome. Finally, the above disorders, when left untreated, result in higher rates of risk-taking behaviors among the infected, thus imposing a danger not only to patients themselves but also to the healthy population.

  8. Detection of HCV core antigen and its diagnostic significance

    Directory of Open Access Journals (Sweden)

    YANG Jie

    2013-02-01

    Full Text Available ObjectiveTo compare the abilities of the hepatitis C virus (HCV core antigen (cAg test and the HCV RNA assay for confirming anti-HCV presence in order to determine the clinical utility of the HCV-cAg as an alternative or confirmatory diagnostic tool. MethodsSerum samples collected from 158 patients diagnosed with HCV infection were subjected to the enzyme-linked immunosorbent assay-based HCV-cAg test. The optical density (OD measured values were used to calculate the ratio of specimen absorbance to the cutoff value (S/CO. Simultaneously, the serum samples were subjected to PCR-based nucleic acid amplification quantitative fluorescence detection of HCV RNA. ResultsNone of the serum samples had a S/CO value <1 for the HCV-cAg test (100% negative, but all of the samples had a S/CO value >5 (100% positive. The HCV-cAg test sensitivity was 87.05%, specificity was 76.67%, positive predictive value was 9653%, and negative predictive value was 44.23%. As the S/CO value gradually increased, the significantly higher positive coincident rate of the HCV RNA test decreased. The HCV RNA negative coincident rate was significantly higher than that of the HCV-cAg test. HCV-cAg S/CO values between 1 and 2 corresponded to an HCV RNA values between 1.0×103 copies/ml and 1.0×104 copies/ml. The highest S/CO value obtained was 1.992. ConclusionThe HCV-cAg test is comparable to the HCV RNA assay for diagnosing HCV infection.

  9. New Insights in Recurrent HCV Infection after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Shih-Hsien Hsu

    2013-01-01

    Full Text Available Hepatitis C virus (HCV is a small-enveloped RNA virus belonging to the Flaviviridae family. Since first identified in 1989, HCV has been estimated to infect 170 million people worldwide. Mostly chronic hepatitis C virus has a uniform natural history, from liver cirrhosis to the development of hepatocellular carcinoma. The current therapy for HCV infection consists of a combination of Pegylated interferon and ribavirin. On the other hand, HCV-related liver disease is also the leading indication for liver transplantation. However, posttransplant HCV re-infection of the graft has been reported to be universal. Furthermore, the graft after HCV re-infection often results in accelerated progression to liver failure. In addition, treatment of recurrent HCV infection after liver transplantation is often compromised by enhanced adverse effects and limited efficacy of interferon-based therapies. Taken together, poor outcome after HCV re-infection, regardless of grafts or recipients, poses a major issue for the hepatologists and transplant surgeons. The aim of this paper is to review several specific aspects regarding HCV re-infection after transplant: risk factors, current therapeutics for HCV in different stages of liver transplantation, cellular function of HCV proteins, and molecular mechanisms of HCV entry. Hopefully, this paper will inspire new strategies and novel inhibitors against recurrent HCV infection after liver transplantation and greatly improve its overall outcome.

  10. Immunological HCV-Associated Thrombocytopenia: Short Review

    Directory of Open Access Journals (Sweden)

    Dimitrios Dimitroulis

    2012-01-01

    Full Text Available Infection with Hepatitis C virus (HCV is affecting about 3% of the world's population, leading to liver damage, end-stage liver disease, and development of hepatocellular carcinoma, being thus the first indication for liver transplantation in the USA. Apart from the cirrhotic-liver-derived clinical signs and symptoms several conditions with immunological origin can also arise, such as, glomerulonephritis, pulmonary fibrosis, and thrombocytopenia. HCV-related autoimmune thrombocytopenia shows specific pathogenetic characteristics as well as symptoms and signs that differ in severity and frequency from symptoms in patients that are not HCV infected. Aim of this short paper is to estimate the epidemiological characteristics of the disease, to investigate the pathogenesis and clinical manifestation, and to propose treatment strategies according to the pertinent literature.

  11. HCV genetic heterogeneity and its host genetics

    Directory of Open Access Journals (Sweden)

    NIE Yonghong

    2013-10-01

    Full Text Available Hepatitis C represents a major worldwide public health problem. Studies have shown that both genetic diversity of hepatitis C virus (HCV and genetic polymorphisms of IL-28B, ITPA, and IP-10 in the host are implicated in the progression of hepatitis C, treatment response, and adverse effects. The research advances in the molecular epidemiology and clinical and therapeutic interventions of HCV genetic heterogeneity and single nucleotide polymorphisms in its host are reviewed. It is suggested that there is a pressing need for reliable data on the molecular epidemiology of HCV and its host, which will assist in the decision making of public health issues and reduce the morbidity and mortality of hepatitis C worldwide.

  12. 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.

  13. HCV viremia is associated with drug use in young HIV-1 and HCV coinfected pregnant and non-pregnant women*

    Science.gov (United States)

    Nikolopoulou, Georgia B.; Nowicki, Marek J.; Du, Wenbo; Homans, James; Stek, Alice; Kramer, Francoise; Kovacs, Andrea

    2011-01-01

    Aims Vertical transmission of HCV is increased among HIV-1/HCV coinfected women and is related to HCV viral load. In this study we assessed clinical and demographic factors associated with HCV viremia in a cohort of young pregnant and non-pregnant mothers coinfected with HIV-1. Design A cross-sectional clinic-based study nested within a prospective cohort study. Methods From 1988 to 2000, HIV-1 + pregnant and non-pregnant women with children followed in a large maternal, child and adolescent HIV-1 clinic were evaluated for HCV infection using EIA 3.0. HCV RNA levels were determined for HCV antibody + women using polymerase chain reaction. Demographic and clinical characteristics between HCV-RNA(+) and HCV-RNA(−) women and between pregnant and non-pregnant HIV-1/HCV coinfected women were compared using univariate and multivariate analyses. Findings Among 359 HIV-1(+) women, 84 (23%) were HCV-ab + and 49/84 (58%) had detectable HCV-RNA in plasma. Median age was 31. CD4 counts, HIV-1 RNA levels and demographic characteristics were similar for viremic and non-viremic women and pregnant and non-pregnant women. However, viremic women were more likely to report a history of (88% versus 43%; P < 0.001) or active injection drug use (AIDU) (83% versus 29%; P < 0.001). Logistic regression analysis showed that HCV viremia was associated significantly with AIDU (adjusted OR: 15.17; 95% CI: 3.56, 64.56) after adjusting for age, race, number of sexual partners, pregnancy status, CD4 counts and HIV-1 viral load. Conclusion In this cohort of young HIV-1 and HCV coinfected women, HCV viremia was associated strongly with active injection drug use, perhaps due to reinfection or reactivation of HCV. Thus, careful evaluation for HCV infection and counseling related to drug use may be necessary. PMID:15847620

  14. HCV tumor promoting effect is dependent on host genetic background.

    Directory of Open Access Journals (Sweden)

    Naama Klopstock

    Full Text Available BACKGROUND: The hepatitis C virus (HCV is one of the major risk factors for the development of hepatocellular carcinoma (HCC. Nevertheless, transgenic mice which express the whole HCV polyprotein (HCV-Tg do not develop HCC. Whereas chronic HCV infection causes inflammation in patients, in HCV-Tg mice, the host immune reaction against viral proteins is lacking. We aimed to test the role of HCV proteins in HCC development on the background of chronic inflammation in vivo. METHODOLOGY/PRINCIPAL FINDINGS: We crossed HCV-Tg mice that do not develop HCC with the Mdr2-knockout (Mdr2-KO mice which develop inflammation-associated HCC, to generate Mdr2-KO/HCV-Tg mice. We studied the effect of the HCV transgene on tumor incidence, hepatocyte mitosis and apoptosis, and investigated the potential contributing factors for the generated phenotype by gene expression and protein analyses. The Mdr2-KO/HCV-Tg females from the N2 generation of this breeding (having 75% of the FVB/N genome and 25% of the C57BL/6 genome produced significantly larger tumors in comparison with Mdr2-KO mice. In parallel, the Mdr2-KO/HCV-Tg females had an enhanced inflammatory gene expression signature. However, in the N7 generation (having 99.2% of the FVB/N genome and 0.8% of the C57BL/6 genome there was no difference in tumor development between Mdr2-KO/HCV-Tg and Mdr2-KO animals of both sexes. The HCV transgene was similarly expressed in the livers of Mdr2-KO/HCV-Tg females of both generations, as revealed by detection of the HCV transcript and the core protein. CONCLUSION: These findings suggest that the HCV transgene accelerated inflammation-associated hepatocarcinogenesis in a host genetic background-dependent manner.

  15. Packaging of HCV-RNA into lentiviral vector

    Energy Technology Data Exchange (ETDEWEB)

    Caval, Vincent [INSERM U966, Universite Francois Rabelais de Tours, Faculte de Medecine, 10 Bd. Tonnelle, 37000 Tours (France); Piver, Eric [INSERM U966, Universite Francois Rabelais de Tours, Faculte de Medecine, 10 Bd. Tonnelle, 37000 Tours (France); Service de Biochimie et Biologie Moleculaire, CHRU de Tours (France); Ivanyi-Nagy, Roland; Darlix, Jean-Luc [LaboRetro, ENS-Lyon INSERM, U758, 46 Allee d' Italie, 69364 Lyon (France); Pages, Jean-Christophe, E-mail: jean-christophe.pages@univ-tours.fr [INSERM U966, Universite Francois Rabelais de Tours, Faculte de Medecine, 10 Bd. Tonnelle, 37000 Tours (France); Service de Biochimie et Biologie Moleculaire, CHRU de Tours (France)

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer Description of HCV-RNA Core-D1 interactions. Black-Right-Pointing-Pointer In vivo evaluation of the packaging of HCV genome. Black-Right-Pointing-Pointer Determination of the role of the three basic sub-domains of D1. Black-Right-Pointing-Pointer Heterologous system involving HIV-1 vector particles to mobilise HCV genome. Black-Right-Pointing-Pointer Full length mobilisation of HCV genome and HCV-receptor-independent entry. -- Abstract: The advent of infectious molecular clones of Hepatitis C virus (HCV) has unlocked the understanding of HCV life cycle. However, packaging of the genomic RNA, which is crucial to generate infectious viral particles, remains poorly understood. Molecular interactions of the domain 1 (D1) of HCV Core protein and HCV RNA have been described in vitro. Since compaction of genetic information within HCV genome has hampered conventional mutational approach to study packaging in vivo, we developed a novel heterologous system to evaluate the interactions between HCV RNA and Core D1. For this, we took advantage of the recruitment of Vpr fusion-proteins into HIV-1 particles. By fusing HCV Core D1 to Vpr we were able to package and transfer a HCV subgenomic replicon into a HIV-1 based lentiviral vector. We next examined how deletion mutants of basic sub-domains of Core D1 influenced HCV RNA recruitment. The results emphasized the crucial role of the first and third basic regions of D1 in packaging. Interestingly, the system described here allowed us to mobilise full-length JFH1 genome in CD81 defective cells, which are normally refractory to HCV infection. This finding paves the way to an evaluation of the replication capability of HCV in various cell types.

  16. Correlation between alanine aminotransferase level, HCV-RNA titer ...

    African Journals Online (AJOL)

    Quantitative HCV-RNA level measurement, HCV genotyping, and abdominal ultrasonography were investigated in all patients. Liver biopsy was done for 80 patients and the remaining 58 patients were examined using Fibroscan. Highly significant higher percentage of cases with high level of HCV viremia was found among ...

  17. Prevalence of HCV Infections Among Hemodialysis Patients in Al ...

    African Journals Online (AJOL)

    1527 patients (11%) who were HCV free at the start of the study. By the end of the study, a total of 42.2% were found to be anti-HCV reactive. Conclusion: The study demonstrated high prevalence of anti-HCV in HD units in Al Gharbiyah Governorate. Similar studies must be conducted in all Egyptian governorates' HD units ...

  18. HCV RNA in peripheral blood mononuclear cells (PBMCs) as a ...

    African Journals Online (AJOL)

    Abdel Fatah Fahmy Hanno

    2013-06-27

    Jun 27, 2013 ... Objectives: To study hepatitis virus C (HCV) RNA in peripheral blood mononuclear cells. (PBMCs) of patients with chronic HCV infection, and explore the relationship between the HCV. RNA in the PBMCs and response to interferon (IFN) therapy. Methods: Twenty-five patients with chronic viral hepatitis C ...

  19. HCV and Oxidative Stress in the Liver

    Directory of Open Access Journals (Sweden)

    Sergey N. Kochetkov

    2013-01-01

    Full Text Available Hepatitis C virus (HCV is the etiological agent accounting for chronic liver disease in approximately 2–3% of the population worldwide. HCV infection often leads to liver fibrosis and cirrhosis, various metabolic alterations including steatosis, insulin and interferon resistance or iron overload, and development of hepatocellular carcinoma or non-Hodgkin lymphoma. Multiple molecular mechanisms that trigger the emergence and development of each of these pathogenic processes have been identified so far. One of these involves marked induction of a reactive oxygen species (ROS in infected cells leading to oxidative stress. To date, markers of oxidative stress were observed both in chronic hepatitis C patients and in various in vitro systems, including replicons or stable cell lines expressing viral proteins. The search for ROS sources in HCV-infected cells revealed several mechanisms of ROS production and thus a number of cellular proteins have become targets for future studies. Furthermore, during last several years it has been shown that HCV modifies antioxidant defense mechanisms. The aim of this review is to summarize the present state of art in the field and to try to predict directions for future studies.

  20. HCV and Oxidative Stress in the Liver

    Science.gov (United States)

    Ivanov, Alexander V.; Bartosch, Birke; Smirnova, Olga A.; Isaguliants, Maria G.; Kochetkov, Sergey N.

    2013-01-01

    Hepatitis C virus (HCV) is the etiological agent accounting for chronic liver disease in approximately 2–3% of the population worldwide. HCV infection often leads to liver fibrosis and cirrhosis, various metabolic alterations including steatosis, insulin and interferon resistance or iron overload, and development of hepatocellular carcinoma or non-Hodgkin lymphoma. Multiple molecular mechanisms that trigger the emergence and development of each of these pathogenic processes have been identified so far. One of these involves marked induction of a reactive oxygen species (ROS) in infected cells leading to oxidative stress. To date, markers of oxidative stress were observed both in chronic hepatitis C patients and in various in vitro systems, including replicons or stable cell lines expressing viral proteins. The search for ROS sources in HCV-infected cells revealed several mechanisms of ROS production and thus a number of cellular proteins have become targets for future studies. Furthermore, during last several years it has been shown that HCV modifies antioxidant defense mechanisms. The aim of this review is to summarize the present state of art in the field and to try to predict directions for future studies. PMID:23358390

  1. Indications for treatment in chronic HCV infection.

    Science.gov (United States)

    Dávalos Moscol, Milagros

    2010-01-01

    HCV Infection is a global burden disease and it is related to the development of progressive liver fibrosis, cirrhosis and hepatocellular carcinoma. At least 80% of the persons that have an acute infection evolve to chronicity. This event affects the patient and their contacts for the risk of acquiring the infection. Once chronic HCV is present some factors accelerate progression: older age, obesity, alcohol consumption, etc. Severity of fibrosis is one of the most important factors to be analyzed before deciding to treat a patient. Pegylated interferon and ribavirin is the .standard of care. for this disease, however, it has many side effects, some of them life threatening. That is the reason why this treatment must be indicated in the right moment in the right patient. A complete medical evaluation must be done previously to initiate treatment. Other concurrent problems must be ruled out or treated. Decompensated cirrhosis, autoimmune diseases or other uncontrolled disease are contraindication to HCV treatment. Previous failure to treatment for HCV must be analyzed to identify the reasons for that event and consider retreatment. Cryoglobulinemia and membranoproliferative glomerulonephritis are indications for treatment independent from the severity of liver disease.

  2. Correlates of HCV seropositivity among familial contacts of HCV positive patients

    Directory of Open Access Journals (Sweden)

    Matera Antonio

    2006-09-01

    Full Text Available Abstract Background Determinants of intrafamilial HCV transmission are still being debated. The aim of this study is to investigate the correlates of HCV seropositivity among familial contacts of HCV positive patients in Italy. Methods A cross-sectional study was conducted with 175 HCV positive patients (index cases, recruited from Policlinico Gemelli in Rome as well as other hospitals in Central Italy between 1995 and 2000 (40% female, mean age 57 ± 15.2 years, and 259 familial contacts. Differences in proportions of qualitative variables were tested with non-parametric tests (χ2, Yates correction, Fisher exact test, and a p value Results Seropositivity for HCV was found in 8.9% of the contacts. From the univariate analysis, risk factors significantly associated to HCV positivity in the contacts were: intravenous drug addiction (p = 0.004 and intercourse with drug addicts (p = 0.005. The only variables associated significantly and independently to HCV seropositivity in patients' contacts were intercourse with drug addicts (OR = 19.28; 95% CI: 2.01 – 184.94, the retirement status from work (OR = 3.76; 95% CI: 1.17 – 11.98, the time of the relationship (OR = 1.06; 95% CI: 1.00 – 1.11 and tattoos (OR = 7.68; 95% CI: 1.00 – 60.20. Conclusion The present study confirms that having intercourse with a drug addict is the most significant risk factor for intrafamilial HCV transmission. The association with retirement status from work could be related to both a long-term relationship with an index case and past exposure to common risk factors.

  3. Hepatitis C virus (HCV) RNA profiles among chronic HIV/HCV-coinfected individuals in ESPRIT; spontaneous HCV RNA clearance observed in nine individuals.

    Science.gov (United States)

    Grint, D; Tedaldi, E; Peters, L; Mocroft, A; Edlin, B; Gallien, S; Klinker, H; Boesecke, C; Kokordelis, P; Rockstroh, J K

    2017-07-01

    Studies have shown that hepatitis C virus (HCV) RNA levels remain stable over time in HIV/HCV-coinfected individuals taking combination antiretroviral therapy (cART), while spontaneous clearance of HCV RNA during the persistent infection phase has been documented only rarely among those with the CC interleukin (IL)-28B genotype. This study describes HCV RNA profiles and factors associated with changes over time in HCV RNA levels in the ESPRIT study. HIV/HCV-coinfected individuals positive for HCV RNA were included in the study. Follow-up was counted from the first HCV RNA positive test and censored at the initiation of interferon-based treatment. HCV RNA and IL-28B measurements were performed in the same reference laboratory. Random effects mixed models were used to analyse changes over time in HCV RNA. A total of 312 ESPRIT patients were included in the study (151 in the arm receiving subcutaneous recombinant IL-2 and 161 in the control arm). Most of the patients were white (89%) and male (76%), and they had a median of 5 HCV RNA measurements per person [interquartile range (IQR) 3-6; range 1-9]. Median follow-up was 5 years (IQR: 2-6 years). At baseline, 96% of patients were taking cART and 93% had undetectable HIV RNA. Mean HCV RNA levels decreased by 13% per year over the study period [95% confidence interval (CI) 8-18%; P < 0.0001]. Baseline HCV RNA levels and the change over time in HCV RNA did not differ by randomization arm (P = 0.16 and P = 0.56, respectively). Nine individuals spontaneously cleared HCV RNA during follow-up [IL-28B genotypes: CC, five patients (56%); CT, four patients (44%)]. HCV RNA levels decreased over time in this population with well-controlled HIV infection. Spontaneous clearance of HCV RNA was documented in five individuals with IL-28B genotype CC and four with the CT genotype. © 2016 British HIV Association.

  4. Seroprevalence of HCV among Cairo University students in Egypt.

    Science.gov (United States)

    Esmat, Gamal; Raziky, Maissa El; Nabeel, Mohammed M; Maher, Rabab; Zakaria, Zeinab

    2016-08-01

    Hepatitis C virus (HCV) is highly prevalent in Egypt. This work aimed at determining the seroprevalence of HCV among Cairo University students. The present study included 3,000 students from Cairo University, Egypt. Blood sample was obtained from each participant to be tested for HCV seromarker. HCV RNA detection by polymerase chain reaction (PCR) was carried out for those with positive anti-HCV. Overall prevalence rate of HCV antibody (anti-HCV) was 4.6%. It showed that the prevalence was relatively higher among females (86/1660; 5.2%) while males (51/1340; 3.8%) with no significant difference. PCR for HCV RNA was detected in 31.4% of the HCV antibody positive subjects (43/137). Which showed statistical significant difference between males (29/51) and females (14/86) at P = 0.001. Despite the prevalence rate reported in the present study was similar to anti-HCV prevalence among persons in the same age group, confirmed that HCV infection is detected among Cairo University students. J. Med. Virol. 88:1384-1387, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. PML tumor suppressor protein is required for HCV production

    Energy Technology Data Exchange (ETDEWEB)

    Kuroki, Misao [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan); Research Fellow of the Japan Society for the Promotion of Science (Japan); Center for AIDS Research, Kumamoto University, Kumamoto 860-0811 (Japan); Ariumi, Yasuo, E-mail: ariumi@kumamoto-u.ac.jp [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan); Center for AIDS Research, Kumamoto University, Kumamoto 860-0811 (Japan); Hijikata, Makoto [Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606-8507 (Japan); Ikeda, Masanori; Dansako, Hiromichi [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan); Wakita, Takaji [Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640 (Japan); Shimotohno, Kunitada [Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba 272-8516 (Japan); Kato, Nobuyuki [Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558 (Japan)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer PML tumor suppressor protein is required for HCV production. Black-Right-Pointing-Pointer PML is dispensable for HCV RNA replication. Black-Right-Pointing-Pointer HCV could not alter formation of PML-NBs. Black-Right-Pointing-Pointer INI1 and DDX5, PML-related proteins, are involved in HCV life cycle. -- Abstract: PML tumor suppressor protein, which forms discrete nuclear structures termed PML-nuclear bodies, has been associated with several cellular functions, including cell proliferation, apoptosis and antiviral defense. Recently, it was reported that the HCV core protein colocalizes with PML in PML-NBs and abrogates the PML function through interaction with PML. However, role(s) of PML in HCV life cycle is unknown. To test whether or not PML affects HCV life cycle, we examined the level of secreted HCV core and the infectivity of HCV in the culture supernatants as well as the level of HCV RNA in HuH-7-derived RSc cells, in which HCV-JFH1 can infect and efficiently replicate, stably expressing short hairpin RNA targeted to PML. In this context, the level of secreted HCV core and the infectivity in the supernatants from PML knockdown cells was remarkably reduced, whereas the level of HCV RNA in the PML knockdown cells was not significantly affected in spite of very effective knockdown of PML. In fact, we showed that PML is unrelated to HCV RNA replication using the subgenomic HCV-JFH1 replicon RNA, JRN/3-5B. Furthermore, the infectivity of HCV-like particle in the culture supernatants was significantly reduced in PML knockdown JRN/3-5B cells expressing core to NS2 coding region of HCV-JFH1 genome using the trans-packaging system. Finally, we also demonstrated that INI1 and DDX5, the PML-related proteins, are involved in HCV production. Taken together, these findings suggest that PML is required for HCV production.

  6. Prediction of Intraoperative Blood Loss during Total Knee Arthroplasty in HCV+ and HCV- Patients with Hemophilia A.

    Science.gov (United States)

    Shurkhina, E S; Polyanskaya, T Yu; Zorenko, V Yu; Nesterenko, V M

    2017-03-01

    We examined HCV+ and HCV- hemophilia A patients with knee arthropathy and hematocrit above 38.5%. The mean density of erythrocytes was studied by the phthalate method, intraoperative blood loss was assessed gravimetrically. The volume of blood loss in HCV+ patients with manifest adhesive process and chronic synovitis varied from 300 to 1900 ml, in patients with moderate adhesive process from 400 to 1500 ml. The volume of blood loss in HCV- patients was 300-800 ml. A positive correlation between the blood loss volume and mean density of erythrocytes was detected. Blood loss >1000 ml during total knee arthroplasty can be expected in patients with hemophilia A with HCV and high mean density of erythrocytes. Blood loss >1000 ml is unlikely in HCV- and HCV+ patients with the mean density of erythrocytes not surpassing the normal values.

  7. Complementary role of HCV and HIV in T-cell activation and exhaustion in HIV/HCV coinfection.

    Science.gov (United States)

    Feuth, Thijs; Arends, Joop E; Fransen, Justin H; Nanlohy, Nening M; van Erpecum, Karel J; Siersema, Peter D; Hoepelman, Andy I M; van Baarle, Debbie

    2013-01-01

    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. 14 HIV/HCV coinfected, 19 HCV monoinfected, 10 HIV monoinfected patients and 15 healthy controls were included in this cross-sectional study. Differences in expression of activation and exhaustion markers (HLA-DR, CD38, PD-1, Tim-3 and Fas) and phenotypic markers on CD4(+) and CD8(+) T-cells were analysed by flow cytometry and were related to HCV disease parameters (HCV-viremia, ALT and liver fibrosis). Frequencies of activated CD4(+) and CD8(+) T-cells were higher in HIV/HCV-coinfected compared to healthy controls and HCV or HIV mono-infected individuals. Coinfected patients also showed high expression of the exhaustion marker PD-1 and death receptor Fas. In contrast, the exhaustion marker Tim-3 was only elevated in HIV-monoinfected patients. T-cell activation and exhaustion were correlated with HCV-RNA, suggesting that viral antigen influences T-cell activation and exhaustion. Interestingly, increased percentages of effector CD8(+) T-cells were found in patients with severe (F3-F4) liver fibrosis compared to those with no to minimal fibrosis (F0-F2). HIV/HCV coinfected patients display a high level of T-cell activation and exhaustion in the peripheral blood. Our data suggest that T-cell activation and exhaustion are influenced by the level of HCV viremia. Furthermore, high percentages of cytotoxic/effector CD8(+) T-cells are associated with liver fibrosis in both HCV monoinfected and HIV/HCV coinfected patients.

  8. 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 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.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.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.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 for HCV. Though >90% of patients were male and

  9. The success of HCV cure: every rose has its thorn.

    Science.gov (United States)

    Salmon-Ceron, Dominique; Mondelli, Mario U; Maticic, Mojca; Arends, Joop E

    2017-11-07

    This review aimed to examine mid-term liver complications and extra-hepatic clinical syndromes in addition to quality of life benefits associated with achieving HCV cure. Also to review the few safety issues that have been associated with the use of oral direct acting antivirals (DAAs) and discuss the potential benefits of the reduction of the burden of HCV infection at the population level. HCV cure is possible with DAAs in more than 95% of the patients treated. The blockage of liver inflammation and halting of fibrosis progression translates in both hepatic and extra-hepatic beneficial improvements and in reduction in the need for liver transplantation secondary to HCV. In addition, a reduction in the frequency of extra-hepatic manifestations like mixed cryoglobulinemia and vasculitis and improvements in quality of life and fatigue have been described. Curing HCV infection also provides a high potential to reduce the burden of HCV infection at the population level. Several modelling studies suggest that dramatic reductions in HCV prevalence and incidence are possible with large scaling-up of HCV treatment. However, obtaining these benefits needs early treatment of HCV-infected individuals preceded by voluntary national policies to improve the screening of HCV and the access to care, particularly in high-risk populations. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Trasmissione sessuale di HCV in coppie eterosessuali monogame

    Directory of Open Access Journals (Sweden)

    C. Vandelli

    2003-05-01

    Full Text Available

    Obiettivi: la trasmissione dell’HCV per via sessuale non è stata ancora confermata in modo inequivocabile. Dai dati della letteratura emerge che il tasso di infezione da HCV in partner sessuali di soggetti anti-HCV positivi varia da valori molto bassi a valori elevati (fino al 30%. Scopo dello studio è stato quello di valutare prospetticamente il rischio di acquisire l’infezione da HCV in una coorte di partner monogami di soggetti con infezione cronica da HCV.

    Metodi: è stata studiata una coorte di 895 partner sessuali monogami di soggetti HCV infetti afferenti al Dipartimento di Medicina Interna dell’Università di Modena. Le coppie sono state seguite prospetticamente per un periodo di 10 anni. I dati disponibili al termine del follow-up riguardavano 776 delle 895 (86.7% coppie arruolate. Tutte le coppie hanno negato rapporti anali, sesso durante il periodo mestruale o uso di profilattico. Il tasso medio settimanale di rapporti sessuali è risultato di 1.8. Tutti i soggetti sono stati annualmente testati per anti-HCV e HCV RNA. Risultati: durante il follow-up sono state osservate 3 nuove infezioni da HCV (tasso di incidenza = 0.37 per 1000 persone-anno. Tuttavia, il genotipo di HCV presente in un coniuge (2a era differente da quello del rispettivo partner (1b. Le rimanenti due coppie avevano genotipo concordante ma l’analisi filogenetica delle sequenze della regione NS5b del genoma di HCV ha indicato che gli isolati virali dei rispettivi partner erano differenti, escludendo quindi la possibilità di una trasmissione per via sessuale.

    Conclusioni: i dati del presente studio indicano che il rischio di trasmissione sessuale di HCV tra coppie eterosessuali monogame è estremamente basso o addirittura assente. Alcuna raccomandazione generale all’uso del profilattico sembra pertanto richiesta per coppie monogami con un partner HCV positivo.

  11. Activation of extrinsic apoptosis pathway in HCV monoinfected and HIV-HCV coinfected patients, irrespective of liver disease severity.

    Science.gov (United States)

    Feuth, Thijs; Van Baarle, Debbie; Hoepelman, Andy I M; Van Erpecum, Karel J; Siersema, Peter D; Arends, Joop E

    2014-07-01

    Chronic hepatitis C virus (HCV) infection is associated with increased levels of peripheral T cell apoptosis. We aimed to study whether T cell apoptosis markers indicate pathways that may contribute to clinical progression in HCV monoinfected and HIV-HCV coinfected patients. Activation of the extrinsic apoptosis pathways was measured by levels of death receptor Fas, initiator caspase 8 and effector caspases 3 and 7 activity and Annexin V binding on peripheral CD4 and CD8 T cells of HCV monoinfected and HIV/HCV coinfected patients, as well as healthy controls and HIV-infected, hepatitis B virus-infected and primary biliary cirrhosis disease controls. Association with liver fibrosis was assessed by biopsy or by transient elastography. HCV monoinfected and HIV-HCV coinfected patients displayed enhanced peripheral CD4 and CD8 T cell apoptosis. Caspase 8 activity was highest in HIV-HCV coinfection, without enhanced downstream activity of caspases 3 and 7. Level of peripheral T cell apoptosis was independent of liver fibrosis or other disease parameters in all disease groups. The extrinsic apoptosis pathway is upregulated in HCV monoinfection and HIV-HCV coinfection, but this is independent of liver disease severity.

  12. Present situation of antiviral therapies for HCV-related cirrhosis

    Directory of Open Access Journals (Sweden)

    LI Qiang

    2015-11-01

    Full Text Available Patients with hepatitis C virus (HCV-related cirrhosis are at a higher risk for the development of hepatic failure and hepatocellular carcinoma (HCC compared with non-cirrhotic patients. Antiviral therapies for HCV-related cirrhosis may reduce the incidence of HCC and hepatic failure. This article introduces current antiviral therapies for HCV-related cirrhosis: P/R, DAA+P/R, and IFN-free regimens, and summarizes the present situation of antiviral therapies for HCV-related cirrhosis. It is thought that the advent of direct-acting antivirals has improved the rate of sustained virologic response and reduced the incidence of adverse events during the treatment of HCV-related cirrhosis. Interferon-free regimens have great advantage and potential in antiviral therapies for HCV-related cirrhosis.

  13. Mechanisms of accelerated liver fibrosis in HIV-HCV coinfection.

    Science.gov (United States)

    Chrysanthidis, Theofilos; Loli, Georgia; Metallidis, Simeon; Germanidis, Georgios

    2017-01-01

    Although there is evidence that HCV progresses rapidly in HIV/HCV coinfected patients in comparison with HCV monoinfected, the HIV-, HCV- and host/genetic-related factors, as well as the exact mechanisms implicated in this process are not fully elucidated. Furthermore, cure of HCV in those coinfected seems possible with the new antiviral drugs, but high cost as well as insufficient identification, linkage with care and treatment hamper the achievement of this goal. Research on the subject, could reveal an important prognostic marker for the effectiveness of persuasion of patients with HIV/HCV coinfection with a predicted accelerated fibrosis course, in order to facilitate and prioritize, not in terms of guidelines but in the real life situation, their treatment with a medically just framework.

  14. Virological Mechanisms in the Coinfection between HIV and HCV

    Directory of Open Access Journals (Sweden)

    Maria Carla Liberto

    2015-01-01

    Full Text Available Due to shared transmission routes, coinfection with Hepatitis C Virus (HCV is common in patients infected by Human Immunodeficiency Virus (HIV. The immune-pathogenesis of liver disease in HIV/HCV coinfected patients is a multifactorial process. Several studies demonstrated that HIV worsens the course of HCV infection, increasing the risk of cirrhosis and hepatocellular carcinoma. Also, HCV might increase immunological defects due to HIV and risk of comorbidities. A specific cross-talk among HIV and HCV proteins in coinfected patients modulates the natural history, the immune responses, and the life cycle of both viruses. These effects are mediated by immune mechanisms and by a cross-talk between the two viruses which could interfere with host defense mechanisms. In this review, we focus on some virological/immunological mechanisms of the pathogenetic interactions between HIV and HCV in the human host.

  15. Impaired Hepatitis C Virus (HCV)–Specific Interferon-γ Responses in Individuals With HIV Who Acquire HCV Infection: Correlation With CD4+ T-Cell Counts

    Science.gov (United States)

    Flynn, Jacqueline K.; Dore, Gregory J.; Matthews, Gail; Hellard, Margaret; Yeung, Barbara; Rawlinson, William D.; White, Peter A.; Kaldor, John M.; Lloyd, Andrew R.; Ffrench, Rosemary A.

    2012-01-01

    Studies examining the effect of coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) on the HCV-specific immune response in acute HCV infection are limited. This study directly compared acute HCV-specific T-cell responses and cytokine profiles between 20 HIV/HCV-coinfected and 20 HCV-monoinfected subjects, enrolled in the Australian Trial in Acute Hepatitis C (ATAHC), using HCV peptide enzyme-linked immunospot (ELISPOT) and multiplex in vitro cytokine production assays. HIV/HCV coinfection had a detrimental effect on the HCV-specific cytokine production in acute HCV infection, particularly on HCV-specific interferon γ (IFN-γ) production (magnitude P = .004; breadth P = .046), which correlated with peripheral CD4+ T-cell counts (ρ = 0.605; P = .005) but not with detectable HIV viremia (ρ = 0.152; P = .534). PMID:22949308

  16. Impaired hepatitis C virus (HCV)-specific interferon-γ responses in individuals with HIV who acquire HCV infection: correlation with CD4(+) T-cell counts.

    Science.gov (United States)

    Flynn, Jacqueline K; Dore, Gregory J; Matthews, Gail; Hellard, Margaret; Yeung, Barbara; Rawlinson, William D; White, Peter A; Kaldor, John M; Lloyd, Andrew R; Ffrench, Rosemary A

    2012-11-15

    Studies examining the effect of coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) on the HCV-specific immune response in acute HCV infection are limited. This study directly compared acute HCV-specific T-cell responses and cytokine profiles between 20 HIV/HCV-coinfected and 20 HCV-monoinfected subjects, enrolled in the Australian Trial in Acute Hepatitis C (ATAHC), using HCV peptide enzyme-linked immunospot (ELISPOT) and multiplex in vitro cytokine production assays. HIV/HCV coinfection had a detrimental effect on the HCV-specific cytokine production in acute HCV infection, particularly on HCV-specific interferon γ (IFN-γ) production (magnitude P = .004; breadth P = .046), which correlated with peripheral CD4(+) T-cell counts (ρ = 0.605; P = .005) but not with detectable HIV viremia (ρ = 0.152; P = .534).

  17. Detection limit of architect hepatitis C core antigen assay in correlation with HCV RNA, and renewed confirmation algorithm for reactive anti-HCV samples.

    Science.gov (United States)

    Ottiger, Cornelia; Gygli, Nicole; Huber, Andreas R

    2013-11-01

    hepatitis C infections are detected by anti-HCV screening tests. Reactive anti-HCV results give no information about the presence or absence of hepatitis C viruses, or of unspecific reactivity. To obtain information about the viral load, HCV RNA measurements, following a reactive anti-HCV result, are performed in well equipped and specialised laboratories. Anti-HCV immunoblots are the only means to exclude non specific reactivity. The measurement of HCV core antigen (HCV-Ag), as an alternative to HCV RNA, is discussed, as it can be analysed on the same instrument as anti-HCV. The detection limit of HCV-Ag is crucial to use it in lieu of HCV RNA, in regard of the different genotypes. A renewed algorithm is proposed to exclude unspecific reactivity of anti-HCV. Samples were tested on Architect i2000SR (Abbott) for anti-HCV and HCV-Ag. HCV RNA measurements were obtained by Cobas Ampliprep/Taqman (Roche) or m2000rt(®) (Abbott). Comparison between HCV-Ag and HCV RNA from 126 samples of 101 patients with chronic hepatitis C gave linear regression R(2) 0.89, slope 0.885 and intercept -2.258, which were independent of the genotypes. The detection limit of HCV-Ag was between 2.4 and 4.5 Log(10)IU/mL. A renewed algorithm for confirmation of reactive anti-HCV results is proposed: active or resolved hepatitis C infections or false reactivity can be differentiated by sequenced reflex testing due to HCV-Ag, anti-HCV immunoblot and HCV RNA. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Animal models for HCV and HBV studies

    Directory of Open Access Journals (Sweden)

    Isabelle Chemin

    2007-02-01

    Full Text Available

    The narrow host range of infection and lack of suitable tissue culture systems for the propagation of hepatitis B and C viruses are limitations that have prevented a more thorough understanding of persistent infection and the pathogenesis of chronic liver disease.

    Despite decades of intensive research and significant progresses in understanding of viral hepatitis, many basic questions and clinical problems still await to be resolved. For example, the HBV cellular receptor and related mechanisms of viral entry have not yet been identified. Little is also known about the function of certain non-structural viral products, such as the hepatitis B e antigen and the X protein, or about the role of excess hepadnavirus subviral particles circulating in the blood stream during infection. Furthermore, the molecular mechanisms involved in the development of hepatocellular carcinoma and the role of the immune system in determining the fate of infection are not fully understood.

    The reason for these drawbacks is essentially due to the lack of reliable cell-based in vitro infection systems and, most importantly, convenient animal models.

    This lack of knowledge has been partially overcome for hepatitis B virus (HBV, by the discovery and characterization of HBV-like viruses in wild animals while for hepatitis C virus (HCV, related flaviviruses have been used as surrogate systems.

    Other laboratories have developed transgenic mice that express virus gene products and/or support virus replication. Some HBV transgenic mouse models

  19. Discovery of potent macrocyclic HCV NS5A inhibitors.

    Science.gov (United States)

    Yu, Wensheng; Vibulbhan, Bancha; Rosenblum, Stuart B; Martin, Gregory S; Vellekoop, A Samuel; Holst, Christian L; Coburn, Craig A; Wong, Michael; Selyutin, Oleg; Ji, Tao; Zhong, Bin; Hu, Bin; Chen, Lei; Dwyer, Michael P; Jiang, Yueheng; Nair, Anilkumar G; Tong, Ling; Zeng, Qingbei; Agrawal, Sony; Carr, Donna; Rokosz, Laura; Liu, Rong; Curry, Stephanie; McMonagle, Patricia; Ingravallo, Paul; Lahser, Fred; Asante-Appiah, Ernest; Fells, James; Kozlowski, Joseph A

    2016-08-01

    HCV NS5A inhibitors have demonstrated impressive in vitro virologic profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed-dose combination (FDC) regimen for the treatment of HCV infection. Merck's effort in this area identified MK-4882 and MK-8325 as early development leads. Herein, we describe the discovery of potent macrocyclic NS5A inhibitors bearing the MK-8325 or MK-4882 core structure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Hepatitis C virus (HCV genotype 1 subtype identification in new HCV drug development and future clinical practice.

    Directory of Open Access Journals (Sweden)

    Stéphane Chevaliez

    Full Text Available BACKGROUND: With the development of new specific inhibitors of hepatitis C virus (HCV enzymes and functions that may yield different antiviral responses and resistance profiles according to the HCV subtype, correct HCV genotype 1 subtype identification is mandatory in clinical trials for stratification and interpretation purposes and will likely become necessary in future clinical practice. The goal of this study was to identify the appropriate molecular tool(s for accurate HCV genotype 1 subtype determination. METHODOLOGY/PRINCIPAL FINDINGS: A large cohort of 500 treatment-naïve patients eligible for HCV drug trials and infected with either subtype 1a or 1b was studied. Methods based on the sole analysis of the 5' non-coding region (5'NCR by sequence analysis or reverse hybridization failed to correctly identify HCV subtype 1a in 22.8%-29.5% of cases, and HCV subtype 1b in 9.5%-8.7% of cases. Natural polymorphisms at positions 107, 204 and/or 243 were responsible for mis-subtyping with these methods. A real-time PCR method using genotype- and subtype-specific primers and probes located in both the 5'NCR and the NS5B-coding region failed to correctly identify HCV genotype 1 subtype in approximately 10% of cases. The second-generation line probe assay, a reverse hybridization assay that uses probes targeting both the 5'NCR and core-coding region, correctly identified HCV subtypes 1a and 1b in more than 99% of cases. CONCLUSIONS/SIGNIFICANCE: In the context of new HCV drug development, HCV genotyping methods based on the exclusive analysis of the 5'NCR should be avoided. The second-generation line probe assay is currently the best commercial assay for determination of HCV genotype 1 subtypes 1a and 1b in clinical trials and practice.

  1. HCV-RNA quantification in liver bioptic samples and extrahepatic compartments, using the abbott RealTime HCV assay.

    Science.gov (United States)

    Antonucci, FrancescoPaolo; Cento, Valeria; Sorbo, Maria Chiara; Manuelli, Matteo Ciancio; Lenci, Ilaria; Sforza, Daniele; Di Carlo, Domenico; Milana, Martina; Manzia, Tommaso Maria; Angelico, Mario; Tisone, Giuseppe; Perno, Carlo Federico; Ceccherini-Silberstein, Francesca

    2017-08-01

    We evaluated the performance of a rapid method to quantify HCV-RNA in the hepatic and extrahepatic compartments, by using for the first time the Abbott RealTime HCV-assay. Non-tumoral (NT), tumoral (TT) liver samples, lymph nodes and ascitic fluid from patients undergoing orthotopic-liver-transplantation (N=18) or liver resection (N=4) were used for the HCV-RNA quantification; 5/22 patients were tested after or during direct acting antivirals (DAA) treatment. Total RNA and DNA quantification from tissue-biopsies allowed normalization of HCV-RNA concentrations in IU/μg of total RNA and IU/10 6 liver-cells, respectively. HCV-RNA was successfully quantified with high reliability in liver biopsies, lymph nodes and ascitic fluid samples. Among the 17 untreated patients, a positive and significant HCV-RNA correlation between serum and NT liver-samples was observed (Pearson: rho=0.544, p=0.024). Three DAA-treated patients were HCV-RNA "undetectable" in serum, but still "detectable" in all tested liver-tissues. Differently, only one DAA-treated patient, tested after sustained-virological-response, showed HCV-RNA "undetectability" in liver-tissue. HCV-RNA was successfully quantified with high reliability in liver bioptic samples and extrahepatic compartments, even when HCV-RNA was "undetectable" in serum. Abbott RealTime HCV-assay is a good diagnostic tool for HCV quantification in intra- and extra-hepatic compartments, whenever a bioptic sample is available. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Therapeutic vaccines in HBV: lessons from HCV.

    Science.gov (United States)

    Barnes, Eleanor

    2015-02-01

    Currently, millions of people infected with hepatitis B virus (HBV) are committed to decades of treatment with anti-viral therapy to control viral replication. However, new tools for immunotherapy that include both viral vectors and molecular checkpoint inhibitors are now available. This has led to a resurgence of interest in new strategies to develop immunotherapeutic strategies with the aim of inducing HBeAg seroconversion--an end-point that has been associated with a decrease in the rates of disease progression. Ultimately, a true cure will involve the elimination of covalently closed circular DNA which presents a greater challenge for immunotherapy. In this manuscript, I describe the development of immunotherapeutic strategies for HBV that are approaching or currently in clinical studies, and draw on observations of T cell function in natural infection supported by recent animal studies that may lead to additional rational vaccine strategies using checkpoint inhibitors. I also draw on our recent experience in developing potent vaccines for HCV prophylaxis based on simian adenoviral and MVA vectors used in prime-boost strategies in both healthy volunteers and HCV infected patients. I have shown that the induction of T cell immune responses is markedly attenuated when administered to people with persistent HCV viremia. These studies and recently published animal studies using the woodchuck model suggest that potent vaccines based on DNA or adenoviral vectored vaccination represent a rational way forward. However, combining these with drugs to suppress viral replication, alongside checkpoint inhibitors may be required to induce long-term immune control.

  3. Modeling HCV disease in animals: virology, immunology and pathogenesis of HCV and GBV-B infections.

    Science.gov (United States)

    Manickam, Cordelia; Reeves, R Keith

    2014-01-01

    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 poses a significant threat due to a lack of vaccines and affordable treatment options. The immune correlates of protection and predisposing factors toward 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.

  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. Molecular epidemiology of HCV monoinfection and HIV/HCV coinfection in injection drug users in Liuzhou, Southern China.

    Directory of Open Access Journals (Sweden)

    Yi Tan

    Full Text Available BACKGROUND: Hepatitis C virus (HCV mono-infection and HCV/HIV (human immunodeficiency virus co-infection are growing problems in injection drug users (IDU. Their prevalence and genotypic patterns vary with geographic locations. Access to harm reduction measures is opening up opportunities for improving the HIV/HCV profiling of IDU in China, where IDUs account for a significant proportion of the two infections especially in the southern part of the country. METHODOLOGY/PRINCIPAL FINDINGS: A cross sectional study was conducted. Through the Liuzhou Methadone Clinic, a total of 117 injection drug users (IDUs were recruited from Guangxi, Southern China. A majority of the IDUs (96% were HCV antibody positive, of which 21% were HIV infected. Unlike HCV monoinfection, there was spatial heterogeneity in the distribution of HIV/HCV coinfection, the latter also characterized by a higher prevalence of needle-sharing. Phylogenetic analysis revealed that genotype 6a was predominant in the study population. There were shorter genetic distances among the 6a sequences compared to the other HCV subtypes-1a, 3a, and 3b. CONCLUSION/SIGNIFICANCE: The results suggested that HIV and HCV were introduced at around the same time to the IDU populations in Southern China, followed by their differential spread as determined by the biologic characteristics of the virus and the intensity of behavioural risk. This pattern is different from that in other South East Asian countries where HCV infections have probably predated HIV.

  6. 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....

  7. HCV clearance patterns in saliva and serum of patients with chronic HCV infection under interferon plus ribavirin therapy.

    Science.gov (United States)

    Diz Dios, P; Castro, A; Rodríguez, I; Reforma, N G; Castro, M; Eirea, M; Hermida, M

    2005-05-01

    Hepatitis C virus (HCV)-RNA is often present in saliva of HCV-infected patients, with plasma viral load being the only known predictable factor. Interferon plus ribavirin therapy yields a sustained reduction in HCV viremia. This study aimed to assess the presence of HCV in saliva and serum specimens from patients undergoing this combination therapy (CT). Paired serum and saliva specimens were collected from 44 chronic HCV-infected patients at basal time, 4 and 12 weeks after CT onset, at the end of treatment and 6 months latter. Serum HCV-RNA levels were determined by the polymerase chain reaction (PCR) Amplicor system. Presence of HCV-RNA in saliva was tested by a highly sensitive non-commercialized nested-PCR. The HCV-RNA was detected in 26 saliva specimens at basal time (59.1%). In 34.1% of cases, a concordance viral clearance pattern in serum and saliva was observed in both responders (pattern 1a) and non-responders (pattern 1b). In pattern 2 (13.6% of cases), HCV was detected longer during CT in serum than in saliva (pattern 2a) or in saliva than in serum (pattern 2b). In 11.3% of patients, viral clearance was corroborated either in their serum (pattern 3a) or in their saliva (pattern 3b), but not in both fluids. Of the eight primary responders with 1a clearance pattern, seven were sustained responders. None of the patients with 2a clearance pattern was a sustained responder. Of the two primary responders showing the 3b salivary pattern, one had already relapsed in the first 6 months of follow up. The present results suggest that the monitoring of salivary levels of HCV would be a helpful means of determining sustained antiviral effects of interferon and ribavirin in the treatment of HCV disease.

  8. Expression of chimeric HCV peptide in transgenic tobacco plants ...

    African Journals Online (AJOL)

    Using plant-virus based transient expression to produce this unique chimeric antigen will facilitate the development and production of an experimental HCV vaccine. A plant derived recombinant HCV vaccine can potentially reduce expenses normally associated with production and delivery of conventional vaccine.

  9. Seroprevalence of Hepatitis C Virus (HCV) antibodies in pregnant ...

    African Journals Online (AJOL)

    Background: Hepatitis C virus (HCV) infection is a major public health concern. The aim of this study was to ascertain the seroprevalence and risk factors of HCV antibodies among pregnant women in Anyigba, Kogi State North Central Nigeria. Materials and methods:Blood samples (5mls) were collected from one hundred ...

  10. 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 thro...

  11. Relation of HCV induced insulin resitance and Hepatocellular ...

    African Journals Online (AJOL)

    It could be concluded from this work that HCV-related metabolic complications as hepatic steatosis and IR may be associated with increased risk of HCC development. c.335T>C and c.3073A>C SNPs of MDR1 gene could be considered as a possible molecular candidates for the HCC development in chronic HCV patients.

  12. Hepatitis C virus (HCV): ever in reliable partnerships? | Yalena ...

    African Journals Online (AJOL)

    There is no preventive vaccine against HCV and treatment, consisting of interferon alpha plus Ribavirin, is generally effective in less than 50% of cases. HCV has evolved ... Issues regarding tropism, disease progression and antiviral treatment response, among other aspects, are discussed. Data accumulated reveal that ...

  13. Correlation between alanine aminotransferase level, HCV-RNA titer ...

    African Journals Online (AJOL)

    Reham Al Swaff

    2012-04-04

    Apr 4, 2012 ... Abstract The relationship of serum alanine aminotransferase (ALT) level and viral replication to liver damage in chronic hepatitis C virus (HCV) patients remains unclear. The aim of the present study was to determine whether the stage of fibrosis correlates with HCV-. RNA titer and/or serum ALT level in ...

  14. HCV-related liver cancer in people with haemophilia

    NARCIS (Netherlands)

    Meijer, K.; Haagsma, E. B.

    . 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).

  15. Treatment of HCV Infection by Targeting MicroRNA

    NARCIS (Netherlands)

    Janssen, Harry L. A.; Reesink, Hendrik W.; Lawitz, Eric J.; Zeuzem, Stefan; Rodriguez-Torres, Maribel; Patel, Keyur; van der Meer, Adriaan J.; Patick, Amy K.; Chen, Alice; Zhou, Yi; Persson, Robert; King, Barney D.; Kauppinen, Sakari; Levin, Arthur A.; Hodges, Michael R.

    2013-01-01

    BACKGROUND The stability and propagation of hepatitis C virus (HCV) is dependent on a functional interaction between the HCV genome and liver-expressed microRNA-122 (miR-122). Miravirsen is a locked nucleic acid-modified DNA phosphorothioate antisense oligonucleotide that sequesters mature miR-122

  16. Hepatitis C virus (HCV): ever in reliable partnerships?

    African Journals Online (AJOL)

    GRACE

    2006-06-16

    Jun 16, 2006 ... hemophiliacs, multiple changes in HCV genotypes were observed in 58 % of the subjects, over a 3–15- ..... increase in HCV RNA levels in hemophiliacs (Eyster et. Amoador-Canizares and Duenas-Carrera .... and colleagues results showed that, among women who continued to receive protease inhibitors ...

  17. HCV RNA in peripheral blood mononuclear cells (PBMCs) as a ...

    African Journals Online (AJOL)

    Abdel Fatah Fahmy Hanno

    2013-06-27

    Jun 27, 2013 ... Abstract Background: Hepatitis C virus (HCV) has been found to infect peripheral blood mono- nuclear cells (PBMCs), using them as a reservoir, which might contribute to the development of resistance to treatment. Objectives: To study hepatitis virus C (HCV) RNA in peripheral blood mononuclear cells.

  18. HCV RNA in peripheral blood mononuclear cells (PBMCs) as a ...

    African Journals Online (AJOL)

    Background: Hepatitis C virus (HCV) has been found to infect peripheral blood mononuclear cells (PBMCs), using them as a reservoir, which might contribute to the development of resistance to treatment. Objectives: To study hepatitis virus C (HCV) RNA in peripheral blood mononuclear cells (PBMCs) of patients with ...

  19. Immune Responses to HCV and Other Hepatitis Viruses

    Science.gov (United States)

    Park, Su-Hyung; Rehermann, Barbara

    2014-01-01

    Summary Five human hepatitis viruses cause most acute and chronic liver disease worldwide. Over the past 25 years hepatitis C virus (HCV) in particular has received much interest because of its ability to persist in most immunocompetent adults and the lack of a protective vaccine. Here we examine innate and adaptive immune responses to HCV infection. Although HCV activates an innate immune response, it employs an elaborate set of mechanisms to evade interferon (IFN)-based antiviral immunity. By comparing innate and adaptive immune responses to HCV with those to hepatitis A and B viruses, we suggest that prolonged innate immune activation impairs the development of successful adaptive immune responses. Comparative immunology furthermore provides insights into the maintenance of immune protection. We conclude by discussing prospects for an HCV vaccine and future research needs for the hepatitis viruses. PMID:24439265

  20. An overview of HCV molecular biology, replication and immune responses

    Directory of Open Access Journals (Sweden)

    Nawaz Zafar

    2011-04-01

    Full Text Available Abstract Hepatitis C virus (HCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage, hepatocellular carcinoma and death. Currently, there is no vaccine available for prevention of HCV infection due to high degree of strain variation. The current treatment of care, Pegylated interferon α in combination with ribavirin is costly, has significant side effects and fails to cure about half of all infections. In this review, we summarize molecular virology, replication and immune responses against HCV and discussed how HCV escape from adaptive and humoral immune responses. This advance knowledge will be helpful for development of vaccine against HCV and discovery of new medicines both from synthetic chemistry and natural sources.

  1. Recent advances in the anti-HCV mechanisms of interferon

    Directory of Open Access Journals (Sweden)

    Menghao Huang

    2014-08-01

    Full Text Available Interferon (IFN in combination with ribavirin has been the standard of care (SOC for chronic hepatitis C for the past few decades. Although the current SOC lacks the desired efficacy, and 4 new direct-acting antiviral agents have been recently approved, interferons are still likely to remain the cornerstone of therapy for some time. Moreover, as an important cytokine system of innate immunity, host interferon signaling provides a powerful antiviral response. Nevertheless, the mechanisms by which HCV infection controls interferon production, and how interferons, in turn, trigger anti-HCV activities as well as control the outcome of HCV infection remain to be clarified. In this report, we review current progress in understanding the mechanisms of IFN against HCV, and also summarize the knowledge of induction of interferon signaling by HCV infection.

  2. 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....... 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...... 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...

  3. The HCV Synthesis Project: Scope, methodology, and preliminary results

    Directory of Open Access Journals (Sweden)

    Scheinmann Roberta

    2008-09-01

    Full Text Available Abstract Background The hepatitis C virus (HCV is hyper-endemic in injecting drug users. There is also excess HCV among non-injection drug users who smoke, snort, or sniff heroin, cocaine, crack, or methamphetamine. Methods To summarize the research literature on HCV in drug users and identify gaps in knowledge, we conducted a synthesis of the relevant research carried out between 1989 and 2006. Using rigorous search methods, we identified and extracted data from published and unpublished reports of HCV among drug users. We designed a quality assurance system to ensure accuracy and consistency in all phases of the project. We also created a set of items to assess study design quality in each of the reports we included. Results We identified 629 reports containing HCV prevalence rates, incidence rates and/or genotype distribution among injecting or non-injecting drug user populations published between January 1989 and December 2006. The majority of reports were from Western Europe (41%, North America (26%, Asia (11% and Australia/New Zealand (10%. We also identified reports from Eastern Europe, South America, the Middle East, and the Caribbean. The number of publications reporting HCV rates in drug users increased dramatically between 1989 and 2006 to 27–52 reports per year after 1998. Conclusion The data collection and quality assurance phases of the HCV Synthesis Project have been completed. Recommendations for future research on HCV in drug users have come out of our data collection phase. Future research reports can enhance their contributions to our understanding of HCV etiology by clearly defining their drug user participants with respect to type of drug and route of administration. Further, the use of standard reporting methods for risk factors would enable data to be combined across a larger set of studies; this is especially important for HCV seroconversion studies which suffer from small sample sizes and low power to examine risk

  4. 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...... (IDUs). The median time between the first and last samples was 3.6 years (interquartile range 2.0-5.8 years). After adjustment, those on combination antiretroviral therapy [odds ratio (OR) 0.44; 95% CI 0.20-0.99; P = 0.046] and older persons (OR 0.51 per 10 years older; 95% CI 0.28-0.95; P = 0.033) were...

  5. HCV subtype characterization among injection drug users: implication for a crucial role of Zhenjiang in HCV transmission in China.

    Directory of Open Access Journals (Sweden)

    Chiyu Zhang

    Full Text Available BACKGROUND: HCV transmission is closely associated with drug-trafficking routes in China. However, the transmission route of HCV in Eastern China remains unclear. Here, we investigate the role of Zhenjiang city of Jiangsu province, an important transportation hub linking Shanghai with other regions of China, in HCV transmission. METHODOLOGY/PRINCIPAL FINDINGS: A total of 141 whole blood samples were collected from injection drug users (IDUs in Zhenjiang and then tested for HCV infection. Of them, 115 HCV positive plasmas were subjected to RNA extraction, RT-PCR amplification, and sequencing. The subtype characterization and the evolutionary origin of HCV strains circulating in Zhenjiang were determined using polygenetic or phylogeographic analyses. Seven HCV subtypes 1b, 2a, 3a, 3b, 6a, 6e and 6n were detected among Zhenjiang IDUs, showing a complex HCV epidemic. The most predominant subtypes were 3a (38% and 1b (26.8%. Among these subtypes, subtypes 3b, 6n and 6e originated from Southwestern China (i.e., Yunnan and/or Guangxi, subtypes 2a and 6a from Southern China (i.e., Guangdong, subtype 1b from Central (i.e., Henan and Northwestern (i.e., Xinjiang China, and subtype 3a from Southwestern (i.e., Yunnan and Northwestern (i.e., Xinjiang China. From Zhenjiang, subtypes 1b and 2a were further spread to Eastern (i.e., Shanghai and Northern (i.e., Beijing China, respectively. CONCLUSIONS/SIGNIFICANCE: The mixing of seven HCV subtypes in Zhenjiang from all quarters of China indicates that as an important middle station, Zhenjiang plays a crucial role in HCV transmission, just as it is important in population migration between other regions of China and Eastern China.

  6. Performance of ARCHITECT HCV core antigen test with specimens from US plasma donors and injecting drug users.

    Science.gov (United States)

    Mixson-Hayden, Tonya; Dawson, George J; Teshale, Eyasu; Le, Thao; Cheng, Kevin; Drobeniuc, Jan; Ward, John; Kamili, Saleem

    2015-05-01

    Hepatitis C virus (HCV) core antigen is a serological marker of current HCV infection. The aim of this study was mainly to evaluate the performance characteristics of the ARCHITECT HCV core antigen assay with specimens from US plasma donors and injecting drug users. A total of 551 serum and plasma samples with known anti-HCV and HCV RNA status were tested for HCV core antigen using the Abbott ARCHITECT HCV core antigen test. HCV core antigen was detectable in 100% of US plasma donor samples collected during the pre-seroconversion phase of infection (anti-HCV negative/HCV RNA positive). Overall sensitivity of the HCV core antigen assay was 88.9-94.3% in samples collected after seroconversion. The correlation between HCV core antigen and HCV RNA titers was 0.959. HCV core antigen testing may be reliably used to identify current HCV infection. Published by Elsevier B.V.

  7. Evolving strategy for HCV testing in an Italian tertiary care hospital.

    Science.gov (United States)

    Medici, Maria Cristina; Chezzi, Carlo; De Conto, Flora; Ferraglia, Francesca; Pinardi, Federica; Arcangeletti, Maria Cristina; Bernasconi, Daniela; Galli, Claudio; Calderaro, Adriana

    2016-04-01

    Diagnostic tests for hepatitis C virus (HCV) infection should be adapted according to the clinical status of the patient. We exploited the application of different HCV diagnostic algorithms in a tertiary care hospital practice. The laboratory clinical reports to the medical orders for HCV testing during three years were clustered by different combinations of assays for anti-HCV antibodies (HCV Ab) (screening and confirmatory), HCV nucleic acid (HCV-RNA), HCV core antigen (HCV Ag). The latter was the first-line assay in acute HCV infections requiring a rapid assessment of the infectious state. The majority (91.9%) of the 2726 subjects whose samples were analyzed were inpatients. Most of the patients/subjects were tested for clinical suspicion of viral hepatitis (49.2%), or occupational accident to health care professionals (20.0%). On 66% of samples HCV Ag test alone was performed and resulted positive in 116 cases (6%), while it was detected in 50.3% of anti-HCV positive samples. The agreement between HCV Ag and HCV-RNA was very high (k=0.97); HCV Ag positivity rates increased according to the signal of the HCV Ab screening test. The use of different testing strategies according to the patients' history and clinical status allowed a significant reduction of the number of tests performed and the time needed to provide a diagnostic response useful for patients' management without compromising the overall diagnostic accuracy for HCV infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Claudin-6 and Occludin Natural Variants Found in a Patient Highly Exposed but Not Infected with Hepatitis C Virus (HCV Do Not Confer HCV Resistance In Vitro.

    Directory of Open Access Journals (Sweden)

    Lucie Fénéant

    Full Text Available The clinical course of Hepatitis C Virus (HCV infection is highly variable between infected individual hosts: up to 80% of acutely HCV infected patients develop a chronic infection while 20% clear infection spontaneously. Spontaneous clearance of HCV infection can be predicted by several factors, including symptomatic acute infection, favorable IFNL3 polymorphisms and gender. In our study, we explored the possibility that variants in HCV cell entry factors might be involved in resistance to HCV infection. In a same case patient highly exposed but not infected by HCV, we previously identified one mutation in claudin-6 (CLDN6 and a rare variant in occludin (OCLN, two tight junction proteins involved in HCV entry into hepatocytes. Here, we conducted an extensive functional study to characterize the ability of these two natural variants to prevent HCV entry. We used lentiviral vectors to express Wildtype or mutated CLDN6 and OCLN in different cell lines and primary human hepatocytes. HCV infection was then investigated using cell culture produced HCV particles (HCVcc as well as HCV pseudoparticles (HCVpp expressing envelope proteins from different genotypes. Our results show that variants of CLDN6 and OCLN expressed separately or in combination did not affect HCV infection nor cell-to-cell transmission. Hence, our study highlights the complexity of HCV resistance mechanisms supporting the fact that this process probably not primarily involves HCV entry factors and that other unknown host factors may be implicated.

  9. Claudin-6 and Occludin Natural Variants Found in a Patient Highly Exposed but Not Infected with Hepatitis C Virus (HCV) Do Not Confer HCV Resistance In Vitro.

    Science.gov (United States)

    Fénéant, Lucie; Ghosn, Jade; Fouquet, Baptiste; Helle, François; Belouzard, Sandrine; Vausselin, Thibaut; Séron, Karin; Delfraissy, Jean-François; Dubuisson, Jean; Misrahi, Micheline; Cocquerel, Laurence

    2015-01-01

    The clinical course of Hepatitis C Virus (HCV) infection is highly variable between infected individual hosts: up to 80% of acutely HCV infected patients develop a chronic infection while 20% clear infection spontaneously. Spontaneous clearance of HCV infection can be predicted by several factors, including symptomatic acute infection, favorable IFNL3 polymorphisms and gender. In our study, we explored the possibility that variants in HCV cell entry factors might be involved in resistance to HCV infection. In a same case patient highly exposed but not infected by HCV, we previously identified one mutation in claudin-6 (CLDN6) and a rare variant in occludin (OCLN), two tight junction proteins involved in HCV entry into hepatocytes. Here, we conducted an extensive functional study to characterize the ability of these two natural variants to prevent HCV entry. We used lentiviral vectors to express Wildtype or mutated CLDN6 and OCLN in different cell lines and primary human hepatocytes. HCV infection was then investigated using cell culture produced HCV particles (HCVcc) as well as HCV pseudoparticles (HCVpp) expressing envelope proteins from different genotypes. Our results show that variants of CLDN6 and OCLN expressed separately or in combination did not affect HCV infection nor cell-to-cell transmission. Hence, our study highlights the complexity of HCV resistance mechanisms supporting the fact that this process probably not primarily involves HCV entry factors and that other unknown host factors may be implicated.

  10. Identification of Variants of Hepatitis C Virus (HCV) Entry Factors in Patients Highly Exposed to HCV but Remaining Uninfected: An ANRS Case-Control Study.

    Science.gov (United States)

    Fouquet, Baptiste; Ghosn, Jade; Quertainmont, Yann; Salmon, Dominique; Rioux, Christophe; Duvivier, Claudine; Delfraissy, Jean-François; Misrahi, Micheline

    2015-01-01

    Hepatitis C virus (HCV) causes persistent infection in 75% of cases and is a major public health problem worldwide. More than 92% of intravenous drug users (IDU) infected by human immunodeficiency virus type 1 (HIV-1) are seropositive for HCV, and it is conceivable that some HIV-1-infected IDU who remain uninfected by HCV may be genetically resistant.Here we conducted a case-control study to identify mutations in HCV entry coreceptors in HIV-infected IDU who remained uninfected by HCV. We recruited 138 patients, comprising 22 HIV+ HCV- case IDU and 116 HIV+ HCV+ control IDU. We focused on coreceptors in which point mutations are known to abolish HCV infectivity in vitro. Our previous study of the Claudin-1 gene revealed no specific variants in the same case population. Here we performed direct genomic sequencing of the Claudin-6, Claudin-9, Occludin and Scavenger receptor-B1 (SCARB1) gene coding regions. Most HIV+ HCV- IDU had no mutations in HCV coreceptors. However, two HIV+ HCV- patients harbored a total of four specific mutations/variants of HCV entry factors that were not found in the HIV+ HCV+ controls. One case patient harbored heterozygous variants of both Claudin-6 and Occludin, and the other case patient harbored two heterozygous variants of SCARB1. This suggests that HCV resistance might involve complex genetic events and factors other than coreceptors, a situation similar to that reported for HIV-1 resistance.

  11. Identification of Variants of Hepatitis C Virus (HCV Entry Factors in Patients Highly Exposed to HCV but Remaining Uninfected: An ANRS Case-Control Study.

    Directory of Open Access Journals (Sweden)

    Baptiste Fouquet

    Full Text Available Hepatitis C virus (HCV causes persistent infection in 75% of cases and is a major public health problem worldwide. More than 92% of intravenous drug users (IDU infected by human immunodeficiency virus type 1 (HIV-1 are seropositive for HCV, and it is conceivable that some HIV-1-infected IDU who remain uninfected by HCV may be genetically resistant.Here we conducted a case-control study to identify mutations in HCV entry coreceptors in HIV-infected IDU who remained uninfected by HCV. We recruited 138 patients, comprising 22 HIV+ HCV- case IDU and 116 HIV+ HCV+ control IDU. We focused on coreceptors in which point mutations are known to abolish HCV infectivity in vitro. Our previous study of the Claudin-1 gene revealed no specific variants in the same case population. Here we performed direct genomic sequencing of the Claudin-6, Claudin-9, Occludin and Scavenger receptor-B1 (SCARB1 gene coding regions. Most HIV+ HCV- IDU had no mutations in HCV coreceptors. However, two HIV+ HCV- patients harbored a total of four specific mutations/variants of HCV entry factors that were not found in the HIV+ HCV+ controls. One case patient harbored heterozygous variants of both Claudin-6 and Occludin, and the other case patient harbored two heterozygous variants of SCARB1. This suggests that HCV resistance might involve complex genetic events and factors other than coreceptors, a situation similar to that reported for HIV-1 resistance.

  12. Acetaminophen-induced acute liver injury in HCV transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U. [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Tech, Katherine; Macdonald, Jeffrey M. [Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Boorman, Gary A. [Covance, Chantilly, VA 20151 (United States); Chatterjee, Saurabh; Mason, Ronald P. [Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, RTP, NC 27713 (United States); Melnyk, Stepan B. [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72201 (United States); Tryndyak, Volodymyr P.; Pogribny, Igor P. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Rusyn, Ivan, E-mail: iir@unc.edu [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States)

    2013-01-15

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  13. Presence of hepatitis C virus (HCV)-RNA in peripheral blood mononuclear cells in HCV serum negative patients during interferon and ribavirin therapy.

    Science.gov (United States)

    Januszkiewicz-Lewandowska, Danuta; Wysocki, Jacek; Pernak, Monika; Nowicka, Karina; Zawada, Mariola; Rembowska, Jolanta; Lewandowski, Krzysztof; Mańkowski, Przemysław; Nowak, Jerzy

    2007-02-01

    Identification of hepatitis C virus (HCV)-RNA in blood serum is crucial for hepatitis C diagnosis and for appropriate treatment. Detection of HCV-RNA in blood serum is used for therapy monitoring of patients with hepatitis C. Despite HCV-RNA elimination from blood serum during treatment in some patients, HCV viremia appears again after the completion of therapy. The aim of this study was to assess HCV-RNA in peripheral blood mononuclear cells (PBMCs) of hepatitis C patients in relation to HCV-RNA and antibodies to HCV in the serum. The study involved 71 patients undergoing anti-viral therapy (interferon and ribavirin). RNA isolated from serum and PBMCs was examined for the presence of HCV-RNA by an RT-PCR technique using specific oligonucleotide primers or by commercially available kits. In order to show the possible presence of HCV sequences in PBMCs, molecular DNA probes were constructed with a PCR amplicon and biotin-labelled by nick translation, and FISH and extended chromatin fibers in situ hybridization (ECFs-FISH) techniques were used. A 24-month follow-up study revealed that 34 out of 59 patients (58%) eliminated HCV-RNA from their sera. In the serum negative group, HCV-RNA was detected in PBMCs of 2 patients. The presence of HCV-RNA in PBMCs was confirmed by the FISH technique. In the ECFs-FISH procedure, no signal was found in all examined patients. Our data suggest that PBMCs infected with HCV can serve as a virus reservoir. HCV-RNA serum negative patients who have HCV-RNA in their leukocytes after completion of anti-viral therapy would be at great risk of hepatitis C recurrence. These HCV-RNA serum negative but PBMCs positive patients would be a potential source of HCV spread.

  14. seroprevalence of hav, hbv, hcv, and hev among acute hepatitis ...

    African Journals Online (AJOL)

    2013-07-30

    00100, Nairobi, J. Ngaira, Jomo Kenyatta. University of ... (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus .... analysis was carried out using SPSS 11.5 computer software.

  15. Development of a VLP-based HCV vaccine candidate

    OpenAIRE

    Fernandes, Marina Isabel Ferreira

    2016-01-01

    Tese de mestrado, Biologia Molecular e Genética, Universidade de Lisboa, Faculdade de Ciências, 2016 The Hepatitis C Virus (HCV) infects approximately 3% of the world population, being one of the major causes of liver cirrhosis and hepatocellular carcinoma. The development of safe, effective and affordable prophylactic and therapeutic vaccines against HCV has become an important medical priority; however, there are many obstacles to its development. In recent years, strategies of viral ant...

  16. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection.

    OpenAIRE

    Afdhal, Nezam; Zeuzem, Stefan; Kwo, Paul Y.; Chojkier, Mario; Gitlin, Norman; Puoti, Massimo; Romero Gomez, Manuel; Zarski, Jean Pierre; Agarwal, Kosh; Buggisch, Peter; Foster, Graham R.; Bräu, Norbert; Buti, Maria; Jacobson, Ira M.; Subramanian, G.Mani

    2014-01-01

    BACKGROUND: In phase 2 studies, treatment with the all-oral combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor ledipasvir resulted in high rates of sustained virologic response among previously untreated patients with hepatitis C virus (HCV) genotype 1 infection. METHODS: We conducted a phase 3, open-label study involving previously untreated patients with chronic HCV genotype 1 infection. Patients were randomly assigned in a 1:1:1:1 ratio to receive ledipasv...

  17. Unsolved Puzzles Surrounding HCV Immunity: Heterologous Immunity Adds Another Dimension

    Science.gov (United States)

    Gupta, Nancy; Li, Wen; Vedi, Satish; Kumar, Rakesh

    2017-01-01

    Chronic infection with hepatitis C virus (HCV) afflicts 3% of the world’s population and can lead to serious and late-stage liver diseases. Developing a vaccine for HCV is challenging because the correlates of protection are uncertain and traditional vaccine approaches do not work. Studies of natural immunity to HCV in humans have resulted in many enigmas. Human beings are not immunologically naïve because they are continually exposed to various environmental microbes and antigens, creating large populations of memory T cells. Heterologous immunity occurs when this pool of memory T cells cross-react against a new pathogen in an individual. Such heterologous immunity could influence the outcome when an individual is infected by a pathogen. We have recently made an unexpected finding that adenoviruses, a common environmental pathogen and an experimental vaccine vector, can induce robust cross-reactive immune responses against multiple antigens of HCV. Our unique finding of previously uncharacterized heterologous immunity against HCV opens new avenues to understand HCV pathogenesis and develop effective vaccines. PMID:28749434

  18. Small molecule inhibitors of HCV replication from Pomegranate

    Science.gov (United States)

    Reddy, B. Uma; Mullick, Ranajoy; Kumar, Anuj; Sudha, Govindarajan; Srinivasan, Narayanaswamy; Das, Saumitra

    2014-06-01

    Hepatitis C virus (HCV) is the causative agent of end-stage liver disease. Recent advances in the last decade in anti HCV treatment strategies have dramatically increased the viral clearance rate. However, several limitations are still associated, which warrant a great need of novel, safe and selective drugs against HCV infection. Towards this objective, we explored highly potent and selective small molecule inhibitors, the ellagitannins, from the crude extract of Pomegranate (Punica granatum) fruit peel. The pure compounds, punicalagin, punicalin, and ellagic acid isolated from the extract specifically blocked the HCV NS3/4A protease activity in vitro. Structural analysis using computational approach also showed that ligand molecules interact with the catalytic and substrate binding residues of NS3/4A protease, leading to inhibition of the enzyme activity. Further, punicalagin and punicalin significantly reduced the HCV replication in cell culture system. More importantly, these compounds are well tolerated ex vivo and`no observed adverse effect level' (NOAEL) was established upto an acute dose of 5000 mg/kg in BALB/c mice. Additionally, pharmacokinetics study showed that the compounds are bioavailable. Taken together, our study provides a proof-of-concept approach for the potential use of antiviral and non-toxic principle ellagitannins from pomegranate in prevention and control of HCV induced complications.

  19. Prediction of HCV vertical transmission: what factors should be optimized using data mining computational analysis.

    Science.gov (United States)

    Elrazek, Abd; Amer, Mohamed; El-Hawary, Bahaa; Salah, Altaher; Bhagavathula, Akshaya S; Alboraie, M; Saab, Samy

    2017-04-01

    Neonates born to hepatitis C virus (HCV)-positive mothers are usually not screened for HCV. Unscreened children may act as active sources for social HCV transmission, and factors contributing for vertical HCV transmitting still remained controversial and needed optimization. We aimed to investigate the factors contributing for vertical HCV transmission in Egypt; the highest HCV prevalence worldwide. We prospectively followed the neonates born to HCV-positive mother in the child-bearing period, to identify mother-to-child transmission (MTCT) factors from January 2015 to March 2016. Data mining computational analysis was used to quantify the findings. Among 3000 randomized pregnant women, prevalence of HCV was 46/3000 (1.53%). HCV vertical transmission was identified in eight neonates (17.39%). Only high viral load identified at 975.000 IU was the predictor risk for MTCT. Hepatitis C virus in pregnancy has substantial risk for vertical HCV transmission: High viral load in HCV-positive women increases the risk of HCV transmission to neonates. Screening pregnant women during early stage of pregnancy and optimizing the HCV viral load in HCV-positive women might prevent vertical HCV transmission to neonates. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    OpenAIRE

    Yousaf, Muhammad Z; Idrees, Muhammad; Saleem, Zafar; Rehman, Irshad U; Ali, Muhammad

    2011-01-01

    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 ...

  1. High awareness of hepatitis C virus (HCV) but limited knowledge of HCV complications among HIV-positive and HIV-negative men who have sex with men

    NARCIS (Netherlands)

    Lambers, Femke A. E.; Prins, Maria; Davidovich, Udi; Stolte, Ineke G.

    2014-01-01

    Hepatitis C virus (HCV) has emerged as a sexually transmitted infection among HIV-positive men who have sex with men (MSM) in high-income countries. Little is reported about HCV awareness among MSM, although this is essential for developing targeted prevention strategies. We, therefore, studied HCV

  2. 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...

  3. Ongoing risk behavior and the presence of HCV-RNA affect the hepatitis C virus (HCV)-Specific CD4(+) T cell response

    NARCIS (Netherlands)

    van den Berg, Charlotte H S B; Nanlohy, Nening M; van de Laar, Thijs J W; Prins, Maria; van Baarle, Debbie

    The largest population of people at risk for HCV-infection is injecting drug users (DU). We hypothesize that recurrent exposure to HCV, by continuing risk behavior, influences the development of an HCV-specific T-cell response. Therefore, we studied the association between repeated exposure to and

  4. Multicentric performance analysis of HCV quantification assays and its potential relevance for HCV treatment.

    Science.gov (United States)

    Wiesmann, F; Naeth, G; Berger, A; Hirsch, H H; Regenass, S; Ross, R S; Sarrazin, C; Wedemeyer, H; Knechten, H; Braun, P

    2016-06-01

    An accurate quantification of low viremic HCV RNA plasma samples has gained importance since the approval of direct acting antivirals and since only one single measurement predicts the necessity of a prolonged or shortened therapy. As reported previously, HCV quantification assays such as Abbott RealTime HCV and Roche COBAS AmpliPrep/COBAS TaqMan HCV version 2 (CTM v2) may vary in sensitivity and precision particularly in low-level viremia. Importantly, substantial variations were previously demonstrated between some of these assays compared to the Roche High Pure System/COBAS TaqMan assay (HPS) reference assay, which was used to establish the clinical decision points in clinical studies. In this study, the reproducibility of assay performances across several laboratories was assessed by analysing quantification results generated by six independent laboratories (3× RealTime, 3× CTM v2) in comparison with one HPS reference laboratory. The 4th WHO Standard was diluted to 100, 25 and 10 IU/ml, and aliquots were tested in triplicates in 5 independent runs by each assay in the different laboratories to assess assay precision and detection rates. In a second approach, 2 clinical samples (GT 1a & GT 1b) were diluted to 100 and 25 IU/ml and tested as described above. While the result range for WHO 100 IU/ml replicates across all laboratories was similar in this analysis, the CVs of each laboratory ranged from 19.3 to 25.6 % for RealTime laboratories and were lower than CVs of CTM v2 laboratories with a range of 26.1-47.3 %, respectively, and also in comparison with the CV of the HPS reference laboratory (34.9 %). At WHO standard dilution of 25 IU/ml, 24 replicates were quantified by RealTime compared to 8 replicates with CTM v2. Results of clinical samples again revealed a higher variation of CTM v2 results as compared to RealTime values. (CVs at 100 IU/ml: RealTime: 13.1-21.0 % and CTM v2: 15.0-32.3 %; CVs at 25 IU/ml: RealTime 17.6-34.9 % and CTM v2 28

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

    Science.gov (United States)

    Grint, D; Peters, L; Reekie, J; Soriano, V; Kirk, O; Knysz, B; Suetnov, O; Lazzarin, A; Ledergerber, B; Rockstroh, J K; Mocroft, A

    2013-07-01

    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. Mixed models were used to analyse the natural history of HCV RNA changes over time in HIV-positive patients with chronic HCV infection. A total of 1541 individuals, predominantly White (91%), male (73%), from southern (35%) and western central Europe (23%) and with HCV genotype 1 (58%), were included in the analysis. The median follow-up time was 5.0 years [interquartile range (IQR) 2.8 to 8.3 years]. Among patients not on combination antiretroviral therapy (cART), HCV RNA levels increased by a mean 27.6% per year [95% confidence interval (CI) 6.1-53.5%; P = 0.0098]. Among patients receiving cART, HCV RNA levels were stable, increasing by a mean 2.6% per year (95% CI -1.1 to 6.5%; P = 0.17). Baseline HCV RNA levels were 25.5% higher (95% CI 8.8 to 39.1%; P = 0.0044) in individuals with HCV genotype 1 compared with HCV genotypes 2, 3 and 4. A 1 log HIV-1 RNA copies/mL increase in HIV RNA was associated with a 10.9% increase (95% CI 2.3 to 20.2%; P = 0.012) in HCV RNA. While HCV RNA levels increased significantly in patients prior to receiving cART, among those treated with cART HCV RNA levels remained stable over time. © 2013 British HIV Association.

  6. Transmission of HCV infection among long-term hospitalized onco-haematological patients.

    Science.gov (United States)

    Januszkiewicz-Lewandowska, D; Wysocki, J; Rembowska, J; Pernak, M; Lewandowski, K; Nowak, T; Nowicka-Kujawska, K; Nowak, J

    2003-02-01

    Hepatitis C virus (HCV) infection is becoming a substantial problem in long-term hospitalized patients. Onco-haematological patients undergoing chemotherapy are especially prone to HCV infection. These patients are usually immunosuppressed and therefore antibodies to HCV are not produced despite the presence of HCV RNA in peripheral blood. The aim of the study was to see how often long-term hospitalized patients acquired HCV infection, and what were the possible sources and routes of virus transmission. The study involved 129 children with lymphoproliferative diseases, 36 patients with solid tumours, and 61 healthcare workers from onco-haematological wards. All were HCV RNA and anti-HCV negative at the time of first hospitalization. During a two and a half-year follow-up study among 165 onco-haematological patients, HCV RNA appeared in 87 in subsequent hospitalizations. The majority of infections were (82/87) were 1a genotype, 2 were 1b, 1 was 1a + 1b and 1 was 1a + 3a. In an attempt to establish the origin of HCV infection, healthcare workers were screened for HCV genotyping. All HCV-infected staff working on wards had the same genotype (1a). None of the staff was infected with 1b genotype. As the most prevalent genotype in Polish blood donors is 1b, HCV infection in onco-haematological patients is most likely due to horizontal transmission, probably involving genotype 1a, and potential horizontal transmission of HCV is implied by the presence of 1a genotype of HCV in saliva and urine of selected patients. Spread of hospital HCV infection among children may be facilitated by micro-injury of the skin and mucosa. Early detection of HCV RNA is important in such immunosuppressed patients, as they are not able to produce anti-HCV antibodies. This may enable the introduction of prophylactic steps to prevent the spread of HCV infection by horizontal transmission. Copyright 2003 The Hospital Infection Society

  7. Dynamics of HCV RNA levels during acute hepatitis C virus infection

    Science.gov (United States)

    Hajarizadeh, Behzad; Grebely, Jason; Applegate, Tanya; Matthews, Gail V; Amin, Janaki; Petoumenos, Kathy; Hellard, Margaret; Rawlinson, William; Lloyd, Andrew; Kaldor, John; Dore, Gregory J

    2014-01-01

    Understanding viral dynamics during acute hepatitis C virus (HCV) infection can provide important insights into immunopathogenesis and guide early treatment. The aim of this study was investigating the dynamics of HCV RNA and alanine transaminase (ALT) levels during recent HCV infection in the Australian Trial in Acute Hepatitis C (ATAHC). ATAHC was a prospective study of the natural history of recently acquired HCV infection. Longitudinal HCV RNA and ALT levels were compared among individuals with ultimately persistent infection and spontaneous clearance outcomes. Among those with HCV persistence (n=104) and HCV clearance (n=30), median HCV RNA (5.2 vs. 4.1 log IU/mL, respectively) and ALT levels (779 vs. 1765 IU/L, respectively) were high during month two following infection, and then declined during months three and four in both groups. Among those with HCV persistence, median HCV RNA was 2.9 log IU/mL during months four, increased to 5.5 log IU/mL during month five, and remained subsequently relatively stable. Among those with HCV clearance, median HCV RNA was undetectable by month five. Median HCV RNA levels were comparable between individuals with HCV persistence and HCV clearance during month three following infection (3.2 vs. 3.5 log IU/mL, respectively; P=0.935), but markedly different during month five (5.5 vs. 1.0 log IU/mL, respectively; P<0.001). In conclusion, dynamics of HCV RNA levels in those with HCV clearance and HCV persistence diverged between months three and five following infection, with the latter time-point being potentially useful for commencing early treatment. PMID:25042465

  8. Antiretroviral Effects on Host Lipoproteins Are Associated With Changes in Hepatitis C Virus (HCV) RNA Levels in Human Immunodeficiency Virus/HCV Coinfected Individuals

    Science.gov (United States)

    Naggie, Susanna; Patel, Keyur; Yang, Lan-Yan; Chow, Shein-Chung; Johnson, Victoria; Guyton, John R.; Muir, Andrew J.; Sulkowski, Mark; Hicks, Charles

    2015-01-01

    We evaluated the impact of antiretroviral-induced dyslipidemia on hepatitis C virus (HCV) biogenesis in human immunodeficiency virus (HIV)/HCV coinfected patients. This study used serum samples from antiretroviral-naive HIV/HCV patients initiating their first regimen as part of AIDS Clinical Trials Group study protocols (A5142, A5202). Initiation of antiretrovirals increased most lipoproteins and apolipoproteins. In the multivariable model, changes in apolipoproteins were associated with changes in log10 HCV RNA from baseline to week-24 of therapy. Off-target lipogenic changes need to be considered in the context of liver and other metabolic disease in HIV/HCV patients. PMID:26110167

  9. [Serologic prevalence of HCV antibodies in health personnel in Peru].

    Science.gov (United States)

    Colichon Yerosh, Alejandro; Figueroa, Rolando; Moreno, Armando; Zumaeta, Eduardo; Ferrandíz, Jorge; Busalleu, Alejandro; Prado, William; Candella, Ricardo; Colichón, Alejandro; Rodriguez, Wilson; Espinoza, Julio; Kianman, Wilfredo; Amaya, Nelly; García Pérez, Segundo A; Tello Rodriguez, José; Valdez, Jesús; Paucar Sotomayor, Héctor; Sanchez, César

    2004-01-01

    In Peru, new cases of asymptomatic HCV infection are reported with certain frequency in patients with or without antecedents of blood transfusion. Although serologic screening has improved notoriously in the last years, there is still a population of polytransfused patients with high HCV risk (e.g. hemodialyzed patients), making up a major reservoir. Based on this premise, we decided to study the risk of the health worker population in Peru as another major HCV risk group. A total of 2,769 health workers from 7 Public Hospitals and 2 Private Hospitals in the City of Lima and from 7 Public Hospitals in 4 major/main cities of Peru (Chiclayo, Trujillo, Arequipa, and Cusco) were studied. All those workers, who due to their area of work had higher contact with blood and/or blood derivatives (Surgery, ICU, Traumatology, Gynecology, Gastroenterology, Hemodialysis and Laboratories-Blood Banks) were studied. The studied population accounts for 30% of the total health worker population in these services. All serums underwent the EIA-3 test (HCV-Cobas-Core, Lab. Roche, USA). The positive results were confirmed by RT-HCV (Ampiclor, Roche). The positive serums were confirmed by PCR and the positive results with high viral load underwent HCV genotyping (AMPICLOR-Roche Diagnostic, IGEN Diagnostic USA). Of the 2,769 health workers studied in Peru, 32 were positive for HCV antibodies (1.16% of the total number). Lima showed a prevalence slightly higher than the provinces: 26 out of 2,112 vs. 6 out of 657, or 1.23% vs. 0.91%, respectively. The higher risk is assumed by professional with higher level of contact with blood: 2 physicians (Hemodialysis), 5 nurses (HD) and Lab-Blood Bank technicians. The physicians and nurses share the same risk. If we segregate Lima from provinces, it can be seen that the highest risk is in Lima (1.34% compared to 1.07% in provinces). There is a major risk in health workers and the figures are slightly above those that were suspected for Peru (between 0

  10. Evaluation of Relationship between Lichen Planus and HCV Antibody

    Directory of Open Access Journals (Sweden)

    Ali Taghavi Zenouz

    2010-03-01

    Full Text Available Background and aims. Lichen planus is a relatively common chronic mucocutaneaous disease with an unknown cause, and is considered a manifestation of cell-mediated immune response. Hepatitis C virus (HCV and its subgroups have been associated with lichen planus in different geographic locations. The present study was undertaken to evaluate the prevalence of HCV antibody in patients with lichen planus in northwest Iran. Materials and methods. This descriptive analytical study included 30 patients with cutaneous lichen planus, 30 patients with oral lichen planus, and 30 healthy individuals as controls. Anti-HCV test was run for all the subjects. Descriptive statistics as well as chi-square test, to compare means in the three study groups, were applied to the data using SPSS 14.0 computer software. Results. Age and sex differences between the groups were not significant. No statistically significant differences were observed in anti-HCV test results between the groups (P = 0.50. Conclusion. No statistically significant relationships were observed between lichen planus and HCV antibody in the studied samples.

  11. HCV-related central and peripheral nervous system demyelinating disorders.

    Science.gov (United States)

    Mariotto, Sara; Ferrari, Sergio; Monaco, Salvatore

    2014-01-01

    Chronic infection with hepatitis C virus (HCV) is associated with a large spectrum of extrahepatic manifestations (EHMs), mostly immunologic/rheumatologic in nature owing to B-cell proliferation and clonal expansion. Neurological complications are thought to be immune-mediated or secondary to invasion of neural tissues by HCV, as postulated in transverse myelitis and encephalopathic forms. Primarily axonal neuropathies, including sensorimotor polyneuropathy, large or small fiber sensory neuropathy, motor polyneuropathy, mononeuritis, mononeuritis multiplex, or overlapping syndrome, represent the most common neurological complications of chronic HCV infection. In addition, a number of peripheral demyelinating disorders are encountered, such as chronic inflammatory demyelinating polyneuropathy, the Lewis-Sumner syndrome, and cryoglobulin-associated polyneuropathy with demyelinating features. The spectrum of demyelinating forms also includes rare cases of iatrogenic central and peripheral nervous system disorders, occurring during treatment with pegylated interferon. Herein, we review HCV-related demyelinating conditions, and disclose the novel observation on the significantly increased frequency of chronic demyelinating neuropathy with anti-myelin-associated glycoprotein antibodies in a cohort of 59 consecutive patients recruited at our institution. We also report a second case of neuromyelitis optica with serum IgG autoantibody against the water channel aquaporin-4. The prompt recognition of these atypical and underestimated complications of HCV infection is of crucial importance in deciding which treatment option a patient should be offered.

  12. Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection

    Directory of Open Access Journals (Sweden)

    Claudio M. Mastroianni

    2014-05-01

    Full Text Available Chronic hepatitis C virus (HCV infection is an important cause of morbidity and mortality in people coinfected with human immunodeficiency virus (HIV. Several studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis progression, even with HIV replication under full antiretroviral control. The pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals is complex and multifactorial. The most relevant mechanisms involved include direct viral effects, immune/cytokine dysregulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. In addition, metabolic alterations, heavy alcohol use, as well drug use, may have a potential role in liver disease progression. Understanding the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may lead to the development of therapeutic strategies for the management of all patients with ongoing liver disease. In this review, we therefore discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV.

  13. HCV-Related Central and Peripheral Nervous System Demyelinating Disorders

    Science.gov (United States)

    Mariotto, Sara; Ferrari, Sergio; Monaco, Salvatore

    2014-01-01

    Chronic infection with hepatitis C virus (HCV) is associated with a large spectrum of extrahepatic manifestations (EHMs), mostly immunologic/rheumatologic in nature owing to B-cell proliferation and clonal expansion. Neurological complications are thought to be immune-mediated or secondary to invasion of neural tissues by HCV, as postulated in transverse myelitis and encephalopathic forms. Primarily axonal neuropathies, including sensorimotor polyneuropathy, large or small fiber sensory neuropathy, motor polyneuropathy, mononeuritis, mononeuritis multiplex, or overlapping syndrome, represent the most common neurological complications of chronic HCV infection. In addition, a number of peripheral demyelinating disorders are encountered, such as chronic inflammatory demyelinating polyneuropathy, the Lewis-Sumner syndrome, and cryoglobulin-associated polyneuropathy with demyelinating features. The spectrum of demyelinating forms also includes rare cases of iatrogenic central and peripheral nervous system disorders, occurring during treatment with pegylated interferon. Herein, we review HCV-related demyelinating conditions, and disclose the novel observation on the significantly increased frequency of chronic demyelinating neuropathy with anti-myelin-associated glycoprotein antibodies in a cohort of 59 consecutive patients recruited at our institution. We also report a second case of neuromyelitis optica with serum IgG autoantibody against the water channel aquaporin-4. The prompt recognition of these atypical and underestimated complications of HCV infection is of crucial importance in deciding which treatment option a patient should be offered. PMID:25198705

  14. [HCV and HBV prevalence in hemodialyzed pediatric patients. Multicenter study].

    Science.gov (United States)

    Cañero-Velasco, M C; Mutti, J E; Gonzalez, J E; Alonso, A; Otegui, L; Adragna, M; Antonuccio, M; Laso, M; Montenegro, M; Repetto, L; Brandi, M; Canepa, J; Baimberg, E

    1998-01-01

    Hemodialized pediatric patients are a risk population for the hepatitis B and C virus infection. The aim of this paper was to study the serum prevalence of HBV and HCV infection in hemodialized children. We study 61 pediatric patients at hemodialisis, 12 on renal transplant, range between 2 and 20 years old (mean: 12.9 years), 23 male and 38 female. The specific anti-HCV IgC were measured by enzyme immunoassay (ELISA Abbott) and confirmed by LIA-TEK (Organon). The anti-HBV were measured by ELISA Abbott and transaminases by cinetic method (ASAT: 29 UI/L and ALT: 33 UI/L). The 19.7% of studied children were HCV (+) and 29.5% were HBV (+), 38.9% of them were HbsAg (+) and 50% anti-HBs (+). The HCV and HBV infection was more elevated in relation to the transfusion number and the hemodilisis time. The elevation of ALT/ASAT activity isn't a right infection index for HCV and HBV in this children.

  15. Role of HCV Core gene of genotype 1a and 3a and host gene Cox-2 in HCV-induced pathogenesis

    Directory of Open Access Journals (Sweden)

    Ahmad Waqar

    2011-04-01

    Full Text Available Abstract Background Hepatitis C virus (HCV Core protein is thought to trigger activation of multiple signaling pathways and play a significant role in the alteration of cellular gene expression responsible for HCV pathogenesis leading to hepatocellular carcinoma (HCC. However, the exact molecular mechanism of HCV genome specific pathogenesis remains unclear. We examined the in vitro effects of HCV Core protein of HCV genotype 3a and 1a on the cellular genes involved in oxidative stress and angiogenesis. We also studied the ability of HCV Core and Cox-2 siRNA either alone or in combination to inhibit viral replication and cell proliferation in HCV serum infected Huh-7 cells. Results Over expression of Core gene of HCV 3a genotype showed stronger effect in regulating RNA and protein levels of Cox-2, iNOS, VEGF, p-Akt as compared to HCV-1a Core in hepatocellular carcinoma cell line Huh-7 accompanied by enhanced PGE2 release and cell proliferation. We also observed higher expression levels of above genes in HCV 3a patient's blood and biopsy samples. Interestingly, the Core and Cox-2-specific siRNAs down regulated the Core 3a-enhanced expression of Cox-2, iNOS, VEGF, p-Akt. Furthermore, the combined siRNA treatment also showed a dramatic reduction in viral titer and expression of these genes in HCV serum-infected Huh-7 cells. Taken together, these results demonstrated a differential response by HCV 3a genotype in HCV-induced pathogenesis, which may be due to Core and host factor Cox-2 individually or in combination. Conclusions Collectively, these studies not only suggest a genotype-specific interaction between key players of HCV pathogenesis but also may represent combined viral and host gene silencing as a potential therapeutic strategy.

  16. 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.

  17. Evaluation of a total hepatitis C virus (HCV) core antigen assay for the detection of antigenaemia in anti-HCV positive individuals.

    Science.gov (United States)

    Valcavi, Pierpaolo; Medici, Maria Cristina; Casula, Francesca; Arcangeletti, Maria Cristina; De Conto, Flora; Pinardi, Federica; Calderaro, Adriana; Chezzi, Carlo; Dettori, Giuseppe

    2004-07-01

    A new, sensitive enzyme immunoassay has been developed for detecting and quantifying total hepatitis C virus (HCV) core antigen in anti-HCV positive or negative sera ("trak-C", Ortho Clinical Diagnostics, Raritan, NJ). The purpose of this study was to evaluate the performance of trak-C as an additional laboratory diagnostic marker of viraemia. The performance was compared to HCV-RNA detection in the "screening" of sera from a large heterogeneous population of hospitalised patients and outpatients. Six hundred and eighteen anti-HCV negative sera, 405 anti-HCV positive/HCV-RNA negative sera, 604 anti-HCV positive/HCV-RNA positive sera and 67 anti-HCV negative sera containing antigens or antibodies potentially interfering with the performance of the assay were analysed. Supplemental HCV antibody testing was performed using a commercial strip immunoblot assay. HCV-RNA was investigated using a qualitative commercial assay. A quantitative commercial RT-PCR was used for the analysis of selected samples. Sensitivity and specificity values were 94.7 and 100%, respectively. The latter was also confirmed when anti-HCV negative samples containing potentially interfering antigens/antibodies were examined. Sensitivity below 100% was probably due to an antigenaemia below the detection limit of trak-C. Besides, because 65.6% of HCV-RNA positive/trak-C negative samples presented specific antibodies against all four RIBA antigens, the hypothesis was raised that, in some cases, the dissociation step efficiency could be sub-optimal. In conclusion, trak-C seems suitable for identifying HCV infection on large based populations. It is a rapid to perform, reliable and specific assay that can be adapted to any laboratory setting. Copyright 2004 Wiley-Liss, Inc.

  18. Hepatitis C Virus (HCV) Registry Veterans in VHA Care in 2015, for the Nation, by VISN and by Station

    Data.gov (United States)

    Department of Veterans Affairs — This report describes the number of Hepatitis C Virus (HCV) registry Veterans in VHA care in 2015 based on serologic evidence of HCV infection status (HCV Positive)...

  19. Safety analysis of raltegravir/truvada regimen in HIV/HCV co-infected patients without switchback after HCV treatment

    Directory of Open Access Journals (Sweden)

    Robert Ehret

    2014-11-01

    Full Text Available Introduction: Due to drug-drug interactions of HIV- and HCV-specific antivirals when initiating an HCV-therapy, the antiretroviral therapy (ART often has to be changed. The spectrum of applicable antiretrovirals is small, therefore many patients were switched to raltegravir/truvada (RAL/TVD in our cohort. Due to the relatively low genetic barrier of RAL, this regimen may be endangered to fail, if the NRTI backbone is not fully active because of pre-existing NRTI resistance. We investigated the long-term follow-up and safety of RAL/TVD in co-infected patients after hepatitis C virus (HCV therapy was stopped and the protective antiretroviral effect of interferon ended. Materials and Methods: Twenty patients initiated a direct-acting antiviral (DAA containing HCV therapy (8x faldaprevir, 6x telaprevir, 2x daclatasvir and 4x simeprevir between 11/2011 and 01/2013. Seventeen were switched to RAL/TVD, three patients were not treated before, but started with the regimen. Diagnosis of HIV infection was dated between 1985 and 2010. The HI-viral suppression was monitored retrospectively to date. Results: Thirteen of the twenty patients (65% remained on RAL/TVD after finishing HCV treatment, for seven patients, no data about their ART continuation was available, after HCV therapy had stopped. All remaining thirteen patients showed an HI-viral load below detection limit up to date (for 15 to 22 months, median 20 months. Only for four patients, historic resistance data were available but none showed NRTI mutations. Conclusions: Switch to RAL/TVD as HIV ART due to initiating HCV therapy was safe for the observed small cohort even in long-term follow-up without switchback or a second ART switch. However, resistance data for the cohort was little, showing no NRTI mutations, indicating a relatively safe setting. Since no further data is available, physicians should keep in mind ART history, historical therapy failure and HIV-resistance while switching ART to

  20. Intrahepatic cytokine expression is downregulated during HCV/HIV co-infection.

    Science.gov (United States)

    Blackard, Jason T; Komurian-Pradel, Florence; Perret, Magali; Sodoyer, Mireille; Smeaton, Laura; St Clair, J Benjamin; Chapman, Stacey; Taylor, Lynn E; Paranhos-Baccalà, Glaucia; Chung, Raymond T

    2006-02-01

    HIV co-infection is associated with reduced HCV treatment response rates and accelerated HCV-related liver disease. Cytokines play an important role in regulating hepatic inflammation and fibrogenesis during chronic HCV infection, yet the roles of HIV and/or its therapies on cytokine expression are unknown. Total RNA was extracted from liver biopsies of 12 HCV mono-infected and 14 HCV/HIV co-infected persons. We used real-time PCR to quantify cytokines that contribute to innate and adaptive immune responses, including IFNalpha, IFNgamma, TNFalpha, TGFbeta(1), IL-2, IL-4, IL-8, IL-10, and IL-12p40. Positive- and negative-strand HCV RNA levels were quantified using a molecular beacon approach. Detection of positive-strand HCV RNA was 100% in both groups; negative-strand HCV RNA was detected in four (33%) HCV mono-infected persons and in nine (64%) HCV/HIV co-infected persons. Median strand-specific HCV RNA levels were not significantly different between the two groups. Detection rates of cytokine mRNAs were lower for the HCV/HIV co-infected group compared to the HCV mono-infected group; the detection rates for TNFalpha, IL-8, and IL-10 were statistically significant. Overall, cytokine mRNA quantities were lower for HCV/HIV co-infected compared to HCV mono-infected persons, with the exception of TGFbeta1. These data suggest that a defect in cytokine activation may occur in HCV/HIV co-infected persons that limits efficient clearance of HCV from the liver. Copyright 2005 Wiley-Liss, Inc.

  1. HCV RNA traffic and association with NS5A in living cells

    Energy Technology Data Exchange (ETDEWEB)

    Fiches, Guillaume N.; Eyre, Nicholas S.; Aloia, Amanda L.; Van Der Hoek, Kylie [Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, University of Adelaide, Adelaide and Centre for Cancer Biology, SA Pathology, Adelaide, SA (Australia); Betz-Stablein, Brigit; Luciani, Fabio [Systems Immunology, School of Medical Sciences, University of New South Wales, Sydney, NSW (Australia); Chopra, Abha [Institute for Immunology and infectious diseases (IIID), Murdoch University, Perth, WA (Australia); Beard, Michael R., E-mail: michael.beard@adelaide.edu.au [Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, University of Adelaide, Adelaide and Centre for Cancer Biology, SA Pathology, Adelaide, SA (Australia)

    2016-06-15

    The spatiotemporal dynamics of Hepatitis C Virus (HCV) RNA localisation are poorly understood. To address this we engineered HCV genomes harbouring MS2 bacteriophage RNA stem-loops within the 3′-untranslated region to allow tracking of HCV RNA via specific interaction with a MS2-Coat-mCherry fusion protein. Despite the impact of these insertions on viral fitness, live imaging revealed that replication of tagged-HCV genomes induced specific redistribution of the mCherry-tagged-MS2-Coat protein to motile and static foci. Further analysis showed that HCV RNA was associated with NS5A in both static and motile structures while a subset of motile NS5A structures was devoid of HCV RNA. Further investigation of viral RNA traffic with respect to lipid droplets (LDs) revealed HCV RNA-positive structures in close association with LDs. These studies provide new insights into the dynamics of HCV RNA traffic with NS5A and LDs and provide a platform for future investigations of HCV replication and assembly. - Highlights: • HCV can tolerate can bacteriophage MS2 stem-loop insertions within the 3′ UTR. • MS2 stem-loop containing HCV genomes allow for real-time imaging of HCV RNA. • HCV RNA is both static and motile and associates with NS5A and lipid droplets.

  2. Ongoing Transmission of HCV: Should Cesarean Section be Justified? Data Mining Discovery.

    Science.gov (United States)

    Elrazek, Abd; Saab, Samy; Foad, Mahmoud; Elgohary, Elsayed A; Sallam, Mohammad M; Nawara, Abdallah; Ismael, Ali; Morsi, Samar S; Salah, Altaher; Alboraie, Mohamed; Bhagavathula, Akshaya Srikanth; Zayed, Marwa; Elmasry, Hossam; Salem, Tamer Z

    2017-03-01

    Over the past few decades, cesarean section (CS) rates are steadily increasing in most of the middle- and high-income countries. However, most of the pregnant women (particularly undergoing CS) are not screened for hepatitis C virus (HCV); hence, neonates born to HCV-positive mother could be a source of future HCV infection. In this study, the role of the CS and other surgical interventions in HCV transmission in Egypt, the highest endemic country of HCV-4, was investigated. From January to June 2016, a prospective cohort study was conducted among 3,836 pregnant women in both urban and rural areas across Egypt for HCV screening in both mothers and neonates born to HCV-positive mother. All pregnant women were screened during third trimester or just before delivery, neonates born to HCV-positive mothers were evaluated within 24-h postdelivery to record vertical transmission cases. Data mining (DM)-driven computational analysis was used to quantify the findings. Among 3,836 randomized pregnant women, HCV genotype 4 was identified in 80 women (2.08%). Out of 80 HCV-infected women, 18 have experienced surgical intervention (22.5%) and 62 CS (77.5%). HCV vertical transmission was identified in 10 neonates, 10/80 (12.5%). Screening women who had experienced surgical intervention or CS during child bearing period and before pregnancy might prevent HCV mother-to-child transmission (MTCT). CS should be ethically justified to decrease global HCV transmission.

  3. Occult HCV Infection: The Current State of Knowledge

    Science.gov (United States)

    Rezaee-Zavareh, Mohammad Saeid; Hadi, Reza; Karimi-Sari, Hamidreza; Hossein Khosravi, Mohammad; Ajudani, Reza; Dolatimehr, Fardin; Ramezani-Binabaj, Mahdi; Miri, Seyyed Mohammad; Alavian, Seyed Moayed

    2015-01-01

    Context Occult HCV infection (OCI) is defined as the presence of HCV-RNA in hepatocytes and the absence of HCV in the serum according to usual tests. We aimed to define OCI and provide information about the currently available diagnostic methods. Then we focus on specific groups that are at high risk of OCI and finally investigate immune responses to OCI and the available treatment approaches. Evidence Acquisition PubMed, Scopus and Google Scholar were comprehensively searched with combination of following keywords: “occult”, “hepatitis C virus” and “occult HCV infection”. The definition of OCI, diagnostic methods, specific groups that are at high risk and available treatment approaches were extract from literature. An analysis of available articles on OCI also was done based on Scopus search results. Results OCI has been reported in several high-risk groups, especially in hemodialysis patients and subjects with cryptogenic liver disease. Furthermore, some studies have proposed a specific immune response for OCI in comparison with chronic hepatitis C (CHC). Conclusions With a clinical history of approximately 11 years, occult HCV infection can be considered an occult type of CHC. Evidences suggest that considering OCI in these high-risk groups seems to be necessary. We suggest that alternative diagnostic tests should be applied and that there is a need for the participation of all countries to determine the epidemiology of this type of HCV infection. Additionally, evaluating OCI in blood transfusion centers and in patients who receive large amounts of blood and clotting factors, such as patients with hemophilia, should be performed in future projects. PMID:26734487

  4. Strategies to manage hepatitis C virus (HCV) disease burden

    DEFF Research Database (Denmark)

    Wedemeyer, H; Duberg, A S; Buti, M

    2014-01-01

    and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs......The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant...

  5. Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity

    National Research Council Canada - National Science Library

    Pfafferott, Katja; Gaudieri, Silvana; Ulsenheimer, Axel; James, Ian; Heeg, Malte; Nolan, David; John, Mina; Rauch, Andri; Mallal, Simon; Lucas, Andrew; Klenerman, Paul; Diepolder, Helmut M; Lucas, Michaela

    2011-01-01

    .... Most mutations were maintained into the chronic phase of HCV infection (75%). The lack of reversion of adaptations and high proportion of silent substitutions suggests that HCV has structural and functional limitations that constrain evolution...

  6. The negative impact of HBV/HCV coinfection on cirrhosis and its consequences.

    Science.gov (United States)

    Pol, S; Haour, G; Fontaine, H; Dorival, C; Petrov-Sanchez, V; Bourliere, M; Capeau, J; Carrieri, P; Larrey, D; Larsen, C; Marcellin, P; Pawlostky, J-M; Nahon, P; Zoulim, F; Cacoub, P; de Ledinghen, V; Mathurin, P; Negro, F; Pageaux, G-P; Yazdanpanah, Y; Wittkop, L; Zarski, J-P; Carrat, F

    2017-10-09

    Hepatitis B virus (HBV)/hepatitis C virus (HCV) confection has been rarely studied in nonasian series. To compare the characteristics of HBV/HCV coinfected patients to those of HBV- or HCV-monoinfected patients in the ANRS CO22 HEPATHER cohort study. Of the 20 936 included patients, 95 had HBV/HCV coinfection (hepatitis B surface antigen, anti-HCV antibody and HCV RNA positive) and were matched with 375 HBV- and 380 HCV-monoinfected patients on age, gender and time since HBV or HCV diagnosis. F3-F4 fibrosis was more frequent in coinfected patients (58%) than in HBV- (32%, P HBV- (2%, P = .0002) or HCV- (4%, P = .0275) monoinfected patients. Past excessive alcohol use was more frequent in coinfected patients (26%) than in HBV (12%, P = .0011), but similar in HCV monoinfected patients (32%, P = .2868). Coinfected patients had a higher proportion with arterial hypertension (42%) than HBV- (26%) or HCV-monoinfected patients (25%) (P HBV-infected patients (OR = 3.84, 95% CI 1.99-7.43) and the association between decompensated cirrhosis and coinfection in HBV infected (OR = 5.58, 95% CI 1.42-22.0) or HCV infected patients (OR = 3.02, 95% CI 1.22-7.44). HCV coinfection harmfully affects liver fibrosis in HBV patients, while decompensated cirrhosis is increased in coinfected patients compared with HBV- or HCV-monoinfected patients. HCV treatment is as safe and effective in coinfected as monoinfected patients and should be considered following the same rules as HCV monoinfected patients. © 2017 John Wiley & Sons Ltd.

  7. Effect of route of delivery on heterologous protection against HCV induced by an adenovirus vector carrying HCV structural genes

    Directory of Open Access Journals (Sweden)

    Guan Jie

    2011-11-01

    Full Text Available Abstract Background An effective vaccine and new therapeutic methods for hepatitis C virus (HCV are needed, and a potent HCV vaccine must induce robust and sustained cellular-mediated immunity (CMI. Research has indicated that adenoviral and vaccinia vectors may have the ability to elicit strong B and T cell immune responses to target antigens. Results A recombinant replication-defective adenovirus serotype 5 (rAd5 vector, rAd5-CE1E2, and a recombinant Tian Tan vaccinia vector, rTTV-CE1E2, were constructed to express the HCV CE1E2 gene (1-746 amino acid HCV 1b subtype. Mice were prime-immunised with rAd5-CE1E2 delivered via intramuscular injection (i.m., intranasal injection (i.n., or intradermal injection (i.d. and boosted using a different combination of injection routes. CMI was evaluated via IFN-γ ELISPOT and ICS 2 weeks after immunisation, or 16 weeks after boost for long-term responses. The humoral response was analysed by ELISA. With the exception of priming by i.n. injection, a robust CMI response against multiple HCV antigens (core, E1, E2 was elicited and remained at a high level for a long period (16 weeks post-vaccination in mice. However, i.n. priming elicited the highest anti-core antibody levels. Priming with i.d. rAd5-CE1E2 and boosting with i.d. rTTV-CE1E2 carried out simultaneously enhanced CMI and the humoral immune response, compared to the homologous rAd5-CE1E2 immune groups. All regimens demonstrated equivalent cross-protective potency in a heterologous surrogate challenge assay based on a recombinant HCV (JFH1, 2a vaccinia virus. Conclusions Our data suggest that a rAd5-CE1E2-based HCV vaccine would be capable of eliciting an effective immune response and cross-protection. These findings have important implications for the development of T cell-based HCV vaccine candidates.

  8. Prevalence of Hepatitis C Virus (HCV) in healthy adults and Human ...

    African Journals Online (AJOL)

    The prevalence of HCV infection in Abuja, FCT, Nigeria was determined among healthy adults and HIV infected persons. A total of n=520 apparently healthy HIV negative persons and n=1,200 infected persons were tested for antibodies against HCV by rapid chromatographic immunoassay HCV kit (Acon, ACON ...

  9. 21 CFR 610.47 - Hepatitis C virus (HCV) “lookback” requirements.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... Disease Agents § 610.47 Hepatitis C virus (HCV) “lookback” requirements. (a) If you are an establishment... after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under § 610...

  10. 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.

  11. Hepatitis C virus (HCV) interaction with astrocytes: nonproductive infection and induction of IL-18.

    Science.gov (United States)

    Liu, Ziqing; Zhao, Fang; He, Johnny J

    2014-06-01

    Hepatitis C virus (HCV) infection causes the central nervous system (CNS) abnormalities in more than 50 % of chronically infected subjects. However, the underlying mechanisms are largely unknown. In this study, we characterized the HCV interactions with astrocytes, one of the putative HCV target cells in the brain. We demonstrated that primary human astrocytes (PHA) were very inefficiently infected by HCV, either in the cell-free form or through cell-cell contact. We then determined the potential restriction steps of HCV infection and replication in these cells. PHA expressed all known HCV receptors but failed to support HCV entry. HCV IRES-mediated RNA translation was functional in PHA and further enhanced by miR122 expression. Nevertheless, PHA did not support HCV replication regardless of miR122 expression. To our great surprise, we found that HCV exposure induced robust IL-18 expression in PHA and exhibited direct neurotoxicity. Taken together, these results showed that astrocytes did not support productive HCV infection and replication, but HCV interactions with astrocytes and neurons alone might be sufficient to cause CNS dysfunction.

  12. HCV and HBV infections in Nigerian Patients with Liver Cirrhosis ...

    African Journals Online (AJOL)

    The present study is aimed at determining the incidence of HCV and HBV infections in Nigerian patients with Liver Cirrhosis (LC) and Hepatocellular Carcinoma (HCC). The incidence of HBV and antibodies to HVC was determined by Enzyme Linked Immunosorbent Assey (ELISA) in 24 Nigerians with histologically ...

  13. Prevalence of Hepatitis C Virus (HCV) and Human ...

    African Journals Online (AJOL)

    Prevalence of Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) Co-Infection Among Pregnant Women Attending Antenatal Clinics in Abuja, Nigeria. ... with this virus complicates issues related to diagnosis, clinical disease progression, monitoring disease activity, treatment options and basic immunology.

  14. The Case of anti-HCV Negative Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    A. L. Rossina

    2015-01-01

    Full Text Available The paper gives a brief literary reference relating to contemporary aspects of serological diagnosis of hepatitis C, and understands a clinical example of chronic hepatitis C in a child with acute lymphoblastic leukemia, with the absence of circulating antibodies to HCV classes M, and G for almost 2 years.

  15. Phylogenetics of HCV: Recent advances | Bostan | African Journal of ...

    African Journals Online (AJOL)

    Hepatitis C virus (HCV), a virus present in human population from indefinite time period, has affected millions of people globally, by causing liver infection which in majority of cases leads to chronicity, cirrhosis, end stage liver disease and hepatocellular carcinoma (HCC). The disease burden is expected to increase in the ...

  16. Prevalence of HBV and HCV among blood donors in Kosovo

    Science.gov (United States)

    Fejza, Hajrullah; Telaku, Skender

    2009-01-01

    Hepatitis is disease of the liver caused by the infectious and non-infectious agents. The aim of study was to analyze the prevalence of HBV and HCV among voluntary blood donors in Kosovo, during 2000–2003. The data from National Center for Blood Transfusion of Kosovo were collected and analyzed through descriptive and comparative epidemiological method of retrospective study. All samples were tested by ELISA test. Out of 70348 samples of the blood donors, 3145 were positive. From overall positive samples, 2939 were HBV positive, 192 HCV positive while 14 samples were positive for both viruses. The HBV prevalence among the blood donors of Kosovo is 4.2%, which range Kosovo to the second zone according to the CDC classification of the geographical spread of the HBV infection. The HCV prevalence among the blood donors in Kosovo is 0.3%. Compared to the other European countries this level of prevalence is relatively low. Age group 30–39 years old was presented with 34.8% of cases. The higher number was among the workers, 842 or 26.8%. Based on the results we can conclude that Kosovo have the similar prevalence for HBV and HCV infections as other South East European countries. PMID:19216773

  17. Frequencies of HBV, HCV, HIV, and Syphilis Markers Among Blood ...

    African Journals Online (AJOL)

    Purpose: This study aimed to determine the frequency rates of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis among blood donors. Methods: Physically fit persons aged 18 – 48 years who came for blood donation at the blood bank unit of the military hospital in Hodeidah, ...

  18. Glances in Immunology of HIV and HCV Infection

    Science.gov (United States)

    Quaranta, Maria Giovanna; Mattioli, Benedetta; Vella, Stefano

    2012-01-01

    Since the identification of HIV and HCV much progress has been made in the understanding of their life cycle and interaction with the host immune system. Despite these viruses markedly differ in their virological properties and in their pathogenesis, they share many common features in their immune escape and survival strategy. Both viruses have developed sophisticated ways to subvert and antagonize host innate and adaptive immune responses. In the last years, much effort has been done in the study of the AIDS pathogenesis and in the development of efficient treatment strategies, and a fatal infection has been transformed in a potentially chronic pathology. Much of this knowledge is now being transferred in the HCV research field, especially in the development of new drugs, although a big difference still remains between the outcome of the two infections, being HCV eradicable after treatment, whereas HIV eradication remains at present unachievable due to the establishment of reservoirs. In this review, we present current knowledge on innate and adaptive immune recognition and activation during HIV and HCV mono-infections and evasion strategies. We also discuss the genetic associations between components of the immune system, the course of infection, and the outcome of the therapies. PMID:22754568

  19. The Phylogeographic and Spatiotemporal Spread of HCV in Pakistani Population.

    Directory of Open Access Journals (Sweden)

    Noor-Ul-Huda Ghori

    Full Text Available Hepatitis C Virus (HCV is the most prevalent human pathogen in Pakistan and is the major cause of liver cirrhosis and hepatocellular carcinoma in infected patients. It has shifted from being hypo-endemic to being hyper-endemic. There was no information about the origin and evolution of the local variants. Here we use newly developed phyloinformatic methods of sequence analysis to conduct the first comprehensive investigation of the evolutionary and biogeographic history in unprecedented detail and breadth. Considering evolutionary rate and molecular-clock hypothesis in context, we reconstructed the spatiotemporal spread of HCV in the whole territory of its circulation using a combination of Bayesian MCMC methods utilizing all sequences available in GenBank. Comparative analysis were performed and were addressed. Whole genome and individual gene analysis have shown that sub-types 1a, 1b and 3a are recognized as epidemic strains and are distributed globally. Here we confirm that the origin of HCV 3a genotypes is in South Asia and HCV has evolved in the region to become stably adapted to the host environment.

  20. 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.

  1. Diagnostic reliability of Architect anti-HCV assay: Experience of a tertiary care hospital in India.

    Science.gov (United States)

    Fletcher, Gnanadurai John; Raghavendran, Anantharam; Sivakumar, Jayashree; Samuel, Prasanna; Abraham, Priya

    2017-06-28

    Anti-HCV assays are prone to false positive results. Thus, accurate detection of HCV infection is critical for the timely therapeutic management. This study ascertained the reliability of Architect anti-HCV assay (Abbott) and to estimate the agreement of this assay with Ortho HCV 3.0 ELISA Test System with Enhanced SAVe (Ortho), HCV Tri-dot (Tri-dot) and HCV-PCR in a tertiary care setting. A total of 78 788 consecutive sera were routinely screened for anti-HCV antibodies using Architect. All repeatedly reactive anti-HCV sera (n=1000) and anti-HCV negative sera (n=300) were tested in Ortho and in Tri-dot assays. Representative proportions of sera (n=500) with various signal-to-cut-off (S/Co) ratio were also compared with HCV-PCR. When Architect was compared with Ortho, Tri-dot, and HCV-PCR, the level of agreement as assessed by kappa were .26, .16, and .27 respectively. Using Latent class analysis (LCA), we found that sensitivity and specificity were 100% and 36.1% for Architect, 93.8% and 100% for Ortho and 63.8% and 100% for Tri-dot respectively. The median S/CO ratio of Architect and Ortho anti-HCV assays were significantly different between HCV-PCR positive and negative results (PArchitect S/CO ratio of >8 showed higher accuracy indices in both anti-HCV assays. Architect can be used as a screening assay because of its high sensitivity, high throughput, and short turnaround time. However, S/Co ratios of ≥1 to Architect necessitates HCV PCR to identify current infection and or EIA to distinguish true positivity from false biological positivity. © 2017 Wiley Periodicals, Inc.

  2. Glomerular diseases associated with HBV and HCV infection

    Directory of Open Access Journals (Sweden)

    Boriana Kiperova

    2014-03-01

    Full Text Available Hepatitis B and C viruses are human pathogens of major significance. Their extrahepatic manifestations are global health problem. HBV is a well-known cause of membranous nephropathy, membranoproliferative GN and IgA nephropathy, frequently in Asian populations. Polyarteritis nodosa is a rare, but serious systemic complication of chronic HBV. Immunosuppressive therapy in HBV-related GN is not recommended. Interferon alpha treatment produces sustained remission of porteinuria, often associated with clearance of HBeAg and/or HBsAg, however, it has many side effects. Compared to interferon, nucleos(tide analogues offer some advantages. These antiviral agents suppress HBV replication through their inhibitory effect on viral DNA polymerase. They have convenient administration and high tolerability. Lamivudine is well tolerated and safe in long-term studies, but the resistance of HBV is an escalating problem. The resistance to newer polymerase inhibitors Entecavir and Tenofovir is significantly lower. Hepatitis C virus causes cryoglobulinemia-mediated glomerulonephritis and other immune complex forms of GN. The renal manifestations are usually associated with long-lasting HCV infection. HCV glomerular disease is more frequent in adult males, and often leads to chronic renal insufficiency. The first line treatment in patients with mild to moderate clinical and histological kidney damage is the antiviral therapy with pegylated INF alpha and ribavirin. In case of severe HCV-associated cryoglobulinemic GN - nephrotic syndrome, nephritic syndrome and/or progressive renal failure, high activity score of glomerulonephritis on light microscopy, the initial treatment might consist of sequential administration of antiviral and immunosuppressive agents (corticosteroids, cyclophosphamide and plasma exchange, or rituximab. The treatment of HCV-related glomerular disease is still under debate and based on scant experimental evidence. Large randomized and controlled

  3. High awareness of hepatitis C virus (HCV) but limited knowledge of HCV complications among HIV-positive and HIV-negative men who have sex with men.

    Science.gov (United States)

    Lambers, Femke A E; Prins, Maria; Davidovich, Udi; Stolte, Ineke G

    2014-04-01

    Hepatitis C virus (HCV) has emerged as a sexually transmitted infection among HIV-positive men who have sex with men (MSM) in high-income countries. Little is reported about HCV awareness among MSM, although this is essential for developing targeted prevention strategies. We, therefore, studied HCV awareness and knowledge among HIV-positive and HIV-negative MSM from the Amsterdam Cohort Studies (ACS). During two visits, 1 year apart and starting in October 2007, MSM from the ACS answered questions regarding HCV awareness, knowledge of HCV transmission (7 items), complications (8 items) and sexual risk behaviour. We examined the percentage of HCV awareness and correctly answered knowledge items, and whether awareness and knowledge improved significantly over time. Using logistic regression, we studied whether HIV status and sexual risk behaviour were associated with awareness. Seventy percent (312/444) of HIV-negative and 80% (74/92) of HIV-positive MSM reported to have ever heard of HCV on the first visit. Overall, awareness increased with 9% between the first and second visit (p awareness was borderline significant (OR 1.49, 95% CI 0.97-2.30). Compared with knowledge of transmission routes, knowledge of complications appeared to be limited. In the ACS, awareness of HCV is high, particularly among those reporting group sex, an important risk factor for HCV transmission. The majority of participants had good knowledge of transmission routes, but limited knowledge of complications of chronic HCV infection. HCV prevention messages could be strengthened, therefore, by further addressing the complications of HCV infection.

  4. Ledipasvir and sofosbuvir for HCV infection in patients coinfected with HBV.

    Science.gov (United States)

    Gane, Edward J; Hyland, Robert H; An, Di; Svarovskaia, Evguenia S; Brainard, Diana; McHutchison, John G

    2016-01-01

    Currently there are no all-oral treatment regimens for HCV in patients coinfected with HBV. In this pilot study, we evaluated whether ledipasvir and sofosbuvir therapy can suppress HCV infection in patients coinfected with HBV. Patients with HBV and genotype-1 HCV received 90 mg ledipasvir and 400 mg sofosbuvir daily for 12 weeks. The efficacy end point was sustained virological response (HCV RNA ledipasvir/sofosbuvir was a safe and effective treatment for genotype-1 HCV infection in patients coinfected with HBV. Larger studies with longer follow-up are warranted.

  5. Discovery of fused tricyclic core containing HCV NS5A inhibitors with pan-genotype activity.

    Science.gov (United States)

    Yu, Wensheng; Coburn, Craig A; Yang, De-Yi; Meinke, Peter T; Wong, Michael; Rosenblum, Stuart B; Chen, Kevin X; Njoroge, George F; Chen, Lei; Dwyer, Michael P; Jiang, Yueheng; Nair, Anilkumar G; Selyutin, Oleg; Tong, Ling; Zeng, Qingbei; Zhong, Bin; Ji, Tao; Hu, Bin; Agrawal, Sony; Xia, Ellen; Zhai, Ying; Liu, Rong; Kong, Rong; Ingravallo, Paul; Asante-Appiah, Ernest; Nomeir, Amin; Fells, James; Kozlowski, Joseph A

    2016-07-01

    HCV NS5A inhibitors have demonstrated impressive in vitro potency profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed dose combination regimen for the treatment of HCV infection. Herein, we describe research efforts that led to the discovery of a series of fused tricyclic core containing HCV NS5A inhibitors such as 24, 39, 40, 43, and 44 which have pan-genotype activity and are orally bioavailable in the rat. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. 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

  7. HCV - Estimation of the number of diagnosed patients eligible to the new anti-HCV therapies in Italy.

    Science.gov (United States)

    Gardini, I; Bartoli, M; Conforti, M; Mennini, F S; Marcellusi, A; Lanati, E

    2016-12-01

    The present research wants to take a picture of the current epidemiological scenario regarding HCV infection in Italy. Studies used to estimate HCV burden of illness in Italy were so far local and performed a number of years ago, not mirroring the state of the art. EpaC wanted to provide a real number of diagnosed patients, eligible to new anti-HCV therapies. EpaC is the most important Italian NGO for hepatopathic patients. A number of sources were cross-checked. Starting from all regional data regarding HCV-related exemptions, a correction/integration was performed with online questionnaire to associated patients (from which we derived patients cured and also other/no exemptions); survey to all prescribing centers in Italy (from which we derived the percentage of ineligible patients); prevalence of particular subpopulations was also collected (prisoners and HIV/HCV coinfected); calculations of new diagnosed, dead and cured patients in 2015. Excluded patients were illegal immigrants and active drug addicts (subpopulations currently rarely cured). A total of 221,549 patients were derived from regional exemptions databases and the mean national prevalence was 0.364%. Adding patients without exemptions/other exemptions, total was 308,624. We deducted the yearly deaths, cured and not eligible patients and, last, integrated with coinfected and prisoner special groups. Prevalence was also estimated at regional level, highlighting a reduction of the typical North-to-South prevalence gradient. Applying the above-mentioned corrections/integrations, total diagnosed and eligible HCV patients in Italy who can be immediately cured are supposed to range 163,148-187,756. This is a research aimed at filling an informative gap able to provide useful actual information in terms of HCV patients real-life management and future resource allocation. These data may be considered the basis for policy- and decision-makers to plan and manage patients ready to be cured. The research does not

  8. HCV-specific T-cell responses in injecting drug users : evidence for previous exposure to HCV and a role for CD4+ T cells focussing on nonstructural proteins in viral clearance

    NARCIS (Netherlands)

    Ruys, T A; Nanlohy, N M; van den Berg, C H S B; Hassink, E; Beld, M; van de Laar, T; Bruisten, S; Wit, F; Krol, A; Prins, M; Lange, J; van Baarle, D

    In order to understand the parameters associated with resolved hepatitis C virus (HCV)-infection, we analysed the HCV-specific T-cell responses longitudinally in 13 injecting drug-users (IDUs) with a prospectively identified acute HCV infection. Seven IDUs cleared HCV and six IDUs remained

  9. The Rationale for a Preventative HCV Virus-Like Particle (VLP Vaccine

    Directory of Open Access Journals (Sweden)

    Joseph Torresi

    2017-11-01

    Full Text Available HCV represents a global health problem with ~200 million individuals currently infected, worldwide. With the high cost of antiviral therapies, the global burden of chronic hepatitis C infection (CHCV infection will be substantially reduced by the development of an effective vaccine for HCV. The field of HCV vaccines is generally divided into proponents of strategies to induce neutralizing antibodies (NAb and those who propose to elicit cell mediated immunity (CMI. However, for a hepatitis C virus (HCV vaccine to be effective in preventing infection, it must be capable of generating cross-reactive CD4+, CD8+ T cell, and NAb responses that will cover the major viral genotypes. Simulation models of hepatitis C have predicted that a vaccine of even modest efficacy and coverage will significantly reduce the incidence of hepatitis C. A HCV virus like particle (VLP based vaccine would fulfill the requirement of delivering critical conformational neutralizing epitopes in addition to providing HCV specific CD4+ and CD8+ epitopes. Several approaches have been reported including insect cell-derived genotype 1b HCV VLPs; a human liver-derived quadrivalent genotype 1a, 1b, 2, and 3a vaccine; a genotype 1a HCV E1 and E2 glycoprotein/MLV Gag pseudotype VLP vaccine; and chimeric HBs-HCV VLP vaccines. All to result in the production of cross-NAb and/or T cell responses against HCV. This paper summarizes the evidence supporting the development of a HCV VLP based vaccine.

  10. 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.

  11. Clearance of low levels of HCV viremia in the absence of a strong adaptive immune response

    Directory of Open Access Journals (Sweden)

    Manns Michael P

    2007-06-01

    Full Text Available Abstract Spontaneous clearance of hepatitis C virus (HCV has frequently been associated with the presence of HCV-specific cellular immunity. However, there had been also reports in chimpanzees demonstrating clearance of HCV-viremia in the absence of significant levels of detectable HCV-specific cellular immune responses. We here report seven asymptomatic acute hepatitis C cases with peak HCV-RNA levels between 300 and 100.000 copies/ml who all cleared HCV-RNA spontaneously. Patients were identified by a systematic screening of 1176 consecutive new incoming offenders in a German young offender institution. Four of the seven patients never developed anti-HCV antibodies and had normal ALT levels throughout follow-up. Transient weak HCV-specific CD4+ T cell responses were detectable in five individuals which did not differ in strength and breadth from age- and sex-matched patients with chronic hepatitis C and long-term recovered patients. In contrast, HCV-specific MHC-class-I-tetramer-positive cells were found in 3 of 4 HLA-A2-positive patients. Thus, these cases highlight that clearance of low levels of HCV viremia is possible in the absence of a strong adaptive immune response which might explain the low seroconversion rate after occupational exposure to HCV.

  12. Retention in buprenorphine treatment is associated with improved HCV care outcomes.

    Science.gov (United States)

    Norton, B L; Beitin, A; Glenn, M; DeLuca, J; Litwin, A H; Cunningham, C O

    2017-04-01

    Persons who inject drugs, most of whom are opioid dependent, comprise the majority of the HCV infected in the United States. As the national opioid epidemic unfolds, increasing numbers of people are entering the medical system to access treatment for opioid use disorder, specifically with buprenorphine. Yet little is known about HCV care in patients accessing buprenorphine-based opioid treatment. We sought to determine the HCV prevalence, cascade of care, and the association between patient characteristics and completion of HCV cascade of care milestones for patients initiating buprenorphine treatment. We reviewed electronic health records of all patients who initiated buprenorphine treatment at a primary-care clinic in the Bronx, NY between January 2009 and January 2014. Of the 390 patients who initiated buprenorphine treatment, 123 were confirmed to have chronic HCV infection. The only patient characteristic associated with achieving HCV care milestones was retention in opioid treatment. Patients retained (vs. not retained) in buprenorphine treatment were more likely to be referred for HCV specialty care (63.1% vs. 34.0%, pbuprenorphine treatment, there is an unprecedented opportunity to access and treat persons with HCV, reducing HCV transmission, morbidity and mortality. Retention in opioid treatment may improve linkage and retention in HCV care; innovative models of care that integrate opioid drug treatment with HCV treatment are essential. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Peripheral blood mononuclear cells of HIV- and HCV-antibody-positive individuals contain HCV RNA but No HCV DNA despite evidence for reverse transcription of HIV RNA into DNA

    NARCIS (Netherlands)

    Penning, M.; Beld, M.; Goudsmit, J.

    2000-01-01

    Following reports of the finding of cDNA of RNA viruses in cells containing an endogenous retrovirus-encoded reverse transcriptase, we looked for the presence of hepatitis C virus (HCV) DNA in peripheral blood mononuclear cells (PBMC) of injecting drug users seropositive for both HCV and human

  14. Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection.

    Science.gov (United States)

    Bourlière, Marc; Gordon, Stuart C; Flamm, Steven L; Cooper, Curtis L; Ramji, Alnoor; Tong, Myron; Ravendhran, Natarajan; Vierling, John M; Tran, Tram T; Pianko, Stephen; Bansal, Meena B; de Lédinghen, Victor; Hyland, Robert H; Stamm, Luisa M; Dvory-Sobol, Hadas; Svarovskaia, Evguenia; Zhang, Jie; Huang, K C; Subramanian, G Mani; Brainard, Diana M; McHutchison, John G; Verna, Elizabeth C; Buggisch, Peter; Landis, Charles S; Younes, Ziad H; Curry, Michael P; Strasser, Simone I; Schiff, Eugene R; Reddy, K Rajender; Manns, Michael P; Kowdley, Kris V; Zeuzem, Stefan

    2017-06-01

    Patients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options. We conducted two phase 3 trials involving patients who had been previously treated with a DAA-containing regimen. In POLARIS-1, patients with HCV genotype 1 infection who had previously received a regimen containing an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive either the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir (150 patients) or matching placebo (150 patients) once daily for 12 weeks. Patients who were infected with HCV of other genotypes (114 patients) were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group. In POLARIS-4, patients with HCV genotype 1, 2, or 3 infection who had previously received a DAA regimen but not an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir-voxilaprevir (163 patients) or sofosbuvir-velpatasvir (151 patients) for 12 weeks. An additional 19 patients with HCV genotype 4 infection were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group. In the three active-treatment groups, 46% of the patients had compensated cirrhosis. In POLARIS-1, the rate of sustained virologic response was 96% with sofosbuvir-velpatasvir-voxilaprevir, as compared with 0% with placebo. In POLARIS-4, the rate of response was 98% with sofosbuvir-velpatasvir-voxilaprevir and 90% with sofosbuvir-velpatasvir. The most common adverse events were headache, fatigue, diarrhea, and nausea. In the active-treatment groups in both trials, the percentage of patients who discontinued treatment owing to adverse events was 1% or lower. Sofosbuvir-velpatasvir-voxilaprevir taken for 12 weeks provided high rates of sustained virologic response among patients across HCV genotypes in whom treatment with a DAA regimen

  15. Discovery of an irreversible HCV NS5B polymerase inhibitor.

    Science.gov (United States)

    Zeng, Qingbei; Nair, Anilkumar G; Rosenblum, Stuart B; Huang, Hsueh-Cheng; Lesburg, Charles A; Jiang, Yueheng; Selyutin, Oleg; Chan, Tin-Yau; Bennett, Frank; Chen, Kevin X; Venkatraman, Srikanth; Sannigrahi, Mousumi; Velazquez, Francisco; Duca, Jose S; Gavalas, Stephen; Huang, Yuhua; Pu, Haiyan; Wang, Li; Pinto, Patrick; Vibulbhan, Bancha; Agrawal, Sony; Ferrari, Eric; Jiang, Chuan-kui; Li, Cheng; Hesk, David; Gesell, Jennifer; Sorota, Steve; Shih, Neng-Yang; Njoroge, F George; Kozlowski, Joseph A

    2013-12-15

    The discovery of lead compound 2e was described. Its covalent binding to HCV NS5B polymerase enzyme was investigated by X-ray analysis. The results of distribution, metabolism and pharmacokinetics were reported. Compound 2e was demonstrated to be potent (replicon GT-1b EC50 = 0.003 μM), highly selective, and safe in in vitro and in vivo assays. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Drug Abuse, HIV, and HCV in Asian Countries.

    Science.gov (United States)

    Hser, Yih-Ing; Liang, Di; Lan, Yu-Ching; Vicknasingam, Balasingam Kasinather; Chakrabarti, Amit

    2016-09-01

    Drug abuse and co-occurring infections are associated with significant morbidity and mortality. Asian countries are particularly vulnerable to the deleterious consequences of these risks/problems, as they have some of the highest rates of these diseases. This review describes drug abuse, HIV, and hepatitis C (HCV) in Asian countries. The most commonly used illicit drugs include opioids, amphetamine-type stimulants (ATS), cannabis, and ketamine. Among people who inject drugs, HIV rates range from 6.3 % in China to 19 % in Malaysia, and HCV ranges from 41 % in India and Taiwan to 74 % in Vietnam. In the face of the HIV epidemics, drug policies in these countries are slowly changing from the traditional punitive approach (e.g., incarcerating drug users or requiring registration as a drug user) to embrace public health approaches, including, for example, community-based treatment options as well as harm reduction approaches to reduce needle sharing and thus HIV transmission. HIV and HCV molecular epidemiology indicates limited geographic diffusion. While the HIV prevalence is declining in all five countries, use of new drugs (e.g., ATS, ketamine) continues to increase, as well as high-risk sexual behaviors associated with drug use-increasing the risk of sexual transmission of HIV, particularly among men who have sex with men. Screening, early intervention, and continued scaling up of therapeutic options (drug treatment and recovery support, ART, long-term HIV and HCV care for drug users) are critical for effective control or continued reduction of drug abuse and co-infections.

  17. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection.

    Science.gov (United States)

    Afdhal, Nezam; Reddy, K Rajender; Nelson, David R; Lawitz, Eric; Gordon, Stuart C; Schiff, Eugene; Nahass, Ronald; Ghalib, Reem; Gitlin, Norman; Herring, Robert; Lalezari, Jacob; Younes, Ziad H; Pockros, Paul J; Di Bisceglie, Adrian M; Arora, Sanjeev; Subramanian, G Mani; Zhu, Yanni; Dvory-Sobol, Hadas; Yang, Jenny C; Pang, Phillip S; Symonds, William T; McHutchison, John G; Muir, Andrew J; Sulkowski, Mark; Kwo, Paul

    2014-04-17

    Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need. We conducted a phase 3, randomized, open-label study involving patients infected with HCV genotype 1 who had not had a sustained virologic response after treatment with peginterferon and ribavirin, with or without a protease inhibitor. Patients were randomly assigned to receive the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir in a once-daily, fixed-dose combination tablet for 12 weeks, ledipasvir-sofosbuvir plus ribavirin for 12 weeks, ledipasvir-sofosbuvir for 24 weeks, or ledipasvir-sofosbuvir plus ribavirin for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. Among the 440 patients who underwent randomization and were treated, 20% had cirrhosis and 79% had HCV genotype 1a infection. The rates of sustained virologic response were high in all treatment groups: 94% (95% confidence interval [CI], 87 to 97) in the group that received 12 weeks of ledipasvir-sofosbuvir; 96% (95% CI, 91 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir and ribavirin; 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir and ribavirin. No patient discontinued treatment owing to an adverse event. The most common adverse events were fatigue, headache, and nausea. Treatment with a once-daily, single-tablet regimen of ledipasvir and sofosbuvir resulted in high rates of sustained virologic response among patients with HCV genotype 1 infection who had not had a sustained virologic response to prior interferon-based treatment. (Funded by Gilead Sciences; ION-2 ClinicalTrials.gov number, NCT01768286.).

  18. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection.

    Science.gov (United States)

    Afdhal, Nezam; Zeuzem, Stefan; Kwo, Paul; Chojkier, Mario; Gitlin, Norman; Puoti, Massimo; Romero-Gomez, Manuel; Zarski, Jean-Pierre; Agarwal, Kosh; Buggisch, Peter; Foster, Graham R; Bräu, Norbert; Buti, Maria; Jacobson, Ira M; Subramanian, G Mani; Ding, Xiao; Mo, Hongmei; Yang, Jenny C; Pang, Phillip S; Symonds, William T; McHutchison, John G; Muir, Andrew J; Mangia, Alessandra; Marcellin, Patrick

    2014-05-15

    In phase 2 studies, treatment with the all-oral combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor ledipasvir resulted in high rates of sustained virologic response among previously untreated patients with hepatitis C virus (HCV) genotype 1 infection. We conducted a phase 3, open-label study involving previously untreated patients with chronic HCV genotype 1 infection. Patients were randomly assigned in a 1:1:1:1 ratio to receive ledipasvir and sofosbuvir in a fixed-dose combination tablet once daily for 12 weeks, ledipasvir-sofosbuvir plus ribavirin for 12 weeks, ledipasvir-sofosbuvir for 24 weeks, or ledipasvir-sofosbuvir plus ribavirin for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. Of the 865 patients who underwent randomization and were treated, 16% had cirrhosis, 12% were black, and 67% had HCV genotype 1a infection. The rates of sustained virologic response were 99% (95% confidence interval [CI], 96 to 100) in the group that received 12 weeks of ledipasvir-sofosbuvir; 97% (95% CI, 94 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir plus ribavirin; 98% (95% CI, 95 to 99) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 97 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir plus ribavirin. No patient in either 12-week group discontinued ledipasvir-sofosbuvir owing to an adverse event. The most common adverse events were fatigue, headache, insomnia, and nausea. Once-daily ledipasvir-sofosbuvir with or without ribavirin for 12 or 24 weeks was highly effective in previously untreated patients with HCV genotype 1 infection. (Funded by Gilead Sciences; ION-1 ClinicalTrials.gov number NCT01701401.).

  19. Host genetics predict clinical deterioration in HCV-related cirrhosis.

    Directory of Open Access Journals (Sweden)

    Lindsay Y King

    Full Text Available Single nucleotide polymorphisms (SNPs in the epidermal growth factor (EGF, rs4444903, patatin-like phospholipase domain-containing protein 3 (PNPLA3, rs738409 genes, and near the interleukin-28B (IL28B, rs12979860 gene are linked to treatment response, fibrosis, and hepatocellular carcinoma (HCC in chronic hepatitis C. Whether these SNPs independently or in combination predict clinical deterioration in hepatitis C virus (HCV-related cirrhosis is unknown. We genotyped SNPs in EGF, PNPLA3, and IL28B from liver tissue from 169 patients with biopsy-proven HCV cirrhosis. We estimated risk of clinical deterioration, defined as development of ascites, encephalopathy, variceal hemorrhage, HCC, or liver-related death using Cox proportional hazards modeling. During a median follow-up of 6.6 years, 66 of 169 patients experienced clinical deterioration. EGF non-AA, PNPLA3 non-CC, and IL28B non-CC genotypes were each associated with increased risk of clinical deterioration in age, sex, and race-adjusted analysis. Only EGF non-AA genotype was independently associated with increased risk of clinical deterioration (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.31-6.25 after additionally adjusting for bilirubin, albumin, and platelets. Compared to subjects who had 0-1 unfavorable genotypes, the HR for clinical deterioration was 1.79 (95%CI 0.96-3.35 for 2 unfavorable genotypes and 4.03 (95%CI 2.13-7.62 for unfavorable genotypes for all three loci (Ptrend<0.0001. In conclusion, among HCV cirrhotics, EGF non-AA genotype is independently associated with increased risk for clinical deterioration. Specific PNPLA3 and IL28B genotypes also appear to be associated with clinical deterioration. These SNPs have potential to identify patients with HCV-related cirrhosis who require more intensive monitoring for decompensation or future therapies preventing disease progression.

  20. Review article: HCV – STAT-C era of therapy

    OpenAIRE

    Lange, Christian Markus; Sarrazin, Christoph; Zeuzem, Stefan

    2010-01-01

    Abstract Background: Numerous ?specifically targeted antiviral therapy for hepatitis C? (STAT-C) compounds are currently under development to improve treatment opportunities of chronic hepatitis C virus-(HCV)-infection. Aim: To review the potential of STAT-C agents which are currently under clinical development. Methods: Studies evaluating STAT-C compounds were identified by systematic literature search using PubMed and databases of abstracts presented in English at recent l...

  1. Modulations of cell cycle checkpoints during HCV associated disease

    Directory of Open Access Journals (Sweden)

    Jafri Wasim

    2009-08-01

    Full Text Available Abstract Background Impaired proliferation of hepatocytes has been reported in chronic Hepatitis C virus infection. Considering the fundamental role played by cell cycle proteins in controlling cell proliferation, altered regulation of these proteins could significantly contribute to HCV disease progression and subsequent hepatocellular carcinoma (HCC. This study aimed to identify the alterations in cell cycle genes expression with respect to early and advanced disease of chronic HCV infection. Methods Using freshly frozen liver biopsies, mRNA levels of 84 cell cycle genes in pooled RNA samples from patients with early or advanced fibrosis of chronic HCV infection were studied. To associate mRNA levels with respective protein levels, four genes (p27, p15, KNTC1 and MAD2L1 with significant changes in mRNA levels (> 2-fold, p-value Results In the early fibrosis group, increased mRNA levels of cell proliferation genes as well as cell cycle inhibitor genes were observed. In the advanced fibrosis group, DNA damage response genes were up-regulated while those associated with chromosomal stability were down-regulated. Increased expression of CDK inhibitor protein p27 was consistent with its mRNA level detected in early group while the same was found to be negatively associated with liver fibrosis. CDK inhibitor protein p15 was highly expressed in both early and advanced group, but showed no correlation with fibrosis. Among the mitotic checkpoint regulators, expression of KNTC1 was significantly reduced in advanced group while MAD2L1 showed a non-significant decrease. Conclusion Collectively these results are suggestive of a disrupted cell cycle regulation in HCV-infected liver. The information presented here highlights the potential of identified proteins as predictive factors to identify patients with high risk of cell transformation and HCC development.

  2. Peripheral nervous system involvement in HCV-related mixed cryoglobulinemia

    Directory of Open Access Journals (Sweden)

    F. Bravaccio

    2011-09-01

    Full Text Available In HCV-related mixed cryoglobulinemia (MC a peripheral neuropathy (PN may occur. To evaluate the prevalence and the characteristics of PN, 133 consecutive patients with HCV-MC (117 type II, 16 type III were studied. Neurologic evaluation was performed according to the guidelines of Italian Group for the Study of Cryoglobulinemias, using a neurological disability score and a neurological symptom score. In 52/133 patients an electrophysiologic study (ENG of ulnar, peroneal and sural nerves was performed. For 27/52 patients ENG data registered at different times (interval 12-96 months were available. In 11 patients a sural nerve biopsy was obtained. An overt PN, mostly as sensory asymmetrical or symmetrical nerve impairement, was found in 107/133 patients (80.4%. ENG abnormalities-reduction or absence of sensory and sometimes of motor action potential, normal or slightly impaired nerve conduction velocity, consistent with axonal damage- were detected in 48/52 patients (92.3%. In 26 out of the 27 patients observed at different times an evolution of PN was found. Nerve biopsies showed a prevalent axonal damage, swollen endotelial cells in epi- and perineurial vessels and scarce mononuclear perivascular infiltrates. No leukocytoclastic vasculitis was observed. Immunoglobulins and complement in sub-perineurial vessel wall were detected. Conclusions. In HCV-MC a PN is frequent. It is mostly a sensory and progressively worsenig axonopathy. Different mechanisms may be involved in the pathogenesis of this disorder and a direct role of HCV cannot be excluded.

  3. Engaging HIV-HCV co-infected patients in HCV treatment: the roles played by the prescribing physician and patients' beliefs (ANRS CO13 HEPAVIH cohort, France

    Directory of Open Access Journals (Sweden)

    Salmon-Ceron Dominique

    2012-03-01

    Full Text Available Abstract Background Treatment for the hepatitis C virus (HCV may be delayed significantly in HIV/HCV co-infected patients. Our study aims at identifying the correlates of access to HCV treatment in this population. Methods We used 3-year follow-up data from the HEPAVIH ANRS-CO13 nationwide French cohort which enrolled patients living with HIV and HCV. We included pegylated interferon and ribavirin-naive patients (N = 600 at enrolment. Clinical/biological data were retrieved from medical records. Self-administered questionnaires were used for both physicians and their patients to collect data about experience and behaviors, respectively. Results Median [IQR] follow-up was 12[12-24] months and 124 patients (20.7% had started HCV treatment. After multiple adjustment including patients' negative beliefs about HCV treatment, those followed up by a general practitioner working in a hospital setting were more likely to receive HCV treatment (OR[95%CI]: 1.71 [1.06-2.75]. Patients followed by general practitioners also reported significantly higher levels of alcohol use, severe depressive symptoms and poor social conditions than those followed up by other physicians. Conclusions Hospital-general practitioner networks can play a crucial role in engaging patients who are the most vulnerable and in reducing existing inequities in access to HCV care. Further operational research is needed to assess to what extent these models can be implemented in other settings and for patients who bear the burden of multiple co-morbidities.

  4. Look-back of anti-HCV ELISA-positive, HCV-RNA PCR-negative donors and recipients of their blood products

    NARCIS (Netherlands)

    Vrielink, H.; Reésink, H. W.; Zaaijer, H. L.; Scholten, E.; Kremer, L. C.; Cuypers, H. T.; Lelie, P. N.; van Oers, M. H.; van der Poel, C. L.

    1997-01-01

    BACKGROUND AND OBJECTIVES: To establish the infectivity of anti-HCV ELISA-positive, but cDNA-PCR-negative blood components transfused before the introduction of routine anti-HCV blood donor screening, we enrolled recipients of such blood products in a look-back programme. MATERIALS AND METHODS: The

  5. Are RA patients from a non-endemic HCV population screened for HCV? A cross-sectional analysis of three different settings.

    Science.gov (United States)

    Skinner-Taylor, Cassandra Michelle; Erhard-Ramírez, Alejandro; Garza-Elizondo, Mario Alberto; Esquivel-Valerio, Jorge Antonio; Abud-Mendoza, Carlos; Martínez-Martínez, Marco Ulises; Vega-Morales, David; Arana-Guajardo, Ana

    In Mexico, other risk factors are associated with hepatitis C virus (HCV): prior heroin users, living alone, widower, and northern region residence. Rheumatoid arthritis (RA) patients are considered immunosuppressed and HCV testing is recommended before treatment. The aim of the study was to describe the characteristics of HCV testing in RA patients in three different medical care settings in a non-endemic area. A retrospective observational study was performed using medical records from 960 RA patients describing the indications for HCV testing. The test was performed in 28.6% and the HCV overall frequency was 0.36%. Population characteristics were not associated with an increased risk of HCV infection; therefore, anti-HCV positivity was low. The main reason for testing was before starting biological agents. Due to the low pre-test probability, testing for HCV infection should be personalized; i.e., according to disease prevalence in a particular geographical location and the individual risk factors. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  6. HEPATITIS C VIRUS (HCV) SEROPREVALENCE, ANTIGENAEMIA AND ASSOCIATED RISK FACTORS AMONG PREGNANT WOMEN IN NIGERIA.

    Science.gov (United States)

    Owolabi, Omolola Beatrice; Adesina, Kikelomo Temilola; Fadeyi, Abayomi; Popoola, Gbenga

    2015-10-01

    Hepatitis C viral infection is a significant public health challenge with potential risk of progressing to liver cirrhosis and hepatocellular carcinoma (HCC). Actively infected mothers can transmit the virus to their babies who may develop liver cirrhosis and HCC as young adults. We determined the seroprevalence of HCV, its antigenaemia and associated risk factors among pregnant women. We recruited 400 pregnant women and tested their serum for HCV antibodies using immune-chromatographic test and determined the HCV core antigenaemia among HCV sero-positives by enzyme-immunoassay (EIA). The bio-socio-demographic variables of the participants were statistically correlated to the test results. Seroprevalence of HCV was 5.8% (23/400) and the prevalence of HCV core antigenaemia was 73.9% (17/23). None of the bio-socio-demographic variables of the participants and other known risk factors evaluated had. significant influence on either seroprevalence of HCV or its antigenaemia. Only the employment status of the participants' husbands (p = 0.01) significantly affected seropositivity of HCV. HCV core antigenaemia is high among pregnant women who have antibodies to HCV in our environment and this signifies an active hepatitis C virus infection.

  7. 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

  8. Intrahepatic Vγ9Vδ2 T-cells from HCV-infected patients show an exhausted phenotype but can inhibit HCV replication.

    Science.gov (United States)

    Cimini, E; Bordoni, V; Sacchi, A; Visco-Comandini, U; Montalbano, M; Taibi, C; Casetti, R; Lalle, E; D'Offizi, G; Capobianchi, M R; Agrati, C

    2018-01-02

    Hepatitis C virus (HCV) persistence results from inefficiencies of both innate and adaptive immune responses to eradicate the infection. A functional impairment of circulating Vγ9Vδ2 T-cells was described but few data are available on Vγ9Vδ2 T-cells in the liver that, however, represents the battlefield in the HCV/host interaction. Aim of this work was to compare circulating and intrahepatic Vγ9Vδ2 T-cells in chronic HCV-infected patients (HCVpos) and in HCV-negative (HCVneg) subjects. Phenotypic and functional analysis was performed by flow cytometry. Anti-HCV activity was analyzed by using an in vitro autologous liver culture system. Independently from HCV infection, the liver was enriched of Vγ9Vδ2 T-cells expressing an effector/activated phenotype. In contrast, an enrichment of PD-1 expressing Vγ9Vδ2 T-cells was observed both in the peripheral blood and in the liver of HCVpos patients, probably due to a persistent antigenic stimulation. Moreover, a lower frequency of IFN-γ producing Vγ9Vδ2 T-cells was observed in the liver of HCVpos patients, suggesting a functional impairment in the cytokine production in HCVpos liver. Despite this hypo-responsiveness, intrahepatic Vγ9Vδ2 T-cells are able to exert an anti-HCV activity after specific stimulation. Altogether, our data show that HCV infection induced a dysregulation of intrahepatic Vγ9Vδ2 T cells that maintain their anti-HCV activity after specific stimulation. A study aimed to evaluate the mechanisms of the antiviral activity may be useful to identify new pathways able to improve Vγ9Vδ2 T-cells intrahepatic function during HCV infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Transcriptomic assay of CD8+ T cells in treatment-naïve 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.

  10. Detection of hepatitis C virus RNA in saliva samples from patients with seric anti-HCV antibodies

    Directory of Open Access Journals (Sweden)

    Patrícia L. Gonçalves

    Full Text Available We examined the frequency of HCV-RNA in saliva samples from anti-HCV positive patients. Both plasma and saliva samples from 39 HCV patients (13 with normal liver enzymes, 19 with abnormal liver enzymes and 13 with cirrhosis were investigated. Stimulated saliva and fresh plasma were centrifuged (900 x g,10 min and stored at -70ºC, after the addition of guanidine isothiocyanate RNA extraction buffer. HCV-RNA was detected by RT- nested-PCR (amplification of HCV-cDNA for two rounds, using HCV primers 939/209 and 940/211. HCV genotyping was carried out by RFLP (using Mva I and Hinf 1 or Hae III and Rsa I restriction enzymes. Thirty-two out of 39 (82%; 95% CI=70-94% anti-HCV-positive patients had HCV-RNA in plasma samples. Eight out of 39 (20.5%; 95% CI=6.6-34.4% had HCV-RNA in the saliva. The HCV genotype in saliva samples from these patients matched the genotype found for plasma HCV-RNA. No significant correlation between the presence of HCV and either age, gender, HCV genotype or any risk factor for HCV infection was found. The observed prevalence (20.5% of anti HCV positive patients or 25% of the patients with HCV-RNA in plasma was lower than that previously reported from other countries. The low frequency of HCV-RNA in saliva samples observed in our study may be due to the use of cell-free saliva. Other authors reporting higher frequencies of HCV-RNA in saliva used whole saliva, without centrifugation.

  11. Sofosbuvir and Ledipasvir for 8 Weeks for the Treatment of Chronic Hepatitis C Virus (HCV) Infection in HCV-Monoinfected and HIV-HCV-Coinfected Individuals: Results From the German Hepatitis C Cohort (GECCO-01).

    Science.gov (United States)

    Ingiliz, Patrick; Christensen, Stefan; Kimhofer, Torben; Hueppe, Dietrich; Lutz, Thomas; Schewe, Knud; Busch, Heiner; Schmutz, Günther; Wehmeyer, Malte H; Boesecke, Christoph; Simon, Karl-Georg; Berger, Florian; Rockstroh, Jürgen K; Schulze zur Wiesch, Julian; Baumgarten, Axel; Mauss, Stefan

    2016-11-15

    Shortening the duration of treatment with HCV direct-acting antivirals (DAAs) leads to substantial cost reductions. According to the label, sofosbuvir and ledipasvir can be prescribed for 8 weeks (SL8) in noncirrhotic women or men with HCV genotype 1 and low viral loads. However, real-world data about the efficacy and safety of SL8 are largely missing. Interim results from an ongoing prospective, multicenter cohort of 9 treatment centers in Germany (GECCO). All patients started on treatment with HCV DAAs since January 2014 were included. This report describes safety and efficacy outcomes in 210 patients with HCV monoinfection and 35 with human immunodeficiency virus (HIV)-HCV coinfection given SL8 in a real-world setting. Of 1353 patients included into the GECCO cohort until December 2015, a total of 1287 had complete data sets for this analysis; 337 (26.2%) fulfilled the criteria for SL8 according to the package insert, but only 193 (57.2%) were eventually treated for 8 weeks. Another 52 patients did not fulfill the criteria but were treated for 8 weeks. SL8 was generally well tolerated. The overall sustained virologic response rate 12 weeks after the end of treatment was 93.5% (186 of 199). The on-treatment response rate was 99.4% (159 of 160) in HCV-monoinfected and 96.4% (27 of 28) in HIV-HCV-coinfected patients. Ten patients were lost to follow-up. SL8 seems highly effective and safe in well-selected HCV-monoinfected and HIV-HCV-coinfected patients in a real-world setting. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  12. Sofosbuvir and ledipasvir for HIV/HCV co-infected patients.

    Science.gov (United States)

    Rosenthal, Elana S; Kottilil, Shyam; Polis, Michael A

    2016-01-01

    Hepatitis C virus (HCV) is a chronic infection that disproportionately impacts people living with HIV. In the past, HCV therapy was less effective in individuals with HIV co-infection. However, the advent of direct-acting antivirals has revolutionized HCV treatment with high rates of success in patients both with and without HIV. In this paper, we review the evidence supporting the use of ledipasvir and sofosbuvir (LDV/SOF) for the treatment of HCV in patients with HIV co-infection. Articles searchable on MEDLINE/PubMed were reviewed to provide context for use of LDV/SOF in individuals with HCV and HIV co-infection. This treatment is highly effective in achieving HCV cure or sustained virologic response, however further studies need to done to address efficacy of treatment in people with uncontrolled HIV, concerns regarding drug-interactions with antiretroviral therapy, and potential for shorter duration treatment.

  13. 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...

  14. Should HCV discordant couples with a seropositive male partner be treated with assisted reproduction techniques (ART)?

    Science.gov (United States)

    Savasi, Valeria; Oneta, Monica; Parrilla, Bina; Cetin, Irene

    2013-04-01

    The debate on HCV discordant couples requiring assisted reproduction is still open today, and specific guidelines have not yet been established on whether or not physicians should treat HCV discordant couples who require ART. We studied the results of our reproductive assistance with sperm washing in HCV discordant couples, all treated in a single center, including the serological status of mothers and babies, and the outcome of the pregnancies. Prospective study conducted between January 2008 and December 2010 in our Reproductive Center in Sacco Hospital, University of Milan. Thirty-five HCV serodiscordant infertile couples with an HCV viremic positive male partner were enrolled. All of them completed the immuno-virological and fertility triage, and were treated according to our clinical protocols. Forty-seven superovulation and IUI and 38 second-level ART procedures are reported. The pregnancy rates for IUI and ICSI are similar to those reported by the Italian ART register. All the 85 sperm samples were treated with sperm washing technique to reduce HCV in semen and the possible risk of transmission. We did not observe any preterm delivery or negative perinatal outcome. No mothers or babies are infected by HCV. This is the biggest prospective study conducted in a single center involving HCV discordant infertile couples in an ART program. Although sexual transmission of HCV is very low, in subfertile or infertile couples sperm washing should be used to treat HCV positive semen before ART. We suggest that it is not necessary to perform nested PCR to detect HCV RNA in the final swim-up. Since the presence of HCV in semen implies a possible risk of nosocomial contamination, safety regulations must be strictly applied in assisted reproduction laboratories. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. The antiviral protein viperin inhibits HCV replication via interaction with NS5A

    OpenAIRE

    Helbig, Karla J.; Nicholas S Eyre; Yip, Evelyn; Narayana, Sumudu; Li, Kui; Fiches, Guillaume; McCartney, Erin M; Jangra, Rohit K.; Lemon, Stanley M.; Beard, Michael R.

    2011-01-01

    The interferon-stimulated gene viperin has been shown to have antiviral activity against hepatitis C virus (HCV) in the context of the HCV replicon, although the molecular mechanisms responsible are not well understood. Here we demonstrate that viperin plays an integral part in the ability of interferon to limit replication of cell culture derived HCV (JFH-1) that accurately reflects the complete viral life cycle. Using confocal microscopy and Fluorescence Resonance Energy Transfer (FRET) ana...

  16. Prevalence of HBV and HCV Infections and Associated Risk Factors in Addict Prisoners

    OpenAIRE

    AA Javadi; M Avijgan; M Hafizi

    2006-01-01

    High prevalence of HBV and HCV infections in prisoners suggests them as one of the main infection source in community. Preventive measures can possibly decrease their rate of infection and infectivity. We evaluated prevalence of HBV and HCV infections and their relation to dangerous behavior in addict prisoners. This was a cross-sectional study included prisoners of central provinces of Iran who were evaluated for HBV and HCV in 2003. All of 1431 prisoners filled out questionnaires that were ...

  17. Prevalence and characteristics of HIV/HBV and HIV/HCV coinfections in Tuscany

    Directory of Open Access Journals (Sweden)

    Monia Puglia

    2016-07-01

    Conclusions: We have observed less advanced disease in HIV and HCV-HIV patients compared with HBV–HIV coinfected patients. Moreover, our results show a higher prevalence of HIV/HCV among drug addicts and in the age-group 35–59, corresponding to those born in years considered most at risk for addiction. This study also confirms the finding of a less advanced HIV disease in HIV/HCV coinfected patients.

  18. HCV infection enhances Th17 commitment, which could affect the pathogenesis of autoimmune diseases.

    Directory of Open Access Journals (Sweden)

    Yasuteru Kondo

    Full Text Available Various kinds of autoimmune diseases have been reported to have a significant relationship with persistent hepatitis c virus (HCV infection and Th17 cells. Previously, our group reported that the existence of HCV in T lymphocytes could affect the development of CD4+ helper T cells and their proliferation, in addition to the induction of immunoglobulin hyper-mutation.Therefore, we analyzed the relationship between persistent infection of HCV and the mechanism of Th17 cell induction ex vivo and in vitro.The prevalence of autoimmune-related diseases in chronic hepatitis c patients (CH-C was significantly higher than in other types of chronic hepatitis (hepatitis B and NASH. A significantly higher frequency of IL6 and TGF-β double-high patients was detected in CH-C than in other liver diseases. Moreover, these double-high patients had significantly higher positivity of anti-nuclear antibody, cryoglobulinemia, and lymphotropic HCV and higher amounts of IL1-β, IL21, IL23. In addition to the previously reported lymphotropic SB-HCV strain, we found a novel, genotype 1b lymphotropic HCV (Ly-HCV, by deep sequencing analysis. Lymphotropic-HCV replication could be detected in the lymphoid cells with various kinds of cytokine-conditions including IL1β, IL23, IL6 and TGF-β in vitro. Infection by HCV could significantly enhance the development of Th17 cells. The HCV protein responsible for inducing the Th17 cells was HCV-Core protein, which could enhance the STAT-3 signaling and up-regulate the expression of RORγt as a Th17 master gene.Infection by lymphotropic HCV might enhance the Th17 development and contribute to understanding the pathogenesis of autoimmune-related diseases.

  19. HCV infection enhances Th17 commitment, which could affect the pathogenesis of autoimmune diseases.

    Science.gov (United States)

    Kondo, Yasuteru; Ninomiya, Masashi; Kimura, Osamu; Machida, Keigo; Funayama, Ryo; Nagashima, Takeshi; Kobayashi, Koju; Kakazu, Eiji; Kato, Takanobu; Nakayama, Keiko; Lai, Michael M C; Shimosegawa, Tooru

    2014-01-01

    Various kinds of autoimmune diseases have been reported to have a significant relationship with persistent hepatitis c virus (HCV) infection and Th17 cells. Previously, our group reported that the existence of HCV in T lymphocytes could affect the development of CD4+ helper T cells and their proliferation, in addition to the induction of immunoglobulin hyper-mutation. Therefore, we analyzed the relationship between persistent infection of HCV and the mechanism of Th17 cell induction ex vivo and in vitro. The prevalence of autoimmune-related diseases in chronic hepatitis c patients (CH-C) was significantly higher than in other types of chronic hepatitis (hepatitis B and NASH). A significantly higher frequency of IL6 and TGF-β double-high patients was detected in CH-C than in other liver diseases. Moreover, these double-high patients had significantly higher positivity of anti-nuclear antibody, cryoglobulinemia, and lymphotropic HCV and higher amounts of IL1-β, IL21, IL23. In addition to the previously reported lymphotropic SB-HCV strain, we found a novel, genotype 1b lymphotropic HCV (Ly-HCV), by deep sequencing analysis. Lymphotropic-HCV replication could be detected in the lymphoid cells with various kinds of cytokine-conditions including IL1β, IL23, IL6 and TGF-β in vitro. Infection by HCV could significantly enhance the development of Th17 cells. The HCV protein responsible for inducing the Th17 cells was HCV-Core protein, which could enhance the STAT-3 signaling and up-regulate the expression of RORγt as a Th17 master gene. Infection by lymphotropic HCV might enhance the Th17 development and contribute to understanding the pathogenesis of autoimmune-related diseases.

  20. Recent trends of Japanese hepatocellular carcinoma due to HCV in aging society.

    Science.gov (United States)

    Hiraoka, Atsushi; Hidaka, Satoshi; Shimizu, Yukou; Utsunomiya, Hiroki; Imai, Yusuke; Tatsukawa, Haruka; Tazuya, Nayu; Yamago, Hiroka; Yorimitsu, Nobukazu; Tanihira, Tetsuya; Hasebe, Aki; Miyamoto, Yasunao; Ninomiya, Tomoyuki; Kawasaki, Hideki; Hirooka, Masashi; Abe, Masanori; Hiasa, Yoichi; Matsuura, Bunzo; Onji, Morikazu; Michitaka, Kojiro

    2012-09-01

    The mean age of hepatocellular carcinoma (HCC) patients has increased (=65 years old). We want to identify the recent trend of the clinical features of HCC patients due to hepatitis C virus (HCV) (HCV-HCC). From 2000 to 2009, 855 naive HCC patients were admitted. HCV-HCC patients were divided into two groups, first period group (2000-04, n=270) and second period group (2005-09, n=343) and the clinical features of HCV-HCC were investigated. There was no difference in gender, TNM stage and percentages of HCV-HCC between the periods. On the other hand, the ratio of HCV-HCC patients with worse liver function (Child-Pugh B or C), elderly (=75 years old) and the population of patients treated with low invasive radiofrequency ablation were increased (30.0% to 42.0%, 17.2% to 35.8% and 25.1% to 36.2%, respectively; paged HCV-HCC as well as HCV-HCC patients with worse liver function was increased. The less invasive treatment for HCC in these patients and the quick anti-viral treatment for HCV patients should be considered to avoid occurrence of HCC in Japan.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Structural basis of hepatitis C virus neutralization by broadly neutralizing antibody HCV1

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Leopold; Giang, Erick; Robbins, Justin B.; Stanfield, Robyn L.; Burton, Dennis R.; Wilson, Ian A.; Law, Mansun (Scripps)

    2012-10-29

    Hepatitis C virus (HCV) infects more than 2% of the global population and is a leading cause of liver cirrhosis, hepatocellular carcinoma, and end-stage liver diseases. Circulating HCV is genetically diverse, and therefore a broadly effective vaccine must target conserved T- and B-cell epitopes of the virus. Human mAb HCV1 has broad neutralizing activity against HCV isolates from at least four major genotypes and protects in the chimpanzee model from primary HCV challenge. The antibody targets a conserved antigenic site (residues 412-423) on the virus E2 envelope glycoprotein. Two crystal structures of HCV1 Fab in complex with an epitope peptide at 1.8-{angstrom} resolution reveal that the epitope is a {beta}-hairpin displaying a hydrophilic face and a hydrophobic face on opposing sides of the hairpin. The antibody predominantly interacts with E2 residues Leu{sup 413} and Trp{sup 420} on the hydrophobic face of the epitope, thus providing an explanation for how HCV isolates bearing mutations at Asn{sup 415} on the same binding face escape neutralization by this antibody. The results provide structural information for a neutralizing epitope on the HCV E2 glycoprotein and should help guide rational design of HCV immunogens to elicit similar broadly neutralizing antibodies through vaccination.

  3. 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.

  4. Association of HCV with diabetes mellitus: an Egyptian case-control study

    Directory of Open Access Journals (Sweden)

    Esmat Gamal G

    2011-07-01

    Full Text Available Abstract Background The highest Hepatitis C Virus (HCV prevalence in the world occurs in Egypt. Several studies from different parts of the world have found that 13% to 33% of patients with chronic HCV have associated diabetes, mostly type II Diabetes Mellitus (DM. In Egypt the prevalence of DM is 25.4% among HCV patients. Therefore, it is important to identify the magnitude of the problem of diabetes in order to optimize the treatment of chronic hepatitis C. Methods The objective of this case-control study was to evaluate the prevalence of DM and other extrahepatic (EH manifestations among patients with different HCV morbidity stages including asymptomatic, chronic hepatic and cirrhotic patients. In this study, 289 HCV patients older than 18 were selected as cases. Also, 289 healthy controls were included. Laboratory investigations including Liver Function tests (LFT and blood glucose level were done. Also serological assays including cryoglobulin profile, rheumatoid factor, antinuclear antibody, HCV-PCR were performed. Results Out of 289 HCV cases, 40 (13.84% were diabetic. Out of 289 healthy controls, 12 (4.15% were diabetic. It was found that the diabetic HCV group mean age was [48.1 (± 9.2]. Males and urbanians represented 72.5% and 85% respectively. Lower level of education was manifested in 52.5% and 87.5% were married. In the nondiabetic HCV group mean age was [40.7 (± 10.4]. Males and urbanians represented 71.5% and 655% respectively. secondary and higher level of education was attained in 55.4% and 76.7% were married. Comparing between the diabetic HCV group and the non diabetic HCV group, age, residence and alcohol drinking were the only significant factors affecting the incidence of diabetes between the two groups. There was no significant difference regarding sonar findings although cirrhosis was more prevalent among diabetic HCV cases and the fibrosis score was higher in diabetic HCV patients than among the non diabetic HCV cases

  5. Multicenter evaluation of the Elecsys® anti-HCV II assay for the diagnosis of hepatitis C virus infection.

    Science.gov (United States)

    Esteban, Juan I; van Helden, Josef; Alborino, Flora; Bürgisser, Philippe; Cellerai, Cristina; Pantaleo, Giuseppe; Eiras, Adolfo; Rodriguez, Maria I; Ghisetti, Valeria; Gleich, Michael; Imdahl, Roland; Kaiser, Claudia; Möller, Petra; Wetlitzky, Olaf; Segovia, Manuel; Schennach, Harald; Mühlbacher, Annelies

    2013-08-01

    Routine screening of patients at risk of hepatitis C virus (HCV) infection has become a priority given recent improvements in therapeutic options and the asymptomatic nature of most chronic infections. The aim of this study was to evaluate the performance of the Elecsys® Anti-HCV II assay, a new qualitative antibody immunoassay, compared with currently available assays, and assess its suitability for routine diagnostic testing. The sensitivity of the Elecsys® Anti-HCV II, ARCHITECT® Anti-HCV, AxSYM® HCV 3.0, PRISM® HCV, Vitros® ECi Anti-HCV, Elecsys® Anti-HCV, and ADVIA Centaur® HCV assays was compared using commercially available seroconversion panels and samples from patients known to be HCV positive and infected with HCV genotypes 1-6. Specificity was investigated using samples from blood donors, unselected hospitalized patients, and patients with potential cross-reacting factors or from high-risk groups. The Elecsys® Anti-HCV II assay detected more positive bleeds than the comparator assays, was more sensitive in recognizing early HCV infection, and correctly identified all 765 samples known to be HCV positive, regardless of genotype. The overall specificity of the Elecsys(®) Anti-HCV II assay was 99.84% (n=6,850) using blood donor samples, 99.66% (n=3,922) using samples from unselected hospitalized patients, and 99.66% (n=2,397) using samples from patients with potentially cross-reacting factors or from high-risk groups. The specificity of the Elecsys® Anti-HCV II assay was superior or equal to the comparator assays. In conclusion, the Elecsys® Anti-HCV II assay is a sensitive and specific assay suitable for routine use in the reliable detection of anti-HCV antibodies. Copyright © 2013 Wiley Periodicals, Inc.

  6. Prevalence and impact of GBV-C, SEN-V and HBV occult infections in HIV-HCV co-infected patients on HCV therapy.

    Science.gov (United States)

    Piroth, Lionel; Carrat, Fabrice; Larrat, Sylvie; Goderel, Isabelle; Martha, Benoit; Payan, Christopher; Lunel-Fabiani, Françoise; Bani-Sadr, Firouze; Perronne, Christian; Cacoub, Patrice; Pol, Stanislas; Morand, Patrice

    2008-12-01

    It has been suggested that, in HIV-HCV co-infected patients, co-infections with other viruses may affect the response to HCV therapy. We aimed to assess the prevalence of GBV-C, SEN-V and occult HBV infections, their impact on HCV and HIV infections and on the response to HCV therapy in HIV-HCV co-infected patients. Three-hundred and sixty eight patients were tested before starting interferon-ribavirin for the presence of occult hepatitis B DNA, GBV-C RNA and SEN-V DNA by using real time PCR. Clinical, immunological, virological, histological characteristics and response to HCV therapy were compared according to the presence or not of each viral co-infection. HBV DNA, GBV-C RNA and SEN-V DNA were found in 5 (1.4%, CI95%: 0.2-2.4%), 104 (29.9%, CI95%: 25.1-34.7%) and 209 patients (57.9%, CI95%: 52.8-63.0%), respectively. GBV-C positive patients had significantly higher CD4 count at baseline, during and after HCV therapy, even after stratification on antiretroviral treatment. No other significant difference was observed according to the presence or not of GBV-C or SEN-V co-infection, in particular regarding virological responses to HCV combination therapy. There is no reason to withhold HCV therapy in HIV infected patients who have access to HAART, because of occult HBV, GBV-C or SEN-V co-infections.

  7. 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

  8. Prevention of HCV infection using a broad cross-neutralizing monoclonal antibody (AR4A) and Epigallocatechin-Gallate

    OpenAIRE

    O'Shea, D.; Law, J.; Egli, A.; Douglas, D.; Lund, G; Forester, S; Lambert, J.; Law, M; Burton, D R; Tyrrell, D. L. J.; Houghton, M; Humar, A; Kneteman, N.

    2016-01-01

    The anti-HCV activity of a novel monoclonal antibody (mAb; AR4A) and Epigallocatechin-gallate (EGCG) were studied in-vitro using an HCV cell culture system and in-vivo using a humanized liver mouse model capable of supporting HCV replication. Alone, both exhibit reliable cross-genotype HCV inhibition in-vitro, and combination therapy completely prevented HCV infection. In-vivo AR4A mAb (alone and combined with EGCG) robustly protects against the establishment of HCV genotype 1a infection. EGC...

  9. Daclatasvir Plus Asunaprevir for Chronic HCV Genotype 1b Infection

    Science.gov (United States)

    Kumada, Hiromitsu; Suzuki, Yoshiyuki; Ikeda, Kenji; Toyota, Joji; Karino, Yoshiyasu; Chayama, Kazuaki; Kawakami, Yoshiiku; Ido, Akio; Yamamoto, Kazuhide; Takaguchi, Koichi; Izumi, Namiki; Koike, Kazuhiko; Takehara, Tetsuo; Kawada, Norifumi; Sata, Michio; Miyagoshi, Hidetaka; Eley, Timothy; McPhee, Fiona; Damokosh, Andrew; Ishikawa, Hiroki; Hughes, Eric

    2014-01-01

    All-oral combinations of direct-acting antivirals may improve efficacy and safety outcomes for patients with hepatitis C virus (HCV) infection, particularly those who are poor candidates for current interferon/ribavirin-based regimens. In this open-label, phase 3 study, 135 interferon-ineligible/intolerant and 87 nonresponder patients with chronic HCV genotype 1b infection were enrolled at 24 centers in Japan. Patients received daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily for 24 weeks. The primary endpoint was sustained virologic response 24 weeks after treatment (SVR24). This study is registered with http://ClinicalTrials.gov (NCT01497834). SVR24 was achieved by 87.4% of interferon-ineligible/intolerant patients and 80.5% of nonresponder (null and partial) patients; rates were similar in cirrhosis (90.9%) and noncirrhosis (84.0%) patients, and in patients with IL28B CC (84.5%) or non-CC (84.8%) genotypes. Fourteen patients in each group (12.6%) discontinued dual therapy, mainly due to adverse events or lack of efficacy. Nine nonresponder patients received additional treatment with peginterferon/ribavirin per protocol-defined criteria. The rate of serious adverse events was low (5.9%) and varied among patients. The most common adverse events were nasopharyngitis, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST), headache, diarrhea, and pyrexia. Conclusion: Interferon-free, ribavirin-free all-oral therapy with daclatasvir and asunaprevir for 24 weeks is well tolerated and can achieve a high rate of SVR in patients with HCV genotype 1b who were ineligible, intolerant, or had not responded to prior interferon-based therapy. (Hepatology 2014;59:2083–2091) PMID:24604476

  10. [siRNAs targeting La, hVAP-33, eIF2Bgamma, and HCV IRES inhibit the replication and expression of HCV in Huh7 cells].

    Science.gov (United States)

    Wang, Mei-xia; Xu, Bin; Duan, Jin; Fu, Xiao-qing; Jin, Ming

    2012-10-01

    To investigate the in vivo functional roles of the La autoantigen (La), the human homologue of the 33-kDa vesicle-associated membrane protein-associated protein (hVAP-33), and the subunit gamma of the human eukaryotic initiation factors 2B (eIF2Bgamma) as co-infection factors supporting chronic infection with hepatitis C virus (HCV). Small interfering (si)RNAs were designed against the HCV internal ribosome entry site (IRES) and transfected into Huh7 cells chronically infected with the HCV pseudovirus (designated as Huh7-HCV cells). The IRES siRNA producing the most effective silencing was selected for further analysis by fluorescence quantitative polymerase chain reaction (qPCR). siRNAs designed against La, hVAP-33, and eIF2Bgamma and the IRES-specific siRNA were then transfected, respectively or in various combinations, into the Huh7-HCV cell line for 48 h. The delta CT values were calculated and used to compare the HCV inhibitive efficacies of the siRNAs in isolation or in combination. Western blotting analysis was used to compare the quantity of core protein expression in each group. The four gene-specific siRNAs, in isolation or in combination, caused inhibition of HCV replication and gene and protein expressions to varying degrees. The combination of La + IRES siRNAs produced the strongest inhibition of HCV core antigen expression. The combinations of hVAP-33 + IRES siRNAs and eIF2Bgamma + IRES siRNAs produced stronger inhibitions of HCV replication and gene and protein expressions than either hVAP-33 siRNA or eIF2Bgamma siRNA alone. La, hVAP-33, and eIF2Bgamma act as co-infection factors of HCV chronic infection in vivo. HCV replication and gene and protein expression can be inhibited significantly by RNA interference of these co-infection factors and/or HCV IRES.

  11. Metabolic and Cardiovascular Complications in HIV/HCV-Co-infected Patients.

    Science.gov (United States)

    Bedimo, Roger; Abodunde, Oladapo

    2016-12-01

    Fifteen to thirty percent of HIV-infected persons in North America and Europe are co-infected with chronic hepatitis C (HCV). The latter is associated with a significant number of extra-hepatic metabolic complications that could compound HIV-associated increased cardiovascular risk. This article reviews the basic science and epidemiologic and clinical evidence for increased cardio-metabolic risk among HIV/HCV-co-infected patients and discusses potential underlying mechanisms. We will finally review the impact of control of HCV viremia on the cardio-metabolic morbidity and mortality of HIV/HCV-co-infected patients. HCV infection is associated with a number of immune-related complications such as cryoglobulinemia but also metabolic complications including dyslipidemias, hepatic steatosis, insulin resistance, diabetes, and chronic kidney disease. The incidence of these complications is higher among HIV-co-infected patients and might contribute to increased mortality. The potential mechanisms of increased cardiovascular risk among HIV/HCV-co-infected subjects include endothelial dysfunction, chronic inflammation and immune activation, the cardio-metabolic effects of HCV-induced hepatic steatosis and fibrosis or insulin resistance, and chronic kidney disease. However, epidemiologic studies show discordant findings as to whether HCV co-infection further increases the risk of atherosclerotic cardiovascular diseases (acute myocardial infarctions and strokes) among HIV-infected patients. Nonetheless, successful treatment of HCV is associated with significant improvements in cardio-metabolic risk factors including diabetes mellitus. HCV co-infection is associated with a higher incidence of metabolic complications-and likely increased risk of cardiovascular events-that might contribute to increased mortality in HIV. These appear to improve with successful HCV therapy.

  12. HCV antibody quantitative levels in liver transplant patients: do they have any relevance in clinical practice?

    Science.gov (United States)

    Jain, Ashok; Menegus, Marilyn; Mohanka, Ravi; Orloff, Mark; Abt, Peter; Mantry, Parvez; Bozorgzadeh, Adel

    2006-06-01

    Hepatitis C virus (HCV) is not directly cytopathic to the hepatocytes; however, host immune response against the virus does cause hepatic injury. Production of the HCV antibody is a host immune response to a viral antigen. The currently used HCV antibody assay is a qualitative, not quantitative, assessment. In this study, we sought to quantitatively estimate HCV antibody levels in patients who had undergone liver transplantations at the University of Rochester Medical Center, Rochester, New York, and correlate these levels with HCV RNA viral load, genotype, severity of recurrence, and anti-HCV treatment. From 39 liver transplantation patients, we obtained 141 blood samples for quantitative HCV RNA to measure HCV antibody levels quantitatively. Most antibody levels were within a narrow range with a mean of 32.9+/-5.1. Samples with undetectable RNA had a mean antibody level of 31.4+/-8.0, and samples with a positive RNA had mean level of 33.0+/-4.6. The mean antibody levels were significantly higher for patients with genotype 1 (n=33) compared with those with genotype 2 (n=5) (33.2 vs 29.1; P=.007). No correlation was found between antibody levels and severity of hepatic injury with regard to hepatitis activity index or fibrosis score. Six patients with no response to anti-HCV treatment had no change in their mean antibody levels (33.7 vs 34.5). Ten patients who responded to anti-HCV therapy had lower mean levels after therapy, but the changes were not significant (34.2 vs 30.4). Antibody levels in this study did not correlate with viral load or hepatic injury. However, genotype-2 patients had significantly lower levels compared with genotype-1 patients, and patients who responded to anti-HCV therapy demonstrated decreased antibody levels.

  13. Prevalence of natural polymorphisms at the HCV NS5A gene associated with resistance to daclatasvir, an NS5A inhibitor.

    Science.gov (United States)

    Plaza, Zulema; Soriano, Vincent; Vispo, Eugenia; del Mar Gonzalez, Maria; Barreiro, Pablo; Seclén, Eduardo; Poveda, Eva

    2012-01-01

    Daclatasvir (BMS-790052) is an investigational molecule that inhibits the HCV NS5A protein and shows potent antiviral activity apparently across all HCV genotypes. Selection of drug resistance mutations has been reported only for HCV genotype 1, and no information exists for other HCV variants and/or in HIV-HCV-coinfected individuals. All interferon-α-naive, HIV-HCV-coinfected patients newly attended at Hospital Carlos III (Madrid, Spain) in 2011 were identified. Changes reported to be associated with daclatasvir resistance in the in vitro replication system for HCV genotype/subtypes 1a/1b (M28T, Q30H/R, L31F/M/V, P32L and Y93C/H/N) were examined. A total of 78 HIV-HCV-coinfected individuals as well as 635 NS5A sequences deposited at Los Alamos HCV database were analysed. None of the NS5A sequences from HCV-1a or HCV-3 showed changes associated with daclatasvir resistance. By contrast, all NS5A sequences from HCV-4 harboured L31M. The double mutant L31M+Y93H was found in 7% of HCV-1b and 13% of HCV-4. Finally, all NS5A sequences from HCV-1b and HCV-4 harboured changes at codon 28 (M28L) and 30 (L30R), which are of unknown significance. The rate of all these NS5A polymorphisms did not differ significantly when comparing HIV-HCV-coinfected patients and sequences from HCV-monoinfected subjects deposited at Los Alamos HCV database. Primary resistance mutations to daclatasvir, an investigational HCV NS5A inhibitor, are not seen in HCV-1a or in HCV-3 as natural polymorphisms. By contrast, they can be recognized in most HCV-1b and HCV-4 strains, regardless HIV coinfection.

  14. Discovery of SCH446211 (SCH6): A New Ketoamide Inhibitor of the HCV NS3 Serine Protease and HCV Subgenomic RNA Replication

    Energy Technology Data Exchange (ETDEWEB)

    Bogen, Stephane L.; Arasappan, Ashok; Bennett, Frank; Chen, Kevin; Jao, Edwin; Liu, Yi-Tsung; Lovey, Raymond G.; Venkatraman, Srikanth; Pan, Weidong; Parekh, Tajel; Pike, Russel E.; Ruan, Sumei; Liu, Rong; Baroudy, Bahige; Agrawal, Sony; Chase, Robert; Ingravallo, Paul; Pichardo, John; Prongay, Andrew; Brisson, Jean-Marc; Hsieh, Tony Y.; Cheng, Kuo-Chi; Kemp, Scott J.; Levy, Odile E.; Lim-Wilby, Marguerita; Tamura, Susan Y.; Saksena, Anil K.; Girijavallabhan, Viyyoor; Njoroge, F. George (SPRI)

    2008-06-30

    Introduction of various modified prolines at P{sub 2} and optimization of the P{sub 1} side chain led to the discovery of SCH6 (24, Table 2), a potent ketoamide inhibitor of the HCV NS3 serine protease. In addition to excellent enzyme potency (K*{sub i} = 3.8 nM), 24 was also found to be a potent inhibitor of HCV subgenomic RNA replication with IC{sub 50} and IC{sub 90} of 40 and 100 nM, respectively. Recently, antiviral activity of 24 was demonstrated with inhibition of the full-length genotype 2a HCV genome. In addition, 24 was found to restore the responsiveness of the interferon regulatory factor 3 (IRF-3) in cells containing HCV RNA replicons.

  15. Discovery of SCH446211 (SCH6): a new ketoamide inhibitor of the HCV NS3 serine protease and HCV subgenomic RNA replication.

    Science.gov (United States)

    Bogen, Stéphane L; Arasappan, Ashok; Bennett, Frank; Chen, Kevin; Jao, Edwin; Liu, Yi-Tsung; Lovey, Raymond G; Venkatraman, Srikanth; Pan, Weidong; Parekh, Tajel; Pike, Russel E; Ruan, Sumei; Liu, Rong; Baroudy, Bahige; Agrawal, Sony; Chase, Robert; Ingravallo, Paul; Pichardo, John; Prongay, Andrew; Brisson, Jean-Marc; Hsieh, Tony Y; Cheng, Kuo-Chi; Kemp, Scott J; Levy, Odile E; Lim-Wilby, Marguerita; Tamura, Susan Y; Saksena, Anil K; Girijavallabhan, Viyyoor; Njoroge, F George

    2006-05-04

    Introduction of various modified prolines at P(2) and optimization of the P(1) side chain led to the discovery of SCH6 (24, Table 2), a potent ketoamide inhibitor of the HCV NS3 serine protease. In addition to excellent enzyme potency (K(i)*= 3.8 nM), 24 was also found to be a potent inhibitor of HCV subgenomic RNA replication with IC(50) and IC(90) of 40 and 100 nM, respectively. Recently, antiviral activity of 24 was demonstrated with inhibition of the full-length genotype 2a HCV genome. In addition, 24 was found to restore the responsiveness of the interferon regulatory factor 3 (IRF-3) in cells containing HCV RNA replicons.

  16. 77 FR 30293 - Recommendations for the Identification of Hepatitis C Virus (HCV) Chronic Infection

    Science.gov (United States)

    2012-05-22

    ... Hepatitis C Virus (HCV) Chronic Infection AGENCY: Centers for Disease Control and Prevention (CDC... an email to [email protected] . SUPPLEMENTARY INFORMATION: Hepatitis C virus infection is a contagious... illness. It results from infection with the hepatitis C virus (HCV), which is spread primarily through...

  17. Daclatasvir plus Asunaprevir Treatment for Real-World HCV Genotype 1-Infected Patients in Japan.

    Science.gov (United States)

    Kanda, Tatsuo; Yasui, Shin; Nakamura, Masato; Suzuki, Eiichiro; Arai, Makoto; Haga, Yuki; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Imazeki, Fumio; Yokosuka, Osamu

    2016-01-01

    Background. All-oral combination of direct-acting antivirals could lead to higher sustained virologic response (SVR) in hepatitis C virus (HCV)-infected patients. In the present study, we examined the efficacy and safety of the dual oral treatment with HCV nonstructural protein (NS) 5A inhibitor daclatasvir (DCV) plus HCV NS3/4A inhibitor asunaprevir (ASV) for 24 weeks in real-world HCV genotype 1-infected Japanese individuals. Methods. After screening for HCV NS5A resistance-associated variants (RAVs) by PCR invader assay, a total of 54 Japanese patients infected with HCV genotype 1 treated with DCV plus ASV were retrospectively analyzed. SVR12 was used for evaluation of the virologic response. Results. Of the total 54 patients, 46 patients (85.2%) were treated with DCV plus ASV for 24 weeks and achieved SVR12. The other 8 patients (14.8%) discontinued this treatment before 24 weeks due to adverse events. Of these 8 patients, 5 and 3 patients did and did not achieve SVR12, respectively. Finally, 51 of 54 (94.4%) patients achieved SVR12. Conclusion. Treatment with DCV and ASV after screening for HCV NS5A RAVs by PCR invader assay is effective and safe in the treatment of real-world HCV genotype 1-infected patients in Japan.

  18. 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.

  19. Etiology of hepatitis G virus (HGV) and hepatitis type C virus (HCV ...

    African Journals Online (AJOL)

    Hepatitis G virus (HGV) and hepatitis type C virus (HCV) may implicate malignant lymphoma including non-Hodgkin's lymphoma (NHL) for inducing the proliferative process of lymphocytes. In this study, the molecular and serologic prevalence of HGV and HCV infections was evaluated in patients with NHL and compared ...

  20. Impact of duration of therapy on side effect profile of anti-HCV ...

    African Journals Online (AJOL)

    Purpose: To evaluate the plausible risks and adverse effects related to the duration of therapy in hepatitis C (HCV) patients in Lahore, Pakistan. Method: A retrospective observational study involving 250 HCV patients who received combination therapy with ribavirin and interferon was conducted. The patients were ...

  1. 75 FR 39035 - Housing Choice Voucher (HCV) Family Self-Sufficiency (FSS) Program

    Science.gov (United States)

    2010-07-07

    ... URBAN DEVELOPMENT Housing Choice Voucher (HCV) Family Self-Sufficiency (FSS) Program AGENCY: Office of... independence and self- sufficiency. Housing agencies consult with local officials to develop an Action Plan... Title of Proposal: Housing Choice Voucher (HCV) Family Self- Sufficiency (FSS) Program. OMB Approval...

  2. Genotyping of HCV RNA Reveals That 3a Is the Most Prevalent Genotype in Mardan, Pakistan

    Directory of Open Access Journals (Sweden)

    Sajid Ali

    2014-01-01

    Full Text Available The clinical outcomes of patients infected with hepatitis C virus (HCV range from acute resolving hepatitis to chronic liver diseases such as liver cirrhosis or hepatocellular carcinoma. Identification of the infecting virus genotype is indispensable for the exploration of many aspects of HCV infection, including epidemiology, pathogenesis, and response to antiviral therapy. 1419 individuals were screened for anti-HCV in this study, of which 166 (11.7% were found reactive by ICT (Immunochromatographic test. These 166 anti-HCV positive and 26 normal individuals were further analyzed. RNA was extracted from serum and reverse-transcribed to cDNA and the core region of HCV genome was targeted and amplified by multiplex PCR. HCV RNA was detected in 121 individuals, of which 87 were male and 34 were female. Genotype 3a was the most prevalent among all the genotypes observed followed by 3b. Genotypes 1a, 2a, and 2b were found in 10.89%, 13.22%, and 6.61% patients, respectively. 25.41% of the HCV RNA positive samples were not typed. 6.05% of patients were found having mixed genotypes. These findings will not only help the physicians to prescribe more appropriate treatment for the HCV infection but will also draw the attention of health-related policy makers to devise strategies to curb the disease more effectively.

  3. Toll-like receptor 3-activated macrophages confer anti-HCV activity to hepatocytes through exosomes.

    Science.gov (United States)

    Zhou, Yu; Wang, Xu; Sun, Li; Zhou, Li; Ma, Tong-Cui; Song, Li; Wu, Jian-Guo; Li, Jie-Liang; Ho, Wen-Zhe

    2016-12-01

    Exosomes are a class of cell-released small vesicles that mediate intercellular communication by delivering functional factors to recipient cells. During hepatitis C virus (HCV) infection, the interaction between liver resident macrophages and hepatocytes is a key component in liver innate immunity. In this study, we explored the role of exosomes in the delivery of innate anti-HCV factors to hepatocytes from macrophages. We showed that supernatant from TLR3-activated macrophage cultures could efficiently inhibit HCV replication in Huh7 cells. This macrophage-mediated anti-HCV activity was through exosomes because inhibiting exosomes could abrogate the action of macrophages. Further analyses demonstrated that TLR3-activated macrophages release exosomes that contain anti-HCV microRNA (miRNA)-29 family members. Inhibiting miRNA29 could restore HCV replication. These findings suggest a novel antiviral mechanism in liver innate immunity against HCV infection and provide insights to support further studies on developing exosome-based delivery system for disease treatment.-Zhou, Y., Wang, X., Sun, L., Zhou, L., Ma, T.-C., Song, L., Wu, J.-G., Li, J.-L., Ho, W.-Z. Toll-like receptor 3-activated macrophages confer anti-HCV activity to hepatocytes through exosomes. © FASEB.

  4. Genotypes of HBV and HCV among HIV-1 co-infected individuals in ...

    African Journals Online (AJOL)

    Background: Hepatitis B and Hepatitis C viruses are the major causes of liver disease worldwide. Co-infections with HBV and HCV have turned out to be increasingly very common among people living with HIV, leading to a major public health concern. Objective: To determine HBV and HCV diversity among HIV infected ...

  5. Matched and mixed cap derivatives in the tetracyclic indole class of HCV NS5A inhibitors.

    Science.gov (United States)

    Dwyer, Michael P; Keertikar, Kerry M; Chen, Lei; Tong, Ling; Selyutin, Oleg; Nair, Anilkumar G; Yu, Wensheng; Zhou, Guowei; Lavey, Brian J; Yang, De-Yi; Wong, Michael; Kim, Seong Heon; Coburn, Craig A; Rosenblum, Stuart B; Zeng, Qingbei; Jiang, Yueheng; Shankar, Bandarpalle B; Rizvi, Razia; Nomeir, Amin A; Liu, Rong; Agrawal, Sony; Xia, Ellen; Kong, Rong; Zhai, Ying; Ingravallo, Paul; Asante-Appiah, Ernest; Kozlowski, Joseph A

    2016-08-15

    A matched and mixed capping SAR study was conducted on the tetracyclic indole class of HCV NS5A inhibitors to examine the influence of modifications of this region on the overall HCV virologic resistance profiles. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    NARCIS (Netherlands)

    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

  7. Determinants of persistent spread of HIV in HCV-infected populations of injecting drug users

    NARCIS (Netherlands)

    de Vos, Anneke S.; van der Helm, Jannie J.; Prins, Maria; Kretzschmar, Mirjam E.

    2012-01-01

    Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are both transmitted through populations of injecting drug users (IDU) by the sharing of contaminated syringes. Prevalence of HCV is high in most IDU populations, whereas HIV prevalence varies considerably across populations.

  8. Risk factors of accelerated liver fibrosis in HIV-HCV coinfection: a ...

    African Journals Online (AJOL)

    An ordinal logistic regression analysis was used to identify risk factors. Results: Using Metavir unit system, the mean (+ standard deviation [SD]) estimated fibrosis rates were 0.26 (+ 0.17) and 0.11 (+ 0.09) for HIV-HCV coinfected and HCV-only patients respectively (unmatched analysis p=0.001). The mean (+ SD) duration ...

  9. Mitochondrial Dysfunctions and Altered Metals Homeostasis: New Weapons to Counteract HCV-Related Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Mario Arciello

    2013-01-01

    Full Text Available The hepatitis C virus (HCV infection produces several pathological effects in host organism through a wide number of molecular/metabolic pathways. Today it is worldwide accepted that oxidative stress actively participates in HCV pathology, even if the antioxidant therapies adopted until now were scarcely effective. HCV causes oxidative stress by a variety of processes, such as activation of prooxidant enzymes, weakening of antioxidant defenses, organelle damage, and metals unbalance. A focal point, in HCV-related oxidative stress onset, is the mitochondrial failure. These organelles, known to be the “power plants” of cells, have a central role in energy production, metabolism, and metals homeostasis, mainly copper and iron. Furthermore, mitochondria are direct viral targets, because many HCV proteins associate with them. They are the main intracellular free radicals producers and targets. Mitochondrial dysfunctions play a key role in the metal imbalance. This event, today overlooked, is involved in oxidative stress exacerbation and may play a role in HCV life cycle. In this review, we summarize the role of mitochondria and metals in HCV-related oxidative stress, highlighting the need to consider their deregulation in the HCV-related liver damage and in the antiviral management of patients.

  10. Angiogenic output in viral hepatitis, C and B, and HCV-associated ...

    African Journals Online (AJOL)

    Mohamed A. Abdel Mohsen

    2014-07-04

    Jul 4, 2014 ... and HCV-associated hepatocellular carcinoma. Mohamed A. Abdel Mohsen a, ... but not significant. Conclusion: The increased hepatic angiogenesis in chronic HCV and HBV could provide the molecular basis for .... On the other hand, HBV encoded proteins as HBx protein which stabilizes and facilitates ...

  11. Molecular signatures associated with HCV-induced hepatocellular carcinoma and liver metastasis.

    Directory of Open Access Journals (Sweden)

    Valeria De Giorgi

    Full Text Available Hepatocellular carcinomas (HCCs are a heterogeneous group of tumors that differ in risk factors and genetic alterations. In Italy, particularly Southern Italy, chronic hepatitis C virus (HCV infection represents the main cause of HCC. Using high-density oligoarrays, we identified consistent differences in gene-expression between HCC and normal liver tissue. Expression patterns in HCC were also readily distinguishable from those associated with liver metastases. To characterize molecular events relevant to hepatocarcinogenesis and identify biomarkers for early HCC detection, gene expression profiling of 71 liver biopsies from HCV-related primary HCC and corresponding HCV-positive non-HCC hepatic tissue, as well as gastrointestinal liver metastases paired with the apparently normal peri-tumoral liver tissue, were compared to 6 liver biopsies from healthy individuals. Characteristic gene signatures were identified when normal tissue was compared with HCV-related primary HCC, corresponding HCV-positive non-HCC as well as gastrointestinal liver metastases. Pathway analysis classified the cellular and biological functions of the genes differentially expressed as related to regulation of gene expression and post-translational modification in HCV-related primary HCC; cellular Growth and Proliferation, and Cell-To-Cell Signaling and Interaction in HCV-related non HCC samples; Cellular Growth and Proliferation and Cell Cycle in metastasis. Also characteristic gene signatures were identified of HCV-HCC progression for early HCC diagnosis.A diagnostic molecular signature complementing conventional pathologic assessment was identified.

  12. A Review of Hepatitis C Virus (HCV) and the Current Management ...

    African Journals Online (AJOL)

    DATONYE ALASIA

    deliveries from HCV infected women . The incidence is higher (14%-17%) in patients co- infected ... from women of childbearing age before initiation of HCV treatment. Women who are pregnant or attempting to ... infection; persons with hemophilia who received clotting factor concentrate prior to 1987, persons who have ...

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Alterations of the NK cell pool in HIV/HCV co-infection.

    Science.gov (United States)

    Kaczmarek, Dominik J; Kokordelis, Pavlos; Krämer, Benjamin; Glässner, Andreas; Wolter, Franziska; Goeser, Felix; Lutz, Philipp; Schwarze-Zander, Carolynne; Boesecke, Christoph; Strassburg, Christian P; Rockstroh, Jürgen K; Spengler, Ulrich; Nattermann, Jacob

    2017-01-01

    A relevant proportion of human immunodeficiency virus (HIV) infected patients is co-infected with the hepatitis C virus (HCV). HCV co-infection in HIV-positive patients is associated with faster progression of liver disease in comparison to HCV mono-infection. Natural killer (NK) cells critically modulate the natural course of HCV infection. Both HIV and HCV mono-infection are associated with alterations of the NK cell pool. However, little data is available concerning phenotype and function of NK cells in HIV/HCV co-infection. A total of 34 HIV/HCV co-infected, 35 HIV and 39 HCV mono-infected patients and 43 healthy control persons were enrolled into this study. All HIV-positive patients were under effective antiretroviral therapy. NK cell phenotype, IFN-γ production and degranulation were studied by flow cytometry. NK cell frequency in HIV/HCV co-infection was significantly lower than in healthy individuals but did not differ from HIV and HCV mono-infection. HIV/HCV co-infection was associated with significantly decreased expression of the maturation/differentiation markers CD27/62L/127 on NK cells but increased expression of CD57 compared to healthy controls. Of note, expression also differed significantly from HCV mono-infection but was similar to HIV mono-infection, suggesting a pronounced impact of HIV on these alterations. Similar findings were made with regard to the NK cell receptors NKG2A/C and NKp30. More importantly, NK cells in co-infection displayed a highly impaired functional activity with significantly lower IFN-γ production and degranulation than in healthy donors as well as HIV and HCV mono-infection, suggesting a synergistic effect of both viruses. Our data indicate that HIV/HCV co-infection is associated with significant alterations of the NK cell pool, which might be involved in the rapid progression of liver disease in co-infected patients and which mainly reflect alterations observed in HIV mono-infection.

  15. Gene profiling, biomarkers and pathways characterizing HCV-related hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Buonaguro Luigi

    2009-10-01

    Full Text Available Abstract Background Hepatitis C virus (HCV infection is a major cause of hepatocellular carcinoma (HCC worldwide. The molecular mechanisms of HCV-induced hepatocarcinogenesis are not yet fully elucidated. Besides indirect effects as tissue inflammation and regeneration, a more direct oncogenic activity of HCV can be postulated leading to an altered expression of cellular genes by early HCV viral proteins. In the present study, a comparison of gene expression patterns has been performed by microarray analysis on liver biopsies from HCV-positive HCC patients and HCV-negative controls. Methods Gene expression profiling of liver tissues has been performed using a high-density microarray containing 36'000 oligos, representing 90% of the human genes. Samples were obtained from 14 patients affected by HCV-related HCC and 7 HCV-negative non-liver-cancer patients, enrolled at INT in Naples. Transcriptional profiles identified in liver biopsies from HCC nodules and paired non-adjacent non-HCC liver tissue of the same HCV-positive patients were compared to those from HCV-negative controls by the Cluster program. The pathway analysis was performed using the BRB-Array- Tools based on the "Ingenuity System Database". Significance threshold of t-test was set at 0.001. Results Significant differences were found between the expression patterns of several genes falling into different metabolic and inflammation/immunity pathways in HCV-related HCC tissues as well as the non-HCC counterpart compared to normal liver tissues. Only few genes were found differentially expressed between HCV-related HCC tissues and paired non-HCC counterpart. Conclusion In this study, informative data on the global gene expression pattern of HCV-related HCC and non-HCC counterpart, as well as on their difference with the one observed in normal liver tissues have been obtained. These results may lead to the identification of specific biomarkers relevant to develop tools for detection

  16. News on HIV-HCV Coinfection: Update From the 2015 GEHEP Conference.

    Science.gov (United States)

    Poveda, Eva; Wyles, David; Morano, Luis; Pineda, Juan Antonio; García, Federico

    2015-01-01

    New therapeutic options for the treatment of HCV infection are highly effective, possess minimal side effects, and allow for a shortened course of therapy, presenting a favorable scenario to treat and cure all patients chronically infected with HCV. However, there are still many challenges to advancement towards HCV eradication, not only related to the cost and the availability of the drugs, but also pertaining to epidemiologic, diagnostic, and treatment issues that remain to be resolved. Advances in the knowledge of all these topics are essential for the optimization of diagnostic and treatment strategies to fight again HCV infection. The latest data presented at the I Conference of the Group for the Study of Viral Hepatitis (GEHEP) (23-26 September, Spain) highlights relevant progress on many of these fronts for an overview of HCV infection at present. This review summarizes some of the major findings presented and discussed during the conference.

  17. Changing HCV genotypes distribution in Poland--relation to source and time of infection.

    Science.gov (United States)

    Chlabicz, Slawomir; Flisiak, Robert; Kowalczuk, Oksana; Grzeszczuk, Anna; Pytel-Krolczuk, Barbara; Prokopowicz, Danuta; Chyczewski, Lech

    2008-06-01

    Understanding the distribution of HCV genotypes has implications for prognosis and therapy of hepatitis C. To describe the distribution of HCV genotypes in Poland in relation to route of transmission and year of infection. Patients with chronic liver disease were evaluated at the Department of Infectious Diseases, Bialystok (Poland). HCV genotype was determined by means of 5'UTR sequencing and comparison with known sequences of particular genotypes. The genotypes mostly frequently detected were genotype 1 (57.5%); genotype 3 (31.3%); and genotype 4 (8.4%). Genotype 1 constituted the majority of HCV infections caused by blood transfusion (68.8%) and only 34.8% of HCV infections in the intravenous drug use (IVDU) group (prelative proportion of genotype 1b in Poland has decreased and that of genotype 3a has increased, especially among IVDU.

  18. Gaining greater insight into HCV emergence in HIV-infected men who have sex with men: the HEPAIG Study.

    Directory of Open Access Journals (Sweden)

    Christine Larsen

    Full Text Available OBJECTIVES: The HEPAIG study was conducted to better understand Hepatitis C virus (HCV transmission among human immuno-deficiency (HIV-infected men who have sex with men (MSM and assess incidence of HCV infection among this population in France. METHODS AND RESULTS: Acute HCV infection defined by anti-HCV or HCV ribonucleic acid (RNA positivity within one year of documented anti-HCV negativity was notified among HIV-infected MSM followed up in HIV/AIDS clinics from a nationwide sampling frame. HIV and HCV infection characteristics, HCV potential exposures and sexual behaviour were collected by the physicians and via self-administered questionnaires. Phylogenetic analysis of the HCV-NS5B region was conducted. HCV incidence was 48/10 000 [95% Confidence Interval (CI:43-54] and 36/10 000 [95% CI: 30-42] in 2006 and 2007, respectively. Among the 80 men enrolled (median age: 40 years, 55% were HIV-diagnosed before 2000, 56% had at least one sexually transmitted infection in the year before HCV diagnosis; 55% were HCV-infected with genotype 4 (15 men in one 4d-cluster, 32.5% with genotype 1 (three 1a-clusters; five men were HCV re-infected; in the six-month preceding HCV diagnosis, 92% reported having casual sexual partners sought online (75.5% and at sex venues (79%, unprotected anal sex (90% and fisting (65%; using recreational drugs (62% and bleeding during sex (55%. CONCLUSIONS: This study emphasizes the role of multiple unprotected sexual practices and recreational drugs use during sex in the HCV emergence in HIV-infected MSM. It becomes essential to adapt prevention strategies and inform HIV-infected MSM with recent acute HCV infection on risk of re-infection and on risk-reduction strategies.

  19. Determinants of persistent spread of HIV in HCV-infected populations of injecting drug users.

    Science.gov (United States)

    de Vos, Anneke S; van der Helm, Jannie J; Prins, Maria; Kretzschmar, Mirjam E

    2012-06-01

    Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are both transmitted through populations of injecting drug users (IDU) by the sharing of contaminated syringes. Prevalence of HCV is high in most IDU populations, whereas HIV prevalence varies considerably across populations. Understanding the dynamics of these interacting infections may allow us to use HCV prevalence as an indicator for the risk of persistent spread of HIV. We developed a mathematical model that describes the spread of both HCV and HIV in an IDU population. The model allows for HCV-HIV co-infection and increased disease related mortality for both infections. Using this model we investigated how HIV and HCV prevalence both depend on level and heterogeneity of injecting risk behaviour, and how HIV and HCV prevalence are related. To gain knowledge of actual risk behaviour we analysed data from the Amsterdam Cohort Study (ACS) of drug users. We find that there is a threshold HCV prevalence at which HIV can invade into an IDU population; below threshold HIV cannot spread. This threshold depends strongly on heterogeneity of risk behaviour in the population, as well as on whether sharing is more likely to occur within or between risk behaviour groups. We find that our model agrees with the observed relationship between HCV and HIV prevalence as described by Vickerman et al. (2010), when in addition to risk heterogeneity as fitted from the ACS, we also assume that most contacts (>90%) occur amongst IDU of the same risk level (assortative mixing). We conclude that HCV prevalence can be used as an indicator of risk for successful HIV introduction into an IDU population. However, information on risk heterogeneity is required for determining this risk, and also for designing effective prevention strategies. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Lipoprotein lipase inhibits hepatitis C virus (HCV infection by blocking virus cell entry.

    Directory of Open Access Journals (Sweden)

    Patrick Maillard

    Full Text Available A distinctive feature of HCV is that its life cycle depends on lipoprotein metabolism. Viral morphogenesis and secretion follow the very low-density lipoprotein (VLDL biogenesis pathway and, consequently, infectious HCV in the serum is associated with triglyceride-rich lipoproteins (TRL. Lipoprotein lipase (LPL hydrolyzes TRL within chylomicrons and VLDL but, independently of its catalytic activity, it has a bridging activity, mediating the hepatic uptake of chylomicrons and VLDL remnants. We previously showed that exogenously added LPL increases HCV binding to hepatoma cells by acting as a bridge between virus-associated lipoproteins and cell surface heparan sulfate, while simultaneously decreasing infection levels. We show here that LPL efficiently inhibits cell infection with two HCV strains produced in hepatoma cells or in primary human hepatocytes transplanted into uPA-SCID mice with fully functional human ApoB-lipoprotein profiles. Viruses produced in vitro or in vivo were separated on iodixanol gradients into low and higher density populations, and the infection of Huh 7.5 cells by both virus populations was inhibited by LPL. The effect of LPL depended on its enzymatic activity. However, the lipase inhibitor tetrahydrolipstatin restored only a minor part of HCV infectivity, suggesting an important role of the LPL bridging function in the inhibition of infection. We followed HCV cell entry by immunoelectron microscopy with anti-envelope and anti-core antibodies. These analyses demonstrated the internalization of virus particles into hepatoma cells and their presence in intracellular vesicles and associated with lipid droplets. In the presence of LPL, HCV was retained at the cell surface. We conclude that LPL efficiently inhibits HCV infection by acting on TRL associated with HCV particles through mechanisms involving its lipolytic function, but mostly its bridging function. These mechanisms lead to immobilization of the virus at the cell

  1. Synthesis and in vitro activity of 4' and 5'-modified analogues of apiosyl nucleosides as potent anti-HCV agents.

    Science.gov (United States)

    Li, Hua; Lee, Wonjae; Hong, Joon Hee

    2009-11-01

    Novel doubly branched apio dideoxynucleosides were synthesized starting from 1,3-dihydroxyacetone using an ozonolysis and Grignard addition as key steps, and evaluated for anti-hepatitis C virus (HCV) activity. The adenine derivative 24 showed significant anti-HCV activity, indicating that the branches at the 4',5'-position of the apiosyl ring led to favorable interaction with HCV polymerase.

  2. Is adding HCV screening to the antenatal national screening program in Amsterdam, the Netherlands cost-effective?

    NARCIS (Netherlands)

    Urbanus, A.; Van Keep, M.; Matser, A.; Rozenbaum, M.; Weegink, C.; Van Den Hoek, A.; Prins, M.; Postma, M.

    Introduction: Hepatitis C virus infection (HCV) can lead to severe liver disease. Recently new improved treatment options have been introduced. Pregnant women are already routinely screened for several infectious diseases, however not yet for HCV infection. Here we examine whether adding HCV

  3. Is adding HCV screening to the antenatal national screening program in Amsterdam, the Netherlands, cost-effective?

    NARCIS (Netherlands)

    Urbanus, Anouk T.; van Keep, Marjolijn; Matser, Amy A.; Rozenbaum, Mark H.; Weegink, Christine J.; van den Hoek, Anneke; Prins, Maria; Postma, Maarten J.

    2013-01-01

    INTRODUCTION: Hepatitis C virus (HCV) infection can lead to severe liver disease. Pregnant women are already routinely screened for several infectious diseases, but not yet for HCV infection. Here we examine whether adding HCV screening to routine screening is cost-effective. METHODS: To estimate

  4. Specificity and sensitivity of 3rd generation EIA for detection of HCV antibodies among intravenous drug-users.

    Science.gov (United States)

    Filice, G; Patruno, S; Campisi, D; Chiesa, A; Orsolini, P; Debiaggi, M; Bruno, R; Tinelli, M

    1993-01-01

    Serum samples from 487 ambulatory I.V. drug users were screened for HIV and HCV antibodies to determine the prevalence of coinfection in this high risk group for AIDS. For anti-HCV antibody screening we first used a 3rd generation EIA using, as antigen synthetic peptides which were not subjected to false positive results due to antibodies against superoxide dismutase or against yeast proteins (which may copurify with the recombinant proteins employed in the first and second generation test). The specimens that were positive in the screening test were confirmed by a more specific EIA system that detect antibodies to proteins encoded by structural (HCV-st EIA) and non structural (HCV-nst-EIA) regions of the HCV genome. A second confirmation assay was also performed: sera were run in presence or absence of blocking reagents which inhibits antibodies to C200 and C22 HCV epitopes for binding to the solid phase. The sensitivity of the HCV EIA screening for human HCV antibody detection revealed a 100% positivity for HCV infection. The confirmatory strategy presented in this paper revealed an HCV EIA specificity of 98.6%. In this work we demonstrated a significantly higher prevalence (p HIV infected individuals compared to the general population. Our experimental data also confirmed that HBV infection in drug-users at high risk for HIV infection was significantly associated with HCV infection (p HIV by sexual contact was not a statistically significant risk factor for HCV coinfection.

  5. Research advances in molecular mechanism of mother-to-child transmission of HCV and related risk factors

    Directory of Open Access Journals (Sweden)

    GAO Luhua

    2017-06-01

    Full Text Available Hepatitis C virus (HCV is a global health problem and people are generally susceptible to HCV. Main routes of transmission include blood transmission, sexual transmission, and mother-to-child transmission. Anti-HCV screening of blood products has substantially reduced the blood transmission of HCV. Remarkable breakthrough has been made in the treatment of hepatitis C with direct-acting antiviral agents and the trend of HCV transmission has been significantly curbed. Since HCV infection is occult, hepatitis C vaccine has not been successfully developed, and there lack effective blocking measures for mother-to-child transmission, which will become one of the major route of HCV transmission. Reducing the rate of mother-to-child transmission of HCV is very important in preventing neonatal HCV infection and reducing the incidence rate of HCV infection. In recent years, many researchers have concentrated on the detailed mechanisms and risk factors of mother-to-child transmission of HCV and made great achievements; however, there are still controversies over some issues. This article reviews the research advances in the specific mechanisms of mother-to-child transmission of HCV in China and other countries.

  6. Natural killer KIR3DS1 is closely associated with HCV viral clearance and sustained virological response in HIV/HCV patients.

    Directory of Open Access Journals (Sweden)

    Antonio Rivero-Juarez

    Full Text Available AIM: To evaluate the influence of the presence of the killer cell immunoglobulin-like receptor (KIR 3DS1 on HCV treatment response in HIV/HCV genotype 1 co-infected patients. METHODS: HIV/HCV co-infected patients were included. KIR3DS1, their specific HLA-B ligands and IL28B gene were genotyped. Reductions of plasma HCV RNA levels between baseline and week 1, week 2 and week 4 were analyzed for IL28B genotype and KIR3DS1 (HLA Bw4 or Bw6. Rapid and sustained virological response (RVR and SVR rates were also analyzed. RESULTS: Sixty HIV/HCV genotype 1 co-infected patients were included. Patients with KIR3DS1 and Bw4 had higher rates of HCV viral decline than those who were not carriers of KIR3DS1 (week 1: p = 0.01; week 2: p = 0.038; week 4: p = 0.03. Patients carrying KIR3DS1/Bw4 had higher rates of RVR and SVR than those who did not carry KIR3DS1 (RVR: 46.15% versus 17.02%, p = 0.012; SVR: 63.6% versus 13 26.5%, p = 0.031. With respect to patients carrying the IL28B-CC genotype, those with KIR3DS1/Bw4 had greater rates of HCV viral clearance (week 1: p<0.001; week 2: p = 0.01; week 4: p = 0.02, RVR (p = 0.015 and SVR (p = 0.029 than those not carrying KIR3DS1. CONCLUSION: Our results show that the KIR3DS1 genotype has a positive effect on HCV viral clearance during the first weeks of Peg-IFN/RBV treatment in HCV/HCV co-infected patients bearing genotype 1, and higher RVR and SVR rates.

  7. Differences in HCV viral decline between low and standard-dose pegylated-interferon-alpha-2a with ribavirin in HIV/HCV genotype 3 patients.

    Directory of Open Access Journals (Sweden)

    Antonio Rivero-Juárez

    Full Text Available BACKGROUND: The aim of the study was to analyze the different impact of standard and low-dose Peg-IFN-α2a/RBV therapies on HCV viral decline in HIV/HCV genotype 3 co-infected patients during the first weeks of treatment. METHODS: Plasma HCV viral decline was analyzed between baseline and weeks 1, 2 and 4 in two groups of treatment-naïve HCV genotype 3 patients with HIV co-infection. The Standard Dose Group (SDG included patients who received Peg-IFN at 180 µg/per week with a weight-adjusted dose of ribavirin; Low-Dose Group (LDG patients received Peg-IFN at 135 µg/per week with 800 mg/day ribavirin. The effect of IL28B genotype on HCV viral decline was evaluated in both groups. HCV viral decline was analyzed using a multivariate linear regression model. RESULTS: One hundred and six patients were included: 48 patients in the SDG and 58 in the LDG. HCV viral decline for patients in the LDG was less than for those in the SDG (week 1:1.72±0.74 log(10 IU/mL versus 1.78±0.67 log(10 IU/mL, p = 0.827; week 2:2.3±0.89 log(10 IU/mL versus 3.01±1.02 log(10 IU/mL, p = 0.013; week 4:3.52±1.2 log(10 IU/mL versus 4.09±1.1 log(10 IU/mL, p = 0.005. The linear regression model identified the Peg-IFN/RBV dose as an independent factor for HCV viral decline at week 4. CONCLUSIONS: Our results showed that HCV viral decline was less for patients in the low-dose group compared to those receiving the standard dose. Until a randomized clinical trial is conducted, clinicians should be cautious about using lower doses of Peg-IFN/RBV in HIV/HCV genotype 3 co-infected patients.

  8. Evaluation of bacterial translocation in patients with chronic HCV infection.

    Science.gov (United States)

    Munteanu, Daniela; Negru, Anca; Radulescu, Mihaela; Mihailescu, Raluca; Arama, St S; Arama, Victoria

    2014-01-01

    The factors involved in the progression of liver disease towards decompensated cirrhosis are not completely elucidated. It seems that bacterial translocation (BT) from the gut to the systemic blood flow has an important role in the disease progression, but literature data are controversial. Our objectives were to evaluate the presence of BT in patients with chronic HCV infection and to assess the correlation between BT and liver fibrosis stages and inflammatory state. We conducted a cross-sectional study on patients with chronic HCV infection in a tertiary care hospital between January and July 2013. Blood samples were collected for aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), total cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides, platelets, lipopolysaccharide (LPS) and tumor necrosis-alpha (TNFα). Plasma LPS were measured by ELISA (Kamiya Biomedical Company Seattle, SUA) and TNFα by DIAsource ImmunoAssay (Louvain-la-Neuve, Belgium) kits. Liver fibrosis was evaluated by means of FibroMax (BioPredictive, Paris, France) in all patients. We enrolled 116 patients with CHC, with a sex ratio M/F of 0.55 and a median age of 54 (45-61) years. Most of the patients (32) had compensated cirrhosis (F4). LPS levels were higher in patients with mild fibrosis--median value of 60.34 (32-91.7) ng/mL, than in cirrhotic patients--median value 40.39 (20.2-74.4) ng/mL (p = 0.051). We found no statistical correlation between LPS levels and fibrosis (p = 0.068) or TNFα levels (p = 0.097) CONCLUSIONS: There was BT in patients with CHC but it was not correlated with liver fibrosis stages or systemic inflammation. This may suggest that LPS evaluation may not be the best technique to assess baterial translocation, but further studies are needed.

  9. On-treatment HCV RNA as a predictor of sustained virological response in HCV genotype 3-infected patients treated with daclatasvir and sofosbuvir.

    Science.gov (United States)

    Kowdley, Kris V; Nelson, David R; Lalezari, Jacob P; Box, Terry; Gitlin, Norman; Poleynard, Gary; Rabinovitz, Mordechai; Ravendhran, Natarajan; Sheikh, Aasim M; Siddique, Asma; Bhore, Rafia; Noviello, Stephanie; Rana, Khurram

    2016-11-01

    Many currently available direct-acting antiviral (DAA) regimens are less effective against HCV genotype 3 than against other HCV genotypes. The all-oral, pangenotypic DAA combination of daclatasvir (NS5A inhibitor) + sofosbuvir (nucleotide NS5B inhibitor) was studied in genotype 3-infected treatment-naive and -experienced patients (ALLY-3) who achieved rates of sustained virological response at post-treatment Week 12 (SVR12) of 90 and 86% respectively. In this analysis, we assessed whether on-treatment responses to daclatasvir + sofosbuvir in genotype 3-infected patients could predict treatment outcome. In ALLY-3, treatment-naive and -experienced patients, with or without cirrhosis, were treated with daclatasvir + sofosbuvir for 12 weeks. HCV RNA kinetics and categorical virological responses on treatment were assessed. The proportions of responders and nonresponders by study week, and time to first undetectable HCV RNA, were analysed for utility in predicting treatment outcome. Overall, HCV RNA levels declined rapidly during Week 1 of treatment in both treatment-naive and -experienced cohorts. Although patients with cirrhosis had a slower initial virological response as measured by the proportion of patients with HCV RNA below the lower limit of quantification at Week 1, responses converged thereafter. Positive and negative predictive values calculated for on-treatment responses were generally comparable with the overall SVR12 rate and were therefore limited indicators of outcome. SVR12 rates were not impacted by time to first undetectable HCV RNA. On-treatment responses are not useful predictors of ultimate virological response to the daclatasvir + sofosbuvir regimen. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. 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.

  11. Most common genotypes and risk factors for HCV in Gaza strip: a cross sectional study

    Directory of Open Access Journals (Sweden)

    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.

  12. HCV-induced immune responses influence the development of operational tolerance after liver transplantation in humans.

    Science.gov (United States)

    Bohne, Felix; Londoño, María-Carlota; Benítez, Carlos; Miquel, Rosa; Martínez-Llordella, Marc; Russo, Carolina; Ortiz, Cecilia; Bonaccorsi-Riani, Eliano; Brander, Christian; Bauer, Tanja; Protzer, Ulrike; Jaeckel, Elmar; Taubert, Richard; Forns, Xavier; Navasa, Miquel; Berenguer, Marina; Rimola, Antoni; Lozano, Juan-José; Sánchez-Fueyo, Alberto

    2014-06-25

    Pathogen-induced immune responses prevent the establishment of transplantation tolerance in experimental animal models. Whether this occurs in humans as well remains unclear. The development of operational tolerance in liver transplant recipients with chronic hepatitis C virus (HCV) infection allows us to address this question. We conducted a clinical trial of immunosuppression withdrawal in HCV-infected adult liver recipients to elucidate (i) the mechanisms through which allograft tolerance can be established in the presence of an ongoing inflammatory response and (ii) whether anti-HCV heterologous immune responses influence this phenomenon. Of 34 enrolled liver recipients, drug withdrawal was successful in 17 patients (50%). Tolerance was associated with intrahepatic overexpression of type I interferon and immunoregulatory genes and with an expansion of exhausted PD1/CTLA4/2B4-positive HCV-specific circulating CD8(+) T cells. These findings were already present before immunosuppression was discontinued and were specific for HCV infection. In contrast, the magnitude of HCV-induced proinflammatory gene expression and the breadth of anti-HCV effector T cell responses did not influence drug withdrawal outcome. Our data suggest that in humans, persistent viral infections exert immunoregulatory effects that could contribute to the restraining of alloimmune responses, and do not necessarily preclude the development of allograft tolerance. Copyright © 2014, American Association for the Advancement of Science.

  13. Inhibition of HCV 3a core gene through Silymarin and its fractions

    Directory of Open Access Journals (Sweden)

    Nawaz Zafar

    2011-04-01

    Full Text Available Abstract Hepatitis C is a major health problem affecting 270 million individuals in world including Pakistan. Current treatment regimen, interferon alpha and ribavirin only cure half of patients due to side effects and high cost. Results In the present study Silybum marianum (Milk thistle seeds were collected, extracted and analyzed against HCV 3a core gene by transiently transfecting the liver cells with HCV core plasmid. Our results demonstrated that Silymarin (SM dose dependently inhibit the expression or function of HCV core gene at a non toxic concentration while the GAPDH remained constant. To identify the active ingredient, SM was fractioned by thin layer chromatography (TLC, column chromatography and HPLC. Purified fractions were tested for HCV core gene and western blotting results showed that two factions of SM (S1 and S2 inhibit HCV 3a core expression or function in liver cells Conclusion Our results suggest SM and its fractions (S1 and S2 inhibit HCV core gene of 3a genotype and combination of SM and its fractions with interferon will be a better option to treat HCV infection

  14. The effect of HCV Core protein on the expression of miR-150

    Directory of Open Access Journals (Sweden)

    Sayad Khanizadeh

    2016-09-01

    Full Text Available Background : Hepatitis C virus (HCV is considered as one of the major pathogenic agents of chronic liver diseases. Previous studies have shown that HCV proteins can interaction with gene regulatory networks such as microRNAs. The aim of this study was to investigate the effect of HCV core protein on the expression of miR-150 in a cell culture model. Materials and Methods: Plasmids expressing full HCV core protein was transfected into Huh7 cell lines while a GFP expressing plasmid employed as negative control. Subsequently, total RNA extracted and Real-Time PCR performed to measure the expression level of miR-150 expression. Moreover, trypan blue exclusion assay was performed to investigate the effect of core protein on cell viability. Results: The gene expression analysis of miR-150 in Huh7 cells showed that endogenous HCV core protein could significantly down regulation of miR-150 when compared to GFP control plasmid and normal cells (P<0.01. Beside, core protein induced no significant proliferative or cytotoxic effects on hepatic cells as determined by trypan blue exclusion assay (P<0.05. Conclusion: Our study suggests that HCV core protein can led to down regulation of miR-150 expression. This data revealed that HCV protein interactions with cell regulatory machinery may contribute to pathogenesis of chronic liver diseases.

  15. Discovery of Cellular Proteins Required for the Early Steps of HCV Infection Using Integrative Genomics

    Science.gov (United States)

    Yang, Jae-Seong; Kwon, Oh Sung; Kim, Sanguk; Jang, Sung Key

    2013-01-01

    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. PMID:23593195

  16. HBV and HCV Coinfection among HIV/AIDS Patients in the National Hospital of Tropical Diseases, Vietnam

    OpenAIRE

    Bùi Vũ Huy; Kanxay Vernavong; Nguyễn Văn Kính

    2014-01-01

    Aim. To examine prevalence and characterization of HBV and HCV coinfection among HIV/AIDS patients. Methods. This cross-sectional, retrospective study analyzed 724 HIV/AIDS patients in the HIV clinic at the National Hospital of Tropical Diseases (NHTD), from 5/2005 to 4/2011. Results. The prevalence of HBV, HCV, and HIV coinfection was 50.3% (364/724), of which HbsAg, HCV, and both of HbsAg, and HCV positivity were 8.4%, 35.4%, and 6.5%, respectively. The cohort (364 patients) with HBV, HCV, ...

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. Prevalence and Incidence of HCV Infection among Prisoners in Central Brazil.

    Directory of Open Access Journals (Sweden)

    Marco Antonio Moreira Puga

    Full Text Available The aim of this multicenter, cross sectional study was to assess the prevalence, incidence and associated risk factors among incarcerated populations from twelve Brazilian prisons. The total of 3,368 individuals from twelve prisons was randomly recruited between March 2013 and March 2014. Participants were interviewed, and provided blood samples which were tested for antibodies to Hepatitis C (HCV ab. One year after the first investigation, a cohort study was conducted with 1,656 inmates who participated the cross sectional study. Positive samples were tested for the presence of HCV RNA. Out of 3,368 inmates, 520 (15.4% were females, and 2,848 (84.6% were males. The overall prevalence of HCV was 2.4% (95% CI: 1.9 to 2.9, with 0.6% (95% CI: 0.4 to 0.8 in females, and 2.7% (95% CI: 2.1 to 3.3 in males (p<0.01. HCV RNA was detected in 51/80 (63.7% samples. Among men prisoners, multivariate analysis of associated factors showed independent associations between HCV exposure and increasing age, inject drug use, length of incarceration, smoking hashish, sharing needle and syringe and HIV positivity. During the cohort study, 7/1,656 new cases of HCV infection were detected, and the incidence rate was 0.4/100 person-year. Once high frequency rates of specific HCV risk behaviors and new HCV infections have been identified inside prisons, effective interventions strategies such as screening, clinical evaluation and treatment to reduce the spread of HCV infection are essential.

  20. Analysis of in vitro replicated human hepatitis C virus (HCV for the determination of genotypes and quasispecies

    Directory of Open Access Journals (Sweden)

    Chelyapov Nickolas

    2006-09-01

    Full Text Available Abstract Isolation and self-replication of infectious HCV has been a difficult task. However, this is needed for the purposes of developing rational drugs and for the analysis of the natural virus. Our recent report of an in vitro system for the isolation of human HCV from infected patients and their replication in tissue culture addresses this challenge. At California Institute of Molecular Medicine several isolates of HCV, called CIMM-HCV, were grown for over three years in cell culture. This is a report of the analysis of CIMM-HCV isolates for subtypes and quasispecies using a 269 bp segment of the 5'UTR. HCV RNA from three patients and eleven CIMM-HCV were analyzed for this purpose. All isolates were essentially identical. Isolates of HCV from one patient were serially transmitted into fresh cells up to eight times and the progeny viruses from each transmission were compared to each other and also to the primary isolates from the patient's serum. Some isolates were also transmitted to different cell types, while others were cultured continuously without retransmission for over three years. We noted minor sequence changes when HCV was cultured for extended periods of time. HCV in T-cells and non-committed lymphoid cells showed a few differences when compared to isolates obtained from immortalized B-cells. These viruses maintained close similarity despite repeated transmissions and passage of time. There were no subtypes or quasispecies noted in CIMM-HCV.

  1. An integrated transcriptomic and meta-analysis of hepatoma cells reveals factors that influence susceptibility to HCV infection.

    Directory of Open Access Journals (Sweden)

    Jamie I MacPherson

    Full Text Available Hepatitis C virus (HCV is a global problem. To better understand HCV infection researchers employ in vitro HCV cell-culture (HCVcc systems that use Huh-7 derived hepatoma cells that are particularly permissive to HCV infection. A variety of hyper-permissive cells have been subcloned for this purpose. In addition, subclones of Huh-7 which have evolved resistance to HCV are available. However, the mechanisms of susceptibility or resistance to infection among these cells have not been fully determined. In order to elucidate mechanisms by which hepatoma cells are susceptible or resistant to HCV infection we performed genome-wide expression analyses of six Huh-7 derived cell cultures that have different levels of permissiveness to infection. A great number of genes, representing a wide spectrum of functions are differentially expressed between cells. To focus our investigation, we identify host proteins from HCV replicase complexes, perform gene expression analysis of three HCV infected cells and conduct a detailed analysis of differentially expressed host factors by integrating a variety of data sources. Our results demonstrate that changes relating to susceptibility to HCV infection in hepatoma cells are linked to the innate immune response, secreted signal peptides and host factors that have a role in virus entry and replication. This work identifies both known and novel host factors that may influence HCV infection. Our findings build upon current knowledge of the complex interplay between HCV and the host cell, which could aid development of new antiviral strategies.

  2. NS4A protein as a marker of HCV history suggests that different HCV genotypes originally evolved from genotype 1b

    Science.gov (United States)

    2011-01-01

    Background The 9.6 kb long RNA genome of Hepatitis C virus (HCV) is under the control of RNA dependent RNA polymerase, an error-prone enzyme, for its transcription and replication. A high rate of mutation has been found to be associated with RNA viruses like HCV. Based on genetic variability, HCV has been classified into 6 different major genotypes and 11 different subtypes. However this classification system does not provide significant information about the origin of the virus, primarily due to high mutation rate at nucleotide level. HCV genome codes for a single polyprotein of about 3011 amino acids which is processed into structural and non-structural proteins inside host cell by viral and cellular proteases. Results We have identified a conserved NS4A protein sequence for HCV genotype 3a reported from four different continents of the world i.e. Europe, America, Australia and Asia. We investigated 346 sequences and compared amino acid composition of NS4A protein of different HCV genotypes through Multiple Sequence Alignment and observed amino acid substitutions C22, V29, V30, V38, Q46 and Q47 in NS4A protein of genotype 1b. Furthermore, we observed C22 and V30 as more consistent members of NS4A protein of genotype 1a. Similarly Q46 and Q47 in genotype 5, V29, V30, Q46 and Q47 in genotype 4, C22, Q46 and Q47 in genotype 6, C22, V38, Q46 and Q47 in genotype 3 and C22 in genotype 2 as more consistent members of NS4A protein of these genotypes. So the different amino acids that were introduced as substitutions in NS4A protein of genotype 1 subtype 1b have been retained as consistent members of the NS4A protein of other known genotypes. Conclusion These observations indicate that NS4A protein of different HCV genotypes originally evolved from NS4A protein of genotype 1 subtype 1b, which in turn indicate that HCV genotype 1 subtype 1b established itself earlier in human population and all other known genotypes evolved later as a result of mutations in HCV genotype 1b

  3. Potential for Drug-Drug Interactions between Antiretrovirals and HCV Direct Acting Antivirals in a Large Cohort of HIV/HCV Coinfected Patients.

    Directory of Open Access Journals (Sweden)

    Isabelle Poizot-Martin

    Full Text Available Development of direct acting antivirals (DAA offers new benefits for patients with chronic hepatitis C. The combination of these drugs with antiretroviral treatment (cART is a real challenge in HIV/HCV coinfected patients. The aim of this study was to describe potential drug-drug interactions between DAAs and antiretroviral drugs in a cohort of HIV/HCV coinfected patients.Cross-sectional study of all HIV/HCV coinfected patients attending at least one visit in 2012 in the multicenter French Dat'AIDS cohort. A simulation of drug-drug interactions between antiretroviral treatment and DAAs available in 2015 was performed.Of 16,634 HIV-infected patients, 2,511 had detectable anti-HCV antibodies, of whom 1,196 had a detectable HCV-RNA and were not receiving HCV treatment at the time of analysis. 97.1% of these patients were receiving cART and 81.2% had a plasma HIV RNA <50 copies/mL. cART included combinations of nucleoside reverse transcriptase inhibitors with a boosted protease inhibitor in 43.6%, a non-nucleoside reverse transcriptase inhibitor in 17.3%, an integrase inhibitor in 15.4% and various combinations or antiretroviral drugs in 23.7% of patients. A previous treatment against HCV had been administered in 64.4% of patients. Contraindicated associations/potential interactions were expected between cART and respectively sofosbuvir (0.2%/0%, sofosbuvir/ledipasvir (0.2%/67.6%, daclatasvir (0%/49.4%, ombitasvir/boosted paritaprevir (with or without dasabuvir (34.4%/52.2% and simeprevir (78.8%/0%.Significant potential drug-drug interactions are expected between cART and the currently available DAAs in the majority of HIV/HCV coinfected patients. Sofosbuvir/ledipasvir and sofosbuvir/daclatasvir with or without ribavirin appeared the most suitable combinations in our population. A close collaboration between hepatologists and HIV/AIDS specialists appears necessary for the management of HCV treatment concomitantly to cART.

  4. Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics.

    Directory of Open Access Journals (Sweden)

    Min Chen

    Full Text Available The human immunodeficiency virus 1 (HIV-1 epidemic in China historically stemmed from intravenous drug users (IDUs in Yunnan. Due to a shared transmission route, hepatitis C virus (HCV/HIV-1 co-infection is common. Here, we investigated HCV genetic characteristics and baseline drug resistance among HIV-infected IDUs in Yunnan.Blood samples of 432 HIV-1/HCV co-infected IDUs were collected from January to June 2014 in six prefectures of Yunnan Province. Partial E1E2 and NS5B genes were sequenced. Phylogenetic, evolutionary and genotypic drug resistance analyses were performed.Among the 293 specimens successfully genotyped, seven subtypes were identified, including subtypes 3b (37.9%, 111/293, 3a (21.8%, 64/293, 6n (14.0%, 41/293, 1b (10.6%, 31/293, 1a (8.2%, 24/293, 6a (5.1%, 15/293 and 6u (2.4%, 7/293. The distribution of HCV subtypes was mostly related to geographic location. Subtypes 3b, 3a, and 6n were detected in all six prefectures, however, the other four subtypes were detected only in parts of the six prefectures. Phylogeographic analyses indicated that 6n, 1a and 6u originated in the western prefecture (Dehong and spread eastward and showed genetic relatedness with those detected in Burmese. However, 6a originated in the southeast prefectures (Honghe and Wenshan bordering Vietnam and was transmitted westward. These subtypes exhibited different evolutionary rates (between 4.35×10-4 and 2.38×10-3 substitutions site-1 year-1 and times of most recent common ancestor (tMRCA, between 1790.3 and 1994.6, suggesting that HCV was multiply introduced into Yunnan. Naturally occurring resistance-associated mutations (C316N, A421V, C445F, I482L, V494A, and V499A to NS5B polymerase inhibitors were detected in direct-acting antivirals (DAAs-naïve IDUs.This work reveals the temporal-spatial distribution of HCV subtypes and baseline HCV drug resistance among HIV-infected IDUs in Yunnan. The findings enhance our understanding of the characteristics and

  5. NS4A protein as a marker of HCV history suggests that different HCV genotypes originally evolved from genotype 1b

    Directory of Open Access Journals (Sweden)

    Asad Sultan

    2011-06-01

    Full Text Available Abstract Background The 9.6 kb long RNA genome of Hepatitis C virus (HCV is under the control of RNA dependent RNA polymerase, an error-prone enzyme, for its transcription and replication. A high rate of mutation has been found to be associated with RNA viruses like HCV. Based on genetic variability, HCV has been classified into 6 different major genotypes and 11 different subtypes. However this classification system does not provide significant information about the origin of the virus, primarily due to high mutation rate at nucleotide level. HCV genome codes for a single polyprotein of about 3011 amino acids which is processed into structural and non-structural proteins inside host cell by viral and cellular proteases. Results We have identified a conserved NS4A protein sequence for HCV genotype 3a reported from four different continents of the world i.e. Europe, America, Australia and Asia. We investigated 346 sequences and compared amino acid composition of NS4A protein of different HCV genotypes through Multiple Sequence Alignment and observed amino acid substitutions C22, V29, V30, V38, Q46 and Q47 in NS4A protein of genotype 1b. Furthermore, we observed C22 and V30 as more consistent members of NS4A protein of genotype 1a. Similarly Q46 and Q47 in genotype 5, V29, V30, Q46 and Q47 in genotype 4, C22, Q46 and Q47 in genotype 6, C22, V38, Q46 and Q47 in genotype 3 and C22 in genotype 2 as more consistent members of NS4A protein of these genotypes. So the different amino acids that were introduced as substitutions in NS4A protein of genotype 1 subtype 1b have been retained as consistent members of the NS4A protein of other known genotypes. Conclusion These observations indicate that NS4A protein of different HCV genotypes originally evolved from NS4A protein of genotype 1 subtype 1b, which in turn indicate that HCV genotype 1 subtype 1b established itself earlier in human population and all other known genotypes evolved later as a result of

  6. [Antigenicity of hepatitis C virus F protein and serum prevalence of anti-F in HCV-infected patients].

    Science.gov (United States)

    Shao, Sheng-Wen; Wu, Wen-Bin; Yu, Jian-Guo; Zhao, Ping; Qi, Zhong-Tian

    2006-12-01

    To examine the antigenicity of hepatitis C virus (HCV) F protein and investigate serum prevalence of anti-F in HCV-infected patients. Eleven pairs of overlapping primers were used to synthesize the full-length HCV f gene, from which the truncated HCV f65 gene fragment was amplified by PCR. HCV f65 gene was then cloned into pET32a(+), and transformed into E. coli strain Plyss (DE3). This recombinant E.coli was induced by IPTG for the production of HCV F65 protein. The expressed HCV F65 protein, purified by Ni-NTA agarose, was further used in ELISA to detect serum anti-F, and to immunize rabbits for making polyclonal anti-F. The rabbit polyclonal anti-F was purified by Staphylococcus aureus protein A agarose. After recombinant pET32a(+)-f65 was constructed successfully, HCV F65 protein was expressed and purified. The purified HCV F65 protein was used as a capture antigen in ELISA to detect serum anti-F in HCV infected patients (n = 30). The result showed that the mean A450 value and the positive rate of serum anti-F were 0.125+/-0.061 and 63.3%, respectively. The rabbit-derived polyclonal anti-F reacted specifically with HCV F65 protein, of which the titer was 1:30,000. Our expressed HCV F65 protein is of antigenicity, and can be used to determine serum anti-F. Anti-F IgG does exist in the sera of the HCV-infected patients. Moreover, the rabbit-derived polyclonal anti-F can be used to detect HCV F protein.

  7. Effect of abacavir on sustained virologic response to HCV treatment in HIV/HCV co-infected patients, Cohere in Eurocoord

    DEFF Research Database (Denmark)

    Smit, Colette; Arends, Joop; Peters, Lars

    2015-01-01

    collaboration. Logistic regression was used to evaluate the impact of abacavir on achieving a sustained virologic response (SVR) to HCV treatment. RESULTS: In total 1309 HIV/HCV co-infected patients who had received HCV therapy were included, of whom 490 (37 %) had achieved an SVR. No statistically significant...... to achieve an SVR compared to patients using a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen (OR: 0.61, 95 % CI: 0.41-0.91). The backbone combinations zidovudine&lamivudine (AZT + 3TC) and stavudine&lamivudine (d4t + 3TC) were associated with lower SRV rates (0.45 (0.24-0.82) and 0...

  8. Antiviral phytochemicals identification from Azadirachta indica leaves against HCV NS3 protease: an in silico approach.

    Science.gov (United States)

    Ashfaq, Usman Ali; Jalil, Asma; Ul Qamar, Muhammad Tahir

    2016-08-01

    Hepatitis C virus (HCV) is a major health problem across the world affecting the people of all age groups. It is the main cause of hepatitis and at chronic stage causes liver cirrhosis and hepatocellular carcinoma. Various therapeutics are made against HCV but still there is a need to find out potential therapeutics to combat the virus. The goal of this study is to identify the phytochemicals of Azadirachta indica leaves having antiviral activity against HCV NS3 protease through molecular docking and simulation approach. Results show that the compound 3-Deacetyl-3-cinnamoyl-azadirachtin possesses good binding properties with HCV NS3/4A protease. It can be concluded from this study that Deacetyl-3-cinnamoyl-azadirachtin may serve as a potential inhibitor against NS3/4A protease.

  9. Rapid screening for co-infection of HIV and HCV in pregnant women ...

    African Journals Online (AJOL)

    Administrator

    were screened for HIV and HCV using rapid screening test kits. Using closed ended ... Two percent of the pregnant women had equivocal (ambivalent) HIV-1 results. .... Laboratories, San Diego, California, USA) detection test kits were used in ...

  10. Anti-HCV RNA Aptamers Targeting the Genomic cis-Acting Replication Element

    Directory of Open Access Journals (Sweden)

    Alfredo Berzal-Herranz

    2011-12-01

    Full Text Available Hepatitis C virus (HCV replication is dependent on the existence of several highly conserved functional genomic RNA domains. The cis-acting replication element (CRE, located within the 3' end of the NS5B coding region of the HCV genome, has been shown essential for efficient viral replication. Its sequence and structural features determine its involvement in functional interactions with viral RNA-dependent RNA polymerase and distant RNA domains of the viral genome. This work reports the use of an in vitro selection strategy to select aptamer RNA molecules against the complete HCV-CRE. After six selection cycles, five potential target sites were identified within this domain. Inhibition assays using a sample of representative aptamers showed that the selected RNAs significantly inhibit the replication (>80% of a subgenomic HCV replicon in Huh-7 cell cultures. These results highlight the potential of aptamer RNA molecules as therapeutic antiviral agents.

  11. Assessing the impact of educational campaigns on controlling HCV among women in prison settings

    Science.gov (United States)

    Mushayabasa, S.; Bhunu, C. P.; Smith?, Robert J.

    2012-04-01

    Prior studies have shown that imprisonment is a major risk factor for hepatitis C infection, with the risk of infection directly proportional to the length of incarceration. Women are at least twice as likely as men to contract HCV as they have limited access to information, health services and safe intravenous drug injecting equipments. We develop a mathematical model to assess the impact of educational campaigns on controlling HCV among women in prison settings. Equilibria for the model are determined and their stability are examined. Population-level effects of increased educational campaigns to encourage safe injecting practices among women in prison are evaluated through numerical simulations. The results suggest that educating women prisoners about abstaining from intravenous drug misuse may significantly reduce HCV prevalence among women in prison settings. Targeted education campaigns, which are effective at stopping transmission of HCV more than 80% of the time, will be highly effective at controlling the disease among women in prisons.

  12. High HCV seroprevalence and HIV drug use risk behaviors among injection drug users in Pakistan

    Directory of Open Access Journals (Sweden)

    Zafar Tariq

    2006-08-01

    Full Text Available Abstract Introduction HIV and HCV risk behaviors among injection drug users (IDUs in two urban areas in Pakistan were identified. Methods From May to June 2003, 351 IDUs recruited in harm-reduction drop-in centers operated by a national non-governmental organization in Lahore (Punjab province and Quetta (Balochistan province completed an interviewer-administered survey and were tested for HIV and HCV. Multivariable logistic regression identified correlates of seropositivity, stratifying by site. All study participants provided written, informed consent. Results All but two were male; median age was 35 and Discussion Despite no HIV cases, overall HCV prevalence was very high, signaling the potential for a future HIV epidemic among IDUs across Pakistan. Programs to increase needle exchange, drug treatment and HIV and HCV awareness should be implemented immediately.

  13. Alkyl substituted aminal derivatives of HCV NS5A inhibitor MK-8742.

    Science.gov (United States)

    Yu, Wensheng; Coburn, Craig A; Nair, Anilkumar G; Wong, Michael; Tong, Ling; Dwyer, Michael P; Hu, Bin; Zhong, Bin; Hao, Jinglai; Yang, De-Yi; Selyutin, Oleg; Jiang, Yueheng; Rosenblum, Stuart B; Kim, Seong Heon; Lavey, Brian J; Zhou, Guowei; Rizvi, Razia; Shankar, Bandarpalle B; Zeng, Qingbei; Chen, Lei; Agrawal, Sony; Carr, Donna; Rokosz, Laura; Liu, Rong; Curry, Stephanie; McMonagle, Patricia; Ingravallo, Paul; Lahser, Fred; Asante-Appiah, Ernest; Nomeir, Amin; Kozlowski, Joseph A

    2016-08-01

    HCV NS5A inhibitors have demonstrated impressive in vitro potency profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed dose combination regimen for the treatment of HCV infection. Herein we describe our continued research efforts around the alkyl "Z group" modification of the tetracyclic indole-based NS5A inhibitor MK-8742, which led to the discovery of a series of potent NS5A inhibitors. Compounds 10 and 19 are of particular interests since they are as potent as our previous leads and have much improved rat pharmacokinetic profiles. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Prevalência de anti-HCV em uma população privada de liberdade Prevalence of anti-HCV in an inmate population

    Directory of Open Access Journals (Sweden)

    Fernanda da Rosa

    2012-10-01

    Full Text Available OBJETIVO: Estimar a prevalência do vírus da hepatite (HCV através de um teste rápido em um grupo carcerário do interior do Rio Grande do Sul. MÉTODOS: Por meio de um estudo descritivo do tipo inquérito, foram avaliados 195 apenados por amostragem aleatória. RESULTADOS: Um total de 9,7% dos apenados era reagente. Nesta análise, a variável que se mostrou preditora para infecção pelo HCV foi o uso de drogas injetáveis. CONCLUSÃO: A alta prevalência da sorologia reagente para o HCV observada entre os internos causa particular preocupação, uma vez que é bem maior em relação à população em geral. Portanto, é necessária a realização de campanhas de abordagens específicas para mais informações sobre doenças infecciosas em ambientes prisionais, além de um adequado tratamento para evitar a disseminação viral.OBJECTIVE: To estimate the prevalence of hepatitis C using a rapid hepatitis C virus (HCV test in an inmate population from the countryside of Rio Grande do Sul, Brazil. METHODS: Through a descriptive study, 195 inmates were evaluated by random sampling. RESULTS: A total of 9.7% of the inmates were positive. In this analysis, the variable injectable drug use was predictive of HCV infection. CONCLUSION: The high prevalence of positive serology for HCV observed among the inmates is of particular concern, as it is much higher than in the general population. Therefore, it is necessary to conduct specific approach campaigns to gather more information on infectious diseases in prison settings, as well as to provide appropriate treatment to prevent viral dissemination.

  15. GB virus C (GBV-C) infection in hepatitis C virus (HCV)/HIV-coinfected patients receiving HCV treatment: importance of the GBV-C genotype.

    Science.gov (United States)

    Schwarze-Zander, Carolynne; Blackard, Jason T; Zheng, Hui; Addo, Marylyn M; Lin, Wenyu; Robbins, Gregory K; Sherman, Kenneth E; Zdunek, Dietmar; Hess, Georg; Chung, Raymond T

    2006-08-15

    Persistent GB virus C (GBV-C) coinfection leads to slower human immunodeficiency virus (HIV) progression. Despite the existence of multiple GBV-C genotypes, their relevance to the progression of HIV disease is unknown. We therefore investigated (1) the prevalence and genotype of GBV-C in hepatitis C virus (HCV)/HIV-coinfected patients and (2) the impact of HCV treatment on GBV-C RNA clearance. We retrospectively studied 130 HCV/HIV-coinfected patients initiating HCV therapy. Anti-E2 enzyme-linked immunosorbent assay, reverse-transcription polymerase chain reaction (PCR), and real-time PCR were used to detect and quantify GBV-C infection. GBV-C genotype was determined by sequencing the 5' untranslated region. GBV-C infection (past or current) was identified in 111 (85%) of the patients. Ongoing GBV-C replication was detected in 40 patients. Coinfection with GBV-C genotype 2 was associated with significantly higher CD4(+) cell counts. After 24 weeks of HCV therapy, GBV-C RNA clearance was observed in 50% of patients, although this was not associated with changes in HIV load or with CD4(+) cell counts. Sustained GBV-C RNA clearance was observed in 31% of patients with GBV-C RNA detected at baseline. GBV-C coinfection was extremely common. GBV-C RNA clearance with HCV therapy was associated with neither short-term loss of HIV control nor impaired immune status. The association of GBV-C genotype 2 with higher CD4(+) cell counts merits further study.

  16. Microarray analysis identifies a common set of cellular genes modulated by different HCV replicon clones

    Directory of Open Access Journals (Sweden)

    Gerosolimo Germano

    2008-06-01

    Full Text Available Abstract Background Hepatitis C virus (HCV RNA synthesis and protein expression affect cell homeostasis by modulation of gene expression. The impact of HCV replication on global cell transcription has not been fully evaluated. Thus, we analysed the expression profiles of different clones of human hepatoma-derived Huh-7 cells carrying a self-replicating HCV RNA which express all viral proteins (HCV replicon system. Results First, we compared the expression profile of HCV replicon clone 21-5 with both the Huh-7 parental cells and the 21-5 cured (21-5c cells. In these latter, the HCV RNA has been eliminated by IFN-α treatment. To confirm data, we also analyzed microarray results from both the 21-5 and two other HCV replicon clones, 22-6 and 21-7, compared to the Huh-7 cells. The study was carried out by using the Applied Biosystems (AB Human Genome Survey Microarray v1.0 which provides 31,700 probes that correspond to 27,868 human genes. Microarray analysis revealed a specific transcriptional program induced by HCV in replicon cells respect to both IFN-α-cured and Huh-7 cells. From the original datasets of differentially expressed genes, we selected by Venn diagrams a final list of 38 genes modulated by HCV in all clones. Most of the 38 genes have never been described before and showed high fold-change associated with significant p-value, strongly supporting data reliability. Classification of the 38 genes by Panther System identified functional categories that were significantly enriched in this gene set, such as histones and ribosomal proteins as well as extracellular matrix and intracellular protein traffic. The dataset also included new genes involved in lipid metabolism, extracellular matrix and cytoskeletal network, which may be critical for HCV replication and pathogenesis. Conclusion Our data provide a comprehensive analysis of alterations in gene expression induced by HCV replication and reveal modulation of new genes potentially useful

  17. Men who have sex with men starting pre-exposure prophylaxis (PrEP) are at risk of HCV infection: evidence from the Amsterdam PrEP study.

    Science.gov (United States)

    Hoornenborg, Elske; Achterbergh, Roel C A; Schim Van Der Loeff, Maarten F; Davidovich, Udi; Hogewoning, Arjan; Vries, Henry J C de; Schinkel, Janke; Prins, Maria; Laar, Thijs J W van de

    2017-05-01

    Hepatitis C virus (HCV) has been recognised as an emerging sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). However, HIV-negative MSM at high risk for HIV might also be at increased risk for HCV. We studied the HCV prevalence in HIV-negative MSM who start pre-exposure prophylaxis (PrEP) in Amsterdam. Phylogenetic analysis was used to compare HCV strains obtained from HIV-negative and HIV-positive MSM. At enrolment in the Amsterdam PrEP (AMPrEP) demonstration project, HIV-negative MSM were tested for the presence of HCV antibodies and HCV RNA. If positive for HCV RNA, an HCV NS5B gene fragment (709 bp) was sequenced and compared with HCV isolates from HIV-positive MSM (n = 223) and risk groups other than MSM (n = 153), using phylogenetic analysis. Of 375 HIV-negative MSM enrolled in AMPrEP, 18 (4.8%, 95%CI 2.9%-7.5%) of participants were anti-HCV and/or HCV RNA positive at enrolment; 15/18 (83%) had detectable HCV RNA. HCV genotyping showed genotype 1a (73%), 4d (20%) and 2b (7%). All HCV-positive MSM starting PrEP were part of MSM-specific HCV clusters containing MSM with and without HIV. HCV prevalence among HIV-negative MSM who started PrEP was higher than previously reported. All HIV-negative HCV-positive MSM were infected with HCV strains already circulating among HIV-positive MSM. The increasing overlap between sexual networks of HIV-positive and HIV-negative MSM might result in an expanding HCV-epidemic irrespective of HIV-status. Hence, routine HCV testing should be offered to MSM at high risk for HIV, especially for those enrolling in PrEP programs.

  18. Obstetric management does not influence vertical transmission of HCV infection: results of the ALHICE group study.

    Science.gov (United States)

    Delotte, Jérôme; Barjoan, Eugènia Mariné; Berrébi, Alain; Laffont, Catherine; Benos, Paul; Pradier, Christian; Bongain, André

    2014-05-01

    To investigate the impact of variation in obstetric practice during labor and childbirth upon the rate of neonatal transmission of HCV. Pregnant mothers were included in this prospective study from six hospitals in Southern France on the basis of positive HCV serology. Data recorded for the study included maternal factors, delivery details and laboratory data concerning mother and child. Pediatric follow-up was documented for a minimum of 1 year and for up to 2 years for children with circulating HCV RNA. Two hundred and fourteen mother-child pairs were investigated. HIV/HCV co-infected mothers had a rate of HCV transmission significantly higher (11%) than that observed for mono-infected mothers (3.8%) (odds ratio=3.08 [95% CI:0.95 to 9.99] p=0.05). When the HCV viral load was greater than or equal to 6 log copies/ml, the transmission rate was 14.3% [95% CI:5.4-28.5], this representing a risk of transmission four times higher than for women with a lower viral load (OR=4 [95% CI:1.3-12.4]). Among co-infected mothers, the risk of transmission was significantly increased even when the load was less than 6 log copies/ml (p=0.006). Risk factors were identified related to labor (duration and induction type); the birth process (rupture of the amniotic sac, complete opening of the sac, appearance of the amniotic fluid); fetal characteristics (prematurity) and obstetric maneuvers (instrumental extractions, spontaneous or induced perineal trauma) and none of these factors were associated with an increased rate of HCV maternal-fetal transmission. HCV infection does not appear to be a legitimate indication for modifying obstetric practices with regards to type of induction, monitoring of labor, route of delivery, fetal and perineal obstetric maneuvers or care of the newborn in the delivery room.

  19. 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.

  20. Association of HCV Core Antigen Seropositivity with Long-Term Mortality in Patients on Regular Hemodialysis

    Directory of Open Access Journals (Sweden)

    Akihiko Kato

    2012-03-01

    Full Text Available Anti-hepatitis C virus (HCV antibody seropositivity is independently associated with poor prognosis in hemodialysis (HD patients. However, anti-HCV antibody cannot distinguish between patients with active infection and those who have recovered from infection. We therefore aimed in this study to examine the association of HCV core antigen (HCVcAg seropositivity with mortality in HD patients. We first measured serum HCVcAg using an immunoradiometric assay and anti-HCV antibody in 405 patients on regular HD, and followed them for 104 months. There were 82 patients (20.2% who had been positive for anti-HCV antibodies; 57 (69.5% of these were positive for HCVcAg. During the follow-up, 29 patients were excluded, so we tested the association of HCVcAg seropositivity with all-cause, cardiovascular (CV and non-CV mortalities in 376 patients. A total of 209 patients (55.6% had expired during the observational period, 92 out of them due to CV causes. After adjusting for comorbid parameters, HCVcAg was independently associated with overall mortality (HR 1.61, 95% CI 1.05–2.47, p < 0.05. HCV infection was significantly related to liver disease-related mortality. Past HCV infection also contributed to CV mortality (HR 2.63, 95% CI 1.27–5.45, p < 0.01. In contrast, anti-HCV antibody and HCVcAg seropositivities did not associate with infectious disease-related and cancer-related (expect for hepatocellular carcinoma mortality. It follows from these findings that HCVcAg serology is associated with all-cause and CV mortality in HD patients.

  1. Reasons for HCV non-treatment in underserved African Americans: implications for treatment with new therapeutics.

    Science.gov (United States)

    Schaeffer, Sarah; Khalili, Mandana

    2015-01-01

    African Americans are disproportionately affected by hepatitis C (HCV) and are less likely to undergo HCV treatment. Underserved populations are especially at risk for experiencing health disparity. Aim. To identify reasons for HCV non-treatment among underserved African Americans in a large safetynet system. Medical records of HCV-infected African Americans evaluated at San Francisco General Hospital liver specialty clinic from 2006-2011 who did not receive HCV treatment were reviewed. Treatment eligibility and reasons for non-treatment were assessed. Factors associated with treatment ineligibility were assessed using logistic regression modeling. Among 118 patients, 42% were treatment ineligible, 18% treatment eligible, and 40% were undergoing work-up to determine eligibility. Reasons for treatment ineligibility were medical (54%), non-medical (14%), psychiatric (4%), or combined (28%). When controlling for age and sex, active/recent substance abuse (OR 6.65, p = 0.001) and having two or more medical comorbidities (OR 3.39, p = 0.005) predicted treatment ineligibility. Excluding those ineligible for treatment, 72% of all other patients were lost to follow-up; they were older (55 vs. 48 years, p = 0.01) and more likely to be undergoing work up to determine treatment eligibility (86 vs. 21%, p treatment ineligibility in underserved African Americans. Importantly, the majority of those undergoing work-up to determine HCV treatment eligibility were lost to follow-up. While newer anti-HCV agents may increase treatment eligibility, culturally appropriate interventions to increase compliance with evaluation and care remain critical to HCV management in underserved African Americans.

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

    Directory of Open Access Journals (Sweden)

    Daniel Bradshaw

    Full Text Available This study aimed to investigate the potential influence of venue-based networks on HCV transmission in HIV-positive gay and bisexual men (GBM.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.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.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.

  3. A survey of HIV and HCV among female prison inmates in Portugal.

    Science.gov (United States)

    Barros, Henrique; Ramos, Elisabete; Lucas, Raquel

    2008-09-01

    HIV and hepatitis C virus (HCV) monitoring among prison inmates is instrumental in countries with concentrated HIV/AIDS epidemics. Knowledge on these dynamics in imprisoned women in Portugal is scarce. The HIV and HCV prevalence was estimated among inmates in the largest Portuguese prison for women, which holds 57% of all female inmates in Portugal, according to sociodemographic and behavioural variables and characterised attitudes towards HIV/AIDS according to serological status. Collected variables included age, education, country of birth, penal status, and accumulated time in prison. Drug injection and sharing of injection material were inquired, as well as age at first sexual intercourse. Inmates also characterised their attitudes towards HIV/AIDS. A venous blood sample was collected and tested for anti-HIV and anti-HCV antibodies. In this sample of 445 female inmates, 10% were HIV-positive, while 11% were HCV-positive. Longer imprisonment periods were associated with relatively higher HCV prevalence and women with later ages at first sexual intercourse were less frequently HIV-positive, regardless of drug injecting behaviour. HIV prevalence was 44% in women who had ever injected drugs and 6% in those who had never injected. HCV frequency was 69% among injecting drug users (IDUs) and 4% among non-IDUs. In women who injected drugs both HIV and HCV were more frequent when the number of injections was higher and when women reported sharing of injection material. Similar attitudes towards HIV/AIDS were found for HIV-positive and negative women, but those living with HIV had more tolerant positions. This study emphasizes the role of injecting drug use in the transmission of HIV and HCV in women in Portuguese prisons and reinforces the need for the systematic adoption of harm reduction measures.

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

    Science.gov (United States)

    Daw, Mohamed A; Shabash, Amira; El-Bouzedi, Abdallah; Dau, Aghnya A

    2014-01-01

    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. 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. 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. 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.

  5. Low levels of microbial translocation marker LBP are associated with sustained viral response after anti-HCV treatment in HIV-1/HCV co-infected patients.

    Directory of Open Access Journals (Sweden)

    Jessica Nyström

    Full Text Available Microbial translocation (MT contributes to immune activation during HIV and HCV infections. We investigated the kinetics of MT markers during anti-HCV and anti-HIV treatments, and if baseline plasma levels of lipopolysaccharide (LPS, lipopolysaccharide binding protein (LBP and soluble CD14 (sCD14 could predict anti-HCV treatment outcome.Plasma from 78 HIV-infected patients was evaluated for LPS, LBP and sCD14. The patients starting anti-HCV treatment (with ongoing antiretroviral (ART treatment were categorized into sustained viral responders (SVR; n = 21 or non-responders (NR; n = 15 based on treatment outcome. ART starting subjects--were categorized into chronically HCV-infected (CH; n = 24 and mono-infected (HIV; n = 18, based on the HCV infection status. Samples were collected before start (at baseline of pegylated-interferon-alpha/ribavirin (peg-IFN/RBV or antiretroviral-therapy and two years after treatment start (at follow up. χ2-test, non-parametric statistics and logistic regression were applied to determine the associations with treatment response and changes of the soluble markers.Plasma levels of LPS and sCD14 were elevated in all subjects before antiviral-treatment but remained unchanged at follow-up. Elevated levels of LBP were present in patients with HIV and HIV/HCV co-infection and were reduced by ART. Additionally, higher levels of LBP were present at baseline in NR vs. SVR. Higher levels of LBP at baseline were associated with non-response to peg-IFN/RBV treatment in both bivariate (OR: 0.19 95% CI: 0.06-0.31, p = 0.004 and multivariate analysis (OR: 1.43, 95% CI: 1.1-1.86, p = 0.07.In HIV/HCV co-infected patients high baseline LBP levels are associated with non-response to peg-IFN/RBV therapy. Plasma LBP (decreased by ART may be a more relevant MT marker than LPS and sCD14.

  6. A Unique Pattern of HCV Genotype Distribution on Hainan Island in China Revealed by Evolutionary Analysis.

    Science.gov (United States)

    Wu, Tao; Xiong, Lu; Wang, Fuli; Xu, Xiaozhen; Wang, Jiao; Lin, Feng; Li, Chunhua; Lu, Ling; Zhou, Yuanping

    2016-01-01

    Different genotypes of HCV may differ in both disease progression and response to antiviral therapies. Hainan Island has been inhabited by the "Li" aboriginal minority for centuries. We aimed to provide a better understanding of HCV infection on Hainan Island, so that the information would help improve strategies for HCV prevention and control on the island and in the wider country. Using RT-PCR and DNA sequencing, we determined HCV sequences from 100 patients living on Hainan Island. Phylogenetic analysis classified these sequences into six subtypes: 6a (n=35), 1b (n=31), 3b (n=16), 2a (n=8), 3a (n=6), and 1a (n=4). By including reference sequences reported from elsewhere in China, phylogeographic trees were reconstructed to indicate their migration patterns. While the predominant 6a isolates were estimated to have origins in Guangdong and Guangxi provinces, the increase in 3b strains must have resulted from IDU network transmission from the southwest. A Bayesian Skyline Plot for subtype 1a, which is rare in China, showed a rapid population growth since 1998. Although slowed in rate around 2005, this growth continued to the present. Not found for any other HCV lineage. Overall, a delayed growth pattern may indicate the unique history of 1a dissemination in China and its recently increasing prevalence, despite measures taken to improve HCV prevention. © 2016 The Author(s) Published by S. Karger AG, Basel.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. HCV Core Protein Uses Multiple Mechanisms to Induce Oxidative Stress in Human Hepatoma Huh7 Cells

    Science.gov (United States)

    Ivanov, Alexander V.; Smirnova, Olga A.; Petrushanko, Irina Y.; Ivanova, Olga N.; Karpenko, Inna L.; Alekseeva, Ekaterina; Sominskaya, Irina; Makarov, Alexander A.; Bartosch, Birke; Kochetkov, Sergey N.; Isaguliants, Maria G.

    2015-01-01

    Hepatitis C virus (HCV) infection is accompanied by the induction of oxidative stress, mediated by several virus proteins, the most prominent being the nucleocapsid protein (HCV core). Here, using the truncated forms of HCV core, we have delineated several mechanisms by which it induces the oxidative stress. The N-terminal 36 amino acids of HCV core induced TGFβ1-dependent expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 1 and 4, both of which independently contributed to the production of reactive oxygen species (ROS). The same fragment also induced the expression of cyclo-oxygenase 2, which, however, made no input into ROS production. Amino acids 37–191 of HCV core up-regulated the transcription of a ROS generating enzyme cytochrome P450 2E1. Furthermore, the same fragment induced the expression of endoplasmic reticulum oxidoreductin 1α. The latter triggered efflux of Ca2+ from ER to mitochondria via mitochondrial Ca2+ uniporter, leading to generation of superoxide anions, and possibly also H2O2. Suppression of any of these pathways in cells expressing the full-length core protein led to a partial inhibition of ROS production. Thus, HCV core causes oxidative stress via several independent pathways, each mediated by a distinct region of the protein. PMID:26035647

  10. A Unique Pattern of HCV Genotype Distribution on Hainan Island in China Revealed by Evolutionary Analysis

    Directory of Open Access Journals (Sweden)

    Tao Wu

    2016-06-01

    Full Text Available Background/Aims: Different genotypes of HCV may differ in both disease progression and response to antiviral therapies. Hainan Island has been inhabited by the “Li” aboriginal minority for centuries. We aimed to provide a better understanding of HCV infection on Hainan Island, so that the information would help improve strategies for HCV prevention and control on the island and in the wider country. Methods: Using RT-PCR and DNA sequencing, we determined HCV sequences from 100 patients living on Hainan Island. Results: Phylogenetic analysis classified these sequences into six subtypes: 6a (n=35, 1b (n=31, 3b (n=16, 2a (n=8, 3a (n=6, and 1a (n=4. By including reference sequences reported from elsewhere in China, phylogeographic trees were reconstructed to indicate their migration patterns. While the predominant 6a isolates were estimated to have origins in Guangdong and Guangxi provinces, the increase in 3b strains must have resulted from IDU network transmission from the southwest. A Bayesian Skyline Plot for subtype 1a, which is rare in China, showed a rapid population growth since 1998. Although slowed in rate around 2005, this growth continued to the present. Not found for any other HCV lineage. Conclusions: Overall, a delayed growth pattern may indicate the unique history of 1a dissemination in China and its recently increasing prevalence, despite measures taken to improve HCV prevention.

  11. Transient elastography: A non-invasive tool for assessing liver fibrosis in HIV/HCV patients

    Science.gov (United States)

    Li Vecchi, Valentina; Soresi, Maurizio; Colomba, Claudia; Mazzola, Giovanni; Colletti, Pietro; Mineo, Maurizio; Di Carlo, Paola; La Spada, Emanuele; Vizzini, Giovanni; Montalto, Giuseppe

    2010-01-01

    AIM: To assess the prevalence of advanced liver fibrosis (ALF) in human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HIV/HCV patients using transient elastography, and to identify factors associated with ALF. METHODS: Between September 2008 and October 2009, 71 HIV mono-infected, 57 HIV/HCV co-infected and 53 HCV mono-infected patients on regular follow-up at our Center were enrolled in this study. Alcohol intake, the main parameters of liver function, presence of HCV-RNA, HIV-RNA, duration of highly active anti-retroviral therapy (HAART) and CD4 cell count were recorded. ALF was defined as liver stiffness (LS) ≥ 9.5 kPa. To estimate liver fibrosis (LF) a further 2 reliable biochemical scores, aspartate aminotransferase platelet ratio index (APRI) and FIB-4, were also used. RESULTS: LS values of co-infected patients were higher than in either HIV or HCV mono-infected patients (χ2MH = 4, P 9.5 kPa. There was no significant correlation between extent of LF and HAART exposure or duration of HAART exposure, in particular with specific dideoxynucleoside analogues. CONCLUSION: ALF was more frequent in co-infected than mono-infected patients. This result correlated with lower CD4 levels. Protective immunological effects of HAART on LF progression outweigh its hepatotoxic effects. PMID:21049556

  12. Strong correlation between ASPM gene expression and HCV cirrhosis progression identified by co-expression analysis.

    Science.gov (United States)

    Wang, Fan; Chang, Ying; Li, Jin; Wang, Hongling; Zhou, Rui; Qi, Jian; Liu, Jing; Zhao, Qiu

    2017-01-01

    Hepatitis C virus (HCV) cirrhosis is at a high risk of hepatocellular carcinoma (HCC), and its progression is influenced by a complex network of gene interactions. A weighted gene co-expression network was constructed to identify gene modules associated with the seven-stage disease progression from HCV cirrhosis to HCV-related HCC (n=65). In the significant module (R2=0.86), a total of 25 network hub genes were identified, half of which were also hub nodes in the protein-protein interaction network of the module genes. In validation, most hub genes showed a moderate correlation with the disease progression, and only ASPM was highly correlated (R2=0.801). In the test set (n=63), ASPM was also more highly expressed in HCV cirrhosis with concomitant HCC than in those without HCC (P=0.0054). Gene set enrichment analysis (GSEA) demonstrated that the gene set of "regulation of protein amino acid phosphorylation" (n=20) was enriched in HCV cirrhosis samples with ASPM highly expressed (false discovery rate (FDR)=0.049). In gene ontology (GO) analysis, genes in the enriched set were associated with liver neoplasms and other neoplastic diseases. In conclusion, through co-expression analysis, ASPM was identified and validated in association with the progression of HCV cirrhosis probably by regulating tumor-related phosphorylation. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  13. HCV Core Protein Uses Multiple Mechanisms to Induce Oxidative Stress in Human Hepatoma Huh7 Cells

    Directory of Open Access Journals (Sweden)

    Alexander V. Ivanov

    2015-05-01

    Full Text Available Hepatitis C virus (HCV infection is accompanied by the induction of oxidative stress, mediated by several virus proteins, the most prominent being the nucleocapsid protein (HCV core. Here, using the truncated forms of HCV core, we have delineated several mechanisms by which it induces the oxidative stress. The N-terminal 36 amino acids of HCV core induced TGF\\(\\upbeta\\1-dependent expression of nicotinamide adenine dinucleotide phosphate (NADPH oxidases 1 and 4, both of which independently contributed to the production of reactive oxygen species (ROS. The same fragment also induced the expression of cyclo-oxygenase 2, which, however, made no input into ROS production. Amino acids 37–191 of HCV core up-regulated the transcription of a ROS generating enzyme cytochrome P450 2E1. Furthermore, the same fragment induced the expression of endoplasmic reticulum oxidoreductin 1\\(\\upalpha\\. The latter triggered efflux of Ca2+ from ER to mitochondria via mitochondrial Ca2+ uniporter, leading to generation of superoxide anions, and possibly also H2O2. Suppression of any of these pathways in cells expressing the full-length core protein led to a partial inhibition of ROS production. Thus, HCV core causes oxidative stress via several independent pathways, each mediated by a distinct region of the protein.

  14. HIV-1 coinfection profoundly alters intrahepatic chemokine but not inflammatory cytokine profiles in HCV-infected subjects.

    Directory of Open Access Journals (Sweden)

    Sishun Hu

    Full Text Available The pathogenesis of accelerated liver damage in subjects coinfected with hepatitis C virus (HCV and human immunodeficiency virus type 1 (HIV-1 remains largely unknown. Recent studies suggest that ongoing chronic liver inflammation is responsible for the liver injury in HCV-infected patients. We aimed to determine whether HIV-1 coinfection altered intrahepatic inflammatory profiles in HCV infection, thereby hastening liver damage. We used a real-time RT-PCR-based array to comparatively analyze intrahepatic inflammation gene profiles in liver biopsy specimens from HCV-infected (n = 16, HCV/HIV-1-coinfected (n = 8 and uninfected (n = 8 individuals. We then used human hepatocytes to study the molecular mechanisms underlying alternations of the inflammatory profiles. Compared with uninfected individuals, HCV infection and HCV/HIV-1 coinfection markedly altered expression of 59.5% and 50.0% of 84 inflammation-related genes tested, respectively. Among these genes affected, HCV infection up-regulated the expression of 24 genes and down-regulated the expression of 26 genes, whereas HCV/HIV-1 coinfection up-regulated the expression of 21 genes and down-regulated the expression of 21 genes. Compared with HCV infection, HCV/HIV-1 coinfection did not dramatically affect intrahepatic gene expression profiles of cytokines and their receptors, but profoundly altered expression of several chemokine genes including up-regulation of the CXCR3-associated chemokines. Human hepatocytes produced these chemokines in response to virus-related microbial translocation, viral protein stimulation, and antiviral immune responses.HIV-1 coinfection profoundly alters intrahepatic chemokine but not cytokine profiles in HCV-infected subjects. The altered chemokines may orchestrate the tissue-specific and cell-selective trafficking of immune cells and autoimmunity to accelerate liver disease in HCV/HIV-1 coinfection.

  15. Studies on the interference of ganciclovir to HCV liver fibrosis.

    Science.gov (United States)

    Li, J; Pan, C-W; Zhou, G-Y; Zhuge, L; Fang, P-P; Jin, L-X; Lin, W; Lin, X-Z; Zheng, Y

    2016-10-01

    To investigate the significance of the combined treatment with ganciclovir and interferon for patients with hepatitis C (HCV) liver fibrosis. We retrospectively summarize 86 patients with hepatitis C treated in our hospital from October 2013 to October 2015. 49 cases, considered as control group, received combined treatment with α-interferon and ribavirin; 37 cases, considered as observation group, received combined treatment with ganciclovir and interferon. The changes of liver fibrosis, viral replication and liver function of both groups were compared for two weeks and six months. The levels of sera hyaluronic acid (HA), laminin (LN), type IV collagen (IVC) and type III procollagen (PIII NP) of both groups were reduced after treatment, and the observation group improved more significantly (p 0.05). The level of alanine aminotransferase (ALT) of the control group increased after treatment, compared with that before. This was done along with the decrease of the level of albumin. By contrast, the level of ALT in the observation group was reduced and the level of albumin was increased compared with that before (p Ganciclovir combined with interferon may further reduce the fibrosis process of patients with hepatitis C, and may improve liver function. The effect of antiviral was similar as ganciclovir combined with Interferon was comparatively good applied, safety and effectiveness.

  16. Improve screening of HCV infection by targeting high prevalence aged groups: analysis of a cohort of HCV and HIV co-infected patients

    Directory of Open Access Journals (Sweden)

    Pedro Brogueira

    2014-11-01

    Full Text Available Introduction: Hepatitis C constitutes a major public health burden. In Portugal, the prevalence is estimated at 1–1.5% (1. Of these, only 30% are presumed to be diagnosed, which reveals that most infections go unknown. The objective of this study is to identify the age-range distribution at HCV diagnosis and to identify the high-prevalence birth groups that could be targeted for screening, as a strategy to increase diagnosis and identify patients who would benefit most from treatment. Methods: Retrospective observational study of a cohort of chronic HCV-infected and HIV co-infected patients followed at an Infectious Diseases Center, diagnosed between 1979 and 2014 (Figure 1. Hepatic fibrosis evaluation was performed by real time elastography using METAVIR score. Epidemiological, demographic, clinical, virological and therapeutic data was retrieved from clinical registries. Statistical analysis was performed using Microsoft Excel 2010®. Chi2, Student T were used for a significant p value of <0.05. Results: Our study assessed a cohort of 665 patients: 442 (66.5% HCV/HIV co-infected and 223 (33.5% HCV monoinfected. There was a male predominance in both groups (74.9% vs 70.9%. The mean age was 47 HCV/HIV vs 49 years; Portuguese origin in 80% vs 83% and African in 14% vs 12%. The most frequently assumed transmission route was by intravenous drug use (IVDU (81% vs 72%, followed by sexual contact (18% vs 20%. Mean age at diagnosis was 32 vs 40 years. Mean time since HCV diagnosis was 14, 6 vs 9, 6 years. Fibrosis stage evaluation by real time elastography was available for 133 (30% and 99 (44.4% patients (HCV/HIV vs HCV: 16% vs 13% F1; 32% vs 33% F2; 31% vs 35% F3; 21% vs 18% F4. The peak prevalence occurred between the birth intervals of 1960–1969 and 1970–1979 for both groups, corresponding to 81% vs 66,8% (p=0.003 (Figure 1. About three quarters of all patients (76% were born between the year of 1960 and 1979, with a prevalence of 70% of IVDU

  17. Prevalence and characteristics of HIV/HBV and HIV/HCV coinfections in Tuscany

    Directory of Open Access Journals (Sweden)

    Monia Puglia

    Full Text Available Abstract Introduction Worldwide about 30% of HIV-infected patients are coinfected with HCV or HBV. The HIV/HCV coinfection is more common in individuals who have a history of drug addiction. The aims of this study were to assess the HCV and HBV prevalence in HIV-infected patients and analyze their characteristics. Methods We considered the new HIV diagnoses notified by the regional surveillance system of Tuscany from 2009 to 2013. Descriptive analyses were conducted on the socio-demographic characteristics, routes of transmission, and reason to perform the test. In coinfected patients we assessed the risk for being late presenter (LP or the risk of having AIDS. Results In 5 years of surveillance a total of 1354 new HIV diagnoses were notified: 1188 (87.7% were HIV alone, 106 (7.8% HIV/HCV, 56 (4.1% HIV/HBV, and 4 (0.33% HIV/HCV/HBV. The main risk factor was injection drug use in 52.8% of HCV/HIV cases, while in HIV/HBV patients the main risk factor was sexual exposure. HIV/HBV coinfected patients showed worse clinical and immunological features than HIV and HIV/HCV patients: 78.6% had CD4 count less than 350 mm−3 (vs. 54.6% and 62.1%, respectively and 39.4% had AIDS (vs 20.7% and 7.6%. The risk for being LP triples for HIV/HBV (OR 2.98; 95% IC: 1.56–5.70 than patients with HIV alone. Conclusions We have observed less advanced disease in HIV and HCV-HIV patients compared with HBV–HIV coinfected patients. Moreover, our results show a higher prevalence of HIV/HCV among drug addicts and in the age-group 35–59, corresponding to those born in years considered most at risk for addiction. This study also confirms the finding of a less advanced HIV disease in HIV/HCV coinfected patients.

  18. Direct binding of ledipasvir to HCV NS5A: mechanism of resistance to an HCV antiviral agent.

    Directory of Open Access Journals (Sweden)

    Hyock Joo Kwon

    Full Text Available Ledipasvir, a direct acting antiviral agent (DAA targeting the Hepatitis C Virus NS5A protein, exhibits picomolar activity in replicon cells. While its mechanism of action is unclear, mutations that confer resistance to ledipasvir in HCV replicon cells are located in NS5A, suggesting that NS5A is the direct target of ledipasvir. To date co-precipitation and cross-linking experiments in replicon or NS5A transfected cells have not conclusively shown a direct, specific interaction between NS5A and ledipasvir. Using recombinant, full length NS5A, we show that ledipasvir binds directly, with high affinity and specificity, to NS5A. Ledipasvir binding to recombinant NS5A is saturable with a dissociation constant in the low nanomolar range. A mutant form of NS5A (Y93H that confers resistance to ledipasvir shows diminished binding to ledipasvir. The current study shows that ledipasvir inhibits NS5A through direct binding and that resistance to ledipasvir is the result of a reduction in binding affinity to NS5A mutants.

  19. Direct binding of ledipasvir to HCV NS5A: mechanism of resistance to an HCV antiviral agent.

    Science.gov (United States)

    Kwon, Hyock Joo; Xing, Weimei; Chan, Katie; Niedziela-Majka, Anita; Brendza, Katherine M; Kirschberg, Thorsten; Kato, Darryl; Link, John O; Cheng, Guofeng; Liu, Xiaohong; Sakowicz, Roman

    2015-01-01

    Ledipasvir, a direct acting antiviral agent (DAA) targeting the Hepatitis C Virus NS5A protein, exhibits picomolar activity in replicon cells. While its mechanism of action is unclear, mutations that confer resistance to ledipasvir in HCV replicon cells are located in NS5A, suggesting that NS5A is the direct target of ledipasvir. To date co-precipitation and cross-linking experiments in replicon or NS5A transfected cells have not conclusively shown a direct, specific interaction between NS5A and ledipasvir. Using recombinant, full length NS5A, we show that ledipasvir binds directly, with high affinity and specificity, to NS5A. Ledipasvir binding to recombinant NS5A is saturable with a dissociation constant in the low nanomolar range. A mutant form of NS5A (Y93H) that confers resistance to ledipasvir shows diminished binding to ledipasvir. The current study shows that ledipasvir inhibits NS5A through direct binding and that resistance to ledipasvir is the result of a reduction in binding affinity to NS5A mutants.

  20. Analytical and clinical performance of the Hologic Aptima HCV Quant Dx Assay for the quantification of HCV RNA in plasma samples

    DEFF Research Database (Denmark)

    Schønning, Kristian; Pedersen, Martin Schou; Johansen, Kim

    2017-01-01

    dilution series of four HCV genotypes (slope of the regression line: 1.00-1.02). The Aptima assay detected significantly more replicates below targeted 2 Log IU/mL than the CAPCTMv2 test, and yielded clearly interpretable results when used to analyze samples from patients treated with DAAs. CONCLUSIONS...

  1. Liver fibrosis, microbial translocation and immune activation markers in HIV and HCV infections and in HIV/HCV co-infection.

    Science.gov (United States)

    Sacchi, Paolo; Cima, Serena; Corbella, Marta; Comolli, Giuditta; Chiesa, Antonella; Baldanti, Fausto; Klersy, Catherine; Novati, Stefano; Mulatto, Patrizia; Mariconti, Mara; Bazzocchi, Chiara; Puoti, Massimo; Pagani, Laura; Filice, Gaetano; Bruno, Raffaele

    2015-03-01

    Liver fibrosis is accelerated in patients co-infected with human immunodeficiency virus and hepatitis C viruses. We investigated the correlation between liver fibrosis, immune activation and microbial translocation. This cross-sectional study included patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) mono-infections, HIV/HCV co-infection, and healthy controls (20 subjects/group). Peripheral blood was analysed to determine the levels of Forkhead box 3 (Foxp3) T cells, TGF-β1, CD14 (soluble and surface isoforms), IL-17 and bacterial translocation products. These measurements were correlated to the severity of liver fibrosis, measured with the FIB-4 score and transient elastography. Foxp3T cell levels were significantly elevated in HIV mono-infected and co-infected groups (p<0.0005). FIB-4 and liver stiffness values inversely correlated with TGF-β1 (p=0.0155 and p=0.0498). Bacterial DNA differed significantly in the HIV-positive compared to the other groups: HIV/HCV co-infected subjects had significantly higher serum levels of bacterial translocation products, CD14, and IL-17 levels (p<0.001). Fibrosis stage in HIV/HCV co-infection may be influenced by immune activation due either by viral infections or to bacterial translocation. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  2. Restoration of HCV-specific T cell functions by PD-1/PD-L1 blockade in HCV infection: effect of viremia levels and antiviral treatment.

    Science.gov (United States)

    Urbani, Simona; Amadei, Barbara; Tola, Daniela; Pedrazzi, Giuseppe; Sacchelli, Luca; Cavallo, Maria Cristina; Orlandini, Alessandra; Missale, Gabriele; Ferrari, Carlo

    2008-04-01

    HCV-specific T cells in acute hepatitis C with subsequent chronic evolution are dysfunctional and most of them express PD-1. The aim of the study was to investigate to what extent the antiviral T cell function can be restored by reversing T cell exhaustion by PD-1/PD-L1 blockade and to assess whether this restoration is favored by IFN-alpha treatment. PD-1 and PD-L1 expression was studied on T cells and dendritic cells, respectively, of 14 patients with acute hepatitis C and different evolutions of infection. The effect of anti-PD-L1 was analyzed on proliferation, cytokine production and cytolytic activity of CD4 and CD8 T cells. While PD-1 expression dropped concurrently with spontaneous or IFN-alpha induced HCV-RNA decline, PD-L1 levels on dendritic cells increased during IFN-alpha treatment. Anti-PD-L1 antibodies improved expansion and cytokine production but not the cytolytic activity of HCV-specific T cells. This restoration tended to be greater at lower levels of viremia and PD-1 expression and during PEG-IFNalpha treatment. PD-1/PD-L1 blockade has an immunoregulatory activity which may synergize with the antiviral effect of IFN-alpha therapy and should be thus explored further in long-lasting chronic HCV infections in the perspective of improving the efficacy of available antiviral treatments.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

  5. Detection of HCV RNA in saliva does not correlate with salivary flow or xerostomia in patients with chronic hepatitis C.

    Science.gov (United States)

    de Mattos Camargo Grossmann, Soraya; Teixeira, Rosângela; de Oliveira, Guilherme Corrêa; do Carmo, Maria Auxiliadora Vieira

    2010-06-01

    The objective of this study was to investigate the prevalence of hepatitis C virus (HCV) RNA in saliva and its possible association with xerostomia and hyposalivation in patients with chronic hepatitis C. One hundred and thirty-six patients with confirmed diagnosis of chronic hepatitis C were prospectively analyzed before HCV treatment. The prevalence of xerostomia and hyposalivation was clinically evaluated. HCV RNA was investigated in saliva samples by qualitative PCR test. Univariate and multivariate analyses were used to verify associations. Xerostomia was reported by 48 (35.3%) patients, whereas hyposalivation was observed in 26 (19.1%). HCV RNA was positive in the saliva of 53 (39.0%) patients. An association among HCV RNA-positive saliva with xerostomia or hyposalivation was not observed. Our results demonstrate that the detection of HCV in saliva does not correlate with salivary flow or xerostomia in patients with chronic hepatitis C. Copyright 2010 Mosby, Inc. All rights reserved.

  6. [Prevalence of response to anti-HBV infection in patients on maintenance hemodialysis infected with hepatitis C virus (HCV)].

    Science.gov (United States)

    Muszytowski, M; Manitius, J; Ruszkiewicz-Fołda, M

    1996-01-01

    We have studied the antibody response to hepatitis B vaccine in 42 hemodialysis patients; 8 of them were diagnosed as having HCV infection before vaccination. Hemodialysis patients received four doses of recombinant HB vaccine (Engerix-B, SKB, 40 micrograms per dose). Seroconversion occurred in 71.4% of all hemodialysis patients; in 79.4% of HCV-negative and in 37.5% of HCV-positive patients. Effective immunity (anti-HBs titer higher than 100 m IU/ml) was observed in 12.5% of HCV positive and in 35.3% of HCV-negative patients. We conclude that HCV infection may modify or postpone the response to hepatitis B vaccine.

  7. Maintenance of Th1 hepatitis C virus (HCV)-specific responses in individuals with acute HCV who achieve sustained virological clearance after treatment.

    Science.gov (United States)

    Flynn, Jacqueline K; Dore, Gregory J; Hellard, Margaret; Yeung, Barbara; Rawlinson, William D; White, Peter A; Kaldor, John M; Lloyd, Andrew R; Ffrench, Rosemary A

    2013-11-01

    T-cell responses against hepatitis C are believed to be critical in achieving both natural and treatment-induced clearance. However, rapid clearance of antigen with early treatment of primary infection may result in reduced or poorly sustained cellular immunity. This study longitudinally examined Th1 and Th2 hepatitis C virus (HCV)-specific cytokine production and T-cell effector function from subjects enrolled in the Australian Trial in Acute Hepatitis C comparing three groups: treatment-induced clearance (sustained virological response [SVR]), treatment non-response, and untreated spontaneous clearance. HCV-specific T-cell responses were characterized by HCV peptide ELISpot, in vitro cytokine production, and T-cell flow cytometry assays. Treated subjects with a sustained virological response (SVR) displayed a better maintenance of HCV-specific Th1 responses compared to treatment non-responders (higher interferon [IFN]-γ and interleukin (IL)-2 magnitude at week 24, broader IFN-γ responses at weeks 24 and 48, P < 0.05) and significantly increased IFN-γ responses between screening and week 48 (magnitude P = 0.026, breadth P = 0.009). Treatment-induced viral clearance was also associated with a trend toward decreased IL-10 responses (screening to week 48, P = 0.070), higher expression of CD45RO (P = 0.042) and CD38 (P = 0.088) on CD4+ T cells, and higher IFN-γR expression (CD56+ IFN-γR+ P = 0.033) compared to treatment non-responders. Untreated subjects with viral clearance also displayed high magnitude and broad HCV-specific IFN-γ and IL-2 responses early in infection; however, IFN-γ responses were not as well maintained compared to treated subjects with a SVR (week 48 magnitude, breadth P = 0.064). Treatment-induced viral clearance of recent HCV infection is associated with maintenance of HCV-specific Th1 responses. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  8. Mechanism of cell infection with hepatitis C virus (HCV)--a new paradigm in virus-cell interaction.

    Science.gov (United States)

    Budkowska, Agata

    2009-01-01

    Hepatitis C virus (HCV) is an enveloped, single-stranded RNA virus, belonging to the Flaviviridae family. HCV infection is a major cause of chronic hepatitis worldwide, leading to steatosis, liver cirrosis and hepatocellular carcinoma. Significant advances in understanding the mechanisms of HCV infection have been made since the development of a cell culture system reproducing the complete HCV cell cycle in vitro. HCV represents a new paradigm in interactions between the virus and its target cell, the human hepatocyte, due to the central role of lipoproteins in the HCV life cycle. Very low density lipoproteins are required for virus particle assembly and secretion. Upon the release, the infectious virus circulates in the blood as triglyceride-rich particles and infects cells using lipoprotein-receptor dependent mechanisms. HCV cell entry is a multi-step process: heparan sulphate and/or low-density lipoprotein receptor are cell surface factors mediating an initial virus attachment; subsequent virus interaction with tetraspanin CD81 and the human scavenger receptor SR-BI, the main HCV receptors, triggers virus movement to the tight junctions and its uptake via Claudin-1 and occludin. Another originality of HCV is that initiation of productive infection requires dynamic microtubules. Whereas other viruses use kinesin or dynein-dependent transport, HCV exploits mechanisms driven by microtubule polymerization to efficiently infect its target cell, in which virus nucleocapsid protein might play a particular role. An improved of understanding of the cellular events involved in HCV cell entry and transport, leading to the initiation of productive HCV infection, may reveal novel targets for anti-viral interventions.

  9. [Model-based estimates of the risk of HCV transmission from infected patients to gynaecologic and obstetric staff].

    Science.gov (United States)

    Gańczak, Maria; Szczeniowski, Adam; Jurewicz, Alina; Karakiewicz, Beata; Szych, Zbigniew

    2012-01-01

    The risk of acquiring the hepatitis C virus (HCV) through percutaneous occupational exposure is dependent on three key variables: number of injuries, probability of a percutaneous injury transmitting HCV and prevalence of HCV infection in the patient population. To estimate the prevalence of HCV infection in the gynaecological/obstetric patient population and thereafter estimate the risk of HCV transmission to personnel through occupational exposure. The prevalence of anti-HCV was estimated through an anonymous serosurvey of gynaecological/ obstetric patients in 15 randomly selected hospitals in West Pomerania, Poland, from February 2008 to January 2009. Using own published data on the percutaneous injuries during gynaecological/obstetric surgeries and results obtained from serologic survey, the risk of annual occupational transmission of HCV to personnel was then derived with the use of a mathematical model. The prevalence of anti-HCV infection for 528 gynaecological/obstetric patients, aged 18-83 (median 45), was 0.76% (4/528; 95%CI: 0.29-1.93%). The estimated risk of HCV transmission from an HCV infected patient to an uninfected staff member may vary over a wide range (0.00007-0.1%), being dependent on the type of exposure; the average risk for a midwife was 0.0038% per annum (0.15% risk over a 40 year professional career). The estimated risk for a gynaecologist/obstetrician was 0.0076% and 0.30% respectively. The risk of an individual member of a gynaecological/obstetric staff acquiring HCV through occupational exposure is low, however a credible hazard still exists. One in 130 patients hospitalized at gynaecological/obstetric wards showed markers of HCV infection. Therefore, staff members should be encouraged to observe standard precautions regarding sharps injury prevention and present themselves for post-exposure management in case of need.

  10. Outcome and management of HCV/HIV coinfection pre- and post-liver transplantation. A 2015 update.

    Science.gov (United States)

    Miro, Jose M; Stock, Peter; Teicher, Elina; Duclos-Vallée, Jean-Charles; Terrault, Norah; Rimola, Antoni

    2015-03-01

    Liver transplantation is increasingly performed in selected HIV-infected patients in most developed countries, with excellent results reported in patients with liver diseases unrelated to HCV. In contrast, survival in HCV/HIV-coinfected liver recipients is poorer than in HCV-monoinfected patients, due to more aggressive recurrence of HCV and consequent graft loss and death. Results from American, French, and Spanish cohort studies showed a 5-year survival rate of only 50-55%. Therefore, it is debated whether liver transplantation should be offered to HCV/HIV-coinfected patients. Studies have shown that the variables more consistently associated with poor outcome are: (1) the use of old or HCV-positive donors, (2) dual liver-kidney transplantation, (3) recipients with very low body mass index and (4) less site experience. However, the most effective factor influencing transplantation outcome is the successful treatment of HCV recurrence with anti-HCV. Survival is 80% in patients whose HCV infection resolves. Unfortunately, the rates of sustained virological response with pegylated-interferon plus ribavirin in coinfected recipients are low, particularly for genotype 1 (only 10%). Here we present a non-systematic review of the literature based on our own experience in different liver transplant scenarios. This review covers selection criteria in HIV-infected patients, pre- and post-LT management, donor selection, anti-HCV treatment, drug interactions with antiretrovirals and anti-HCV direct antiviral agents, hepatocellular carcinoma, and liver retransplantation. Recommendations are rated. Finally, we explain how the introduction of new effective and more tolerable direct antiviral agents may improve significantly the outcome of HCV/HIV-coinfected liver recipients. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  11. Discovery of silyl proline containing HCV NS5A inhibitors with pan-genotype activity: SAR development.

    Science.gov (United States)

    Nair, Anilkumar G; Zeng, Qingbei; Selyutin, Oleg; Rosenblum, Stuart B; Jiang, Yueheng; Yang, De-Yi; Keertikar, Kerry; Zhou, Guowei; Dwyer, Michael P; Kim, Seong Heon; Shankar, Bandarpalle; Yu, Wensheng; Tong, Ling; Chen, Lei; Mazzola, Robert; Caldwell, John; Tang, Haiqun; Allard, Melissa L; Buckle, Ronald N; Gauuan, Polivina Jolicia F; Holst, Christian L; Martin, Gregory S; Naicker, Kannan P; Vellekoop, Samuel; Agrawal, Sony; Liu, Rong; Kong, Rong; Ingravallo, Paul; Xia, Ellen; Zhai, Ying; Nomeir, Amin; Kozlowski, Joseph A

    2016-03-01

    HCV NS5A inhibitors have shown impressive in vitro potency profiles in HCV replicon assays thus making them attractive components for inclusion in an all oral fixed dose combination treatment regimen. Herein we describe the research efforts that led to the discovery of silyl proline containing HCV NS5A inhibitors such as 7e and 8a with pan-genotype activity profile and acceptable pharmacokinetic properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Low prevalence of HCV infection with predominance of genotype 4 among HIV patients living in Libreville, Gabon.

    Directory of Open Access Journals (Sweden)

    Angélique Ndjoyi-Mbiguino

    Full Text Available Gabon is an endemic area for human immunodeficiency virus (HIV and hepatitis C virus (HCV and the risk of co-infection is high.Between November 2015 and April 2016, we conducted retrospective study on HCV infection among people living with HIV/AIDS (PLHA. A total of 491 PLHA were included in this study and tested for the presence of HCV infection. HIV viral loads were obtained using the Generic HIV viral Load® assay and the CD4+ T cells count was performed using BD FACSCount™ CD4 reagents. HCV screening was performed using the MP Diagnostics HCV ELISA 4.0 kit. HCV genotypes were determined by sequence analysis of NS5B and Core regions. The Mann-Whitney test was used to compare the groups. Chi-2 test and Fisher's Exact Test were used to compare prevalence.HCV seroprevalence was 2.9% (14/491, (95% confidence interval (CI:1.4-4.3%. The percentage of HCV viremic patients, defined by the detection of HCV RNA in plasma, was 57% (8/14, representing 1.6% of the total population. HCV seroprevalence and replicative infection were not statistically differ with gender. The percentage of co-infection increased with age. No correlation with CD4+ T cells count and HIV viral load level was registered in this study. Identified HCV strains were predominantly of genotype 4 (87.5% including 4k, 4e, 4g, 4p, 4f and 4c subtypes. Only one strain belonged to genotype 2 (subtype 2q. Analysis of the NS5B region did not reveal the presence of resistance-associated substitutions for sofosbuvir.A systematic screening of hepatitis C is therefore strongly recommended as well as genotyping of HCV strains in order to adapt treatments for the specific case of people living with HIV/AIDS in Central Africa.

  13. Use of Daclatasvir in HCV/HIV-Coinfected Patients in a Real-Life Setting.

    Science.gov (United States)

    Bonora, Stefano; Puoti, Massimo

    2017-01-01

    The burden of HIV and HCV coinfection is estimated to affect 5-7 million people worldwide, with approximately 15-30% of people with HIV coinfected with HCV. The first oral direct-acting antivirals have shown to improve the response in patients with HIV/HCV coinfection, and more recently, other direct-acting antivirals that target various stages of the HCV life cycle have been developed, among them daclatasvir. The objective of this article is to examine recent clinical studies investigating the efficacy and safety of daclatasvir in comparison with other antiretroviral drugs, focusing on its efficacy in the coinfected HIV patient and real-life data. Daclatasvir is a direct-acting antiviral first-in-class HCV NS5A replication complex inhibitor, approved in June 2014 by the European Medicines Agency for use in combination with other medicinal products for the treatment of chronic HCV infection in adults, and in July 2015 by the Food and Drug Administration. Its efficacy was demonstrated in several trials, with a mean sustained virologic response 12 weeks after therapy completion above 90%. The majority of adverse events related to treatment were mild-to-moderate in severity, with no discontinuation of therapy because of an adverse event and no clinically significant interactions with most of HIV antiretrovirals. The efficacy of daclatasvir in HIV/HCV-coinfected patients was demonstrated in many studies, and confirmed by real-life data for patients with different genotypes, patients with cirrhosis, and in association with ribavirin, opening a new frontier in the treatment of these patients.

  14. Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1

    Science.gov (United States)

    Naggie, Susanna; Cooper, Curtis; Saag, Michael; Workowski, Kimberly; Ruane, Peter; Towner, William J.; Marks, Kristen; Luetkemeyer, Anne; Baden, Rachel P.; Sax, Paul E.; Gane, Edward; Santana-Bagur, Jorge; Stamm, Luisa M.; Yang, Jenny C.; German, Polina; Dvory-Sobol, Hadas; Ni, Liyun; Pang, Phillip S.; McHutchison, John G.; Stedman, Catherine A.M.; Morales-Ramirez, Javier O.; Bräu, Norbert; Jayaweera, Dushyantha; Colson, Amy E.; Tebas, Pablo; Wong, David K.; Dieterich, Douglas; Sulkowski, Mark

    2016-01-01

    BACKGROUND Effective treatment for hepatitis C virus (HCV) in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains an unmet medical need. METHODS We conducted a multicenter, single-group, open-label study involving patients coinfected with HIV-1 and genotype 1 or 4 HCV receiving an antiretroviral regimen of tenofovir and emtricitabine with efavirenz, rilpivirine, or raltegravir. All patients received ledipasvir, an NS5A inhibitor, and sofosbuvir, a nucleotide polymerase inhibitor, as a single fixed-dose combination for 12 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS Of the 335 patients enrolled, 34% were black, 55% had been previously treated for HCV, and 20% had cirrhosis. Overall, 322 patients (96%) had a sustained virologic response at 12 weeks after the end of therapy (95% confidence interval [CI], 93 to 98), including rates of 96% (95% CI, 93 to 98) in patients with HCV genotype 1a, 96% (95% CI, 89 to 99) in those with HCV genotype 1b, and 100% (95% CI, 63 to 100) in those with HCV genotype 4. Rates of sustained virologic response were similar regardless of previous treatment or the presence of cirrhosis. Of the 13 patients who did not have a sustained virologic response, 10 had a relapse after the end of treatment. No patient had confirmed HIV-1 viro-logic rebound. The most common adverse events were headache (25%), fatigue (21%), and diarrhea (11%). No patient discontinued treatment because of adverse events. CONCLUSIONS Ledipasvir and sofosbuvir for 12 weeks provided high rates of sustained virologic response in patients coinfected with HIV-1 and HCV genotype 1 or 4. (Funded by Gilead Sciences; ION-4 ClinicalTrials.gov number, NCT02073656.) PMID:26196665

  15. Computer aided screening of Accacia nilotica phytochemicals against HCV NS3/4a.

    Science.gov (United States)

    Khan, Mahim; Qasim, Muhammad; Ashfaq, Usman Ali; Idrees, Sobia; Shah, Masoud

    2013-01-01

    HCV has become a leading cause of liver cirrhosis and hepatocellular carcinoma and is a major health concern worldwide. To date, there is no vaccine available in the market to tackle this disease, therefore there is a strong need to develop antiviral compounds that can target all genotypes of HCV with the same efficiency. Medicinal plants have low cost and are less toxic therefore, extracts of medicinal plants can serve as important antiviral agents against HCV. This study was designed to screen phytochemicals of Accacia nilotica to find a potent drug candidate that can inhibit HCV infection effectively. Docking of NS3/4A protease and Flavonoids of Accacia nilotica revealed that most of the flavonoids bound deeply with the active site of NS3/4A protease. Compound 01 showed a high ranking on docking score. All other compounds also showed reliable docking scores and had interactions with the binding cavity of NS3/4A protease, suggesting them as a potent drug candidate to block HCV replication. To recognize binding interactions of Accacia nilotica phytochemicals with NS3/4A protease, molecular docking was performed to find potential inhibitor against NS3/4A protease of HCV. After post docking analysis, important interactions were found between active compounds and active site of NS3/4A protease. It can be concluded from the study that phytochemicals of Accacia nilotica may serve as a potential drug candidate with relatively simple structural changes against HCV NS3/4A protease.

  16. Point -of -care testing (POCT) in molecular diagnostics: Performance evaluation of GeneXpert HCV RNA test in diagnosing and monitoring of HCV infection.

    Science.gov (United States)

    Gupta, Ekta; Agarwala, Pragya; Kumar, Guresh; Maiwall, Rakhi; Sarin, Shiv Kumar

    2017-03-01

    Molecular testing at the point-of-care may turn out to be game changer for HCV diagnosis and treatment monitoring, through increased sensitivity, reduced turnaround time, and ease of performance. One such assay GeneXpert(®) has recently been released. Comparative analysis between performances of GeneXpert(®) and Abbott HCV-RNA was done. 174 HCV infected patients were recruited and, one time plasma samples from 154 patients and repeated samples from 20 patients, obtained at specific treatment time-points (0, 4, 12 and 24) weeks were serially re-tested on Xpert(®). Genotype 3 was the commonest, seen in 80 (66%) of the cases, genotype 1 in 34 (28.3%), genotype 4 in 4 (3.3%) and genotypes 2 and 5 in 1 (0.8%) each. Median HCV RNA load was 4.69 log10 (range: 0-6.98log10) IU/ml. Overall a very good correlation was seen between the two assays (R(2)=0.985), concordance of the results between the assays was seen in 138 samples (89.6%). High and low positive standards were tested ten times on Xpert(®) to evaluate the precision and the coefficient of variation was 0.01 for HPC and 0.07 for the LPC. Monitoring of patients on two different regimes of treatment, pegylated interferon plus ribavirin and sofosbuvir plus ribavirin was done by both the systems at baseline, 4, 12 and 24 weeks. Perfect correlation between the assays in the course of therapy at different treatment time- point in genotypes 3 and 1 was seen. The study demonstrates excellent performance of the Xpert(®) HCV assay in viral load assessment and in treatment course monitoring consistency. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Developing a community HCV service: project ITTREAT (integrated community-based test - stage - TREAT) service for people who inject drugs.

    Science.gov (United States)

    Hashim, Ahmed; O'Sullivan, Margaret; Williams, Hugh; Verma, Sumita

    2017-12-04

    Background and aims Majority of the individuals with hepatitis C virus (HCV) infection in England are people who inject drugs, a vulnerable and disenfranchised cohort with poor engagement with secondary care. Our aim is to describe our experiences in setting up a successful nurse led HCV service at a substance misuse service (SMS). We justify the need for a community HCV service and review the different community based models. Our experiences in engaging with stakeholders, obtaining funding, service set up, challenges faced and key recommendations are discussed. Finally, a summary of interim clinical outcomes is presented. A successful community based "one-stop" nurse led HCV service was set up in Dec 2013 at a large SMS. It provides all aspects of care (blood borne virus screening, non-invasive assessment of hepatic fibrosis, Hepatology input, HCV treatment, peer mentor, social and psychiatrist support, and opiod substitution) at one site. Interim clinical data indicate high service uptake with HCV treatment outcomes comparable to secondary care. The advent of direct acting antivirals provides a unique opportunity for HCV elimination in England by 2030. Our "one-stop" integrated and multidisciplinary community HCV model suggests that HCV care can be successfully delivered outside of a hospital setting and warrants national adoption.

  18. HCV and HIV infection and co-infection: injecting drug use and sexual behavior, AjUDE-Brasil I Project

    Directory of Open Access Journals (Sweden)

    Keli Bahia Felicíssimo Zocratto

    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.

  19. The associated markers and their limitations for the primary screening of HCV carriers in public health examination.

    Science.gov (United States)

    Miyazaki, Teruo; Honda, Akira; Ikegami, Tadashi; Hara, Takashi; Saitoh, Yoshifumi; Hirayama, Takeshi; Doy, Mikio; Matsuzaki, Yasushi

    2009-07-01

    Although the anti-hepatitis C virus (HCV) antibody test has been recommended to the whole Japanese population, most countries have not implemented it. The present study aims to re-evaluate the usefulness of markers examined in the general health examination for the initial screening of HCV carriers. Of the overall population, 25 142 individuals (8876 males, 16 266 females) participated in health examinations with HCV tests in 2005, and the most commonly associated markers for HCV-positive subjects were explored by multivariate analysis, based on blood biochemical, physical, sphygmomanometric and hematological parameters. Thereafter, the efficiencies of the markers were estimated from a total population of 85 013 individuals (29 502 males, 55 511 females) in 2003-2005. The most significantly associated markers for HCV positivity were aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Optimal limits of ALT and AST by receiver-operator characteristic (ROC) analysis were 24 and 27 IU (male, 33 and 28 IU; female, 22 and 26 IU), respectively. However, one-quarter of HCV carriers were not found to be positive using the optimal limits of aminotransferases. The present study confirmed the limitation of serum aminotransferase levels as markers of HCV for primary screening. Therefore, at present, an anti-HCV antibody test is required for the efficient screening of HCV carriers in all health examinations.

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

    Directory of Open Access Journals (Sweden)

    Masato Nakai

    2015-10-01

    Full Text Available 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 (dsRNA. 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.

  1. Pretransplant interferon prevents hepatitis C virus-associated glomerulonephritis in renal allografts by HCV-RNA clearance.

    Science.gov (United States)

    Cruzado, Josep M; Casanovas-Taltavull, Teresa; Torras, Joan; Baliellas, Carme; Gil-Vernet, Salvador; Grinyó, Josep M

    2003-03-01

    The purpose of this study was to examine the effect of pretransplant interferon administration on the occurrence of post-transplant de novo glomerulonephritis in hepatitis C virus (HCV)-positive renal allografts. From December 1992 to December 2000, 78 HCV-positive patients received a renal allograft in our unit. Fifteen out of 78 received pretransplant interferon for 1 year. Hepatitis C virus was investigated by serology and qualitative polymerase chain reaction (PCR). Hepatitis C virus-related de novo glomerulonephritis (membranoproliferative or membranous) was suggested by proteinuria (>1.5 g/24 h) and/or microhematuria and always diagnosed by renal biopsy. Of 15 HCV-positive recipients who received pretransplant interferon, 10 (67%) became HCV-RNA negative at the time of transplantation and only one out of the 15 (6.7%) developed de novo glomerulonephritis (this patient was HCV-RNA positive at transplantation). Among non-interferon-treated allograft recipients, 28.7% had negative HCV-RNA and 12 out of 63 (19%) developed de novo glomerulonephritis (9, membranoproliferative; 3 membranous), all 12 having positive HCV-RNA at transplantation (p < 0.0001). In conclusion, pretransplant interferon may reduce the occurrence of post-transplant HCV-related de novo glomerulonephritis. Our results suggest that the indication for pretransplant interferon should be extended to treat all HCV-RNA positive candidates for renal transplantation.

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

    Directory of Open Access Journals (Sweden)

    Martin Zalesak

    Full Text Available 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.

  3. Serial follow-up of repeat voluntary blood donors reactive for anti-HCV ELISA

    Directory of Open Access Journals (Sweden)

    Choudhury N

    2011-01-01

    Full Text Available Background : Voluntary non-remunerated repeat blood donors are perceived to be safer than the first time blood donors. This study was planned for follow-up of previous hepatitis C virus (HCV test results of anti-HCV enzyme-linked immunosorbent assay (ELISA reactive repeat blood donors. The aim was to suggest a protocol for re-entry of the blood donors who are confirmed HCV negative by nucleic acid test (NAT and recombinant immunoblot assay (RIBA. A group of repeat voluntary donors were followed retrospectively who became reactive on a cross sectional study and showed HCV reactivity while donating blood regularly. Material and Methods: A total of 51,023 voluntary non remunerated blood donors were screened for anti-HCV ELISA routinely. If anybody showed positivity, they were tested by two ELISA kits (screening and confirmatory and then confirmed infection status by NAT and or RIBA. The previous HCV test results of repeat donors reactive by anti-HCV ELISA were looked back from the records. Data of donors who were repeat reactive with single ELISA kit (in the present study were analyzed separately from those reactive with two ELISA kits (in the present study. Results: In this study, 140 (0.27% donors who were reactive by anti HCV ELISA were included. Out of them, 35 were repeat voluntary donors and 16 (11.43% were reactive with single ELISA kit. All 16 donors were reactive by single ELISA kit occasionally in previous donations. Their present ELISA positive donations were negative for HCV NAT and RIBA. A total of 19 (13.57% donors were reactive with two ELISA kits. In their previous donations, the donors who were reactive even once with two ELISA kits were consistently reactive by the same two ELISA kits in their next donations also. Conclusion: Donor sample reactive by only single ELISA kit may not be considered as infectious for disposal as they were negative by NAT and or RIBA. One time ELISA positivity was found probably due to ELISA kit

  4. High seroprevalence of HBV and HCV infection in HIV-infected adults in Kigali, Rwanda.

    Science.gov (United States)

    Rusine, John; Ondoa, Pascale; Asiimwe-Kateera, Brenda; Boer, Kimberly R; Uwimana, Jean Marie; Mukabayire, Odette; Zaaijer, Hans; Mugabekazi, Julie; Reiss, Peter; van de Wijgert, Janneke H

    2013-01-01

    Data on prevalence and incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in Rwanda are scarce. HBV status was assessed at baseline and Month 12, and anti-HCV antibodies at baseline, in a prospective cohort study of HIV-infected patients in Kigali, Rwanda: 104 men and 114 women initiating antiretroviral therapy (ART) at baseline, and 200 women not yet eligible for ART. Baseline prevalence of active HBV infection (HBsAg positive), past or occult HBV infection (anti-HBc positive and HBsAg negative) and anti-HCV was 5.2%, 42.9%, and 5.7%, respectively. The active HBV incidence rate was 4.2/1,000 person years (PY). In a multivariable logistic regression model using baseline data, participants with WHO stage 3 or 4 HIV disease were 4.19 times (95% CI 1.21-14.47) more likely to have active HBV infection, and older patients were more likely to have evidence of past exposure to HBV (aRR 1.03 per year; 95%CI 1.01-1.06). Older age was also positively associated with having anti-HCV antibodies (aOR 1.09; 95%CI 1.04-1.14) while having a higher baseline HIV viral load was negatively associated with HCV (aOR 0.60; 95% CI 0.40-0.98). The median CD4 increase during the first 12 months of ART was lower for those with active HBV infection or anti-HCV at baseline. Almost all participants (88%) with active HBV infection who were on ART were receiving lamivudine monotherapy for HBV. HBV and HCV are common in HIV-infected patients in Rwanda. Regular HBsAg screening is needed to ensure that HIV-HBV co-infected patients receive an HBV-active ART regimen, and the prevalence of occult HBV infection should be determined. Improved access to HBV vaccination is recommended. Active HCV prevalence and incidence should be investigated further to determine whether HCV RNA PCR testing should be introduced in Rwanda.

  5. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Viral Outcome in Patients with Occult HBV Infection or HCV-Ab Positivity Treated for Lymphoma.

    Science.gov (United States)

    Guarino, Maria; Picardi, Marco; Vitello, Anna; Pugliese, Novella; Rea, Matilde; Cossiga, Valentina; Pane, Fabrizio; Caporaso, Nicola; Morisco, Filomena

    2017-01-01

    HBV and HCV reactivation has been widely reported in patients undergoing immunosuppressive therapy for oncohaematological diseases. We aimed to evaluate the HBV and HCV reactivation events in patients with non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) underwent cytotoxic chemotherapy containing or not rituximab. This is a retrospective observational study, including all patients with NHL and HL attending an Italian tertiary referral hospital, the University of Naples "Federico II". A total of 322 patients were enrolled. We evaluated serum HBV and HCV markers. A total of 47 (38%) patients with occult HBV infection were enrolled. Seven/47 were treated with therapeutic cytotoxic schedule containing rituximab. Of them, 6/7 received prophylaxis with lamivudine. HBV reactivation was observed in two patients treated with rituximab. A reactivation was observed in the only patient (HBcAb+/HBsAb+) not receiving lamivudine prophylaxis, and the other one was observed in 1 patient with isolated HBcAb positivity during lamivudine prophylaxis. Moreover, 8 patients with HCV-Ab positivity were enrolled. No viral reactivation was observed in these patients. In conclusion, patients with occult HBV infection receiving chemotherapy containing rituximab for lymphoma without antiviral prophylaxis are at risk of viral reactivation. On the contrary, there is no risk of reactivation in patients undergoing rituximab-free schedule. Our findings suggest that there is also very low risk of HCV reactivation. This preliminary report underlines the concept that HBV reactivationis strongly related to the type of immunosuppressive therapy administered and that antiviral prophylaxis needs to be tailored.

  7. Limiting the access to direct-acting antivirals against HCV: an ethical dilemma.

    Science.gov (United States)

    Gentile, Ivan; Maraolo, Alberto E; Niola, Massimo; Graziano, Vincenzo; Borgia, Guglielmo; Paternoster, Mariano

    2016-11-01

    Hepatitis C virus (HCV) infection affects about 200 million people worldwide and represents a leading cause of liver-related mortality. Eradication of HCV infection, achieved mainly through direct-acting antivirals (DAA), results in a decrease of mortality and an improvement of quality of life. These drugs have a maximal efficacy and an optimal tolerability. However, their high cost precludes a universal access even in wealthy countries. Areas covered: This article deals with the policies adopted for the use of the new anti-HCV drugs, especially in Europe and most of all in Italy, supposedly the developed country with the highest HCV prevalence. The literature search was performed using Pubmed and Web of Science. Moreover, national regulatory institutional websites were consulted. Expert commentary: The current policy of limitation to the access of the DAA presents a series of ethical issues that makes it non-applicable. A 'treat-all' strategy should resolve all ethical dilemmas, by virtue of the wide benefits of anti-HCV treatment not only for the advanced stage of infection, but also for the initial stages. A reduction in price of the drugs is the actual condition to achieve such a change.

  8. In vitro anti-HCV activities of Saxifraga melanocentra and its related polyphenolic compounds.

    Science.gov (United States)

    Zuo, Guo-Ying; Li, Zheng-Quan; Chen, Li-Rong; Xu, Xiao-Jie

    2005-01-01

    The aim of this study was to search for new natural anti-HCV agents from Chinese herbal medicine. Bioactivity-guided extraction and isolation methods were used. Active part and pure compounds were obtained from ethanolic extract of Saxifraga melanocentra Franch. and their in vitro inhibitory activities (IC50) against HCV NS3 serine protease were tested by enzyme-linked immunosorbent assay. Results showed that the polyphenolic ethyl acetate part of the herbal extract was the most active, and from this 18 polyphenols representing active compounds were isolated and identified. IC50 values of these compounds and five related ones were obtained. A broad-degree of anti-HCV activity was observed among them in the following order: gallated esters of D-glucose and rutin (0.68-4.86 microM)> flavonoids (33.11-370.37 microM)> gallic acid and its methyl and ethyl esters, Bergenin and others (over 1000 microM). The most active compound was 1,2,3,4,6-penta-O-galloyl-beta-D-glucoside (0.68 microM). In conclusion, polyphenols were responsible for the anti-HCV constitution of S. melanocentra, and multigallated esters of D-glucose possessed the strongest inhibition against HCV NS3 serine protease and little cytotoxic effect, suggesting the potential use of these compounds for designing and developing drugs for treatment of the viral infection.

  9. Ledipasvir : a novel synthetic antiviral for the treatment of HCV infection.

    Science.gov (United States)

    Gentile, Ivan; Buonomo, Antonio Riccardo; Borgia, Federico; Castaldo, Giuseppe; Borgia, Guglielmo

    2014-04-01

    About 150,000,000 people worldwide are chronically infected with hepatitis C virus (HCV). HCV infection can lead to liver cirrhosis, hepatocellular carcinoma and death. Treatment was based previously only on pegylated interferon combined with other antiviral drugs. Recently, the first interferon-free combination for patients with genotype 2 or 3 was approved in the USA and Europe, and several molecules are in an advanced phase of clinical development. This review focuses on the pharmacokinetics, pharmacodynamics and tolerability of ledipasvir , an inhibitor of HCV nonstructural 5A protein. The authors also highlight the drug's safety and resistance profile. The pharmacokinetic profile and antiviral activity of ledipasvir are ideal. However, given the high rate of natural and drug-related ledipasvir-resistant HCV mutations, ledipasvir is administered in combination regimens with other antiviral drugs, which resulted in a cure rate up to 100%. While ledipasvir is effective in patients with genotype 1 chronic hepatitis C, its efficacy remains to be established in patients with genotype 4, 5 or 6, in subjects with HIV coinfection, in hemodialyzed and elderly patients and in subjects with decompensated cirrhosis. If the excellent results of combination therapy be confirmed in larger trials, hepatologists will have the possibility to cure most HCV-positive patients in the near future.

  10. Decrease of HCV seroprevalence in Mexico: Results from the National Health and Nutrition Survey 2012

    Directory of Open Access Journals (Sweden)

    Juan Pablo Gutiérrez

    2016-01-01

    Full Text Available Objective. To estimate seroprevalence of hepatitis C virus (HCV among 15-49 years old Mexicans living in households and to describe the profile of seroreactive individuals. Materials and methods. Cross-sectional study implemented in 2012 using a national probabilistic sample with behavioral data from face-to-face interviews at households and HCV antibodies screening using capillary blood from same individuals. Results. HCV seroprevalence in Mexico was estimated at 0.27% (IC95% 0.12-0.60, representing 161 000 persons. Seroprevalence was significantly higher among males (0.45% CI95% 0.01-0.89 than females (0.10% CI95% 0.00-0.22. Multivariate analysis suggests a higher possibility of HCV reactivity among men, increasing with age and higher among those sexually active, and lower for higher socioeconomic level. Conclusion. HCV seroprevalence in Mexico by 2012 seems significantly lower than the estimation from 2000 of 1.2% for the same age-group. Evidence of infection among individuals 15-19 years old suggests the need to strength pre- ventive actions, particularly in subjects with risky behaviors.

  11. [Decrease of HCV seroprevalence in Mexico: Results from the National Health and Nutrition Survey 2012].

    Science.gov (United States)

    Gutiérrez, Juan Pablo; Sucilla-Pérez, Héctor; Conde-González, Carlos J; Izazola, José Antonio; Romero-Martínez, Martin; Hernández-Ávila, Mauricio

    2016-01-01

    To estimate seroprevalence of hepatitis C virus (HCV) among 15-49 years old Mexicans living in households and to describe the profile of seroreactive individuals. Cross-sectional study implemented in 2012 using a national probabilistic sample with behavioral data from face-to-face interviews at households and HCV antibodies screening using capillary blood from same individuals. HCV seroprevalence in Mexico was estimated at 0.27% (IC95% 0.12-0.60), representing 161 000 persons. Seroprevalence was significantly higher among males (0.45% CI95% 0.01-0.89) than females (0.10% CI95% 0.00-0.22). Multivariate analysis suggests a higher possibility of HCV reactivity among men, increasing with age and higher among those sexually active, and lower for higher socioeconomic level. HCV seroprevalence in Mexico by 2012 seems significantly lower than the estimation from 2000 of 1.2% for the same age-group. Evidence of infection among individuals 15-19 years old suggests the need to strength preventive actions, particularly in subjects with risky behaviors.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Preoperative Seroprevalence of HBsAg, Anti-HCV, Anti-HIV in general surgery patients

    Directory of Open Access Journals (Sweden)

    Sadullah Girgin

    2009-01-01

    Full Text Available Objectives: Exposure to blood borne pathogens is the most serious occupational health risk faced by health-care workers. The aim of this study was to evaluate the preoperative seroprevalences of HBsAg, anti-HCV and anti-HIV.Materials and methods: In this study we evaluated the seroprevalence of HBsAg, anti-HCV and anti-HIV in 486 preoperative patients who admitted to Dicle University Medical Faculty General Surgery Clinic for elective sur-gical procedures between January 2007 and July 2007; retrospectively. The results were compared with those of 14354 blood donations during the same period as con-trol group.Results: The seroprevalence of HBsAg and anti-HCV were; %6.6 and %1.6 subsequently in preoperative pa-tients. HBsAg and anti-HCV seropositivity rates were lower in the control group. Thus, the positively rates of HBsAg and anti-HCV for preoperative patients should be assessed higher than the data obtained from the blood bank. Anti-HIV seropositivity was not detected in both patient and control group. Conclusion: All healthcare workers must be trained about occupational diseases and vaccinated against he-patitis B. Establishment of universal precautions is nec-essary and these precautions must be strictly followed particularly in the operating room. In addition all patients should be considered as potential carriers.

  14. Prevalence and Factors Associated with HCV (Hepatitis C Virus Seropositivity in Islamabad, Pakistan

    Directory of Open Access Journals (Sweden)

    Hammad Ali Qazi

    2010-12-01

    Full Text Available An estimated 150-200 million people worldwide are infected with hepatitis C. Prevalence is higher in some countries in Asia and Africa. Only limited information about the epidemiology of Hepatitis C Virus (HCV infection especially in females is available. The aim of this study is to determine the prevalence of anti-HCV antibodies and the possible factors for transmission in the female population of a largely urban city Islamabad. A cross sectional study was conducted from May 2006 to August 2006 in Islamabad. We select 252 female households (n=252 following the selection criteria. The primary outcome variables were HCV seropositivity and factors like history of major surgical procedure, blood transfusion, Intravenous drug use etc. The results showed mean age of the sample was 33.21 (±9.95 years and HCV seropositivity was present in 62 (24.6% females. Final Forward Stepwise multiple logistic regression showed blood transfusion [OR, 10.094 95% CI 1.950-52.257], dental procedure [OR, 5.381 95% CI 2.315-12.507] and dilation and curettage [OR, 3.869 95% 1.867-8.015] were significantly associated with HCV seropositivity in females. The study highlights poor quality of care provided and a massive need to educate general population including patients as well as health professionals and allied health workers.

  15. Prevalence and Factors Associated with HCV (Hepatitis C Virus Seropositivity in Islamabad, Pakistan

    Directory of Open Access Journals (Sweden)

    Hammad Ali Qazi

    2010-11-01

    Full Text Available "nAn estimated 150-200 million people worldwide are infected with hepatitis C. Prevalence is higher in some countries in Asia and Africa. Only limited information about the epidemiology of Hepatitis C Virus (HCV infection especially in females is available. The aim of this study is to determine the prevalence of anti-HCV antibodies and the possible factors for transmission in the female population of a largely urban city Islamabad. A cross sectional study was conducted from May 2006 to August 2006 in Islamabad. We select 252 female households (n=252 following the selection criteria. The primary outcome variables were HCV seropositivity and factors like history of major surgical procedure, blood transfusion, Intravenous drug use etc. The results showed mean age of the sample was 33.21 (±9.95 years and HCV seropositivity was present in 62 (24.6% females. Final Forward Stepwise multiple logistic regression showed blood transfusion [OR, 10.094 95% CI 1.950-52.257], dental procedure [OR, 5.381 95% CI 2.315-12.507] and dilation and curettage [OR, 3.869 95% 1.867-8.015] were significantly associated with HCV seropositivity in females. The study highlights poor quality of care provided and a massive need to educate general population including patients as well as health professionals and allied health workers.

  16. The effect of HIV infection and HCV viremia on inflammatory mediators and hepatic injury-The Women's Interagency HIV Study.

    Directory of Open Access Journals (Sweden)

    Sheila M Keating

    Full Text Available Hepatitis C virus infection induces inflammation and while it is believed that HIV co-infection enhances this response, HIV control may reduce inflammation and liver fibrosis in resolved or viremic HCV infection. Measurement of systemic biomarkers in co-infection could help define the mechanism of inflammation on fibrosis and determine if HIV control reduces liver pathology. A nested case-control study was performed to explore the relationship of systemic biomarkers of inflammation with liver fibrosis in HCV viremic and/or seropositive women with and without HIV infection. Serum cytokines, chemokines, growth factors and cell adhesion molecules were measured in HIV uninfected (HIV-, n = 18, ART-treated HIV-controlled (ARTc, n = 20, uncontrolled on anti-retroviral therapy (ARTuc, n = 21 and elite HIV controllers (Elite, n = 20. All were HCV seroreactive and had either resolved (HCV RNA-; <50IU/mL or had chronic HCV infection (HCV RNA+. In HCV and HIV groups, aspartate aminotransferase to platelet ratio (APRI was measured and compared to serum cytokines, chemokines, growth factors and cell adhesion molecules. APRI correlated with sVCAM, sICAM, IL-10, and IP-10 levels and inversely correlated with EGF, IL-17, TGF-α and MMP-9 levels. Collectively, all HCV RNA+ subjects had higher sVCAM, sICAM and IP-10 compared to HCV RNA-. In the ART-treated HCV RNA+ groups, TNF-α, GRO, IP-10, MCP-1 and MDC were higher than HIV-, Elite or both. In ARTuc, FGF-2, MPO, soluble E-selectin, MMP-9, IL-17, GM-CSF and TGF-α are lower than HIV-, Elite or both. Differential expression of soluble markers may reveal mechanisms of pathogenesis or possibly reduction of fibrosis in HCV/HIV co-infection.

  17. Exploiting hepatitis C virus activation of NFkappaB to deliver HCV-responsive expression of interferons alpha and gamma.

    Science.gov (United States)

    Matskevich, A A; Strayer, D S

    2003-10-01

    Chronic infection with hepatitis C virus (HCV) may lead to liver failure and hepatocellular carcinoma. Current treatment for HCV includes high systemic doses of interferonalpha (IFNalpha), which is effective in less than half of patients and may have severe side effects. We designed conditional IFNalpha and IFNgamma expression constructs to be triggered by HCV-induced activation of NFkappaB, and delivered these using highly efficient recombinant Tag-deleted SV40-derived vectors. NFkappaB activates the HIV-1NL4-3 long terminal repeat (HIVLTR) as a promoter, which accounts for the conditional transgene expression. Human hepatocyte lines and primary rat hepatocytes (PRH) were transduced with SV[HIVLTR](IFN) vectors, and transfected with HCV cDNA. Production of human and murine IFNalpha and IFNgamma in cytosol and culture supernatants was measured. HCV activated the HIVLTR to produce and secrete IFNs, and did so largely through the NFkappaB binding sites of the HIVLTR. Levels of IFNs secreted, and the magnitude of induction in response to HCV, were greater in hepatocyte lines than in primary cultured hepatocytes. However, even in the latter, supernatant IFNalpha concentrations achieved by this approach were similar to therapeutic serum concentrations sought in systemic IFNalpha-treated patients. In coculture studies, secreted IFNalpha activated its cognate response elements in untransduced cells, suggesting that its potential inhibitory effects on HCV may not be limited to transduced cells. Although HCV replication in culture is difficult to assess, HCV-induced IFNalpha production demonstrably reduced HCV transcription. Conditional expression of IFNs within the liver may represent an attractive approach to therapy of severe chronic HCV infection that could avoid the side effects of systemic treatment regimens.

  18. Social determinants and risk behaviors associated with prevalent Hepatitis C and HIV/HCV co-infection among male injection drug users in Nepal.

    Science.gov (United States)

    Kakchapati, Sampurna; Maharjan, Manju; Rawal, Bir Bahadhur; Dixit, Sameer Mani

    2017-01-01

    Nepal is facing double burden of injecting drug use and HIV, yet the problem of Hepatitis C Virus (HCV) has not been so well addressed, where there is large population known to be at risk for HCV. This study assessed the prevalence of HCV infection and HIV/HCV co-infection among male injection drug users (IDUs) in Nepal and identified factors associated with infection. Cross-sectional surveys in 2015 aimed to sample 1045 male IDUs in the Kathmandu valley, Pokhara Valley and Eastern Terai districts of Nepal. Information about socio demographic characteristics, injecting and sexual risk behaviours were obtained, and biological specimens tested for HCV and HIV. The logistic regression model was used to identify the determinants associated with HCV and HIV/HCV co-infection. HCV prevalence was 28.8% and HIV/HCV co-infection was 4%. Among the 6% of HIV positive male IDUs, 65% were found to be co-infected. The multivariate logistic analysis revealed that HCV prevalence was higher in Eastern Terai districts, longer duration of drug use and injecting drugs and presence of HIV. Similarly, HIV/HCV co-infection was associated with Eastern highway districts, older age and longer duration of injecting drugs. The factors strongly contributing to HCV and HIV/HCV co-infection was longer duration of injecting drugs. Highest HCV and HIV/HCV co-infection was found in Eastern Terai districts. Target health interventions need to be focused in Eastern Terai districts and IDUs with longer duration of injecting drugs for the prevention of HCV and HIV/HCV transmission.

  19. Exosomes from Hepatitis C Infected Patients Transmit HCV Infection and Contain Replication Competent Viral RNA in Complex with Ago2-miR122-HSP90

    Science.gov (United States)

    Kodys, Karen; Bala, Shashi; Szabo, Gyongyi

    2014-01-01

    Antibodies targeting receptor-mediated entry of HCV into hepatocytes confer limited therapeutic benefits. Evidence suggests that exosomes can transfer genetic materials between cells; however, their role in HCV infection remains obscure. Here, we show that exosomes isolated from sera of chronic HCV infected patients or supernatants of J6/JFH1-HCV-infected Huh7.5 cells contained HCV RNA. These exosomes could mediate viral receptor-independent transmission of HCV to hepatocytes. Negative sense HCV RNA, indicative of replication competent viral RNA, was present in exosomes of all HCV infected treatment non-responders and some treatment-naïve individuals. Remarkably, HCV RNA was associated with Ago2, HSP90 and miR-122 in exosomes isolated from HCV-infected individuals or HCV-infected Huh7.5 cell supernatants. Exosome-loading with a miR-122 inhibitor, or inhibition of HSP90, vacuolar H+-ATPases, and proton pumps, significantly suppressed exosome-mediated HCV transmission to naïve cells. Our findings provide mechanistic evidence for HCV transmission by blood-derived exosomes and highlight potential therapeutic strategies. PMID:25275643

  20. Exosomes from hepatitis C infected patients transmit HCV infection and contain replication competent viral RNA in complex with Ago2-miR122-HSP90.

    Science.gov (United States)

    Bukong, Terence N; Momen-Heravi, Fatemeh; Kodys, Karen; Bala, Shashi; Szabo, Gyongyi

    2014-10-01

    Antibodies targeting receptor-mediated entry of HCV into hepatocytes confer limited therapeutic benefits. Evidence suggests that exosomes can transfer genetic materials between cells; however, their role in HCV infection remains obscure. Here, we show that exosomes isolated from sera of chronic HCV infected patients or supernatants of J6/JFH1-HCV-infected Huh7.5 cells contained HCV RNA. These exosomes could mediate viral receptor-independent transmission of HCV to hepatocytes. Negative sense HCV RNA, indicative of replication competent viral RNA, was present in exosomes of all HCV infected treatment non-responders and some treatment-naïve individuals. Remarkably, HCV RNA was associated with Ago2, HSP90 and miR-122 in exosomes isolated from HCV-infected individuals or HCV-infected Huh7.5 cell supernatants. Exosome-loading with a miR-122 inhibitor, or inhibition of HSP90, vacuolar H+-ATPases, and proton pumps, significantly suppressed exosome-mediated HCV transmission to naïve cells. Our findings provide mechanistic evidence for HCV transmission by blood-derived exosomes and highlight potential therapeutic strategies.

  1. Sustained virologic response following HCV eradication in two brothers with X-linked agammaglobulinaemia.

    LENUS (Irish Health Repository)

    Houlihan, Diarmaid D

    2009-08-21

    X-linked agammaglobulinaemia (XLA) is a humoral immunodeficiency syndrome characterized from childhood by the absence of circulating B lymphocytes, absent or reduced levels of serum immunoglobulin and recurrent bacterial infections. For many affected patients, regular treatment with immunoglobulin is life saving. Hepatitis C viral (HCV) infection acquired through contaminated blood products is widely described in this patient cohort. The natural history of HCV infection in patients with XLA tends to follow a more rapid and aggressive course compared to immunocompetent individuals. Furthermore, standard anti-viral therapy appears to be less efficacious in this patient cohort. Here we report the cases of two brothers with XLA who contracted HCV through contaminated blood products. They were treated with a six month course of Interferon alpha-2b and Ribavirin. We report a sustained virologic response five years after completing treatment.

  2. Ledipasvir/sofosbuvir: the fixed dose combination in the new era of treatment for HCV

    Directory of Open Access Journals (Sweden)

    Alessia Ciancio

    2015-07-01

    Full Text Available Interferon-based treatment is not suitable for many patients with hepatitis C virus (HCV infection because of contraindications, other reasons for ineligibility and side-effects. The fixed dosed combination ledipasvir/sofosbuvir (LDV / SOF is the first approved regimen that doesn’t require administration with interferon or ribavirin. LDV / SOF is also the first single-pill approved for the treatment of chronic HCV genotype 1 in both treatment-naïve and treatment-experienced patients. The results of the phase III studies demonstrate the combination has been very well tolerated and SVR rates consistently above 90%. Objective of this review is to present clinical evidence of efficacy and safety of the combination LDV / SOF in different subgroups of patients with HCV.

  3. Potent inhibitors of HCV-NS3 protease derived from boronic acids

    Energy Technology Data Exchange (ETDEWEB)

    Venkatraman, Srikanth; Wu, Wanli; Prongay, Andrew; Girijavallabhan, Viyyoor; Njoroge, F. George; (SPRI)

    2009-07-23

    Chronic hepatitis C infection is the leading causes for cirrhosis of the liver and hepatocellular carcinoma, leading to liver failure and liver transplantation. The etiological agent, HCV virus produces a single positive strand of RNA that is processed with the help of serine protease NS3 to produce mature virus. Inhibition of NS3 protease can be potentially used to develop effective drugs for HCV infections. Numerous efforts are now underway to develop potent inhibitors of HCV protease that contain ketoamides as serine traps. Herein we report the synthesis of a series of potent inhibitors that contain a boronic acid as a serine trap. The activity of these compounds were optimized to 200 pM. X-ray structure of compound 17 bound to NS3 protease is also discussed.

  4. [Cognitive performances in workers with chronic virus hepatitis (HBV-HCV)].

    Science.gov (United States)

    Micali, E; Squadrito, G; Abbate, C; Raimondo, G; Trimarchi, F; Barbaro, M

    2007-01-01

    Chronic condition in subjects with chronic viral hepatitis determines issues neuropsychic. The sample of 21 workers suffering from chronic viral hepatitis in drug treatment has been studied with a battery of standardized tests to assess the cognitive performance, the neurobehavioral effects and psychological disorders that interfere with quality of life, comparing the results of subjects with HBV with those of subjects suffering from HCV. The results showed that both subjects with chronic HBV and HCV have relational-work restrictions that determine long periods of absence from the workplace, with the depression, anxiety, irritability and dysphoria. It is that in patients with chronic HCV physical functioning is significantly impaired with clinical manifestations of the disease that lead to major depression and deficit cognitive function.

  5. The Shift in Emphasis From Risk-Based to Age-Based Hepatitis C Virus (HCV) Testing in the US Tends to Remove Injection Drug Use From Discourse on HCV.

    Science.gov (United States)

    Jordan, Ashly E; Perlman, David C

    2017-02-23

    Hepatitis C virus (HCV) infection is hyperendemic among people who inject drugs; nonsterile drug injection is the principle risk for HCV acquisition. Due to gaps in the HCV care continuum, there have been recommendations in the United States emphasizing age-rather than risk-based testing strategies. The central research focus of this project is to explore the meanings and implications of the shift in emphasis from risk-based to age-based HCV testing with regard to people who use drugs. Content analysis and critical discourse analysis, informed by eco-social theory, were used to examine relevant documents. Fifteen documents were assessed for eligibility; 6 documents comprised the final set reviewed. In content analysis, age-based testing was both mentioned more frequently and was supported more strongly than risk-based testing. Risk-based testing was frequently mentioned in terms minimizing its use and drug use was often mentioned only euphemistically. The reframed emphasis largely removed discussion of injection drug use from discussion of HCV risks. Shifting the emphasis of HCV testing from testing based on specific routes of transmission and risk to testing based on age removes injection drug use from HCV discourse. This has the potential to either facilitate HCV care for drug users or to further stigmatize and marginalize drug use and people who use drugs. The potential implications of this shift in testing emphasis for public health merit further investigation.

  6. PEG-Interferon-α ribavirin-induced HCV viral clearance: a pharmacogenetic multicenter Spanish study

    Directory of Open Access Journals (Sweden)

    Javier Milara

    2015-01-01

    Full Text Available Objective: Dual PEGylated interferon-(PEG-IFN and ribavirin therapy has been the main hepatitis C virus (HCV treatment of the last decade. Current direct-acting antiviral agents have improved the outcome of therapy but also have increased the cost and management complexity of treatment. The current study analyzes host genetics, viral and clinical predictors of sustained viral response (SVR to dual PEG-IFN and ribavirin therapy in a representative Spanish population. Methods: Observational prospective multicentre pharmacogenetic cohort study conducted in 12 different hospitals of 12 different Spanish regions. A total of 98 patients with SVR and 106 with non-SVR in response to PEG-IFN and ribavirin therapy were included. 33 single nucleotide polymorphisms located in 24 different genes related with inflammatory, immune and virus response were selected. Clinical and viral data were also analyzed as candidate of SVR predictors. Results: IL-28B (rs12979860, rs7248668, rs8105790, rs8099917 and TNFRSF1B (rs1061622 genotypes, as well as TNFRSF1B/IL-10/TNF(-308 non-TTG and TNFRSF1B/IL- 10/IL-4 non-TTC haplotypes together with lower age, lower basal HCV RNA load, higher basal serum LDL cholesterol values, VHC genotypes 2 and 3 and basal low grade fibrosis 0-2 were associated with a SVR in the univariate analysis. Independent predictors of SVR in the multivariate analysis were IL-28B rs12979860 CC, TNFRSF1B/IL-10/IL-4 non-TTC along with low baseline HCV RNA load and HCV genotypes 2 and 3. Conclusions: IL-28B rs12979860 CC, TNFRSF1B/ IL-10/ IL-4 non-TTC haplotype, low baseline HCV RNA load and HCV genotypes 2 and 3 may help to predict successful outcome to PEG-IFN/ribavirin therapy in Spanish population

  7. HCV eradication does not impact gut dysbiosis or systemic inflammation in cirrhotic patients.

    Science.gov (United States)

    Bajaj, J S; Sterling, R K; Betrapally, N S; Nixon, D E; Fuchs, M; Daita, K; Heuman, D M; Sikaroodi, M; Hylemon, P B; White, M B; Ganapathy, D; Gillevet, P M

    2016-09-01

    Eradication of hepatitis C virus (HCV) is increasing but its residual impact on the pro-inflammatory milieu in cirrhosis, which is associated with gut dysbiosis, is unclear. To define the impact of sustained virological response (SVR) on gut dysbiosis and systemic inflammation in HCV cirrhosis patients. Cirrhotic out-patients with HCV with/without SVR (achieved >1 year prior) and age-matched healthy controls underwent serum and stool collection. Serum was analysed for IL-6, TNF-α and endotoxin while stool microbiota analysis was performed using multitagged pyrosequencing. Microbial comparisons were made using UNIFRAC and cirrhosis dysbiosis ratio (lower score indicates dysbiosis). Comparisons were performed between cirrhotics with/without SVR and controls vs. cirrhotic patients. A total of 105 HCV cirrhotics and 45 age-matched healthy controls were enrolled. Twenty-one patients had achieved SVR using pegylated interferon + ribavrin a median of 15 months prior. No significant differences on demographics, cirrhosis severity, concomitant medications or diabetes were seen between cirrhotics with/without SVR. There was no significant difference in overall microbiota composition (UNIFRAC P = 0.3) overall or within specific microbial families (cirrhosis dysbiosis ratio median 1.3 vs. 1.0, P = 0.45) between groups with/without SVR. This also extended towards IL-6, TNF-α and endotoxin levels. Both cirrhosis groups, however, had significant dysbiosis compared to healthy controls [UNIFRAC P = 0.01, cirrhosis dysbiosis ratio (1.1 vs. 2.9, P dysbiosis and a pro-inflammatory systemic milieu, are found in HCV cirrhosis regardless of SVR. This persistent dysbiosis could contribute towards varying rates of improvement after HCV eradication in cirrhosis. © 2016 John Wiley & Sons Ltd.

  8. Large scale screening of human sera for HCV RNA and GBV-C RNA.

    Science.gov (United States)

    Keys, Jessica R; Leone, Peter A; Eron, Joseph J; Alexander, Kelcie; Brinson, Myra; Swanstrom, Ronald

    2014-03-01

    North Carolina locates acute HIV cases by pooled nucleic acid testing of HIV-antibody negative serum samples. Here, 224 pools of 80 HIV-negative samples (N = 17,920) were screened for viral RNA from HCV, GBV-C, and influenza A. No evidence of influenza A was found, but HCV and GBV-C were common (1.2% and 1.7% prevalence, respectively), demonstrating the utility of pooled testing in locating individuals that may remain undiagnosed otherwise. By sequencing positive pools, potential transmission clusters may be located as well. © 2013 Wiley Periodicals, Inc.

  9. HBV reactivation in patients with HCV/HBV cirrhosis on treatment with direct-acting antivirals.

    Science.gov (United States)

    Calvaruso, V; Ferraro, D; Licata, A; Bavetta, M G; Petta, S; Bronte, F; Colomba, G; Craxì, A; Di Marco, V

    2017-07-13

    Anecdotal reports suggest that patients with chronic hepatitis C virus (HCV) hepatitis and overt or occult hepatitis B virus (HBV) coinfection may reactivate HBV when HCV is suppressed or cleared by direct-acting antivirals (DAAs). We assessed the prevalence of overt or previous HBV coinfection and the risk of HBV reactivation in patients with HCV cirrhosis treated with DAAs. This was a retrospective cohort of 104 consecutive patients with HCV cirrhosis treated with DAAs. Serum HCV-RNA and HBV-DNA were tested at weeks 4, 8 and 12 of DAAs therapy and at week 12 of follow-up. At the start of DAAs, eight patients (7.7%) were HBsAg positive/HBeAg negative with undetectable HBV-DNA and low levels of quantitative HBsAg (four on nucleos(t)ide analogues [NUCs] and four inactive carriers), 37 patients (35.6%) had markers of previous HBV infection (25 anti-HBc positive, 12 anti-HBc/anti-HBs positive) and 59 (56.7%) had no evidence of HBV infection. Sixty-seven patients (64.4%) were HCV-RNA negative at week 4 and 98 (94.2%) achieved sustained virological response. All four HBsAg-positive patients treated with NUCs remained HBV-DNA negative, but three of four untreated patients showed an increase in HBV-DNA of 2-3 log without a biochemical flare and achieved HBV-DNA suppression when given NUCs. During or after DAAs, by conventional assay, HBV-DNA remained not detectable in all 37 anti-HBc-positive patients but in three of them (8.1%) HBV-DNA became detectable with a highly sensitive PCR. HBV reactivation is likely to occur in untreated HBV/HCV-coinfected cirrhotic patients when they undergo HCV treatment with DAAs. Pre-emptive therapy with NUCs should be considered in this setting. Anti-HBc-positive patients rarely reactivate HBV without clinical or virological outcomes. © 2017 John Wiley & Sons Ltd.

  10. Dynamics of an HBV/HCV infection model with intracellular delay and cell proliferation

    Science.gov (United States)

    Zhang, Fengqin; Li, Jianquan; Zheng, Chongwu; Wang, Lin

    2017-01-01

    A new mathematical model of hepatitis B/C virus (HBV/HCV) infection which incorporates the proliferation of healthy hepatocyte cells and the latent period of infected hepatocyte cells is proposed and studied. The dynamics is analyzed via Pontryagin's method and a newly proposed alternative geometric stability switch criterion. Sharp conditions ensuring stability of the infection persistent equilibrium are derived by applying Pontryagin's method. Using the intracellular delay as the bifurcation parameter and applying an alternative geometric stability switch criterion, we show that the HBV/HCV infection model undergoes stability switches. Furthermore, numerical simulations illustrate that the intracellular delay can induce complex dynamics such as persistence bubbles and chaos.

  11. Late Diabetic Complications in Patients with Diabetis Mellitus Type 2 Combined with HCV-Infection

    Directory of Open Access Journals (Sweden)

    M.A. Derbak

    2013-09-01

    Full Text Available The study presents the examinations results of 317 patients with dіabetes mellіtus (DM type 2, who underwent treatment іn the endocrіnological and surgical departments of the Transcarpathіan regional clinical hospital named after A. Novak in 2010–2012. We studied the frequency and characteristics of late diabetic complications in patients with DM type 2 with HCV-infection and without it. It was found that in patients with DM type 2 with HCV-infection such complications as diabetic foot and diabetic nephropathy were registered significantly more often than in patients without the virus.

  12. HCV core protein promotes hepatocyte proliferation and chemoresistance by inhibiting NR4A1

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Yongsheng, E-mail: yongshengtanwhu@126.com; Li, Yan, E-mail: liyansd2@163.com

    2015-10-23

    This study investigated the effect of HCV core protein on the proliferation of hepatocytes and hepatocellular carcinoma cells (HCC), the influence of HCV core protein on HCC apoptosis induced by the chemotherapeutic agent cisplatin, and the mechanism through which HCV core protein acts as a potential oncoprotein in HCV-related HCC by measuring the levels of NR4A1 and Runt-related transcription factor 3 (RUNX3), which are associated with tumor suppression and chemotherapy resistance. In the present study, PcDNA3.1-core and RUNX3 siRNA were transfected into LO2 and HepG2 cells using Lipofectamine 2000. LO2-core, HepG2-core, LO2-RUNX3 {sup low} and control cells were treated with different concentrations of cisplatin for 72 h, and cell proliferation and apoptosis were assayed using the CellTiter 96{sup ®}Aqueous Non-Radioactive Cell Proliferation Assay Kit. Western blot and real time PCR analyses were used to detect NR4A1, RUNX3, smad7, Cyclin D1 and BAX. Confocal microscopy was used to determine the levels of NR4A1 in HepG2 and HepG2-core cells. The growth rate of HepG2-core cells was considerably greater than that of HepG2 cells. HCV core protein increased the expression of cyclin D1 and decreased the expressions of NR4A1 and RUNX3. In LO2 – RUNX3 {sup low}, the rate of cell proliferation and the level of cisplatin resistance were the same as in the LO2 -core. These results suggest that HCV core protein decreases the sensitivity of hepatocytes to cisplatin by inhibiting the expression of NR4A1 and promoting the expression of smad7, which negatively regulates the TGF-β pathway. This effect results in down regulation of RUNX3, a target of the TGF-β pathway. Taken together, these findings indicate that in hepatocytes, HCV core protein increases drug resistance and inhibits cell apoptosis by inhibiting the expressions of NR4A1 and RUNX3. - Highlights: • HCV core protein inhibits HepG2 cell sensitivity to cisplatin. • Core expression in HepG2 decreases

  13. Model projections on the impact of HCV treatment in the prevention of HCV transmission among people who inject drugs in Europe"

    DEFF Research Database (Denmark)

    Fraser, Hannah; Martin, Natasha K; Brummer-Korvenkontio, Henrikki

    2018-01-01

    among PWID. RESULTS: At baseline, chronic HCV prevalence varied from 55% (Finland/Sweden), and Hamburg/Norway/Denmark/Sweden) to 5% (Slovenia/Czech Republic) of chronically infected PWID were treated annually. Current treatment rates using new direct...... acting antivirals (DAAs) may achieve observable reductions in chronic prevalence (38-63%) in 10 years in Czech Republic, Slovenia and Amsterdam. Doubling HCV-treatment rates will reduce prevalence in other sites (12-24%, Belgium/Denmark/Hamburg/Norway/Scotland) but is unlikely to reduce prevalence...... to substantial increases in current treatment rates are required to achieve the same impact elsewhere, from 1.4-3 times (Czech Republic/France), 5-17 times (France/Scotland/Hamburg/Norway/Denmark/Belgium/Sweden), to 200 times (Finland). Scaling-up OST and NSP coverage to 80% in all sites reduces treatment scale...

  14. Epidemic dispersion of HIV and HCV in a population of co-infected Romanian injecting drug users.

    Science.gov (United States)

    Paraschiv, Simona; Banica, Leontina; Nicolae, Ionelia; Niculescu, Iulia; Abagiu, Adrian; Jipa, Raluca; Pineda-Peña, Andrea-Clemencia; Pingarilho, Marta; Neaga, Emil; Theys, Kristof; Libin, Pieter; Otelea, Dan; Abecasis, Ana

    2017-01-01

    Co-infections with HIV and HCV are very frequent among people who inject drugs (PWID). However, very few studies comparatively reconstructed the transmission patterns of both viruses in the same population. We have recruited 117 co-infected PWID during a recent HIV outbreak in Romania. Phylogenetic analyses were performed on HIV and HCV sequences in order to characterize and compare transmission dynamics of the two viruses. Three large HIV clusters (2 subtype F1 and one CRF14_BG) and thirteen smaller HCV transmission networks (genotypes 1a, 1b, 3a, 4a and 4d) were identified. Eighty (65%) patients were both in HIV and HCV transmission chains and 70 of those shared the same HIV and HCV cluster with at least one other patient. Molecular clock analysis indicated that all identified HIV clusters originated around 2006, while the origin of the different HCV clusters ranged between 1980 (genotype 1b) and 2011 (genotypes 3a and 4d). HCV infection preceded HIV infection in 80.3% of cases. Coincidental transmission of HIV and HCV was estimated to be rather low (19.65%) and associated with an outbreak among PWID during detention in the same penitentiary. This study has reconstructed and compared the dispersion of these two viruses in a PWID population.

  15. The Molecular Epidemiological Study of HCV Subtypes among Intravenous Drug Users and Non-Injection Drug Users in China.

    Directory of Open Access Journals (Sweden)

    Jun Tao

    Full Text Available More than half of intravenous drug users (IDUs in China suffer from the Hepatitis C virus (HCV. The virus is also more prevalent in non-injection drug users (NIDUs than in the general population. However, not much is known about HCV subtype distribution in these populations.Our research team conducted a cross-sectional study in four provinces in China. We sampled 825 IDUs and 244 NIDUs (1162 total, genotyped each DU's virus, and performed a phylogenetic analysis to differentiate HCV subtypes.Nucleic acid testing (NAT determined that 82% percent (952/1162 of samples were HCV positive; we subtyped 90% (859/952 of these. We found multiple HCV subtypes: 3b (249, 29.0%, 3a (225, 26.2%, 6a (156, 18.2%, 1b (137, 15.9%, 6n (50, 5.9%, 1a (27, 3.1%, and 2a (15, 1.7%. An analysis of subtype distributions adjusted for province found statistically significant differences between HCV subtypes in IDUs and NIDUs.HCV subtypes 3b, 3a, 6a, and 1b were the most common in our study, together accounting for 89% of infections. The subtype distribution differences we found between IDUs and NIDUs suggested that sharing syringes was not the most likely pathway for HCV transmission in NIDUs. However, further studies are needed to elucidate how NIDUs were infected.

  16. Comparison of seropositivity of HCV between oral lichen planus and healthy control group in Hamedan province (west of Iran

    Directory of Open Access Journals (Sweden)

    Ahmad Reza Mobaien

    2011-10-01

    Full Text Available Background: Lichen planus is an idiopathic inflammatory disease of the skin, nail, hair and mucous membranes. Oral lichen planus (LP is a chronic inflammatory condition that affects the oral mucous membranes with a variety of clinical presentations. Various etiologies include HCV suggested for LP, and the aim of this study was comparison of seropositivity of HCV in LP patients and control group. Methods: All oral LP patients that were referred to dermatology clinic of farshchian hospitalwere entered in the study. Five cc of clot blood was taken from each patient and tested for anti-HCVand when anti-HCV tested positive another 2cc clot bloodwas taken for HCV-Rt-PCR test. The results were analyzed with SPSS 16. Results: This prospective cross-sectional study was conducted on 30 oral lichen planus patients [males 13(43.3% females 17(56.7%] with mean ages of 46±13.7years and 60 healthy individual [males 26(43.3% females 34(56.7%]. There was no oral lichen planus patients who had anti-HCV positive whiles 2 males(3.3% of healthy group had anti-HCV positive which was confirmed by HCV-Rt-PCR. Conclusions: This study showed that there is no correlation between seropositivity of HCV and oral lichen planus in our patients in the west of Iran.

  17. 21 CFR 610.48 - Hepatitis C virus (HCV) “lookback” requirements based on review of historical testing records.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... STANDARDS Testing Requirements for Communicable Disease Agents § 610.48 Hepatitis C virus (HCV) “lookback... the following actions: (1) You must: (i) Review all records of donor testing for hepatitis C virus...

  18. High prevalence of antibodies to core+1/ARF protein in HCV-infected patients with advanced cirrhosis.

    Science.gov (United States)

    Kassela, Katerina; Karakasiliotis, Ioannis; Charpantidis, Stefanos; Koskinas, John; Mylopoulou, Theodora; Mimidis, Konstantinos; Sarrazin, Christoph; Grammatikos, Georgios; Mavromara, Penelope

    2017-07-01

    Hepatitis C virus (HCV) possesses a second open reading frame (ORF) within the core gene encoding an additional protein, known as the alternative reading frame protein (ARFP), F or core+1. The biological significance of the core+1/ARF protein remains elusive. However, several independent studies have shown the presence of core+1/ARFP antibodies in chronically HCV-infected patients. Furthermore, a higher prevalence of core+1/ARFP antibodies was detected in patients with HCV-associated hepatocellular carcinoma (HCC). Here, we investigated the incidence of core+1/ARFPantibodies in chronically HCV-infected patients at different stages of cirrhosis in comparison to chronically HCV-infected patients at earlier stages of disease. Using ELISA, we assessed the prevalence of anti-core+1 antibodies in 30 patients with advanced cirrhosis [model for end-stage liver disease (MELD) ≥15] in comparison with 50 patients with mild cirrhosis (MELD core+1 antibodies, in contrast with 16.5 % of non-cirrhotic HCV patients. Moreover, there was significantly higher positivity for anti-core+1 antibodies in HCV patients with advanced cirrhosis (36.7 %) compared to those with early cirrhosis (24 %) (Pcore+1 antibodies in HCV patients with HCC, suggest that core+1 protein may have a role in virus-associated pathogenesis, and provide evidence to suggest that the levels of anti-core+1 antibodies may serve as a marker for disease progression.

  19. Anti-HCV reactive volunteer blood donors distribution character and genotypes switch in Xi'an, China

    Directory of Open Access Journals (Sweden)

    Yue Qiao-hong

    2010-08-01

    Full Text Available Abstract HCV is prevailed in the world as well as in China. Blood transfusion is one of the most common transmission pathways of this pathogen. Although data of HCV infection character were reported during the past years, anti-HCV reactive profile of China donors was not fully clear yet. Furthermore, infection progress was found related to the HCV genotype. Different genotype led to different efficacy when interferon was introduced into HCV therapy. Here we provided character data of HCV infection in China blood donors from the year of 2000 to 2009. The infection rate in local donors was lower than general population and descended from 0.80% to 0.40% or so in recent years. About 83% HCV strains were categorized into genotypes 1b and 2a. But 1b subtype cases climbed and 2a subtype cases decreased. The current study threw more light on HCV infection of blood donors in China, at least in the Northern region.

  20. Changes in HIV RNA and CD4 cell count after acute HCV infection in chronically HIV-infected individuals

    NARCIS (Netherlands)

    Gras, Luuk; de Wolf, Frank; Smit, Colette; Prins, Maria; van der Meer, Jan T. M.; Vanhommerig, Joost W.; Zwinderman, Aeilko H.; Schinkel, Janke; Geskus, Ronald B.; Kuijpers, T. W.; Scherpbier, H. J.; Godfried, M. H.; Reiss, P.; van der Poll, T.; Nellen, F. J. B.; Lange, J. M. A.; Geerlings, S. E.; van Vugt, M.; Pajkrt, D.; Bos, J. C.; van der Valk, M.; Wiersinga, W. J.; Goorhuis, A.; Hovius, J. W. R.; Lowe, S.; Oude Lashof, A.; Posthouwer, D.; Pronk, M. J. H.; Ammerlaan, H. S. M.; van der Ende, M. E.; de Vries-Sluijs, T. E. M. S.; Schurink, C. A. M.; Nouwen, J. L.; Verbon, A.; Rijnders, B. J. A.; van Gorp, E. C. M.; van der Feltz, M.; Driessen, G. J. A.; van Rossum, A. M. C.; Branger, J.; Schippers, E. F.; van Nieuwkoop, C.; van Elzakker, E. P.; Groeneveld, H. P.; Bouwhuis, J. W.; Soetekouw, R.; ten Kate, R. W.; Kroon, F. P.; van Dissel, J. T.; Arend, S. M.; de Boer, M. G. J.; Jolink, H.; Vollaard, A. M.; Bauer, M. P.; den Hollander, J. G.; Pogany, K.; van Twillert, G.; Kortmann, W.; Cohen Stuart, J. W. T.; Diederen, B. M. W.; Leyten, E. M. S.; Gelinck, L. B. S.; Kootstra, G. J.; Delsing, C. E.; Brinkman, K.; Blok, W. L.; Frissen, P. H. J.; Schouten, W. E. M.; van den Berk, G. E. L.; van Kasteren, M. E. E.; Brouwer, A. E.; Veenstra, J.; Lettinga, K. D.; Mulder, J. W.; Vrouenraets, S. M. E.; Lauw, F. N.; van Eeden, A.; Verhagen, D. W. M.; Sprenger, H. G.; Scholvinck, E. H.; van Assen, S.; Bierman, W. F. W.; Wilting, K. R.; Stienstra, Y.; Koopmans, P. P.; Keuter, M.; van der Ven, A. J. A. M.; ter Hofstede, H. J. M.; Dofferhoff, A. S. M.; Warris, A.; van Crevel, R.; Hoepelman, A. I. M.; Mudrikova, T.; Schneider, M. M. E.; Ellerbroek, P. M.; Oosterheert, J. J.; Arends, J. E.; Wassenberg, W. W. M.; Barth, R. E.; van Agtmael, M. A.; Perenboom, R. M.; Claessen, F. A. P.; Bomers, M.; Peters, E. J. G.; Geelen, S. P. M.; Wolfs, T. F. W.; Bont, L. J.; Richter, C.; van der Berg, J. P.; Gisolf, E. H.; van den Berge, M.; Stegeman, A.; van Vonderen, M. G. A.; van Houte, D. P. F.; Weijer, S.; el Moussaoui, R.; Winkel, C.; Muskiet, F.; Durand, N. N.; Voigt, R.

    2015-01-01

    Little is known about the impact of acute hepatitis C virus (HCV) co-infection on HIV-1 disease progression. We investigated CD4 cell count and HIV RNA concentration changes after HCV infection in individuals chronically infected with HIV-1. We selected individuals that had the last negative and

  1. Increase in HCV incidence among men who have sex with men in Amsterdam most likely caused by sexual transmission

    NARCIS (Netherlands)

    van de Laar, T.J.W.; van der Bij, A.K.; Prins, M.; Bruisten, S.M.; Brinkman, K.; Ruys, T.A.; van der Meer, J.T.M.; de Vries, H.J.C.; Mulder, J.W.; van Agtmael, M.; Jurriaans, S.; Wolthers, K.C.; Coutinho, R.A.

    2007-01-01

    We retrospectively screened 1836 men who have sex with men (MSM) participating in the Amsterdam Cohort Studies (1984-2003) for hepatitis C virus (HCV) antibodies. HCV incidence was 0.18/100 person-years (PY) in human immunodeficiency virus (HIV)-positive MSM (8/4408 PY [95% confidence interval {CI},

  2. From principles to practice: Description of a novel equity-based HCV primary care treatment model for PWID.

    Science.gov (United States)

    Milne, Rozalyn; Price, Morgan; Wallace, Bruce; Drost, Anne; Haigh-Gidora, Irene; Nezil, Frank A; Fraser, Chris

    2015-10-01

    Knowledge is increasing regarding effective models of HCV care for people who inject drugs (PWID). However, examples implementing such models in primary care are lacking, leaving a gap in our applied understanding of how practically we best scale-up such care: this is critical and urgent if the benefits of treatment advances are to be realized for PWID. The Cool Aid Community Health Centre (CHC) provides HCV programming for PWID, putting recent advances into practice. A case study of the CHC's HCV programming describes the practice experience and outcomes of its novel, multidisciplinary, primary care, inner-city HCV treatment program for PWID. This paper describes how this model of care functions to address the many barriers to treatment and successfully facilitate adherence to treatment. Medical advances for HCV will be ineffectual without effective management of complex barriers to care related to substance use, mental health, trauma, poverty, homelessness, criminalization, cultural issues, stigma and marginalization. HCV treatment for PWIDs benefits from low-threshold settings which are culturally appropriate and where trusting relationships between clients and providers are nurtured. Public investment in primary care treatment for PWID living with HCV, including investments in supports that address the social barriers faced by these vulnerable populations would build on existing evidence and improve HCV outcomes for PWID. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Strong vaccine-induced CD8 T-cell responses have cytolytic function in a chimpanzee clearing HCV infection

    NARCIS (Netherlands)

    B.E. Verstrepen (Babs); E.J. Verschoor (Ernst); Z. Fagrouch (Zahra); P. Mooij (Petra); N.G. Groot (Natasja); R.E. Bontrop (Ronald ); W. Bogers (Willy); J.L. Heeney (Jonathan); G. Koopman (Gerrit)

    2014-01-01

    textabstractA single correlate of effective vaccine protection against chronic HCV infection has yet to be defined. In this study, we analyzed T-cell responses in four chimpanzees, immunized with core-E1-E2-NS3 and subsequently infected with HCV1b. Viral clearance was observed in one animal, while

  4. A meta-analysis of single HCV-untreated arm of studies evaluating outcomes after curative treatments of HCV-related hepatocellular carcinoma.

    Science.gov (United States)

    Cabibbo, Giuseppe; Petta, Salvatore; Barbàra, Marco; Missale, Gabriele; Virdone, Roberto; Caturelli, Eugenio; Piscaglia, Fabio; Morisco, Filomena; Colecchia, Antonio; Farinati, Fabio; Giannini, Edoardo; Trevisani, Franco; Craxì, Antonio; Colombo, Massimo; Cammà, Calogero

    2017-08-01

    Determining risk for recurrence or survival after curative resection or ablation in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is important for stratifying patients according to expected outcomes in future studies of adjuvant therapy in the era of direct-acting antivirals (DAAs). The aims of this meta-analysis were to estimate the recurrence and survival probabilities of HCV-related early HCC following complete response after potentially curative treatment and to identify predictors of recurrence and survival. Studies reporting time-dependent outcomes (HCC recurrence or death) after potentially curative treatment of HCV-related early HCC were identified in MEDLINE through May 2016. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using a distribution-free summary survival curve. Primary outcomes were actuarial probabilities of recurrence and survival. Eleven studies met the inclusion criteria. Pooled estimates of actuarial recurrence rates were 7.4% at 6 months and 47.0% at 2 years. Pooled estimates of actuarial survival rates were 79.8% at 3 years and 58.6% at 5 years. Heterogeneity among studies was highly significant for all outcomes. By univariate meta-regression analyses, lower serum albumin, randomized controlled trial study design and follow-up were independently associated with higher recurrence risk, whereas tumour size and alpha-foetoprotein levels were associated with higher mortality. This meta-analysis showed that recurrence risk and survival are extremely variable in patients with successfully treated HCV-related HCC, providing a useful benchmark for indirect comparisons of the benefits of DAAs and for a correct design of randomized controlled trials in the adjuvant setting. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. [Seroprevalence of HBs Ag and of anti-HCV antibodies among HIV infected people in N'Djamena, Chad].

    Science.gov (United States)

    Bessimbaye, N; Moussa, A M; Mbanga, D; Tidjani, A; Mahamat, S O; Ngawara, M Nahor; Ngarnayal, G; Fissou, H Y; Sangare, L; Ndoutamia, G; Barro, N

    2014-12-01

    This is a prospective study conducted as part of a voluntary testing for HBV, HCV and HIV. The aim of the study is to determine the seroprevalence of HBs Ag and anti-HCV antibodies among HIV infected people and a control group of HIV negative people. HIV prevalence among newly diagnosed volunteers is 9.1%. The overall seroprevalence of HBs Ag and anti-HCV antibodies is respectively 13.5% and 2.0%. The seroprevalence of HBs Ag and anti-HCVantibodies in the control group (HIV-negative) is respectively 12.2% and 2%. The seroprevalence of HBs Ag and anti-HCV antibodies among HIV infected people (old and new) is respectively 16.1% and 1%.This study, the first one conducted in Chad, has allowed us to know the seroprevalence of HBs Ag and anti-HCV antibodies among HIV infected people.

  6. Robust HCV Genotype 3a Infectious Cell Culture System Permits Identification of Escape Variants With Resistance to Sofosbuvir

    DEFF Research Database (Denmark)

    Ramirez Almeida, Santseharay; Mikkelsen, Lotte S.; Gottwein, Judith M.

    2016-01-01

    to sofosbuvir—the only nucleotide analog approved for treatment of chronic HCV infection. Methods The developed HCV genotype 3a full-length genome (DBN3a), with a strain-DBN coding sequence, modified NS5B consensus sequence, pS52 untranslated regions, and coding mutations from a culture-efficient JFH1-based......Background & Aims Direct-acting antivirals (DAAs) effectively eradicate chronic hepatitis C virus (HCV) infection, although HCV genotype 3a is less responsive to these drugs. We aimed to develop genotype 3a infectious cultures and study the effects of inhibitors of NS5A and NS5B and resistance....... Sofosbuvir, MK-3682, dasabuvir, or combinations of sofosbuvir and ledipasvir or sofosbuvir and velpatasvir had decreased efficacy against infection with the DBN3a sofosbuvir escape variant. Conclusions We developed a system for highly efficient culture of HCV genotype 3a. Genotype 1a has a high genetic...

  7. Hepatitis C virus recurrence after liver transplantation: relationship to anti-HCV core IgM, genotype, and level of viremia.

    Science.gov (United States)

    Crespo, J; Carte, B; Lozano, J L; Casafont, F; Rivero, M; de la Cruz, F; Pons-Romero, F

    1997-09-01

    Factors that determine the severity of hepatitis C virus (HCV)-recurrent disease in patients undergoing orthotopic liver transplantation (OLT) for HCV cirrhosis have not been clearly identified. To address this issue, we evaluated the histological and virological outcome in 25 patients who underwent OLT for HCV cirrhosis. HCV-RNA was detected by qualitative and quantitative polymerase chain reaction. The HCV genotype also was determined by polymerase chain reaction. Anti-HCV core IgM was tested by ELISA. Disease severity was expressed as a histological score. Sixteen patients had evidence of HCV-recurrent disease. HCV-RNA levels before transplantation (p = 0.029) and after transplantation (15 days, p = 0.004; 90 days, p = 0.040; 360 days, p = 0.010) were significantly higher among patients who subsequently developed recurrent hepatitis than among those who did not. The presence of anti-HCV core IgM before (p = 0.044) and after OLT (15 days, p = 0.017; 90 days, p = 0.037; and 360 days, p = 0.040) was significantly related to recurrence of hepatitis. The genotype was not related to the level of viremia, to the prevalence of recurrent hepatitis, to the presence of anti-HCV core IgM, or to disease severity. The recurrence of HCV hepatitis in patients undergoing OLT for HCV cirrhosis is related to higher levels of viremia and the presence of anti-HCV core IgM, but not to the HCV genotype. However, disease severity is not related to viremia levels, HCV genotype, or positivity of anti-HCV core IgM.

  8. Baseline HCV Antibody Prevalence and Risk Factors among Drug Users in China's National Methadone Maintenance Treatment Program.

    Directory of Open Access Journals (Sweden)

    Changhe Wang

    Full Text Available Hepatitis C virus (HCV is the most common viral infection among injecting drug users worldwide. We aimed to assess HCV antibody prevalence and associated risk factors among clients in the Chinese national methadone maintenance treatment (MMT program.Data from 296,209 clients who enrolled in the national MMT program between March 2004 and December 2012 were analyzed to assess HCV antibody prevalence, associated risk factors, and geographical distribution.Anti-HCV screening was positive for 54.6% of clients upon MMT entry between 2004 and 2012. HCV antibody prevalence at entry declined from 66.8% in 2005 to 45.9% in 2012. The most significant predictors of HCV seropositivity were injecting drug use (adjusted odds ratio [AOR]: 8.34, 95% confidence interval [CI]: 8.17-8.52, p<0.0001 and a history of drug use ≥9 years (AOR: 2.01, 95% CI: 1.96-2.06, p<0.0001. Being female, of Uyghur or Zhuang ethnicity, and unmarried were identified as demographic risk factors (all p-values<0.0001. Of the 28 provincial-level divisions included in the study, we found that 5 divisions had HCV antibody prevalence above 70% and 20 divisions above 50%. The HCV screening rate within 6 months after MMT entry greatly increased from 30.4% in 2004 to 93.1% in 2012.The current HCV antibody prevalence remains alarmingly high among MMT clients throughout most provincial-level divisions in China, particularly among injecting drug users and females. A comprehensive prevention strategy is needed to control the HCV epidemic among MMT clients in China.

  9. The effect of HIV infection and HCV viremia on inflammatory mediators and hepatic injury-The Women's Interagency HIV Study.

    Science.gov (United States)

    Keating, Sheila M; Dodge, Jennifer L; Norris, Philip J; Heitman, John; Gange, Stephen J; French, Audrey L; Glesby, Marshall J; Edlin, Brian R; Latham, Patricia S; Villacres, Maria C; Greenblatt, Ruth M; Peters, Marion G

    2017-01-01

    Hepatitis C virus infection induces inflammation and while it is believed that HIV co-infection enhances this response, HIV control may reduce inflammation and liver fibrosis in resolved or viremic HCV infection. Measurement of systemic biomarkers in co-infection could help define the mechanism of inflammation on fibrosis and determine if HIV control reduces liver pathology. A nested case-control study was performed to explore the relationship of systemic biomarkers of inflammation with liver fibrosis in HCV viremic and/or seropositive women with and without HIV infection. Serum cytokines, chemokines, growth factors and cell adhesion molecules were measured in HIV uninfected (HIV-, n = 18), ART-treated HIV-controlled (ARTc, n = 20), uncontrolled on anti-retroviral therapy (ARTuc, n = 21) and elite HIV controllers (Elite, n = 20). All were HCV seroreactive and had either resolved (HCV RNA-; infection (HCV RNA+). In HCV and HIV groups, aspartate aminotransferase to platelet ratio (APRI) was measured and compared to serum cytokines, chemokines, growth factors and cell adhesion molecules. APRI correlated with sVCAM, sICAM, IL-10, and IP-10 levels and inversely correlated with EGF, IL-17, TGF-α and MMP-9 levels. Collectively, all HCV RNA+ subjects had higher sVCAM, sICAM and IP-10 compared to HCV RNA-. In the ART-treated HCV RNA+ groups, TNF-α, GRO, IP-10, MCP-1 and MDC were higher than HIV-, Elite or both. In ARTuc, FGF-2, MPO, soluble E-selectin, MMP-9, IL-17, GM-CSF and TGF-α are lower than HIV-, Elite or both. Differential expression of soluble markers may reveal mechanisms of pathogenesis or possibly reduction of fibrosis in HCV/HIV co-infection.

  10. Modeling HIV-HCV coinfection epidemiology in the direct-acting antiviral era: the road to elimination.

    Science.gov (United States)

    Virlogeux, Victor; Zoulim, Fabien; Pugliese, Pascal; Poizot-Martin, Isabelle; Valantin, Marc-Antoine; Cuzin, Lise; Reynes, Jacques; Billaud, Eric; Huleux, Thomas; Bani-Sadr, Firouze; Rey, David; Frésard, Anne; Jacomet, Christine; Duvivier, Claudine; Cheret, Antoine; Hustache-Mathieu, Laurent; Hoen, Bruno; Cabié, André; Cotte, Laurent

    2017-12-18

    HCV treatment uptake has drastically increased in HIV-HCV coinfected patients in France since direct-acting antiviral (DAA) treatment approval, resulting in HCV cure in 63% of all HIV-HCV patients by the end of 2015. We investigated the impact of scaling-up DAA on HCV prevalence in the whole HIV population and in various risk groups over the next 10 years in France using a transmission dynamic compartmental model. The model was based on epidemiological data from the French Dat'AIDS cohort. Eight risk groups were considered, including high-risk (HR) and low-risk (LR) men who have sex with men (MSM) and male/female heterosexuals, intra-venous drug users, or patients from other risk groups. The model was calibrated on prevalence and incidence data observed in the cohort between 2012 and 2015. On January 1, 2016, 156,811 patients were registered as infected with HIV in France (24,900 undiagnosed patients) of whom 7938 (5.1%) had detectable HCV-RNA (722 undiagnosed patients). Assuming a treatment coverage (TC) rate of 30%/year (i.e., the observed rate in 2015), model projections showed that HCV prevalence among HIV patients is expected to drop to 0.81% in 2026. Sub-analyses showed a similar decrease of HIV-HCV prevalence in most risk groups, including LR MSM. Due to higher infection and reinfection rates, predicted prevalence in HR MSM remained stable from 6.96% in 2016 to 6.34% in 2026. Increasing annual TC rate in HR MSM to 50/70% would decrease HCV prevalence in this group to 2.35/1.25% in 2026. With a 30% TC rate, undiagnosed patients would account for 34% of HCV infections in 2026. Our model suggests that DAA could nearly eliminate coinfection in France within 10 years for most risk groups, including LR MSM. Elimination in HR MSM will require increased TC.

  11. Men who have sex with men starting pre-exposure prophylaxis (PrEP) are at risk of HCV infection: evidence from the Amsterdam PrEP study

    NARCIS (Netherlands)

    Hoornenborg, Elske; Achterbergh, Roel C. A.; Schim van der Loeff, Maarten F.; Davidovich, Udi; Hogewoning, Arjan; de Vries, Henry J. C.; Schinkel, Janke; Prins, Maria; van de Laar, Thijs J. W.

    2017-01-01

    Hepatitis C virus (HCV) has been recognised as an emerging sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). However, HIV-negative MSM at high risk for HIV might also be at increased risk for HCV. We studied the HCV prevalence in HIV-negative MSM who start

  12. Differential efficacy of protease inhibitors against HCV genotypes 2a, 3a, 5a, and 6a NS3/4A protease recombinant viruses

    DEFF Research Database (Denmark)

    Gottwein, Judith M; Scheel, Troels K H; Jensen, Tanja B

    2011-01-01

    The hepatitis C virus (HCV) genotype influences efficacy of interferon (IFN)-based therapy. HCV protease inhibitors are being licensed for treatment of genotype 1 infection. Because there are limited or no data on efficacy against HCV genotypes 2-7, we aimed at developing recombinant infectious c...... cell culture systems expressing genotype-specific nonstructural (NS) protein 3 protease (NS3P)....

  13. Usefulness of a fourth generation ELISA assay for the reliable identification of HCV infection in HIV-positive adults from Gabon (Central Africa).

    Science.gov (United States)

    Rouet, François; Deleplancque, Luc; Mboumba, Berthold Bivigou; Sica, Jeanne; Mouinga-Ondémé, Augustin; Liégeois, Florian; Goudeau, Alain; Dubois, Frédéric; Gaudy-Graffin, Catherine

    2015-01-01

    Guidelines for optimized HCV screening are urgently required in Africa, especially for patients infected with HIV, who sometimes show false positive or false negative reactivity in anti-HCV antibody assays. Here, we assessed the usefulness of a fourth-generation HCV Ag-Ab ELISA for the identification of active HCV infection in HIV-positive patients. This cross-sectional study was conducted between 03/2010 and 01/2013 and included 762 Gabonese HIV-positive adult patients. The results of ELISA (Monolisa HCV Ag-Ab ULTRA, Bio-Rad) were compared with those obtained by RT-PCR (gold standard). The optimal ELISA signal-to-cutoff (S/CO) ratio to identify patients with active hepatitis C (positive HCV RNA) was determined. Specimens were further tested by the INNO-LIA HCV Score assay (Innogenetics) and the Architect HCV Ag kit (Abbott) to define the best diagnostic strategy. Sixty-seven patients tested positive for HCV (S/CO ratio ≥ 1) by ELISA. Of these, 47 (70.1%) tested positive for HCV RNA. The optimal S/CO associated with active HCV infection was 1.7. At this threshold, the sensitivity of ELISA was 97.9% (95% confidence interval (CI) 90.0-99.9%), its specificity was 91.3% (95% CI 85.0-95.5%), and HCV seroprevalence rate was 7.3% (56/762) (95% CI 5.6-9.4%). Among 57 HCV-seropositive patients with available INNO-LIA results, false reactivity was identified in 14 (24.6%), resolved HCV infection in two (3.5%), possible acute HCV infections in nine (15.8%) and likely chronic HCV infections in 32 (56.1%) patients. HCV core Ag was undetectable in 14/15 (93.3%) specimens that tested negative for HCV RNA whereas it was quantified in 34 (out of 39, 87.2%) samples that tested positive for HCV RNA. Our study provides comprehensive guidance for HCV testing in Gabon, and will help greatly clinicians to improve case definitions for both the notification and surveillance of HCV in patients co-infected with HIV.

  14. Preclinical evaluation of multi antigenic HCV DNA vaccine for the prevention of Hepatitis C virus infection.

    Science.gov (United States)

    Lee, Hyojin; Jeong, Moonsup; Oh, Jooyeon; Cho, Youngran; Shen, Xuefei; Stone, John; Yan, Jian; Rothkopf, Zachary; Khan, Amir S; Cho, Byung Mun; Park, Young K; Weiner, David B; Son, Woo-Chan; Maslow, Joel N

    2017-03-07

    Direct-acting antiviral treatment for hepatitis C virus (HCV) infection is costly and does not protect from re-infection. For human and chimpanzees, recovery from acute HCV infection correlates with host CD4+ and CD8+ T cell responses. DNA plasmids targeting the HCV non-structural antigens NS3, NS4, and NS5, were previously reported to induce robust and sustained T cell responses in mice and primates. These plasmids were combined with a plasmid encoding cytokine IL-28B, together named as VGX-6150. The dose-dependent T cell response and safety of VGX-6150 administered intramuscularly and followed by electroporation was assessed in mice. Immune responses plateaued at 20 μg/dose with IL-28B demonstrating significant immunoadjuvant activity. Mice administered VGX-6150 at 40, 400, and 800 μg given either as a single injection or as 14 injections given bi-weekly over 26 weeks showed no vaccine related changes in any clinical parameter compared to placebo recipients. There was no evidence of VGX-6150 accumulation at the injection site or in any organ 1 month following the 14th vaccination. Based on these studies, the approximate lethal dose (ALD) exceeds 800 μg/dose and the NOAEL was 800 μg/dose in mouse. In conclusion, VGX-6150 appears safe and a promising preventive vaccine candidate for HCV infection.

  15. Incidence of Severe Hepatotoxicity Related to Antiretroviral Therapy in HIV/HCV Coinfected Patients

    Directory of Open Access Journals (Sweden)

    Emily L. Heil

    2010-01-01

    Full Text Available Introduction. Hepatotoxicity is a concern in HIV/hepatitis C virus (HCV coinfected patients due to their underlying liver disease. This study assessed the incidence of hepatotoxicity in HIV/HCV co-infected patients in two outpatient infectious diseases clinics. Methods. HIV/HCV co-infected adults were included in this retrospective study if they were PI or NNRTI naïve at their first clinic visit and were initiated on an NNRTI- and/or PI-based antiretroviral regimen. Patients were excluded if they had active or chronic hepatitis B virus (HBV. The primary objective was to determine the overall incidence of severe hepatotoxicity. Results. Fifty-six of the 544 patients identified met inclusion criteria. The incidence of severe hepatotoxicity was 10.7% (6/56 patients. Severe hepatotoxicity occurred with efavirenz (=2, nevirapine (=1, indinavir (=1, nelfinavir (=1, and saquinavir/ritonavir (=1. Conclusion. The incidence of severe hepatotoxicity appears to be low in this retrospective analysis of HIV/HCV co-infected patients receiving a PI-and/or NNRTI-based regimen.

  16. Genotyping and infection rate of GBV-C among Iranian HCV- infected patients.

    Science.gov (United States)

    Ghanbari, Reza; Ravanshad, Mehrdad; Hosseini, Seyed Younes; Yaghobi, Ramin; Shahzamani, Kiana

    2010-01-01

    Hepatitis G virus/GB virus-C (HGV/GBV-C) is a newly identified member of the Flaviviridae family. Its clinical significance in chronic hepatitis C infection remains controversial. There is a geographical difference in the distribution of GBV-C in the world. The frequency of GBV-C infection among hepatitis C virus (HCV) infected patients varies. The aim of the current study was to determine the prevalence and genotypes of GBV-C among Iranian patients infected with chronic HCV. Infection with GBV-C was surveyed in 71 chronic confirmed hepatitis C infected patients. These samples were collected at the Digestive Disease Research Center (DDRC) of Shariati Hospital, Tehran, Iran from January to October 2007. The 5'-UTR region of GBV-C RNA was detected using a novel in-house touchdown nested reverse transcription polymerase chain reaction (RT-PCR), the products were sequenced and the results were aligned and phylogenically analyzed. Of the 71 HCV-infected patients, 31 (43.6%) were found positive for GBV-C RNA. Sequencing and phylogenic analysis showed that the samples were Genotype 2 of GBV-C. It seems that there is a high rate of GBV-C infection among Iranian patients infected with chronic HCV. In comparison with the six reference genotypes, it was observed that all the samples were categorized in Genotype 2 of GBV-C, prevalent in North America, Africa and in European countries.

  17. Look-back study of infectivity of anti-HCV ELISA-positive blood components

    NARCIS (Netherlands)

    Vrielink, H.; van der Poel, C. L.; Reesink, H. W.; Zaaijer, H. L.; Scholten, E.; Kremer, L. C.; Cuypers, H. T.; Lelie, P. N.; van Oers, M. H.

    1995-01-01

    The infectivity of blood components from donors who were later found to be anti-HCV ELISA-positive was investigated in recipients who were enrolled in a look-back programme. Recipients received ELISA-positive blood components from donors who were PCR-positive and/or RIBA-2-positive (n = 22, group A)

  18. Differences in immune response between HCV positive, HIV negative haemophilia A and B patients

    NARCIS (Netherlands)

    Meijer, K; Smid, WM; Verspiek, SPJ; Smit, JW; van der Meer, J

    We measured numbers of lymphocytes and subsets in seven HIV negative, HCV positive severe haemophilia B patients, before and after substitution was changed from prothrombin complex concentrate to monoclonally purified concentrate. Data were compared with controls and our previous findings in

  19. ITPA polymorphisms are associated with hematological side effects during antiviral therapy for chronic HCV infection

    NARCIS (Netherlands)

    R. Maan (Raoel); A.J.P. van der Meer (Adriaan); W.P. Brouwer (Willem); E.P.C. Plompen (Elisabeth); M.J. Sonneveld (Milan); R. Roomer (Robert); A.A. Eijck (Annemiek); Z.M.A. Groothuismink (Zwier); B.E. Hansen (Bettina); B.J. Veldt (Bart); H.L.A. Janssen (Harry); P.A. Boonstra (André); R.J. de Knegt (Robert)

    2015-01-01

    textabstractBackground/Objective Genetic polymorphisms in the inosine triphosphatase (ITPA) gene have been associated with the protection from early ribavirin(RBV)-induced hemolytic anemia among patients with chronic hepatitis C virus (HCV) infection. The aim of the present study was to investigate

  20. 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 tot...

  1. A Review of Hepatitis C Virus (HCV) and the Current Management ...

    African Journals Online (AJOL)

    Background: Chronic Hepatitis C virus (HCV) is the primary cause of cirrhosis, hepatocellular carcinoma (HCC), and end- stage liver disease. The addition of protease inhibitor with peginterferon alfa and ribavirin (triple therapy) for genotype 1 infected patients, are the current standard of care. Method: Data was sourced ...

  2. Favourable SVR12 rates with boceprevir or telaprevir triple therapy in HIV/HCV coinfected patients

    NARCIS (Netherlands)

    Arends, J. E.|info:eu-repo/dai/nl/314063242; van der Meer, J. T M; Posthouwer, D.; Kortmann, W.; Brinkman, K.; van Assen, S.; Smit, C.; van der Valk, M.; van der Ende, M.; Schinkel, J.; Reiss, P.; Richter, C.; Hoepelman, A. I M|info:eu-repo/dai/nl/074382160

    2015-01-01

    Background: Recent publications have reported superior efficacy of telaprevir- or boceprevir-based triple therapy over conventional peginterferon-alfa/ribavirin therapy, albeit with varying rates of adverse events and treatment discontinuations in HIV/ HCV coinfected patients. Therefore, the aim of

  3. PPARs and HCV-Related Hepatocarcinoma: A Mitochondrial Point of View

    Directory of Open Access Journals (Sweden)

    Francesca Agriesti

    2012-01-01

    Full Text Available Hepatitis-C-virus-related infective diseases are worldwide spread pathologies affecting primarily liver. The infection is often asymptomatic, but when chronically persisting can lead to liver scarring and ultimately to cirrhosis, which is generally apparent after decades. In some cases, cirrhosis will progress to develop liver failure, liver cancer, or life-threatening esophageal and gastric varices. HCV-infected cells undergo profound metabolic dysregulation whose mechanisms are yet not well understood. An emerging feature in the pathogenesis of the HCV-related disease is the setting of a pro-oxidative condition caused by dysfunctions of mitochondria which proved to be targets of viral proteins. This causes deregulation of mitochondria-dependent catabolic pathway including fatty acid oxidation. Nuclear receptors and their ligands are fundamental regulators of the liver metabolic homeostasis, which are disrupted following HCV infection. In this contest, specific attention has been focused on the peroxisome proliferator activated receptors given their role in controlling liver lipid metabolism and the availability of specific pharmacological drugs of potential therapeutic utilization. However, the reported role of PPARs in HCV infection provides conflicting results likely due to different species-specific contests. In this paper we summarize the current knowledge on this issue and offer a reconciling model based on mitochondria-related features.

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

    NARCIS (Netherlands)

    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

  5. Treatment extension benefits HCV genotype I patients without rapid virological response : a systematic review

    NARCIS (Netherlands)

    Gevers, T. J. G.; Slavenburg, S.; van Oijen, M. G. H.; Drenth, J. P. H.

    Background: Current guidelines recommend 48 weeks of treatment with pegylated interferon and ribavirin for patients infected with chronic hepatitis C virus (HCV) genotype I. Several clinical trials have investigated the efficacy of treatment duration longer than 48 weeks, but yielded discordant

  6. Alternative core development around the tetracyclic indole class of HCV NS5A inhibitors.

    Science.gov (United States)

    Tong, Ling; Yu, Wensheng; Coburn, Craig A; Meinke, Peter T; Nair, Anilkumar G; Dwyer, Michael P; Chen, Lei; Selyutin, Oleg; Rosenblum, Stuart B; Jiang, Yueheng; Fells, James; Hu, Bin; Zhong, Bin; Soll, Richard M; Liu, Rong; Agrawal, Sony; Xia, Ellen; Zhai, Ying; Kong, Rong; Ingravallo, Paul; Nomeir, Amin; Asante-Appiah, Ernest; Kozlowski, Joseph A

    2016-10-15

    Herein, we describe our research efforts to develop unique cores in molecules which function as HCV nonstructural protein 5A (NS5A) inhibitors. In particular, various fused tetracyclic cores were identified which showed genotype and mutant activities comparable to the indole-based tetracyclic core. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Association of genotypes with viral load and biochemical markers in HCV-infected Sindhi patients

    Directory of Open Access Journals (Sweden)

    Saba Riaz

    Full Text Available Abstract The presented study had two objectives. The first was to examine distributions of Hepatitis C Virus (HCV genotypes in Sindh, Pakistan, where HCV is prevalent. The other was to explore clinically relevant relationships between the genotypes, viral load (measured by real-time polymerase chain reaction assays and biochemical markers. For this, 1471 HCV-infected patients in six cities in Sindh were recruited and sampled. HCV genotype distributions varied among the cities, but genotype 3a was most prevalent, followed by 3b, 1a and 1b (detected in 51.5, 22.7. 9.25 and 3.2% of the cases, respectively. No type-specific sequences were detected in serum samples from 189 (12.8% of the 1471 patients. Frequencies of low (600,000 IU/mL serum viral loads were respectively 45.4, 16.5 and 38.1% for patients infected with genotype 3, and 16.9, 36.9 and 46.2%, respectively, for patients with other genotypes. Infection with genotype 1a was associated with significantly higher (p < 0.005 alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase titers than infection with genotype 3a. The results will help in the formulation of treatment strategies.

  8. Anti-HCV antibody among newly diagnosed HIV patients in Ughelli ...

    African Journals Online (AJOL)

    Appropriate questionnaires were used to ascertain other important information which include social behaviour such as whether the patients were MSM (males), IDU, tattoo and/or have received blood transfusion in the past. Results: The prevalence of HCV among the study population was determined to be 15.0%. A higher ...

  9. Impact of duration of therapy on side effect profile of anti- HCV protocol

    African Journals Online (AJOL)

    Purpose: To evaluate the plausible risks and adverse effects related to the duration of therapy in hepatitis C (HCV) patients in ... Results: Patients who underwent treatment for ≤ 6 months frequently encountered side-effects such as. GIT disturbance (23.77 .... in both the arms include, respiratory tract infection (≤ 6 months ...

  10. Anti-HCV antibody among newly diagnosed HIV patients in Ughelli ...

    African Journals Online (AJOL)

    ingly well above several other studies done in the past in Nigeria and other countries of sub-Saharan Africa. ... Future studies involving HCV-RNA ..... port_2013_en.pdf. Joint United Nations Programme on HIV/AIDS (UNAIDS), 2013. 8. Maria Dorrucci, P. P., Andrew N. Phillips, Alessan- dro Cozzi Lepri, and Giovanni Rezza.

  11. Beneficial therapeutic effects of Nigella sativa and/or Zingiber officinale in HCV patients in Egypt.

    Science.gov (United States)

    Abdel-Moneim, Adel; Morsy, Basant M; Mahmoud, Ayman M; Abo-Seif, Mohamed A; Zanaty, Mohamed I

    2013-01-01

    Hepatitis C is a major global health burden and Egypt has the highest prevalence of hepatitis C virus (HCV) worldwide. The current study was designed to evaluate the beneficial therapeutic effects of ethanolic extracts of Nigella sativa, Zingiber officinale and their mixture in Egyptian HCV patients. Sixty volunteer patients with proven HCV and fifteen age matched healthy subjects were included in this study. Exclusion criteria included patients on interferon alpha (IFN-α) therapy, infection with hepatitis B virus, drug-induced liver diseases, advanced cirrhosis, hepatocellular carcinoma (HCC) or other malignancies, blood picture abnormalities and major severe illness. Liver function enzymes, albumin, total bilirubin, prothrombin time and concentration, international normalized ratio, alpha fetoprotein and viral load were all assessed at baseline and at the end of the study. Ethanolic extracts of Nigella sativa and Zingiber officinale were prepared and formulated into gelatinous capsules, each containing 500 mg of Nigella sativa and/or Zingiber officinale. Clinical response and incidence of adverse drug reactions were assessed initially, periodically, and at the end of the study. Both extracts as well as their mixture significantly ameliorated the altered viral load, alpha fetoprotein, liver function parameters; with more potent effect for the combined therapy. In conclusion, administration of Nigella sativa and/or Zingiber officinale ethanolic extracts to HCV patients exhibited potential therapeutic benefits via decreasing viral load and alleviating the altered liver function, with more potent effect offered by the mixture.

  12. Limited evidence of HCV transmission in stable heterosexual couples from Bahia, Brazil

    Directory of Open Access Journals (Sweden)

    Márcia Bessa

    Full Text Available HCV infected patients frequently ask their physician about the risk of transmission to their partners. Although it is easy to answer that the risk does exist, it is difficult to quantify. We studied the transmission of HCV infection in stable heterosexual couples: anti-HCV positive patients in hemodialytic therapy and their partners. Thirty-four couples were tested by third generation ELISA and RIBA. Blood samples of anti-HCV positive patients were evaluated by RT-PCR and detected sequences were genotyped by restriction fragment length polymorphism. Concordance of infection was observed in only one couple in which both subjects were in dialytic therapy. One other partner had two positive ELISA tests and an indeterminate RIBA, with negative RT-PCR, which may suggest a false positive or a previous resolved infection. Either sexual relations, sharing of personal items and history of parenteral exposure (hemodialysis, blood transfusion could explain transmission in the only couple with concordant infection. We observed, in accordance with previous reports, that this risk is minimal or negligible in stable heterosexual couples.

  13. Down-regulation of IRES containing 5'UTR of HCV genotype 3a using siRNAs

    Directory of Open Access Journals (Sweden)

    Ali Ashfaq Usman

    2011-05-01

    Full Text Available Abstract Background Hepatitis C virus (HCV is a major causative agent of liver associated diseases leading to the development of hepatocellular carcinoma (HCC all over the world and genotype-3a responsible for most of the cases in Pakistan. Due to the limited efficiency of current chemotherapy of interferon-α (IFN-α and ribavirin against HCV infection alternative options are desperately needed out of which the recently discovered RNAi represent a powerful silencing approach for molecular therapeutics through a sequence-specific RNA degradation process to silence virus infection or replication. HCV translation is mediated by a highly conserved internal ribosome entry site (IRES within the 5'UTR region making it a relevant target for new drug development. Materials and methods The present study was proposed to assess and explore the possibility of HCV silencing using siRNA targeting 5'UTR. For this analysis full length HCV 5'UTR of HCV-3a (pCR3.1/5'UTR was tagged with GFP protein for in vitro analysis in Huh-7 cells. siRNA targeting 5'UTR were designed, and tested against constructed vector in Huh-7 cell line both at RNA and Protein levels. Furthermore, the effect of these siRNAs was confirmed in HCV-3a serum infected Huh-7 cell line. Results The expression of 5'UTR-GFP was dramatically reduced both at mRNA and protein levels as compared with Mock transfected and control siRNAs treated cells using siRNAs against IRES of HCV-3a genotype. The potential of siRNAs specificity to inhibit HCV-3a replication in serum-infected Huh-7 cells was also investigated; upon treatment with siRNAs a significant decrease in HCV viral copy number and protein expression was observed. Conclusions Overall, the present work of siRNAs against HCV 5'UTR inhibits HCV-3a expression and represents effective future therapeutic opportunities against HCV-3a genotype.

  14. Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1.

    Science.gov (United States)

    Wyles, David L; Ruane, Peter J; Sulkowski, Mark S; Dieterich, Douglas; Luetkemeyer, Anne; Morgan, Timothy R; Sherman, Kenneth E; Dretler, Robin; Fishbein, Dawn; Gathe, Joseph C; Henn, Sarah; Hinestrosa, Federico; Huynh, Charles; McDonald, Cheryl; Mills, Anthony; Overton, Edgar Turner; Ramgopal, Moti; Rashbaum, Bruce; Ray, Graham; Scarsella, Anthony; Yozviak, Joseph; McPhee, Fiona; Liu, Zhaohui; Hughes, Eric; Yin, Philip D; Noviello, Stephanie; Ackerman, Peter

    2015-08-20

    The combination of daclatasvir, a hepatitis C virus (HCV) NS5A inhibitor, and the NS5B inhibitor sofosbuvir has shown efficacy in patients with HCV monoinfection. Data are lacking on the efficacy and safety of this combination in patients coinfected with human immunodeficiency virus type 1 (HIV-1). This was an open-label study involving 151 patients who had not received HCV treatment and 52 previously treated patients, all of whom were coinfected with HIV-1. Previously untreated patients were randomly assigned in a 2:1 ratio to receive either 12 weeks or 8 weeks of daclatasvir at a standard dose of 60 mg daily (with dose adjustment for concomitant antiretroviral medications) plus 400 mg of sofosbuvir daily. Previously treated patients were assigned to undergo 12 weeks of therapy at the same doses. The primary end point was a sustained virologic response at week 12 after the end of therapy among previously untreated patients with HCV genotype 1 who were treated for 12 weeks. Patients had HCV genotypes 1 through 4 (83% with genotype 1), and 14% had compensated cirrhosis; 98% were receiving antiretroviral therapy. Among patients with genotype 1, a sustained virologic response was reported in 96.4% (95% confidence interval [CI], 89.8 to 99.2) who were treated for 12 weeks and in 75.6% (95% CI, 59.7 to 87.6) who were treated for 8 weeks among previously untreated patients and in 97.7% (95% CI, 88.0 to 99.9) who were treated for 12 weeks among previously treated patients. Rates of sustained virologic response across all genotypes were 97.0% (95% CI, 91.6 to 99.4), 76.0% (95% CI, 61.8 to 86.9), and 98.1% (95% CI, 89.7 to 100), respectively. The most common adverse events were fatigue, nausea, and headache. There were no study-drug discontinuations because of adverse events. HIV-1 suppression was not compromised. Among previously untreated HIV-HCV coinfected patients receiving daclatasvir plus sofosbuvir for HCV infection, the rate of sustained virologic response across

  15. Sero-Epidemiological and Behavioural Survey of HIV, HBV and HCV amongst Indian Armed Forces Trainees.

    Science.gov (United States)

    Singh, M; Kotwal, A; Gupta, R M; Adhya, S; Chatterjee, K; Jayaram, J

    2010-01-01

    Information on the emerging epidemics of Human immunodeficiency virus (HIV), Hepatitis B (HBV) and C (HCV) viruses in younger age groups in India is scanty due to paucity of representative, population based surveys and varied estimation methodology. This study was done to assess the point prevalence of HIV, HBV and HCV infections alongwith the epidemiological factors associated with these infections. Attitudes, beliefs and behaviour related to sexual and injecting drug practices, with a view to assess the need for introduction of screening program for the new entrants of the armed forces was also studied. A multi-centric cross sectional serological and behavioural survey was carried out amongst newly enrolled trainees of the Armed Forces in 2004. The group was selected by multistage random sampling giving equal representation to all regions of India. Study subjects were interviewed using a pretested, validated questionnaire and screened for HIV, HBV and HCV infections by rapid tests. Standard confirmatory tests were carried out for trainees testing positive. Quality assurance measures were integral part of each activity. A database was created in MS Access and SPSS ver 11.0.1 was used for analysis. Out of the 23,000 trainees included in the study, 22666 (98.55%) were included in the analysis. The age, formal education and age at first sexual intercourse of participants ranged from 16-25 years (median 20), 8-17 years (median 10) and 12-25 years, respectively. Partial knowledge about routes of spread of HIV was highly prevalent but complete knowledge was extremely low. Per thousand point prevalence of HIV, HBV and HCV was 0.61 (95% CI, 0.34-10.3, poisson), 9.31 (8.1-10.65) and 4.44 (3.61-5.39), respectively. Clustering of HIV (4.56 per 1000, 2.19-8.38) and HCV (30.54 per 1000, 23.67-38.78) and a higher number of HCV as compared to HBV was found amongst trainees from northeast. A statistically significant association was found between history of injecting drug use

  16. HCV coinfection contributes to HIV pathogenesis by increasing immune exhaustion in CD8 T-cells.

    Science.gov (United States)

    Rallón, Norma; García, Marcial; García-Samaniego, Javier; Rodríguez, Noelia; Cabello, Alfonso; Restrepo, Clara; Álvarez, Beatriz; García, Rosa; Górgolas, Miguel; Benito, José M

    2017-01-01

    There are several contributors to HIV-pathogenesis or insufficient control of the infection. However, whether HIV/HCV-coinfected population exhibits worst evolution of HIV-pathogenesis remains unclear. Recently, some markers of immune exhaustion have been proposed as preferentially upregulated on T-cells during HIV-infection. Herein, we have analyzed T-cell exhaustion together with several other contributors to HIV-pathogenesis that could be affected by HCV-coinfection. Ninety-six patients with chronic HIV-infection (60 HIV-monoinfected and 36 HIV/HCV-coinfected), and 20 healthy controls were included in the study. All patients were untreated for both infections. Several CD4 and CD8 T-cell subsets involved in HIV-pathogenesis were investigated. Non-parametric tests were used to establish differences between groups and associations between variables. Multivariate linear regression was used to ascertain the variables independently associated with CD4 counts. HIV-patients presented significant differences compared to healthy controls in most of the parameters analyzed. Both HIV and HIV/HCV groups were comparable in terms of age, CD4 counts and HIV-viremia. Compared to HIV group, HIV/HCV group presented significantly higher levels of exhaustion (Tim3+PD1- subset) in total CD8+ T-cells (p = 0.003), and higher levels of exhaustion in CD8+HLADR+CD38+ (p = 0.04), CD8+HLADR-CD38+ (p = 0.009) and CD8+HLADR-CD38- (p = 0.006) subsets of CD8+ T-cells. Interestingly these differences were maintained after adjusting by CD4 counts and HIV-viremia. We show a significant impact of HCV-coinfection on CD8 T-cells exhaustion, an important parameter associated with CD8 T-cell dysfunction in the setting of chronic HIV-infection. The relevance of this phenomenon on immunological and/or clinical HIV progression prompts HCV treatment to improve management of coinfected patients.

  17. Costs and absence of HCV-infected employees by disease stage.

    Science.gov (United States)

    Baran, Robert W; Samp, Jennifer C; Walker, David R; Smeeding, James E; Young, Jacob W; Kleinman, Nathan L; Brook, Richard A

    2015-01-01

    Quantify the costs and absenteeism associated with stages of the Hepatitis C virus (HCV). Retrospective analysis of the HCMS integrated database from multiple geographically diverse, US-based employers with employee information on medical, prescription, and absenteeism claims. Employee data were extracted from July 2001-March 2013. Employees with HCV were identified by ICD-9-CM codes and classified into disease severity cohorts using diagnosis/procedure codes assigning the first date of most severe claim as the index date. Non-HCV employees (controls) were assigned random index dates. Inclusion required 6-month pre-/post-index eligibility. Medical, prescription, and absenteeism cost and time were analyzed using two-part regression (logistic/generalized linear) models, controlling for potentially confounding factors. Costs were inflation adjusted to September 2013. All direct costs comparisons were statistically significant (p ≤ 0.05) with mean medical costs of $1813 [SE = $3] for controls (n = 727,588), $4611 [SE = $211] for non-cirrhotic (n = 1007), $4646 [SE = $721] for compensated cirrhosis (CC, n = 87), $12,384 [SE = $1122] for decompensated cirrhosis (DCC, n = 256), $33,494 [SE = $11,753] for hepatocellular carcinoma (HCC, n = 17) and $97,724 [SE = $32,437] for liver transplant (LT, n = 19) cohorts. Mean short-term disability days/costs were significantly greater for the non-cirrhotic (days = 2.03 [SE = 0.36]; $299 [SE = $53]), DCC (days = 6.20 [SE = 1.36]; $763 [SE = $169]), and LT cohorts (days = 21.98 [SE = 8.21]; $2537 [SE = $972]) compared to controls (days = 1.19 [SE = 0.01]; $155 [SE = $1]). Mean sick leave costs were significantly greater for non-cirrhotic ($373 [SE = $22]) and DCC ($460 [SE = $54]) compared to controls ($327 [SE = $1]). Employees with HCV were shown to have greater direct and indirect costs compared to non-HCV employee

  18. Adherence to treatment for recently acquired hepatitis C virus (HCV) infection among injecting drug users.

    Science.gov (United States)

    Grebely, Jason; Matthews, Gail V; Hellard, Margaret; Shaw, David; van Beek, Ingrid; Petoumenos, Kathy; Alavi, Maryam; Yeung, Barbara; Haber, Paul S; Lloyd, Andrew R; Kaldor, John M; Dore, Gregory J

    2011-07-01

    Adherence to HCV therapy impacts sustained virological response (SVR) but there are limited data on adherence, particularly among injecting drug users (IDUs). We assessed 80/80 adherence (≥80% of PEG-IFN doses, ≥80% treatment), on-treatment adherence, and treatment completion in a study of treatment of recent HCV infection (ATAHC). Participants with HCV received pegylated interferon (PEG-IFN) alfa-2a (180μg/week, n=74) and those with HCV/HIV received PEG-IFN alfa-2a with ribavirin (n=35), for a planned 24 weeks. Logistic regression analyses were used to identify predictors of PEG-IFN 80/80 adherence. A total of 109 out of 163 patients received treatment (HCV, n=74; HCV/HIV, n=35), with 75% ever reporting IDU. The proportion with 80/80 PEG-IFN adherence was 82% (n=89). During treatment, 14% missed ≥1 dose (on-treatment adherence=99%). Completion of 0-4, 5-19, 20-23, and all 24 weeks of PEG-IFN therapy occurred in 10% (n=11), 14% (n=15), 6% (n=7) and 70% (n=76) of cases, respectively. Participants with no tertiary education were less likely to have 80/80 PEG-IFN adherence (AOR 0.29, p=0.045). IDU prior to or during treatment did not impact 80/80 PEG-IFN adherence. SVR was higher among those patients with ≥80/80 PEG-IFN adherence (67% vs. 35%, p=0.007), but similar among those with and without missed doses during therapy (73% vs. 60%, p=0.309). SVR in those patients discontinuing therapy between 0-4, 5-19, 20-23, and 24 weeks was 9%, 33%, 43%, and 76%, respectively (p<0.001). High adherence to treatment for recent HCV was observed, irrespective of IDU prior to, or during, therapy. Sub-optimal PEG-IFN exposure was mainly driven by early treatment discontinuation rather than missed doses during therapy. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  19. Low Efficacy of Pegylated Interferon plus Ribavirin plus Nitazoxanide for HCV Genotype 4 and HIV Coinfection.

    Directory of Open Access Journals (Sweden)

    Juan Macías

    Full Text Available Nitazoxanide (NTZ plus pegylated interferon and ribavirin (Peg-IFN/RBV improved the sustained virological response (SVR achieved with Peg-IFN/RBV in hepatitis C virus genotype 4 (HCV-4-monoinfected patients. There are no data currently on the efficacy of Peg-IFN/RBV plus NTZ for human immunodeficiency virus (HIV/HCV-4 coinfection. Therefore, the objectives of this clinical trial were to assess the efficacy and to evaluate the safety of Peg-IFN/RBV plus NTZ in HIV/HCV-4-coinfected patients.This was an open-label, single arm, multicenter phase II pilot clinical trial (NCT01529073 enrolling HIV-infected individuals with HCV-4 chronic infection, naïve to HCV therapy. Patients were treated with NTZ 500 mg bid for 4 weeks, followed by NTZ 500 mg bid plus Peg-IFN alpha-2b 1.5 μg/kg/week plus weight-adjusted RBV during 48 weeks. Analyses were done by intention-to-treat (ITT, missing = failure. A historical cohort of HIV/HCV-4-infected patients treated with Peg-IFN alpha-2b and RBV at the same area was used as control.Two (9.5% of 21 patients included in the trial compared with 5 (21.7% of 23 patients included in the historical cohort achieved SVR (SVR risk difference, -12.2%; 95% confidence interval, -33.2% to 8.8%; p = 0.416. Virological failure was due to lack of response in 13 (62% individuals recruited in the trial. Two (9.5% patients included in the trial and two (9.5% individuals from the historical cohort discontinued permanently due to adverse events.No increase in SVR was observed among HIV/HCV-4-coinfected patients receiving Peg-IFN/RBV plus NTZ compared with a historical cohort treated with Peg-IFN/RBV. Interruptions due to adverse events of Peg-IFN/RBV plus NTZ were similar to those of dual therapy.ClinicalTrials.gov NCT01529073.

  20. HCV Treatment Initiation in Patients with Chronic Kidney Disease: Results from ERCHIVES

    Science.gov (United States)

    Butt, Adeel; Ren, Yanjie; Puenpatom, Amy; Arduino, Jean Marie; Kumar, Ritesh; Abou-Samra, Abdul-Badi

    2017-01-01

    Abstract Background Newer directing antiviral agents against HCV (DAAs) are safe and efficacious in persons with chronic kidney disease (CKD). Whether availability of these newer DAAs has resulted in more persons with CKD initiating HCV treatment remains unknown. Methods We identified HCV+ persons in ERCHIVES. We excluded HIV+ and HBsAg+ and those with missing HCV RNA and eGFR data. We determined the CKD stage according to National Kidney Foundation criteria. We determined the number of persons initiated on any of the approved DAA-regimen (defined as >14 days of DAA prescription). Logistic regression analyses was used to determine factors associated with treatment initiation. Results Among 76,513 evaluable persons, 21.1% initiated DAA treatment. Initiation rates differed significantly by CKD stage: 21.1% (15,136/68,469) for eGFR>90mL/minute/1.73m2 and CKD stage-2; 14.0% 9853/6,086) for CKD stage 3; and 7.6% (148/1,958) for CKD stage-4/5. Those with CKD stage-3 were 35% less likely and those with CKD stage-4/5 were 65% less likely to initiate treatment with a DAA compared with those with baseline eGFR>90mL/minute/1.73m2. Those with Body Mass Index (BMI)>30 were more likely to initiate treatment (OR 1.24, 95% CI 1.19,1.29). Treatment initiation was less likely in HCV genotype 2 or 3 and those with diabetes (OR 0.82, 95% CI 0.78,0.86), cardiovascular disease (OR 0.73, 95% CI 0.68,0.78), alcohol abuse or dependence (OR 0.75, 95% CI 0.72,0.78) or cirrhosis (OR 0.85, 95% CI 0.80,0.89) at baseline. Conclusion Persons with more advanced CKD are less likely to receive treatment for HCV. Strategies are needed to improve treatment rates in the HCV/CKD population. Disclosures A. Butt, Merck: Investigator, Grant recipient. A. Puenpatom, Merck: Employee, Salary. J. M. Arduino, Merck: Employee, Salary. R. Kumar, Merck: Employee, Salary

  1. Modulation of RANTES expression by HCV core protein in liver derived cell lines

    Directory of Open Access Journals (Sweden)

    Rapicetta Maria

    2007-06-01

    Full Text Available Abstract Background Hepatitis C virus (HCV infection is associated with high percentage of chronicity which implies the ability of the virus to evade or modulate host cell immune system. Modulation of chemokines, such as RANTES may be part of the virus induced pathogenicity. We examined the effect of core and structural proteins of HCV on RANTES expression in two liver derived cell lines, HepG2 and Chang Liver (CHL. Methods HepG2 and Chang Liver (CHL cell lines were established and selected for constitutive expression of HCV core and structural genes. Flow cytometry and quantitative RT-PCR analysis were performed to examine the effect of HCV core protein on RANTES expression. Luciferase analysis after RANTES-Luc-promoter transfection of established cell lines was assayed by luminometer measurements (RLU of RANTES promoter activity. IRF-1 and IRF-7 expression was then examined by immunoblotting analysis. Results Results of flow cytometry and RT-PCR analysis indicated that RANTES is differentially regulated by HCV core protein in the two cell lines examined as its expression was inhibited in HepG2 cells, by a reduction of RANTES promoter activity. Conversely, RANTES protein and mRNA were induced by the core protein in CHL cells, through the induction of the promoter. Since HCV genome modulates IRF-1 and IRF-7 in replicon system and IRF-1, IRF-3 and IRF-7 have been reported to regulate RANTES promoter in various cell systems, analysis of the mechanism underlying RANTES modulation by the core protein revealed that IRF-1 expression was induced in HepG2 cells by the core protein, whereas in CHL cells it was expressed at a very low level that was not influenced by transfection with the core protein construct. This suggested that IRF-1 level may mediate the expression of RANTES in cell lines of liver origin. The effect of the core protein on RANTES promoter was countered by co-transfection with NF90, a double-stranded-RNA binding protein that activates

  2. Geographic distribution of HCV genotypes in Libya and analysis of risk factors involved in their transmission.

    Science.gov (United States)

    Daw, Mohamed A; El-Bouzedi, Abdallah; Dau, Aghnaya A

    2015-08-21

    Hepatitis C virus (HCV) genotypes have been shown to be differently distributed between distinct geographical areas. Libya is a large country has the longest coast in the Mediterranean basin. Information regarding hepatitis C genotypes and subtypes circulating in Libya are not well known. The objectives of this study were to determine the frequency of various HCV genotypes cross Libya and the demographic and attributable risk factors associated with HCV transmission among Libyan population. A cross-sectional study was carried out on patients with recently confirmed HCV infection. A total of 3,227 serum samples enrolled at 19 collection center cross Libya. 1,756 belonged to Tripoli region, 452 to West region 355 to North region, 181 South regions and 483 East region. The samples were tested by type specific genotyping assay and correlated with demographic and potential risk factors within the studied populations. A total of 20 discrete genotypes and subtypes were identified among the Libyan population ranging from 11.5 to 0.3% cross the country. Genotype 1 was the most frequent among all regions (19.7-40.5%), reaching the highest value in Tripoli region, followed by genotype 4 which was more prevalent in the South (49.3%) and West (40.0%) regions. Genotype 3, was higher in Tripoli (21.3%) and East (15.9%) regions while genotype 2, common in North (23.6%) and South (22.5%) regions. However, we found evidence that there is a changing relative prevalence of HCV genotypes in relation to age, gender and the mode of transmission which is reflected in the predominance of certain genotypes among Libyan population. Different HCV genotypes were isolated form Libyan population including newly emerged ones. The prevalence of the genotypes varied by geographic region and influenced by demographic and risk factors. Knowing the frequency and distribution of the genotypes would provide key information on understanding the spread of HCV in Libya and this could be greatly reflected

  3. The Combination of Grazoprevir, a Hepatitis C Virus (HCV) NS3/4A Protease Inhibitor, and Elbasvir, an HCV NS5A Inhibitor, Demonstrates a High Genetic Barrier to Resistance in HCV Genotype 1a Replicons.

    Science.gov (United States)

    Lahser, Frederick C; Bystol, Karin; Curry, Stephanie; McMonagle, Patricia; Xia, Ellen; Ingravallo, Paul; Chase, Robert; Liu, Rong; Black, Todd; Hazuda, Daria; Howe, Anita Y M; Asante-Appiah, Ernest

    2016-05-01

    The selection of resistance-associated variants (RAVs) against single agents administered to patients chronically infected with hepatitis C virus (HCV) necessitates that direct-acting antiviral agents (DAAs) targeting multiple viral proteins be developed to overcome failure resulting from emergence of resistance. The combination of grazoprevir (formerly MK-5172), an NS3/4A protease inhibitor, and elbasvir (formerly MK-8742), an NS5A inhibitor, was therefore studied in genotype 1a (GT1a) replicon cells. Both compounds were independently highly potent in GT1a wild-type replicon cells, with 90% effective concentration (EC90) values of 0.9 nM and 0.006 nM for grazoprevir and elbasvir, respectively. No cross-resistance was observed when clinically relevant NS5A and NS3 RAVs were profiled against grazoprevir and elbasvir, respectively. Kinetic analyses of HCV RNA reduction over 14 days showed that grazoprevir and elbasvir inhibited prototypic NS5A Y93H and NS3 R155K RAVs, respectively, with kinetics comparable to those for the wild-type GT1a replicon. In combination, grazoprevir and elbasvir interacted additively in GT1a replicon cells. Colony formation assays with a 10-fold multiple of the EC90 values of the grazoprevir-elbasvir inhibitor combination suppressed emergence of resistant colonies, compared to a 100-fold multiple for the independent agents. The selected resistant colonies with the combination harbored RAVs that required two or more nucleotide changes in the codons. Mutations in the cognate gene caused greater potency losses for elbasvir than for grazoprevir. Replicons bearing RAVs identified from resistant colonies showed reduced fitness for several cell lines and may contribute to the activity of the combination. These studies demonstrate that the combination of grazoprevir and elbasvir exerts a potent effect on HCV RNA replication and presents a high genetic barrier to resistance. The combination of grazoprevir and elbasvir is currently approved for

  4. Can Hepatitis C Virus (HCV) Direct-Acting Antiviral Treatment as Prevention Reverse the HCV Epidemic Among Men Who Have Sex With Men in the United Kingdom? Epidemiological and Modeling Insights

    Science.gov (United States)

    Martin, Natasha K.; Thornton, Alicia; Hickman, Matthew; Sabin, Caroline; Nelson, Mark; Cooke, Graham S.; Martin, Thomas C. S.; Delpech, Valerie; Ruf, Murad; Price, Huw; Azad, Yusef; Thomson, Emma C.; Vickerman, Peter

    2016-01-01

    Background. We report on the hepatitis C virus (HCV) epidemic among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) in the United Kingdom and model its trajectory with or without scaled-up HCV direct-acting antivirals (DAAs). Methods. A dynamic HCV transmission model among HIV–diagnosed MSM in the United Kingdom was calibrated to HCV prevalence (antibody [Ab] or RNA positive), incidence, and treatment from 2004 to 2011 among HIV-diagnosed MSM in the UK Collaborative HIV Cohort (UK CHIC). The epidemic was projected with current or scaled-up HCV treatment, with or without a 20% behavioral risk reduction. Results. HCV prevalence among HIV-positive MSM in UK CHIC increased from 7.3% in 2004 to 9.9% in 2011, whereas primary incidence was flat (1.02–1.38 per 100 person-years). Over the next decade, modeling suggests 94% of infections are attributable to high-risk individuals, comprising 7% of the population. Without treatment, HCV chronic prevalence could have been 38% higher in 2015 (11.9% vs 8.6%). With current treatment and sustained virological response rates (status quo), chronic prevalence is likely to increase to 11% by 2025, but stabilize with DAA introduction in 2015. With DAA scale-up to 80% within 1 year of diagnosis (regardless of disease stage), and 20% per year thereafter, chronic prevalence could decline by 71% (to 3.2%) compared to status quo in 2025. With additional behavioral interventions, chronic prevalence could decline further to <2.5% by 2025. Conclusions. Epidemiological data and modeling suggest a continuing HCV epidemic among HIV-diagnosed MSM in the United Kingdom driven by high-risk individuals, despite high treatment rates. Substantial reductions in HCV transmission could be achieved through scale-up of DAAs and moderately effective behavioral interventions. PMID:26908813

  5. Psychiatric and substance use disorders in HIV/hepatitis C virus (HCV)-coinfected patients: does HCV clearance matter? [Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) HEPAVIH CO13 cohort].

    Science.gov (United States)

    Michel, L; Lions, C; Winnock, M; Lang, J-P; Loko, M-A; Rosenthal, E; Marchou, B; Valantin, M-A; Morlat, P; Roux, P; Sogni, P; Spire, B; Poizot-Martin, I; Lacombe, K; Lascoux-Combe, C; Duvivier, C; Neau, D; Dabis, F; Salmon-Ceron, D; Carrieri, M P

    2016-11-01

    The objective of this nested study was to assess the prevalence of psychiatric disorders in a sample of HIV/hepatitis C virus (HCV)-coinfected patients according to their HCV status. The nested cross-sectional study, untitled HEPAVIH-Psy survey, was performed in a subset of HIV/HCV-coinfected patients enrolled in the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) CO13 HEPAVIH cohort. Psychiatric disorders were screened for using the Mini International Neuropsychiatric Interview (MINI 5.0.0). Among the 286 patients enrolled in the study, 68 (24%) had never received HCV treatment, 87 (30%) were treatment nonresponders, 44 (15%) were currently being treated and 87 (30%) had a sustained virological response (SVR). Of the 286 patients enrolled, 121 patients (42%) screened positive for a psychiatric disorder other than suicidality and alcohol/drug abuse/dependence, 40 (14%) screened positive for alcohol abuse/dependence, 50 (18%) screened positive for drug abuse/dependence, 50 (17.5%) were receiving an antidepressant treatment and 69 (24%) were receiving an anxiolytic. Patients with an SVR did not significantly differ from the other groups in terms of psychiatric disorders. Patients receiving HCV treatment screened positive less often for an anxiety disorder. The highest rate of drug dependence/abuse was among HCV treatment-naïve patients. Psychiatric disorders were frequent in HIV/HCV-coinfected patients and their rates were comparable between groups, even for patients achieving an SVR. Our results emphasize the need for continuous assessment and care of coinfected patients, even after HCV clearance. Drug addiction remains an obstacle to access to HCV treatment. Despite the recent advent and continued development of directly acting antiviral agents (DAAs), it is still crucial to offer screening and comprehensive care for psychiatric and addictive disorders. © 2016 British HIV Association.

  6. Telaprevir-containing triple therapy in acute HCV coinfection: The CHAT Study.

    Science.gov (United States)

    Boesecke, Christoph; Singh, Gurmit K Jagjit; Scholten, Stefan H-A; Lutz, Thomas; Baumgarten, Axel; Schneeweiss, Stephan M; Trein, Andreas; Rausch, Michael; Ingiliz, Patrick; Rockstroh, Jürgen K; Nelson, Mark

    2017-01-01

    No published randomized controlled data on the use of direct-acting antivirals (DAA) in acute hepatitis C (AHC) coinfection exist. However, with the AHC epidemic ongoing among men who have sex with men (MSM) these are urgently needed. The CHAT study is a randomized controlled trial of pegylated interferon + ribavirin (PR) plus telaprevir (TVR) for 12-24 weeks versus PR alone for 24-48 weeks in the response-guided treatment of patients with AHC genotype (GT) 1 infection and HIV-1 coinfection in Germany and Great Britain. 34 patients were included: 15 were randomized to the PR arm (arm 1), 19 to the TVR + PR arm (arm 2). All patients were MSM, median age was 40 years. 55% had IL28B C/C GT. Median baseline HCV RNA was 291,227 IU/ml, median alanine aminotransferase was 105 U/l. 85% received cART, all had baseline HIV RNA <40 copies/ml. Overall sustained virological response (SVR 12 ) rate was 79.4% (27/34). SVR 12 was seen in 12/15 (80%) in arm 1 and in 15/19 (79.8%) in arm 2. Of the four patients without SVR in arm 2, one experienced viraI breakthrough, two were non-responders; in one case HCV protease inhibitor (PI)-associated mutations were selected under TVR (V36M, R155K). Due to moderate response rates and additional toxicities 1st generation HCV PIs should not be used in treating acute HCV. While not being licensed, recent study data and guidelines support the use of dual DAA therapy but optimal treatment duration in acute HCV needs further investigation.

  7. Daclatasvir and Peginterferon/Ribavirin for Black/African-American and Latino Patients with HCV infection.

    Science.gov (United States)

    Rodriguez-Torres, Maribel; Lawitz, Eric; Yangco, Bienvenido; Jeffers, Lennox; Han, Steven-Huy; Thuluvath, Paul J; Rustgi, Vinod; Harrison, Stephen; Ghalib, Reem; Vierling, John M; Luketic, Velimir; Zamor, Philippe J; Ravendhran, Natarajan; Morgan, Timothy R; Pearlman, Brian; O'Brien, Christopher; Khallafi, Hicham; Pyrsopoulos, Nikolaos; Kong, George; McPhee, Fiona; Yin, Philip D; Hughes, Eric; Treitel, Michelle

     Background. Patient race and ethnicity have historically impacted HCV treatment response. This phase 3 study evaluated daclatasvir with peginterferon-alfa-2a/ribavirin (pegIFN alfa-2a/RBV) in treatment-naive black/African American (AA), Latino, and white non-Latino patients with chronic HCV genotype 1 infection. In this single-arm, open-label study, 246 patients received daclatasvir plus pegIFN alfa-2a and weight-based RBV. Patients with an extended rapid virologic response (eRVR; undetectable HCV-RNA at treatment weeks 4 and 12) received 24 weeks of treatment; those without eRVR received an additional 24 weeks of treatment with pegIFN alfa-2a/RBV. The primary endpoint was sustained virologic response at post-treatment week 12 (SVR12; HCV-RNA 4-log10) in HCV-RNA levels were observed. Only 60.9% (78/128) of black/AA and 63.6% (68/107) of Latino patients completed treatment. On-treatment serious adverse events (SAEs) occurred in 21 patients. Discontinuations due to adverse events (AEs) occurred in 9 black/AA and 6 Latino patients. SVR12 rates for black/AA (50.8%) and Latino (58.9%) cohorts treated with daclatasvir plus pegIFN alfa-2a/RBV and the lower bound of the 95% CIs were higher than the estimated historical control (black/AA, 26% SVR; Latino, 36% SVR) treated with pegIFN alfa-2a/RBV. These data support daclatasvir use in all-oral direct-acting antiviral combinations.

  8. A brief review on molecular, genetic and imaging techniques for HCV fibrosis evaluation

    Directory of Open Access Journals (Sweden)

    Sumrin Aleena

    2011-02-01

    Full Text Available Abstract Background Chronic HCV is one of the major causes of morbidity and mortality in the present day world. The assessment of disease progression not only provides useful information for diagnosis and therapeutic supervision judgment but also for monitoring disease. Different invasive and non invasive methods are applied to diagnose the disease from initial to end stage (mild fibrosis to cirrhosis. Although, liver biopsy is still considered as gold standard to identify liver histological stages, an assessment of the disease development based on non-invasive clinical findings is also emerging and this may replace the need of biopsy in near future. This review gives brief insight on non-invasive methods currently available for predicting liver fibrosis in HCV with their current pros and cons to make easier for a clinician to choose better marker to assess liver fibrosis in HCV infected patients. Methods More than 200 studies regarding invasive and noninvasive markers available for HCV liver disease diagnosis were thoroughly reviewed. We examined year wise results of these markers based on their sensitivity, specificity, PPV, NPV and AUROCs. Results We found that in all non-invasive serum markers for HCV, FibroTest, Forn's Index, Fibrometer and HepaScore have high five-year predictive value but with low AUROCs (0.60~0.85 and are not comparable to liver biopsy (AUROC = 0.97. Even though from its beginning, Fibroscan is proved to be best with high AUROCs (> 0.90 in all studies, no single noninvasive marker is able to differentiate all fibrosis stages from end stage cirrhosis. Meanwhile, specific genetic markers may not only discriminate fibrotic and cirrhotic liver but also differentiate individual fibrosis stages. Conclusions There is a need of marker which accurately determines the stage based on simplest routine laboratory test. Genetic marker in combination of imaging technique may be the better non invasive diagnostic method in future.

  9. Introduction and Utilization of High Priced HCV Medicines across Europe; Implications for the Future

    Science.gov (United States)

    de Bruijn, Winnie; Ibáñez, Cristina; Frisk, Pia; Bak Pedersen, Hanne; Alkan, Ali; Vella Bonanno, Patricia; Brkičić, Ljiljana S.; Bucsics, Anna; Dedet, Guillaume; Eriksen, Jaran; Fadare, Joseph O.; Fürst, Jurij; Gallego, Gisselle; Godói, Isabella P.; Guerra Júnior, Augusto A.; Gürsöz, Hakkı; Jan, Saira; Jones, Jan; Joppi, Roberta; Kerman, Saim; Laius, Ott; Madzikwa, Newman; Magnússon, Einar; Maticic, Mojca; Markovic-Pekovic, Vanda; Massele, Amos; Ogunleye, Olayinka; O'Leary, Aisling; Piessnegger, Jutta; Sermet, Catherine; Simoens, Steven; Tiroyakgosi, Celda; Truter, Ilse; Thyberg, Magnus; Tomekova, Kristina; Wladysiuk, Magdalena; Vandoros, Sotiris; Vural, Elif H.; Zara, Corinne; Godman, Brian

    2016-01-01

    Background: Infection with the Hepatitis C Virus (HCV) is a widespread transmittable disease with a diagnosed prevalence of 2.0%. Fortunately, it is now curable in most patients. Sales of medicines to treat HCV infection grew 2.7% per year between 2004 and 2011, enhanced by the launch of the protease inhibitors (PIs) boceprevir (BCV) and telaprevir (TVR) in addition to ribavirin and pegylated interferon (pegIFN). Costs will continue to rise with new treatments including sofosbuvir, which now include interferon free regimens. Objective: Assess the uptake of BCV and TVR across Europe from a health authority perspective to offer future guidance on dealing with new high cost medicines. Methods: Cross-sectional descriptive study of medicines to treat HCV (pegIFN, ribavirin, BCV and TVR) among European countries from 2008 to 2013. Utilization measured in defined daily doses (DDDs)/1000 patients/quarter (DIQs) and expenditure in Euros/DDD. Health authority activities to influence treatments categorized using the 4E methodology (Education, Engineering, Economics and Enforcement). Results: Similar uptake of BCV and TVR among European countries and regions, ranging from 0.5 DIQ in Denmark, Netherlands and Slovenia to 1.5 DIQ in Tayside and Catalonia in 2013. However, different utilization of the new PIs vs. ribavirin indicates differences in dual vs. triple therapy, which is down to factors including physician preference and genotypes. Reimbursed prices for BCV and TVR were comparable across countries. Conclusion: There was reasonable consistency in the utilization of BCV and TVR among European countries in comparison with other high priced medicines. This may reflect the social demand to limit the transmission of HCV. However, the situation is changing with new curative medicines for HCV genotype 1 (GT1) with potentially an appreciable budget impact. These concerns have resulted in different prices across countries, with their impact on budgets and patient outcomes

  10. Introduction and utilisation of high priced HCV medicines across Europe; implications for the future

    Directory of Open Access Journals (Sweden)

    Winnie de Bruijn

    2016-07-01

    Full Text Available Background: Infection with the Hepatitis C Virus (HCV is a widespread transmittable disease with a diagnosed prevalence of 2.0%. Fortunately, it is now curable in most patients. Sales of medicines to treat HCV infection grew 2.7% per year between 2004 and 2011, enhanced by the launch of the protease inhibitors (PIs boceprevir (BCV and telaprevir (TVR in addition to ribavirin and pegylated interferon (pegIFN. Costs will continue to rise with new treatments including sofosbuvir, which now include interferon free regimens. Objective: Assess the uptake of BCV and TVR across Europe from a health authority perspective to offer future guidance on dealing with new high cost medicines. Methods: Cross-sectional descriptive study of medicines to treat HCV (pegIFN, ribavirin, BCV and TVR among European countries from 2008 to 2013. Utilisation measured in defined daily doses (DDDs/ 1000 patients/ quarter (DIQs and expenditure in Euros/ DDD. Health authority activities to influence treatments categorised using the 4E methodology (Education, Engineering, Economics and Enforcement. Results: Similar uptake of BCV and TVR among European countries and regions, ranging from 0.5 DIQ in Denmark, Netherlands and Slovenia to 1.5 DIQ in Tayside and Catalonia in 2013. However, different utilisation of the new PIs versus ribavirin indicates differences in dual versus triple therapy, which is down to factors including physician preference and genotypes. Reimbursed prices for BCV and TVR were comparable across countries. Conclusion: There was reasonable consistency in the utilisation of BCV and TVR among European countries in comparison with other high priced medicines. This may reflect the social demand to limit the transmission of HCV. However, the situation is changing with new curative medicines for HCV genotype 1 (GT1 with potentially an appreciable budget impact. These concerns have resulted in different prices negotiations across countries, with their impact

  11. Claudin-1 required for HCV virus entry has high potential for phosphorylation and O-glycosylation

    Directory of Open Access Journals (Sweden)

    Fouzia Kiran

    2011-05-01

    Full Text Available Abstract HCV is a leading cause of hepatocellular carcinoma and cirrhosis all over the world. Claudins belong to family of tight junction's proteins that are responsible for establishing barriers for controlling the flow of molecules around cells. For therapeutic strategies, regulation of viral entry into the host cells holds a lot of promise. During HCV infection claudin-1 is highly expressed in liver and believed to be associated with HCV virus entry after HCV binding with or without co-receptor CD81. The claudin-1 assembly with tight junctions is regulated by post translational modifications. During claudins assembly and disassembly with tight junctions, phosphorylation is required at C-terminal tail. In cellular proteins, interplay between phosphorylation and O-β-GlcNAc modification is believed to be functional switch, but it is very difficult to monitor these functional and vibrant changes in vivo. Netphos 2.0 and Disphos 1.3 programs were used for potential phosphorylation; NetPhosK 1.0 and KinasePhos for kinase prediction; and YinOYang 1.2 and OGPET to predict possible O-glycosylation sites. We also identified Yin Yang sites that may have potential for O-β-GlcNAc and phosphorylation interplay at same Ser/Thr residues. We for the first time proposed that alternate phosphorylation and O-β-GlcNAc modification on Ser 192, Ser 205, Ser 206; and Thr 191 may provide an on/off switch to regulate assembly of claudin-1 at tight junctions. In addition these phosphorylation sites may be targeted by novel chemotherapeutic agents to prevent phosphorylation lead by HCV viral entry complex.

  12. Microbial translocation is correlated with HIV evolution in HIV-HCV co-infected patients.

    Directory of Open Access Journals (Sweden)

    Jean-Jacques Tudesq

    Full Text Available Microbial translocation (MT is characterized by bacterial products passing into the blood through the gut barrier and is a key phenomenon in the pathophysiology of Human Immunodeficiency Virus (HIV infection. MT is also associated with liver damage in Hepatitis C Virus (HCV patients. The aim of the study was to assess MT in plasma of HIV-HCV co-infected patients. 16S rDNA (16 S Ribosomal DNA subunit marker and other markers of MT such as Lipopolysaccharide (LPS-binding protein (LBP, soluble CD14 (sCD14, intestinal fatty acid binding protein (I-FABP were used. Clinical, biological and immunological characteristics of the population were studied in order to correlate them with the intensity of the MT. We demonstrate that indirect markers of MT, LBP and CD14s, and a marker of intestinal permeability (I-FABP are significantly higher in HIV-HCV co-infected patients than in healthy controls (17.0 vs 2.6 μg/mL, p < 0.001; 1901.7 vs 1255.0 ng/mL, p = 0.018; 478.3 vs 248.1 pg/mL, p < 0.001, respectively, while a direct marker of MT (16S rDNA copies is not different between these two populations. However, plasma 16S rDNA was significantly higher in co-infected patients with long-standing HIV infections (RGM = 1.47 per 10 years, CI95% = [1.04:2.06], p = 0.03. Our findings show that in HIV-HCV co-infected patients, plasma 16S rDNA levels, directly reflecting MT, seem to be linked to the duration of HIV infection, while elevated levels of LBP and sCD14 reflect only a persistence of immune activation. The levels of these markers were not correlated with HCV evolution.

  13. Chaperone-Mediated Autophagy Targets IFNAR1 for Lysosomal Degradation in Free Fatty Acid Treated HCV Cell Culture.

    Directory of Open Access Journals (Sweden)

    Ramazan Kurt

    Full Text Available Hepatic steatosis is a risk factor for both liver disease progression and an impaired response to interferon alpha (IFN-α-based combination therapy in chronic hepatitis C virus (HCV infection. Previously, we reported that free fatty acid (FFA-treated HCV cell culture induces hepatocellular steatosis and impairs the expression of interferon alpha receptor-1 (IFNAR1, which is why the antiviral activity of IFN-α against HCV is impaired.To investigate the molecular mechanism by which IFNAR1 expression is impaired in HCV cell culture with or without free fatty acid-treatment.HCV-infected Huh 7.5 cells were cultured with or without a mixture of saturated (palmitate and unsaturated (oleate long-chain free fatty acids (FFA. Intracytoplasmic fat accumulation in HCV-infected culture was visualized by oil red staining. Clearance of HCV in FFA cell culture treated with type I IFN (IFN-α and Type III IFN (IFN-λ was determined by Renilla luciferase activity, and the expression of HCV core was determined by immunostaining. Activation of Jak-Stat signaling in the FFA-treated HCV culture by IFN-α alone and IFN-λ alone was examined by Western blot analysis and confocal microscopy. Lysosomal degradation of IFNAR1 by chaperone-mediated autophagy (CMA in the FFA-treated HCV cell culture model was investigated.FFA treatment induced dose-dependent hepatocellular steatosis and lipid droplet accumulation in HCV-infected Huh-7.5 cells. FFA treatment of infected culture increased HCV replication in a concentration-dependent manner. Intracellular lipid accumulation led to reduced Stat phosphorylation and nuclear translocation, causing an impaired IFN-α antiviral response and HCV clearance. Type III IFN (IFN-λ, which binds to a separate receptor, induces Stat phosphorylation, and nuclear translocation as well as antiviral clearance in FFA-treated HCV cell culture. We show here that the HCV-induced autophagy response is increased in FFA-treated cell culture

  14. Chaperone-Mediated Autophagy Targets IFNAR1 for Lysosomal Degradation in Free Fatty Acid Treated HCV Cell Culture.

    Science.gov (United States)

    Kurt, Ramazan; Chandra, Partha K; Aboulnasr, Fatma; Panigrahi, Rajesh; Ferraris, Pauline; Aydin, Yucel; Reiss, Krzysztof; Wu, Tong; Balart, Luis A; Dash, Srikanta

    2015-01-01

    Hepatic steatosis is a risk factor for both liver disease progression and an impaired response to interferon alpha (IFN-α)-based combination therapy in chronic hepatitis C virus (HCV) infection. Previously, we reported that free fatty acid (FFA)-treated HCV cell culture induces hepatocellular steatosis and impairs the expression of interferon alpha receptor-1 (IFNAR1), which is why the antiviral activity of IFN-α against HCV is impaired. To investigate the molecular mechanism by which IFNAR1 expression is impaired in HCV cell culture with or without free fatty acid-treatment. HCV-infected Huh 7.5 cells were cultured with or without a mixture of saturated (palmitate) and unsaturated (oleate) long-chain free fatty acids (FFA). Intracytoplasmic fat accumulation in HCV-infected culture was visualized by oil red staining. Clearance of HCV in FFA cell culture treated with type I IFN (IFN-α) and Type III IFN (IFN-λ) was determined by Renilla luciferase activity, and the expression of HCV core was determined by immunostaining. Activation of Jak-Stat signaling in the FFA-treated HCV culture by IFN-α alone and IFN-λ alone was examined by Western blot analysis and confocal microscopy. Lysosomal degradation of IFNAR1 by chaperone-mediated autophagy (CMA) in the FFA-treated HCV cell culture model was investigated. FFA treatment induced dose-dependent hepatocellular steatosis and lipid droplet accumulation in HCV-infected Huh-7.5 cells. FFA treatment of infected culture increased HCV replication in a concentration-dependent manner. Intracellular lipid accumulation led to reduced Stat phosphorylation and nuclear translocation, causing an impaired IFN-α antiviral response and HCV clearance. Type III IFN (IFN-λ), which binds to a separate receptor, induces Stat phosphorylation, and nuclear translocation as well as antiviral clearance in FFA-treated HCV cell culture. We show here that the HCV-induced autophagy response is increased in FFA-treated cell culture

  15. Electronic medical record alert improves HCV testing for baby boomers in primary care setting: adults born during 1945-1965.

    Science.gov (United States)

    Al-Hihi, Eyad; Shankweiler, Caylin; Stricklen, David; Gibson, Cheryl; Dunn, Winston

    2017-01-01

    This project aims to implement the HCV birth cohort screening guidelines over a 9-month period in the primary care setting at the University of Kansas Health System General Internal Medicine Division. The project team measured the number of patients in the baby boomer population who received a one-time screen for HCV. An electronic medical record (EMR) intervention was implemented to identify baby boomers who did not have an HCV screening or diagnosis. Additionally, education was provided to all primary care providers in the clinic to increase awareness of the HCV birth cohort screening. The quality improvement methods increased the percentage of baby boomers who obtained a one-time screening test for HCV from a baseline of 30% to a 55% screening rate during the nine-month project period. Identifying the HCV screening needs and creating a visual reminder in the EMR can be used to facilitate sustainable awareness and improvement of screening rates. The project team recognizes that continued work is required to close the HCV screening care gaps in the primary care setting.

  16. Electronic medical record alert improves HCV testing for baby boomers in primary care setting: adults born during 1945–1965

    Science.gov (United States)

    Al-hihi, Eyad; Shankweiler, Caylin; Stricklen, David; Gibson, Cheryl; Dunn, Winston

    2017-01-01

    Method This project aims to implement the HCV birth cohort screening guidelines over a 9-month period in the primary care setting at the University of Kansas Health System General Internal Medicine Division. The project team measured the number of patients in the baby boomer population who received a one-time screen for HCV. An electronic medical record (EMR) intervention was implemented to identify baby boomers who did not have an HCV screening or diagnosis. Additionally, education was provided to all primary care providers in the clinic to increase awareness of the HCV birth cohort screening. Results The quality improvement methods increased the percentage of baby boomers who obtained a one-time screening test for HCV from a baseline of 30% to a 55% screening rate during the nine-month project period. Conclusion Identifying the HCV screening needs and creating a visual reminder in the EMR can be used to facilitate sustainable awareness and improvement of screening rates. The project team recognizes that continued work is required to close the HCV screening care gaps in the primary care setting. PMID:29209663

  17. 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.

  18. Substitution treatment and HCV/HIV-infection in a sample of 31 German prisons for sentenced inmates.

    Science.gov (United States)

    Schulte, B; Stöver, H; Thane, K; Schreiter, C; Gansefort, D; Reimer, J

    2009-01-01

    Injection drug use (IDU) and IDU-related infectious diseases such as hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections are highly prevalent among prisoners worldwide. However, little is known about the prevalence of IDUs, HCV/HIV and the availability of respective treatment options in German prisons. Data provided by prison physicians of 31 prisons, representing 14,537 inmates, were included in this analysis. The proportion of IDUs among all prisoners was 21.9%. Substitution treatment was available in three out of four prisons (74.2%). Overall, 1137 substitution treatments were provided annually with a wide range of treatment aims. The prevalence rate was 14.3% for HCV and 1.2% for HIV. Around 5.5% of all HCV-infected prisoners were in antiviral treatment annually, 86.5% of all HIV-positive inmates in antiretroviral HIV-treatment. Generally, substitution treatment, and HCV and HIV testing and treatment are available. However, due to abstinence-orientated treatment aims, substitution treatment is rarely available as maintenance treatment, and HCV/HIV-treatment is mainly provided for patients with an existing treatment before imprisonment. The inconsistent data quality necessitates changes in prison-related policy to improve surveillance and to generate aggregated data in German prisons. The selection process in this analysis might lead to overestimating the provision of substitution and antiviral HCV-treatment.

  19. [Analyses of anti-hCV detected by ELISA and HCV RNA detected by RT-nPCR in chronic hepatitis C virus infectors].

    Science.gov (United States)

    Gao, Qiuju; Liu, Dianwu; Zhang, Shiyong; Tong, Lixin

    2007-01-01

    In order to provide the basis for the clinical test and the blood station screening the health donator, the results of anti-HCV tested by ELISA (enzyme-linked-immuno-absorbed assay ) and HCV RNA tested by RT-nPCR (reverse-transcript-nested-polymerase-chain-reaction) were compared in the chronic hepatitis C virus infectors. Venous blood samples of 133 chronic hepatitis C virus infectors, 52 health controls were collected in May 2005. These infectors were infected with HCV nearly in 1990 through plasma donator and diagnosed in 1993 in a rural area of Zhao County in Hebei Province, which remained the same diagnosis as HCV infectors in 2002 Hebei Province. The anti-HCV was tested by ELISA and HCV RNA was tested by RT-nPCR. (1) In 185 cases, the positive rates of both anti-HCV and HCV RNA were 49.73% (92/185). The rate of anti-HCV negative but HCV RNA positive was 9.73% (18/185). The rate of anti-HCV positive but HCV RNA negative was 11.89% (22/185). The negative rate of both anti-HCV and HCV RNA tested was 28.65% (53/185). The result-agreement rate of ELISA and RT-nPCR methods were 78.38% [(92 + 53)/185]. The disagreement rate between ELISA and RT-nPCR methods was not obviously different (paired chi2 = 0.40, P > 0.05). (2) In the chronic HCV infectors, the sensitivity of anti-HCV tested by ELISA was 82.71%, the specificity was 92.31%, and the omitting rate was 17.29%. The sensitivity of HCV RNA tested by RT-nPCR was 81.20%, the specificity was 96.15%, and the omitting rate was 18.80%. The sensitivity between ELISA and RT-nPCR was not obviously different (chi2 = 0.102, P > 0.05). (3) The sensitivity tested by ELISA combined with RT-nPCR was 96.75%, which was evidently higher than that of single ELISA (82.71%) (chi2 = 9.62, P < 0.01). The false negative rate was nearly 17% when anti-HCV was tested with single ELISA in HCV infectors. The positive testing rate of HCV infection was increased remarkably when ELISA and RT-nPCR were tested simultaneously.

  20. Identification of Genotype 2 HCV in Serotype-1 Hepatitis C Patients Unresponsive to Daclatasvir plus Asunaprevir Treatment.

    Science.gov (United States)

    Inoue, Jun; Kanno, Atsushi; Wakui, Yuta; Miura, Masahito; Kobayashi, Tomoo; Morosawa, Tatsuki; Kogure, Takayuki; Kakazu, Eiji; Ninomiya, Masashi; Fujisaka, Yasuyuki; Umetsu, Teruyuki; Takai, Satoshi; Nakamura, Takuya; Shimosegawa, Tooru

    2017-01-01

    It is important to determine the genotypes or serotypes of hepatitis C virus (HCV) in patients before treatment with direct-acting antiviral agents (DAAs), because the effects of DAAs differ among genotypes. In Japan, two tests for HCV typing are available clinically, but only serotyping, not genotyping, is approved by the public health insurance. Although most serotype-1 Japanese patients are infected with genotype 1b HCV, it is known that a small proportion of patients show different results from two typing methods. This study focused on such patients and the effectiveness of treatment with daclatasvir plus asunaprevir (DCV/ASV) was evaluated. We analyzed 644 DCV/ASV-treated patients with serotype 1 or genotype 1b, and among them, 166 serotype-1 patients received a commercial-based direct sequencing (DS) test for resistant-associated variants of genotype 1b HCV. We found four patients (2.4%) with DS test failure, suggesting that the PCR primers targeting genotype 1b may not match. Importantly, none of the four patients achieved a sustained virological response. Our in-house DS test analyzing the 5'-untranslated region and coding regions for NS4 and NS5B of HCV showed that three of the four patients were infected with genotype 2 HCV, and one patient was infected with genotype 1a HCV. No recombinant virus of different genotypes was found. This study indicates that a subset of serotype-1 hepatitis C patients is infected with HCV of genotype 2 or 1a in Japan and that DCV/ASV is not effective for such patients. Thus, attention should be paid to DAA treatment without HCV genotyping.

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

    Science.gov (United States)

    Shoman, Sahar; Nabil, Mohamed; Tabl, Ashraf; Ghanem, Hussam; kafrawy, Sherif El

    2014-01-01

    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. PMID:25317700

  2. Induction of humoural and cellular immunity by immunisation with HCV particle vaccine in a non-human primate model.

    Science.gov (United States)

    Yokokawa, Hiroshi; Higashino, Atsunori; Suzuki, Saori; Moriyama, Masaki; Nakamura, Noriko; Suzuki, Tomohiko; Suzuki, Ryosuke; Ishii, Koji; Kobiyama, Kouji; Ishii, Ken J; Wakita, Takaji; Akari, Hirofumi; Kato, Takanobu

    2018-02-01

    Although HCV is a major cause of chronic liver disease worldwide, there is currently no prophylactic vaccine for this virus. Thus, the development of an HCV vaccine that can induce both humoural and cellular immunity is urgently needed. To create an effective HCV vaccine, we evaluated neutralising antibody induction and cellular immune responses following the immunisation of a non-human primate model with cell culture-generated HCV (HCVcc). To accomplish this, 10 common marmosets were immunised with purified, inactivated HCVcc in combination with two different adjuvants: the classically used aluminum hydroxide (Alum) and the recently established adjuvant: CpG oligodeoxynucleotide (ODN) wrapped by schizophyllan (K3-SPG). The coadministration of HCVcc with K3-SPG efficiently induced immune responses against HCV, as demonstrated by the production of antibodies with specific neutralising activity against chimaeric HCVcc with structural proteins from multiple HCV genotypes (1a, 1b, 2a and 3a). The induction of cellular immunity was also demonstrated by the production of interferon-γ mRNA in spleen cells following stimulation with the HCV core protein. These changes were not observed following immunisation with HCVcc/Alum preparation. No vaccination-related abnormalities were detected in any of the immunised animals. The current preclinical study demonstrated that a vaccine included both HCVcc and K3-SPG induced humoural and cellular immunity in marmosets. Vaccination with this combination resulted in the production of antibodies exhibiting cross-neutralising activity against multiple HCV genotypes. Based on these findings, the vaccine created in this study represents a promising, potent and safe prophylactic option against HCV. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Rapid screening for co-infection of HIV and HCV in pregnant women in Benin City, Edo State, Nigeria.

    Science.gov (United States)

    Duru, M U; Aluyi, H S A; Anukam, K C

    2009-09-01

    Human Immunodeficiency virus (HIV) and Hepatitis C virus (HCV) are both major global health concerns as they cause high mortality and morbidity in the developing countries. However, while data exists for the co-infection in other countries, little or no information can be found with regard to the sero-prevalence of HIV and HCV co-infection in Nigeria, albeit in pregnant women attending antenatal care clinics in Benin City, Nigeria. The objective of the study was to determine the sero-prevalence of HIV and HCV among pregnant women seeking antenatal care in Benin City. In determining the sero-prevalence in a cross-sectional study, 200 pregnant women, aged between 15 and 49 years were screened for HIV and HCV using rapid screening test kits. Using closed ended structured questionnaires; the respondents volunteered socio-demographic information associated with risk factors of HIV and HCV acquisition. Results indicated sero-prevalence of HIV and HCV in the sampled population was 3% and 5% respectively. Thirty three percent of the pregnant women that were HCV positive were co-infected with HIV-1 infection. HIV sero-prevalence was highest in the age group, 25-29 representing 5.1%, while HCV sero-prevalence was noted highest among the women in the age group 30-34 years, representing 7.9%. Two percent of the pregnant women had equivocal (ambivalent) HIV-1 results. The study has shown a prevalence of HIV-HCV co-infection among the tested pregnant women in Benin City and more epidemiological surveys are needed in larger scale to decipher the prevalence in other states of Nigeria.

  5. Circulating Interferon-λ3, Responsiveness to HBV Vaccination, and HBV/HCV Infections in Haemodialysis Patients

    Directory of Open Access Journals (Sweden)

    Alicja E. Grzegorzewska

    2017-01-01

    Full Text Available The IFN-λ3 gene (IFNL3 plays a role in HCV clearance. We investigated circulating IFN-λ3 and IFNL3 SNPs in haemodialysis patients who differed in their response to HBV vaccination and their HBV/HCV infection status. In 201 patients, plasma IFN-λ3 was determined using ELISA. IFNL3 SNPs (rs12979860, rs8099917 were genotyped using HRM analysis. Differences in IFN-λ3 levels were shown between responders and nonresponders to HBV vaccination and between HBsAg-positive patients and those who developed anti-HBs after infection and became HBsAg negative. HBV vaccine responders without HCV resolution revealed lower IFN-λ3 than noninfected responders. HBsAg/HCV RNA-positive subjects showed lower IFN-λ3 than patients positive only for HCV RNA or subjects who resolved both infections. Circulating IFN-λ3 correlated positively with anti-HBs and negatively with positive HCV RNA testing in the adjusted regression analyses. HBV vaccine nonresponders, HBsAg-positive patients, and subjects with replicating HCV composed a group with unfavourable outcomes. Responders to HBV vaccination, subjects who became HBsAg negative, and those who cleared HCV were analysed as having favourable outcomes. The latter showed higher IFN-λ3 but did not differ in distribution of IFNL3 SNPs compared with subjects with unfavourable outcomes. Higher IFN-λ3 concentrations are associated with response to HBV vaccination, self-limited HBV infection, and HCV resolution.

  6. Investigation of viral escape mutations within HCV p7 during treatment with amantadine in patients with chronic hepatitis C.

    Science.gov (United States)

    Vermehren, Annika; Welsch, Christoph; Elsler, Ulrike; Vermehren, Johannes; Herrmann, Eva; Sarrazin, Christoph; von Wagner, Michael; Susser, Simone; Hofmann, Wolf Peter; Kronenberger, Bernd; Zeuzem, Stefan; Mihm, Ulrike

    2013-01-01

    Combination of several direct-acting antiviral agents will be necessary to overcome viral resistance in interferon-free treatment regimens for chronic HCV infection. HCV p7 inhibitors may be part of such combination regimens. Understanding why amantadine, despite showing inhibition of HCV p7 in vitro, appears ineffective in clinical trials, may help in the design of novel HCV p7 inhibitors. So far it is unknown whether viral escape mutations within HCV p7 explain the ineffectiveness of amantadine in vivo. Pretreatment HCV p7 was directly sequenced in 157 consecutive patients with chronic HCV genotype 1b infection who had been treated with amantadine/placebo plus pegylated interferon (PEG-IFN)-α2a/ribavirin within a multicentre clinical trial. Triple therapy was preceded by 2 weeks of amantadine/placebo monotherapy. In nine patients, clonal sequencing was performed at baseline and after 2 weeks of amantadine/placebo monotherapy. Changes of the relative frequency of amino acid substitutions by ≥20% between pretreatment and week 2 of monotherapy were considered potential resistance mutations if they were only found in patients receiving amantadine but not in patients receiving placebo. Seven substitutions fulfilling these criteria were identified in the subset of patients with clonal sequencing. However, none of these substitutions were associated with treatment outcome in the complete cohort of patients receiving triple therapy with amantadine. Potential viral escape mutations within HCV p7 do not seem to play a major role for treatment response to antiviral therapy with amantadine and PEG-IFN-α2a/ribavirin in patients with chronic HCV genotype 1b infection.

  7. Cost effectiveness of screening strategies for early identification of HIV and HCV infection in injection drug users.

    Directory of Open Access Journals (Sweden)

    Lauren E Cipriano

    Full Text Available To estimate the cost, effectiveness, and cost effectiveness of HIV and HCV screening of injection drug users (IDUs in opioid replacement therapy (ORT.Dynamic compartmental model of HIV and HCV in a population of IDUs and non-IDUs for a representative U.S. urban center with 2.5 million adults (age 15-59.We considered strategies of screening individuals in ORT for HIV, HCV, or both infections by antibody or antibody and viral RNA testing. We evaluated one-time and repeat screening at intervals from annually to once every 3 months. We calculated the number of HIV and HCV infections, quality-adjusted life years (QALYs, costs, and incremental cost-effectiveness ratios (ICERs.Adding HIV and HCV viral RNA testing to antibody testing averts 14.8-30.3 HIV and 3.7-7.7 HCV infections in a screened population of 26,100 IDUs entering ORT over 20 years, depending on screening frequency. Screening for HIV antibodies every 6 months costs $30,700/QALY gained. Screening for HIV antibodies and viral RNA every 6 months has an ICER of $65,900/QALY gained. Strategies including HCV testing have ICERs exceeding $100,000/QALY gained unless awareness of HCV-infection status results in a substantial reduction in needle-sharing behavior.Although annual screening for antibodies to HIV and HCV is modestly cost effective compared to no screening, more frequent screening for HIV provides additional benefit at less cost. Screening individuals in ORT every 3-6 months for HIV infection using both antibody and viral RNA technologies and initiating ART for acute HIV infection appears cost effective.

  8. Genomic analysis reveals a potential role for cell cycle perturbation in HCV-mediated apoptosis of cultured hepatocytes.

    Directory of Open Access Journals (Sweden)

    Kathie-Anne Walters

    2009-01-01

    Full Text Available The mechanisms of liver injury associated with chronic HCV infection, as well as the individual roles of both viral and host factors, are not clearly defined. However, it is becoming increasingly clear that direct cytopathic effects, in addition to immune-mediated processes, play an important role in liver injury. Gene expression profiling during multiple time-points of acute HCV infection of cultured Huh-7.5 cells was performed to gain insight into the cellular mechanism of HCV-associated cytopathic effect. Maximal induction of cell-death-related genes and appearance of activated caspase-3 in HCV-infected cells coincided with peak viral replication, suggesting a link between viral load and apoptosis. Gene ontology analysis revealed that many of the cell-death genes function to induce apoptosis in response to cell cycle arrest. Labeling of dividing cells in culture followed by flow cytometry also demonstrated the presence of significantly fewer cells in S-phase in HCV-infected relative to mock cultures, suggesting HCV infection is associated with delayed cell cycle progression. Regulation of numerous genes involved in anti-oxidative stress response and TGF-beta1 signaling suggest these as possible causes of delayed cell cycle progression. Significantly, a subset of cell-death genes regulated during in vitro HCV infection was similarly regulated specifically in liver tissue from a cohort of HCV-infected liver transplant patients with rapidly progressive fibrosis. Collectively, these data suggest that HCV mediates direct cytopathic effects through deregulation of the cell cycle and that this process may contribute to liver disease progression. This in vitro system could be utilized to further define the cellular mechanism of this perturbation.

  9. Inhibition of core gene of HCV 3a genotype using synthetic and vector derived siRNAs.

    Science.gov (United States)

    Khaliq, Saba; Jahan, Shah; Ijaz, Bushra; Ahmad, Waqar; Asad, Sultan; Pervaiz, Asim; Samreen, Baila; Khan, Mahwish; Hassan, Sajida

    2010-11-13

    Hepatitis C virus (HCV) is a major causative agent of liver associated diseases throughout the world, with genotype 3a responsible for most of the cases in Pakistan. Due to the limited efficiency of current therapy, RNA interference (RNAi) a novel regulatory and powerful silencing approach for molecular therapeutics through a sequence-specific RNA degradation process represents an alternative option. The current study was purposed to assess and explore the possibility of RNAi to silence the HCV-3a Core gene expression, which play complex role in regulation of cell growth and host genes expression essential for infectivity and disease progression. To identify the potent siRNA target sites, 5 small interfering RNAs (siRNAs) against Core gene were designed and in vitro transcribed after consensus sequence analysis of different HCV-3a isolates. Antiviral effects of siRNAs showed upto 80% inhibition of Core gene expression by different siRNAs into Huh-7 cells as compared with Mock transfected and control siRNAs treated cells. For long lasting effect of siRNAs, vector based short hairpin siRNAs (shRNAs) were designed and tested against HCV-3a Core which resulted in a similar pattern of inhibition on RNA and protein expression of HCV Core as synthetic siRNAs. Furthermore, the efficacy of cell culture tested siRNA and shRNA, were evaluated for inhibition of HCV replication in HCV infected serum inoculated Huh-7 cells and a significant decrease in HCV viral copy number was observed. Our results support the possibility of using consensus siRNA and shRNA-based molecular therapy as a promising strategy in effective inhibition of HCV-3a genotype.

  10. HIV and HCV prevalence among entrants to methadone maintenance treatment clinics in China: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Zhuang Xun

    2012-06-01

    Full Text Available Abstract Background Methadone maintenance treatment (MMT was implemented in China since 2004. It was initiated in 8 pilot clinics and subsequently expanded to 738 clinics by the end of 2011. Numerous individual research studies have been conducted to estimate HIV and HCV prevalence among MMT clients but an overview of the epidemics in relations to MMT remains unclear. The aim of this study is to estimate the magnitude and changing trends of HIV, HCV and HIV-HCV co-infections among entry clients to MMT clinics in China during 2004-2010. Methods Chinese and English databases of literature were searched for studies reporting HIV, HCV and co-infection prevalence among MMT clients in China from 2004 to 2010. The prevalence estimates were summarized through a systematic review and meta-analysis of published literatures. Results Ninety eligible articles were selected in this review (2 in English and 88 in Chinese. Nationally, pooled prevalence of HIV-HCV and HIV-HCV co-infection among MMT clients was 6.0% (95%CI: 4.7%-7.7%, 60.1% (95%CI: 52.8%-67.0% and 4.6% (95%CI: 2.9%-7.2%, respectively. No significant temporal trend was found in pooled prevalence estimates. Study location is the major contributor of heterogeneities of both HIV and HCV prevalence among drug users in MMT. Conclusions There was no significant temporal trend in HIV and HCV prevalence among clients in MMT during 2004–2010. Prevalence of HCV is markedly higher than prevalence of HIV among MMT clients. It is recommended that health educational programs in China promote the earlier initiation and wider coverage of MMT among injecting drug users (IDUs, especially HIV-infected IDUs.

  11. Modelling the prevalence of HCV amongst people who inject drugs: an investigation into the risks associated with injecting paraphernalia sharing.

    Science.gov (United States)

    Corson, Stephen; Greenhalgh, David; Taylor, Avril; Palmateer, Norah; Goldberg, David; Hutchinson, Sharon

    2013-11-01

    In order to prevent the spread of the hepatitis C virus (HCV) amongst people who inject drugs (PWID), it is imperative that any injecting risk behaviour which may contribute to the transmission of disease has its role quantified. To inform public health organisations, mathematical modelling techniques were used to explore the risk of HCV infection through the sharing of injecting paraphernalia (including filters, cookers and water). A mathematical model was developed for the spread of HCV based on the injecting behaviour of PWID in Scotland, with transmission occurring through the sharing of needles/syringes and other injecting paraphernalia. Numerical simulations were used to estimate the transmission probability for HCV through the sharing of injecting paraphernalia such that the modelled endemic HCV prevalence fitted with that observed amongst PWID in Scotland. The transmission probability of HCV through injecting paraphernalia was modelled to be over 8 times lower than that through needles/syringes (approximately 0.19-0.30% and 2.5%, respectively), assuming transmission occurs through a combination of at least filters and cookers. In the context of reported needle/syringe and paraphernalia sharing rates in Scotland, it is estimated that 38% and 62% of HCV infections are contributed by these practices, respectively. If needle/syringe sharing rates were to be twice those reported, the contributions would be 70% and 30%, respectively. Given that the sharing of injecting paraphernalia among PWID is common, HCV transmission through this route could be contributing to the growing healthcare burden associated with this chronic disease. Every effort should therefore be made to establish (a) the contribution that paraphernalia sharing is making to the spread of HCV, and (b) the effectiveness of services providing sterile paraphernalia in preventing infection. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Il controllo di qualità nell’impiego della PCR applicata alla determinazione qualitativa dell’HCV-RNA

    Directory of Open Access Journals (Sweden)

    Giuseppe Giuliani

    2004-03-01

    Full Text Available Detection of hepatitis C virus (HCV RNA in samples of plasma/serum has become an essential part of the diagnosis and management of HCV-infected patients. Qualitative HCV-RNA tests are used to identify acute HCV infections as well as chronic HCV carriers.In recent years,a variety of commercial and non commercial test systems have been developed for this purpose. Each of these methods is calibrate with proprietary standards and exhibits its own sensitivity (detection limit and specificity. Obviously, laboratories performing HCV-RNA test should report accurate and reliable results regardless of the type of assay used.Where commercial kit are used for part of or the complete analytical procedure, documented validation points already covered by the kit manufacturer can substitute for the validation by the user.Nevertheless, the performance of the kit with respect to its intended use has to be demonstrated by the user. One of the best ways to assess the performance of individual laboratories for validation of qualitative HCV-RNA test is determine: 1. Specificity. In order to validate the specificity of the analytical procedure, at least 100 HCV-RNA-negative plasma pools should be tested and shown to be non-reactive. 2. Positive cut-off point (detection limit/sensitivity.The positive cut-off point (as defined in the Ph Eur General Method 2. 6. 21 is the minimum number of the target sequences per volume sample which can be detected in 95% of test runs.A dilution series of a working reagent or reference material, which has been calibrated against the WHO HCV International Standard (96/790, should be tested on different days to examine variation between test runs.At least 3 independent dilution series should be tested with a sufficient number of replicates at each dilution to give a total number of 24 test results for each dilution to enable a statistical analysis of the results; 3. Robustness.To demonstrate robustness, at least 20 HCV-RNA negative plasma

  13. Mechanism of HCV's resistance to IFN-α in cell culture involves expression of functional IFN-α receptor 1.

    OpenAIRE

    Lamaze Christophe; Koster Mario; Hauser Hansjorg; Wimley William C; Gunduz Feyza; Poat Bret; Samara¹ Maria; Chandra Partha K; Hazari Sidhartha; Datta Sibnarayan; Balart Luis A; Garry Robert F; Dash Srikanta

    2011-01-01

    Abstract The mechanisms underlying the Hepatitis C virus (HCV) resistance to interferon alpha (IFN-α) are not fully understood. We used IFN-α resistant HCV replicon cell lines and an infectious HCV cell culture system to elucidate the mechanisms of IFN-α resistance in cell culture. The IFN-α resistance mechanism of the replicon cells were addressed by a complementation study that utilized the full-length plasmid clones of IFN-α receptor 1 (IFNAR1), IFN-α receptor 2 (IFNAR2), Jak1, Tyk2, Stat1...

  14. Plasma protein biomarkers of hepatocellular carcinoma in HCV-infected alcoholic patients with cirrhosis.

    Directory of Open Access Journals (Sweden)

    Gustavo Ferrín

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common and lethal cancers in the world, with limited options for treatment unless timely diagnosed. Chronic hepatitis C virus (HCV infection and persistent heavy alcohol consumption are independent risk factors for HCC development, which may induce a specific protein expression pattern different from those caused separately. The aim of the study was to identify protein biomarkers for the detection of HCC in HCV-infected alcoholic patients with cirrhosis in order to improve survival. We compared protein expression profiles of plasma samples from 52 HCV-infected alcoholic patients with and without HCC, using 2-D DIGE coupled with MALDI-TOF/TOF mass spectrometry. The 2-D DIGE results were analyzed statistically using Decyder software, and verified by western-blot and ELISA. In plasma samples from HCV-infected alcoholic patients, we found significantly differential expression profiles of carboxypeptidase-N, ceruloplasmin (CP, complement component 4a (C4a, fibrinogen-alpha (FGA, immunoglobulin mu chain C region, serum albumin, and serum paraoxonase/arylesterase 1 (PON1. Deregulation of plasma/serum levels of the identified proteins was associated to HCV, ethanol consumption, and/or HCC progression. In the validation through ELISA, C4a serum concentration was increased in HCC patients (2.4±1 ng/mg vs 1.8±0.6 ng/mg; p = 0.029, being the only independent predictor of HCC in the multivariate analysis (OR = 2.15; p = 0.015, with an AUROC = 0.70. The combination of C4a, FGA, CP and PON1 improved slightly the predictive ability of C4a alone (AUROC 0.81. In conclusion, we identified proteins related to acute-phase response, oxidative stress, or immune response, whose differential expression in plasma may be attributed to the presence of HCC. Among them, C4a, and its combination with CP, FGA and PON1, could be considered as potentially reliable biomarkers for the detection of HCC in HCV-infected alcoholic

  15. A new decision model for economic evaluation of novel therapies for HCV

    Directory of Open Access Journals (Sweden)

    Matteo Ruggeri

    2014-09-01

    Full Text Available In 2014, the European Medicines Agency (EMA has given the license to two new direct-acting antiviral: sofosbuvir and simeprevir. The evidence provided by the studies, reported a high rate of SVR even in patients with decompensated cirrhosis. This and other innovative elements are potentially adept at changing the entire natural course of HCV. However, the dramatic prevalence rates of HCV observed in Italy, and the high prices that are expected to be required by the pharmaceutical industry, raises some critical issues about how to regulate access to such drugs. The objective of this article is to present a new decision model for the evaluation of novel therapies for HCV. This model is intended to provide a tool for the decision-maker that seeks to address the main issues related to the introduction of HCV new treatments. The model that we have structured follows the classic Bayesian approach, using data from reference literature for staging the action of treatments depending on the level of fibrosis (F0, F1, F2, F3, F4. The model is designed to consider patients with all genotypes and allows to make comparisons between innovative and traditional therapies (dual, triple, IFN free, PI combinations, etc., for both experienced and naïve patients. In addition, the model is used to simulate mixed cohorts of patients, representing a population with HCV with different levels of fibrosis and different genotypes. To show the potential of the model, we created some simple scenarios assuming different levels of SVR and pricing. The results of our model show that, even assuming an SVR rate of 100%, the administration of new treatments for HCV subjects F1 / 2 has an incremental cost-effectiveness ratio not sustainable. In contrast, for the subjects F3 and F4, low incremental SVR rates and an incremental cost of the innovative therapy of € 40,000 would be cost effective. The added value of this model is its versatility and applicability to diverse assessment

  16. Expression of HCV Alternative Reading Frame Protein (Core+1/F) in Baculovirus Expression System and its Evaluation for Assessment of Specific Anti-core+1 Antibody in Iranian HCV Infected Patients.

    Science.gov (United States)

    Rahimi, Pooneh; Vahabpour, Rouhollah; Fard, Farideh Sadat Sajadian; Motevalli, Fatemeh; Chahouki, Fatemeh Fotouhi; Aghasadeghi, Mohammad Reza; Bolhassani, Azam; Sadat, Seyed Mehdi; Mostafavi, Ehsan; Mohajel, Nasir; Jahanian-Najafabadi, Ali; Amiran, Mohammad Reza

    2016-10-01

    Hepatitis C virus (HCV) genome contains an overlapping reading frame which results in alternative core protein (ARFP). Baculovirus expression system was used as a powerful eukaryotic vector system to express core+1/F protein for the first time. This recombinant core+1/F protein was used to assess the anti-core+1 antibody in anti-HCV drug resistant and sustained virologic response (SVR) patients. The core+1 coding sequence from HCV genotype 1 was designed and synthesized in pUC57 vector. It was subcloned into baculovirus donor plasmid pFastBacTM HTA and transposed into baculovirus shuttle vector (bacmid) to transfect Sf9 cells. Recombinant core+1 protein was purified using Ni-NTA agarose under native condition and verified using SDS-PAGE electrophoresis and Western blotting. An enzyme-linked immunosorbent assay (ELISA) was developed using this purified protein to assess anti-core+1 antibody in 28 anti-HCV drug resistant patients and in 34 patients with sustained virologic response (SVR) in comparison with 31 healthy volunteers used as the negative control. Expression of HCV core+1 protein in Sf9 cells was confirmed by using SDS-PAGE and Western blotting. Antibody titer against core+1 protein in anti-HCV drug resistant patients was significantly higher than that in both the healthy volunteers and SVR patients (p < 0.0001). HCV core+1 protein was expressed successfully in a baculovirus expression system in high yield in order to develop an ELISA to assess the anti-core+1 antibody. Further studies are needed to reveal the potential application of core+1 protein in anti-HCV treatment prognosis.

  17. Decreased tacrolimus plasma concentrations during HCV therapy : a drug–drug interaction or is there an alternative explanation?

    NARCIS (Netherlands)

    Smolders, E. J.; Pape, S.; de Kanter, C. T M M; van den Berg, A. P.; Drenth, J. P H; Burger, D. M.

    2017-01-01

    Chronic hepatitis C virus (HCV) infection can cause severe liver cirrhosis, for which liver transplantation is the only therapy. To prevent organ rejection, transplanted patients are treated with immunosuppressive agents. We describe two transplanted patients treated with tacrolimus who were

  18. Presence of hepatitis C (HCV) infection in Baby Boomers with Medicare is independently associated with mortality and resource utilisation.

    Science.gov (United States)

    Sayiner, M; Wymer, M; Golabi, P; Ford, J; Srishord, I; Younossi, Z M

    2016-05-01

    Hepatitis C virus is common among Baby Boomers (BB). As this cohort ages, they will increasingly become Medicare eligible. To evaluate resource utilisation and mortality of BB-Medicare recipients with HCV. We used in-patient and out-patient Medicare databases (2005-2010). HCV was identified using ICD-9 codes. Outcomes included resource utilisation [payment/case and in-patient length of stay (LOS)] and short-term mortality. Of 1 153 862 BB Medicare recipients (2005-2010), 3.2% (N = 37 365) had HCV. During this period, in-patient Medicare-BB (39 793-55 235) and their claims (78 924-106 232) increased. Furthermore, their overall mortality increased from 8.94% to 10.25% (P Baby Boomer Medicare recipients, diagnosis of HCV is independently associated with higher mortality and resource utilisation. © 2016 John Wiley & Sons Ltd.

  19. Evaluation of cellular responses for a chimeric HBsAg-HCV core DNA vaccine in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Maryam Yazdanian

    2015-01-01

    Conclusion: Fusion of HBsAg to HCVcp in the context of a DNA vaccine modality could augment Th1-oriented cellular and CTL responses toward a protective epitope, comparable to that of HCVcp (subunit HCV vaccine immunization.

  20. Patient Characteristics Associated with HCV Treatment Adherence, Treatment Completion, and Sustained Virologic Response in HIV Coinfected Patients

    Directory of Open Access Journals (Sweden)

    Glenn Wagner

    2011-01-01

    Full Text Available Background. Hepatitis C (HCV treatment efficacy among HIV patients is limited by poor treatment adherence and tolerance, but few studies have examined the psychosocial determinants of treatment adherence and outcomes. Methods. Chart abstracted and survey data were collected on 72 HIV patients who had received pegylated interferon and ribavirin to assess correlates of treatment adherence, completion, and sustained virologic response (SVR. Results. Nearly half (46% the sample had active psychiatric problems and 13% had illicit drug use at treatment onset; 28% reported <100% treatment adherence, 38% did not complete treatment (mostly due to virologic nonresponse, and intent to treat SVR rate was 49%. Having a psychiatric diagnosis was associated with nonadherence, while better HCV adherence was associated with both treatment completion and SVR. Conclusions. Good mental health may be an indicator of HCV treatment adherence readiness, which is in turn associated with treatment completion and response, but further research is needed with new HCV treatments emerging.

  1. Multiparametric analyses of human PBMCs loaded ex vivo with a candidate idiotype vaccine for HCV-related lymphoproliferative disorders.

    Directory of Open Access Journals (Sweden)

    Annacarmen Petrizzo

    Full Text Available Hepatitis C virus (HCV has been identified as one of the major risk factors for type II mixed cryoglobulinemia (MC, during the clinical evolution of chronic hepatitis, which may lead to development of B cell non-Hodgkin's lymphoma (NHL. We have previously shown that the candidate idiotype vaccine, based on the IGKV3-20 light chain protein, is able to induce activation and maturation of circulating antigen presenting cells (APCs in both HCV-positive and HCV-negative healthy control subjects, with production of Th2-type cytokines. Here, the effect of the recombinant IGKV3-20 protein on human peripheral blood mononuclear cells (PBMCs from HCV-positive subjects, with known blood levels of cryoglobulins, is shown via gene expression profiling analysis combined to multiparameter flow cytometry and multiplex analyses of cytokines.

  2. Molecular screening of phytochemicals from Amelanchier Alnifolia against HCV NS3 protease/helicase using computational docking techniques.

    Science.gov (United States)

    Khan, Mahim; Masoud, Muhammad Shareef; Qasim, Muhammad; Khan, Muhammad Asaf; Zubair, Muhammad; Idrees, Sobia; Ashraf, Asma; Ashfaq, Usman Ali

    2013-01-01

    Hepatitis C is serious health concern worldwide caused by HCV. It causes liver cirrhosis and hepato-cellular carcinoma. Development of prevention solutions is under progress. Meanwhile, the treatment of the viral disease using compounds isolated from natural medicinal plants is promising. The traditional use of photo-chemicals from medicinal plants like Amelanchier alnifolia for viral treatment is hopeful. Therefore, it is of interest to screen for flavonoids from Amelanchier alnifolia against protein targets of HCV. Hence, we assessed the binding of flavonoids to HCV NS3/4A protease and helicase proteins. Results show that Quercitin 3- galactoside and 3-glucosideshowed good binding score with protease and helicase respectively. Their interaction/binding sites are documented in this report. This data provide insights for the consideration of flavonoids as potential inhibitors of HCV/NS3/4A protease and helicase.

  3. HIV and HCV prevalence and incarceration-related risks among injecting drug users in three West Bank governorates.

    Science.gov (United States)

    Štulhofer, Aleksandar; Jwehan, Isam; AbuRabie, Randa

    2016-09-01

    In the Middle East, the HIV epidemic among injecting drug users (IDUs) seems to be in an early phase, which increases the importance of prevention and systematic risk surveillance. To gain information about HIV and HCV infection rates among IDUs in the West Bank, a biobehavioral survey was conducted using time-location sampling in the Ramallah, Hebron, and Bethlehem governorates in 2013. The researchers recruited 288 Palestinian IDUs ages 16-64 (Mage = 39.2, SD = 11.11). While no HIV cases were found in the sample, 41% of participants tested positive for HCV. Imprisonment was common among participants (83%), so we explored the association of incarceration experience with HCV infection and HIV testing. In multivariate assessments, incarceration was shown to increase the odds of being infected with HCV and ever tested for HIV. HIV prevention should be strengthened in West Bank prisons and correctional facilities, and imprisonment for drug use re-examined.

  4. Decreased tacrolimus plasma concentrations during HCV therapy : A drug-drug interaction or is there an alternative explanation?

    NARCIS (Netherlands)

    Smolders, E. J.; Pape, S.; de Kanter, C. T. M. M.; van den Berg, A. P.; Drenth, J. P. H.; Burger, D. M.

    Chronic hepatitis C virus (HCV) infection can cause severe liver cirrhosis, for which liver transplantation is the only therapy. To prevent organ rejection, transplanted patients are treated with immunosuppressive agents. We describe two transplanted patients treated with tacrolimus who were

  5. Impaired expression of type I and type II interferon receptors in HCV-associated chronic liver disease and liver cirrhosis.

    Directory of Open Access Journals (Sweden)

    Partha K Chandra

    Full Text Available Chronic Hepatitis C Virus (HCV-infected patients with liver cirrhosis (LC respond poorly to interferon-alpha (IFN-α and ribavirin (RBV combination therapy, but the reason for this is unclear. We previously reported that HCV-infection induces endoplasmic reticulum (ER stress and autophagy response that selectively down regulates the type I IFN-α receptor-1 (IFNAR1 and RBV transporters (CNT1 and ENT1, leading to IFN-α/RBV resistance. The goal of this study is to verify whether an increase in ER stress and autophagy response is also associated with the reduced expression of IFNAR1 and RBV transporters in chronic HCV-infected patients.Primary human hepatocytes (PHH were infected with cell culture grown HCV particles (JFH-ΔV3-Rluc. HCV replication was confirmed by the detection of viral RNA by RT-qPCR and HCV-core protein by Western blotting. The ER stress and autophagy response and expression of IFN receptors and RBV transporters in HCV infected PHH and liver tissues derived from patients were measured by Western blotting.HCV infection of PHH showed impaired expression of IFNAR1, IFNγR1 (Type II IFN receptor and RBV transporters but not IL10Rβ (Type III IFN-λ receptor. ER stress markers (BiP, IRE1α and peIF2α and autophagy response (LC3II, Beclin 1 and ATG5 were induced in HCV infected chronic liver disease (CLD and LC patients. Liver biopsies (CLD show a 50% reduced expression of IFNAR1 and RBV transporters. Furthermore, the expression of IFNAR1 and RBV transporters was impaired in almost all LC patients.HCV infection induces ER stress and autophagy response in infected PHH and chronically infected liver tissues. The expression of IFNAR1, IFNγR1 and RBV transporters were significantly impaired in CLD and cirrhotic livers. Our study provides a potential explanation for the reduced response rate of IFN-α and RBV combination therapy in HCV infected patients with liver cirrhosis.

  6. Resistance Patterns Associated with HCV NS5A Inhibitors Provide Limited Insight into Drug Binding

    Directory of Open Access Journals (Sweden)

    Moheshwarnath Issur

    2014-11-01

    Full Text Available Direct-acting antivirals (DAAs have significantly improved the treatment of infection with the hepatitis C virus. A promising class of novel antiviral agents targets the HCV NS5A protein. The high potency and broad genotypic coverage are favorable properties. NS5A inhibitors are currently assessed in advanced clinical trials in combination with viral polymerase inhibitors and/or viral protease inhibitors. However, the clinical use of NS5A inhibitors is also associated with new challenges. HCV variants with decreased susceptibility to these drugs can emerge and compromise therapy. In this review, we discuss resistance patterns in NS5A with focus prevalence and implications for inhibitor binding.

  7. Central nervous system involvement in patients with HCV-related cryoglobulinemia: review and a case report

    Directory of Open Access Journals (Sweden)

    B. Canesi

    2011-09-01

    Full Text Available Introduction: Few well-documented cases of central nervous system involvement in patients with mixed cryoglobulinemia and/or HCV infection have been reported. We can distinguish between acute or subacute diffuse and focal lesions (transient ischemic attack-like syndromes and cerebrovascular accidents. Methods: A search of two electronic databases (Medline and EMBASE was conducted from the year of their inception (1966 for Medline and 1988 for EMBASE to September 2000. The search strategy employed entailed combining these terms: Cryoglobulinemia, Central Nervous System, Hepatitis C, chronic hepatitis. Cryoglobulinemia and Central Nervous System were also used as free test words. We analysed articles with case reports and the most frequent articles on the references list. Pathogenesis: The main pathophysiologic mechanism of cerebral involvement is ischemia (or rarely hemorrhage due to diffuse or segmental vasculitis of the small cerebral vessels. In these cases a brain MRI usually shows single or multiple increased T2 signals. Furthermore an occasional occlusive vasculopathy without vasculitis was documented histologically. In these patients ischemia could be started or enhanced by the engorgement of the microvasculature by clumps of red cells and by aggregates of cryoglobulins. In the same patients vasculitis and hemoreological abnormalities can affect the clinical picture of the cerebral involvement in mixed cryoglobulinemia. Finally, the detection of HCV in the lesions induces a hypothesis that, in some cases, CNS involvement could be directly related to chronic HCV infection, even in the absence of cryoglobulin production. Case report: We describe a 63 year-old woman with acute severe encephalopathy. Laboratory evaluation revealed a high positive test result for rheumatoid factor (3390 U/ml and hypocomplementemia (C4 less than 1.67 mg/dl. Protein immunofixation electrophoresis demonstrated 5% monoclonal proteins (IgM/k and IgG/k, 3

  8. Continued high prevalence of HIV, HBV and HCV among injecting and noninjecting drug users in Italy

    Directory of Open Access Journals (Sweden)

    Laura Camoni

    2010-03-01

    Full Text Available We estimated the prevalence of HIV, HBV and HCV infections among injecting and non-injecting drug users treated within public drug-treatment centres in Italy to determine the correlates of infection. In the sample of 1330 drug users, the prevalence of HIV was 14.4% among drug injectors and 1.6% among non-injectors; the prevalence of HBV was 70.4% among injecting drug users and 22.8% among non-injectors and of HCV was 83.2% among injecting drug users and 22.0% among non-injectors. Old age, unemployment, and intravenous drug use were significantly correlated with each of the infections, as well as a longer history of injecting drug use. The results indicate that these infections continue to circulate among drug users, highlighting the need for monitoring of this group in Italy.

  9. Insights on treatment of a Portuguese cohort of HCV/HIV coinfected patients

    Directory of Open Access Journals (Sweden)

    C Silva

    2012-11-01

    Full Text Available Purpose of the study: This study intends to characterize a Portuguese patient population with chronic HCV and HIV coinfection, followed at our Research Unit, underline the importance of early treatment and incorporate the importance of DDA for retreatment of HCV infection. Methods: Retrospective, observational analysis of medical records of 348 HCV/HIV coinfected patients from 2001 to 2011. Demographic, epidemiological, clinical and laboratory data and virologic response were collected. Summary of results: Review of 348 HCV/HIV coinfected patients, 121 of those (34.7% under treatment, predominantly male (77.0% and Caucasians (94.8% with a median age of 44 yrs old (min 25; max 77 yrs. Intravenous drug use was the main route of HCV infection, in 71.3% of patients, and 8.3% were related with MSM. Frequent morbidities were alcohol abuse (46.8%, illicit drug use (70.1%, methadone (25.6% and mental disturbances (12.3% of patients. Regarding HIV infection, six were HIV-2 and 342 HIV-1; 36.1% were stage A and 29.6% were stage C (CDC Atlanta, 94.8% on antiretroviral treatment and only 21.9% of them with more than 350 TCD4 cell count. Genotype 1 was the most prevalent (58.1%–117 genotype 1a, 26 genotype 1b; 1.6% were genotype 2, 22.8% genotype 3 and 17.5% genotype 4. Previous to treatment initiation, HCV ARN was above 600.000 IU/mL in 56.9% patients. Fibrosis was evaluated by fibroelastography in 41.1% and hepatic biopsy in 26.3% of patients; in those, 44.0% had a score above F2 (METAVIR and ALT was elevated 2 times the limit in 38.0%, with an average value of 94 UI/L. IL 28B testing was performed in only 35 patients at the time, with 45.7% CC and 17.1% CT genotype. Treatment was started in 34.8% of patients, with 1.7 treatments per individual, and regimen was based on peguilated interferon with ribavirin in 93.6% of cases (72.1% with peginterferon alfa 2a. The SVR rate was 51.2%, with 28.9% non responders, 3 relapsers and 9 treatment interruptions due

  10. Aryl or heteroaryl substituted aminal derivatives of HCV NS5A inhibitor MK-8742.

    Science.gov (United States)

    Yu, Wensheng; Coburn, Craig A; Nair, Anilkumar G; Wong, Michael; Rosenblum, Stuart B; Zhou, Guowei; Dwyer, Michael P; Tong, Ling; Hu, Bin; Zhong, Bin; Hao, Jinglai; Ji, Tao; Zan, Shuai; Kim, Seong Heon; Zeng, Qingbei; Selyutin, Oleg; Chen, Lei; Masse, Frederic; Agrawal, Sony; Liu, Rong; Xia, Ellen; Zhai, Ying; Curry, Stephanie; McMonagle, Patricia; Ingravallo, Paul; Asante-Appiah, Ernest; Lin, Mingxiang; Kozlowski, Joseph A

    2016-08-01

    Herein we describe our research efforts around the aryl and heteroaryl substitutions at the aminal carbon of the tetracyclic indole-based HCV NS5A inhibitor MK-8742. A series of potent NS5A inhibitors are described, such as compounds 45-47, 54, 56, and 65, which showed improved potency against clinically relevant and resistance associated HCV variants. The improved potency profiles of these compounds demonstrated an SAR that can improve the potency against GT2b, GT1a Y93H, and GT1a L31V altogether, which was unprecedented in our previous efforts in NS5A inhibition. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Prophylactic and Therapeutic Vaccination against Hepatitis C Virus (HCV: Developments and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Marian E. Major

    2009-08-01

    Full Text Available Studies in patients and chimpanzees that spontaneously clear Hepatitis C Virus (HCV have demonstrated that natural immunity to the virus is induced during primary infections and that this immunity can be cross protective. These discoveries led to optimism regarding prophylactic HCV vaccines and a number of studies in the chimpanzee model have been performed, all of which resulted in modified infections after challenge but did not always prevent persistence of the virus. Therapeutic vaccine strategies have also been pursued in an effort to reduce the costs and side effects associated with anti-viral drug treatment. This review summarizes the studies performed thus far in both patients and chimpanzees for prophylactic and therapeutic vaccination, assesses the progress made and future perspectives.

  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. Alteration of N-glycan expression profile and glycan pattern of glycoproteins in human hepatoma cells after HCV infection.

    Science.gov (United States)

    Xiang, Tian; Yang, Ganglong; Liu, Xiaoyu; Zhou, Yidan; Fu, Zhongxiao; Lu, Fangfang; Gu, Jianguo; Taniguchi, Naoyuki; Tan, Zengqi; Chen, Xi; Xie, Yan; Guan, Feng; Zhang, Xiao-Lian

    2017-05-01

    Hepatitis C virus (HCV) infection causes chronic liver diseases, liver fibrosis and even hepatocellular carcinoma (HCC). However little is known about any information of N-glycan pattern in human liver cell after HCV infection. The altered profiles of N-glycans in HCV-infected Huh7.5.1 cell were analyzed by using mass spectrometry. Then, lectin microarray, lectin pull-down assay, reverse transcription-quantitative real time PCR (RT-qPCR) and western-blotting were used to identify the altered N-glycosylated proteins and glycosyltransferases. Compared to uninfected cells, significantly elevated levels of fucosylated, sialylated and complex N-glycans were found in HCV infected cells. Furthermore, Lens culinaris agglutinin (LCA)-binding glycoconjugates were increased most. Then, the LCA-agarose was used to precipitate the specific glycosylated proteins and identify that fucosylated modified annexin A2 (ANXA2) and heat shock protein 90 beta family member 1 (HSP90B1) was greatly increased in HCV-infected cells. However, the total ANXA2 and HSP90B1 protein levels remained unchanged. Additionally, we screened the mRNA expressions of 47 types of different glycosyltransferases and found that α1,6-fucosyltransferase 8 (FUT8) was the most up-regulated and contributed to strengthen the LCA binding capability to fucosylated modified ANXA2 and HSP90B1 after HCV infection. HCV infection caused the altered N-glycans profiles, increased expressions of FUT8, fucosylated ANXA2 and HSP90B1 as well as enhanced LCA binding to Huh7.5.1. Our results may lay the foundation for clarifying the role of N-glycans and facilitate the development of novel diagnostic biomarkers and therapeutic targets based on the increased FUT8, fucosylated ANXA2 and HSP90B1 after HCV infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Time to decompensated cirrhosis and hepatocellular carcinoma after an HBV or HCV notification: A population-based study.

    Science.gov (United States)

    Alavi, Maryam; Law, Matthew G; Grebely, Jason; Amin, Janaki; Hajarizadeh, Behzad; George, Jacob; Dore, Gregory J

    2016-11-01

    Delayed hepatitis B virus (HBV) or hepatitis C virus (HCV) diagnosis may increase risk of advanced liver disease complications, including decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC). The aim of this study was to characterise "late hepatitis notification" among people with an HBV/HCV notification and advanced liver disease in New South Wales, Australia. HBV/HCV notifications 1995-2012 were linked to cancer registry and hospital admissions. Late hepatitis notification was defined by a notification after, at the time, or within two years before DC/HCC diagnosis. HBV and HCV cohorts comprised 50,958 and 79,727 individuals, respectively. Among people with DC (n=3869), late HBV notification declined from 64% (88/138) during 2001-2002 to 31% (46/149) in 2011-2012 (pHBV notification declined from 68% (59/87) during 2001-2002 to 29% (37/128) in 2011-2012 (pHBV, are required. Late hepatitis notification as described in this study could be used as a measure of population-level HBV/HCV screening. Delayed hepatitis B virus (HBV) or hepatitis C virus (HCV) diagnosis may increase the risk of advanced liver disease complications, including decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC). The aim of this study was to characterise "late hepatitis notification" among people with an HBV or HCV notification in New South Wales, Australia. Late hepatitis notifications have significantly declined since early 2000s; however, efforts to enhance hepatitis screening, particularly for HBV, are required. Late hepatitis notification as described in this study could be used as a measure of population-level HBV/HCV screening. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  15. Interferon lambda 4 (IFNL4 gene polymorphism is associated with spontaneous clearance of HCV in HIV-1 positive patients

    Directory of Open Access Journals (Sweden)

    Camila Fernanda da Silveira Alves

    Full Text Available Abstract Approximately one-third of the individuals infected with human immunodeficiency virus type 1 (HIV-1 are co-infected with hepatitis C virus (HCV. Co-infected patients have an increased risk for developing end-stage liver diseases. Variants upstream of the IFNL3 gene have been associated with spontaneous and treatment-induced clearance of HCV infection. Recently, a novel polymorphism was discovered, denoted IFNL4 ΔG > TT (rs368234815, which seems to be a better predictor of spontaneous clearance than the IFNL4 rs12979860 polymorphism. We aimed to determine the prevalence of the IFNL4 ΔG > TT variants and to evaluate the association with spontaneous clearance of HCV infection in Brazilian HIV-1 patients. The IFNL4 ΔG > TT genotypes were analyzed by polymerase chain reaction followed by restriction digestion in 138 HIV-1 positive patients who had an anti-HCV positive result. Spontaneous clearance of HCV was observed in 34 individuals (24.6%. IFNL4 genotype distribution was significantly different between individuals who had spontaneous clearance and chronic HCV patients (p=0.002. The probability of spontaneous clearance of HCV infection for patients with the IFNL4 TT/TT genotype was 3.6 times higher than for patients carrying the IFNL4 ΔG allele (OR=3.63, 95% CI:1.51-8.89, p=0.001. The IFNL4 ΔG > TT polymorphism seems to be better than IFNL4 rs12979860 to predict spontaneous clearance of the HCV in Brazilian HIV-1 positive patients.

  16. Increased incidence of cancer observed in HIV/HCV-coinfected patients versus HIV-monoinfected, 1993-2014.

    Science.gov (United States)

    Meijide, Héctor; Pértega, Sonia; Rodríguez-Osorio, Iria; Castro-Iglesias, Ángeles; Baliñas, Josefa; Rodríguez-Martínez, Guillermo; Mena, Álvaro; Poveda, Eva

    2017-03-21

    Cancer is a growing problem in persons living with HIV infection (PLWH) and hepatitis C virus (HCV) coinfection could play an additional role in carcinogenesis. Herein, all cancers in an HIV-mono and HIV/HCV-coinfected cohort were evaluated and compared to identify any differences between these two populations. A retrospective cohort study was conducted including all cancers in PLWH between 1993 and 2014. Cancers were classified in two groups, AIDS-defining cancer (ADC) and non AIDS-defining cancer (NADC). Cancer incidence rates were calculated and compared with that observed in the Spanish general population (GLOBOCAN, 2012), computing the standardized incidence ratios (SIR). A competing risk approach was used to estimate the probability of cancer after HIV diagnosis. Cumulative incidence in HIV-monoinfected and HIV/HCV-coinfected was also compared using multivariable analysis. A total of 185 patients (117 HIV-monoinfected and 68 HIV/HCV) developed cancer in the 26,580 patient-years cohort; with an incidence rate of 696 cancers per 100,000 person-years, higher than in the general population (SIR = 3.8). The incidence rate of NADC in HIV/HCV-coinfected was 415.0 (SIR = 3.4), significantly higher than in monoinfected (377.3; SIR = 1.8). After adjustments, HIV/HCV-coinfected patients had a higher cumulative incidence of NADC than HIV-monoinfected (adjusted hazard ratio = 1.80), even when excluding hepatocellular carcinomas (adjusted hazard ratio = 1.26). PLWH have a higher incidence of NADC than the general population and HCV-coinfection is associated with a higher incidence of NADC. This data justifies the need for prevention strategies in these two populations and the importance of eradicating HCV.

  17. Improvements in HCV-related Knowledge Among Substance Users on Opioid Agonist Therapy After an Educational Intervention.

    Science.gov (United States)

    Zeremski, Marija; Zavala, Roberto; Dimova, Rositsa B; Chen, Yang; Kritz, Steven; Sylvester, Clewert; Brown, Lawrence S; Talal, Andrew H

    2016-01-01

    Lack of knowledge about hepatitis C virus (HCV) is a principal barrier to substance users' engagement into care for the infection. As a step toward their increased engagement into HCV care, the objective of this study was to deliver an HCV-related educational intervention to substance users on opioid agonist therapy and to assess the change in HCV-related knowledge after the intervention. We designed a comprehensive and interactive hepatitis C-related educational intervention, composed of two 30 to 60-minute sessions conducted during 2 consecutive weeks. Patients' knowledge about hepatitis C was assessed immediately before and after the intervention using a 7-item questionnaire. A total of 110 patients completed both educational sessions. Patients' mean age was 54.7 ± 7.8 years, 58.7% were men, 70.4% African American, and 30% were Hispanic. We observed a significant increase in HCV-related knowledge after completion of the educational intervention. Whereas 65.45% of patients answered 5 or more questions correctly before the intervention, 83.64% had 5 or more questions answered correctly on the posteducational quiz (P educational intervention, and a higher level of HCV knowledge on the preeducational quiz were found to be significantly associated with HCV-related knowledge after the educational intervention. Patients' knowledge about hepatitis C was found to be significantly improved after the educational intervention. Therefore, HCV-related education could be the first step toward effective enrollment of patients on opioid agonist therapy into hepatitis C care.

  18. Humanisation of a claudin-1-specific monoclonal antibody for clinical prevention and cure of HCV infection without escape.

    Science.gov (United States)

    Colpitts, Che C; Tawar, Rajiv G; Mailly, Laurent; Thumann, Christine; Heydmann, Laura; Durand, Sarah C; Xiao, Fei; Robinet, Eric; Pessaux, Patrick; Zeisel, Mirjam B; Baumert, Thomas F

    2017-03-30

    HCV infection is a leading cause of chronic liver disease and a major indication for liver transplantation. Although direct-acting antivirals (DAAs) have much improved the treatment of chronic HCV infection, alternative strategies are needed for patients with treatment failure. As an essential HCV entry factor, the tight junction protein claudin-1 (CLDN1) is a promising antiviral target. However, genotype-dependent escape via CLDN6 and CLDN9 has been described in some cell lines as a possible limitation facing CLDN1-targeted therapies. Here, we evaluated the clinical potential of therapeutic strategies targeting CLDN1. We generated a humanised anti-CLDN1 monoclonal antibody (mAb) (H3L3) suitable for clinical development and characterised its anti-HCV activity using cell culture models, a large panel of primary human hepatocytes (PHH) from 12 different donors, and human liver chimeric mice. H3L3 pan-genotypically inhibited HCV pseudoparticle entry into PHH, irrespective of donor. Escape was likely precluded by low surface expression of CLDN6 and CLDN9 on PHH. Co-treatment of a panel of PHH with a CLDN6-specific mAb did not enhance the antiviral effect of H3L3, confirming that CLDN6 does not function as an entry factor in PHH from multiple donors. H3L3 also inhibited DAA-resistant strains of HCV and synergised with current DAAs. Finally, H3L3 cured persistent HCV infection in human-liver chimeric uPA-SCID mice in monotherapy. Overall, these findings underscore the clinical potential of CLDN1-targeted therapies and describe the functional characterisation of a humanised anti-CLDN1 antibody suitable for further clinical development to complement existing therapeutic strategies for HCV. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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

    Science.gov (United States)

    Huik, Kristi; Avi, Radko; Pauskar, Merit; Kallas, Eveli; Jõgeda, Ene-Ly; Karki, Tõnis; Rüütel, Kristi; Talu, Ave; Abel-Ollo, Katri; Uusküla, Anneli; Carrillo, Andrew; Ahuja, Sunil K; He, Weijing; Lutsar, Irja

    2016-01-01

    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.

  20. Risks for HIV, HBV, and HCV infections among male injection drug users in northern Vietnam: A case-control study

    OpenAIRE

    Quan, Vu Minh; Go, Vivian F.; Van Nam, Le; Bergenstrom, Anna; Thuoc, Nguyen Phuong; Zenilman, Jonathan; Latkin, Carl; Celentano, David D.

    2009-01-01

    Injection drug use (IDU) and HIV infection are important public health problems in Vietnam. The IDU population increased 70% from 2000 to 2004 and is disproportionately affected by HIV and AIDS--the country’s second leading cause of death. Hepatitis B virus (HBV) and hepatitis C virus (HCV) share transmission routes with HIV and cause serious medical consequences. This study aimed to determine risk factors for acquisition of HIV, HBV, and HCV infections among IDUs in a northern province. We c...

  1. HCV genotype-3a T cell immunity: specificity, function and impact of therapy

    Science.gov (United States)

    Humphreys, Isla S; von Delft, Annette; Brown, Anthony; Hibbert, Linda; Collier, Jane D; Foster, Graham R; Rahman, Monira; Christian, Annabel; Klenerman, Paul; Barnes, Eleanor

    2012-01-01

    Background Hepatitis C virus (HCV) genotype-3a infection is now the dominant strain in South Asia and the UK. Characteristic features include a favourable response to therapy; the reasons for this are unknown but may include distinct genotype-3a-specific T cell immunity. In contrast to genotype-1 infection, T cell immunity to this subtype is poorly defined. Objectives The aims of the study were to (1) define the frequency, specificity and cross-reactivity of T cell immunity across the whole viral genome in genotype-3a infection and (2) assess the impact of interferon (IFN)-α/ribavirin on T cell immunity. Design T cell responses in chronic and resolved HCV genotype-3a were analysed in comparison with genotype-1 infection (total n=85) using specific peptide panels in IFN-γ ELISpot assays. T cell responses were followed longitudinally in a subset of genotype-3a infected patients receiving therapy. Responses were further defined by CD4 and CD8 subset analysis, sequencing of autologous virus and cross-reactivity of genotype-3a with genotype-1a/-1b antigens. Results CD8 T cell responses commonly targeted the non-structural (NS) proteins in chronic genotype-3a infection whereas in genotype-1 infection CD4 responses targeting HCV core predominated (p=0.0183). Resolved infection was associated with CD4 T cells targeting NS proteins. Paradoxically, a sustained response to therapy was associated with a brisk decline in virus-specific and total lymphocyte counts that recovered after treatment. Conclusion HCV genotype-3a exhibits a distinct T cell specificity with implications for vaccine design. However, our data do not support the theory that genotype-3a viral clearance with therapy is associated with an enhanced antiviral T cell response. Paradoxically, a reduction in these responses may serve as a biomarker of IFN responsiveness. PMID:22337948

  2. Nutritional status and food intake of HCV/HIV coinfected patients.

    Science.gov (United States)

    Pinto, Giselle Souza; Zanolla, Anelise Fernanda; Tovo, Cristiane Valle; Gottschall, Catarina Bertaso Andreatta; Buss, Caroline

    2016-10-18

    Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection may cause nutrient deficiency and affect the nutritional status.Objetive: To assess nutritional status, and energy and macronutrient intake in HCV/HIV coinfected patients. Cross-sectional study on HIV/HCV-coinfected patients treated in a public hospital. Nutritional status was assessed by measurements of weight, height, waist circumference (WC), arm circumference (AC), triceps skinfold thickness (TST), non-dominant hand gripltrength (NDHGS), body mass index (BMI) and mid-upper arm circumference (MUAC). Dietary intake was assessed by 24-hour recall. Fifty-seven patients (59.6% women) with mean age of 46 ± 11.2 years were studied. According to BMI, more than half of patients were overweight or obese, and 41% of men and 68% of women had increased or substantially increased WC. The prevalence of malnutrition varied between the methods -10.5% (BMI), 29.8% (AC), 56.2% (TST), 17.6% (MUAC), and 12.3% (NDHGS). We found a high percentage of patients with inadequate intake of protein, fat and energy. The percentage of total energy intake (%TEI) from carbohydrates inversely correlated with WC and AC. A positive correlation was observed between %TEI from protein and NDHGS, and between %TEI from fat and BMI, WC and AC. We found a high prevalence of increased body weight and WC, and inadequate dietary intake in HCV/HIV coinfected patients. We observed a positive association between protein intake and muscle function, and between fat intake and obesity.

  3. Sensitivity and specificity of point-of-care rapid combination syphilis-HIV-HCV tests.

    Directory of Open Access Journals (Sweden)

    Kristen L Hess

    Full Text Available New rapid point-of-care (POC tests are being developed that would offer the opportunity to increase screening and treatment of several infections, including syphilis. This study evaluated three of these new rapid POC tests at a site in Southern California.Participants were recruited from a testing center in Long Beach, California. A whole blood specimen was used to evaluate the performance of the Dual Path Platform (DPP Syphilis Screen & Confirm, DPP HIV-Syphilis, and DPP HIV-HCV-Syphilis rapid tests. The gold-standard comparisons were Treponema pallidum passive particle agglutination (TPPA, rapid plasma reagin (RPR, HCV enzyme immunoassay (EIA, and HIV-1/2 EIA.A total of 948 whole blood specimens were analyzed in this study. The sensitivity of the HIV tests ranged from 95.7-100% and the specificity was 99.7-100%. The sensitivity and specificity of the HCV test were 91.8% and 99.3%, respectively. The treponemal-test sensitivity when compared to TPPA ranged from 44.0-52.7% and specificity was 98.7-99.6%. The non-treponemal test sensitivity and specificity when compared to RPR was 47.8% and 98.9%, respectively. The sensitivity of the Screen & Confirm test improved to 90.0% when cases who were both treponemal and nontreponemal positive were compared to TPPA+/RPR ≥ 1 ∶ 8.The HIV and HCV on the multi-infection tests showed good performance, but the treponemal and nontreponemal tests had low sensitivity. These results could be due to a low prevalence of active syphilis in the sample population because the sensitivity improved when the gold standard was limited to those more likely to be active cases. Further evaluation of the new syphilis POC tests is required before implementation into testing programs.

  4. Sensitivity and specificity of point-of-care rapid combination syphilis-HIV-HCV tests.

    Science.gov (United States)

    Hess, Kristen L; Fisher, Dennis G; Reynolds, Grace L

    2014-01-01

    New rapid point-of-care (POC) tests are being developed that would offer the opportunity to increase screening and treatment of several infections, including syphilis. This study evaluated three of these new rapid POC tests at a site in Southern California. Participants were recruited from a testing center in Long Beach, California. A whole blood specimen was used to evaluate the performance of the Dual Path Platform (DPP) Syphilis Screen & Confirm, DPP HIV-Syphilis, and DPP HIV-HCV-Syphilis rapid tests. The gold-standard comparisons were Treponema pallidum passive particle agglutination (TPPA), rapid plasma reagin (RPR), HCV enzyme immunoassay (EIA), and HIV-1/2 EIA. A total of 948 whole blood specimens were analyzed in this study. The sensitivity of the HIV tests ranged from 95.7-100% and the specificity was 99.7-100%. The sensitivity and specificity of the HCV test were 91.8% and 99.3%, respectively. The treponemal-test sensitivity when compared to TPPA ranged from 44.0-52.7% and specificity was 98.7-99.6%. The non-treponemal test sensitivity and specificity when compared to RPR was 47.8% and 98.9%, respectively. The sensitivity of the Screen & Confirm test improved to 90.0% when cases who were both treponemal and nontreponemal positive were compared to TPPA+/RPR ≥ 1 ∶ 8. The HIV and HCV on the multi-infection tests showed good performance, but the treponemal and nontreponemal tests had low sensitivity. These results could be due to a low prevalence of active syphilis in the sample population because the sensitivity improved when the gold standard was limited to those more likely to be active cases. Further evaluation of the new syphilis POC tests is required before implementation into testing programs.

  5. Monocyte activation in HIV/HCV coinfection correlates with cognitive impairment.

    Directory of Open Access Journals (Sweden)

    Hans Rempel

    Full Text Available Coinfection with human immunodeficiency virus (HIV and hepatitis C virus (HCV challenges the immune system with two viruses that elicit distinct immune responses. Chronic immune activation is a hallmark of HIV infection and an accurate indicator of disease progression. Suppressing HIV viremia by antiretroviral therapy (ART effectively prolongs life and significantly improves immune function. HIV/HCV coinfected individuals have peripheral immune activation despite effective ART control of HIV viral load. Here we examined freshly isolated CD14 monocytes for gene expression using high-density cDNA microarrays and analyzed T cell subsets, CD4 and CD8, by flow cytometry to characterize immune activation in monoinfected HCV and HIV, and HIV-suppressed coinfected subjects. To determine the impact of coinfection on cognition, subjects were evaluated in 7 domains for neuropsychological performance, which were summarized as a global deficit score (GDS. Monocyte gene expression analysis in HIV-suppressed coinfected subjects identified 43 genes that were elevated greater than 2.5 fold. Correlative analysis of subjects' GDS and gene expression found eight genes with significance after adjusting for multiple comparisons. Correlative expression of six genes was confirmed by qPCR, five of which were categorized as type 1 IFN response genes. Global deficit scores were not related to plasma lipopolysaccharide levels. In the T cell compartment, coinfection significantly increased expression of activation markers CD38 and HLADR on both CD4 and CD8 T cells but did not correlate with GDS. These findings indicate that coinfection is associated with a type 1 IFN monocyte activation profile which was further found to correlate with cognitive impairment, even in subjects with controlled HIV infection. HIV-suppressed coinfected subjects with controlled HIV viral load experiencing immune activation could benefit significantly from successful anti-HCV therapy and may be

  6. Seropositivity of HBsAg, anti-HCV and anti-HIV in preoperative patients

    Directory of Open Access Journals (Sweden)

    Berrin Karaayak Uzun

    2014-12-01

    Full Text Available Objective: The infections caused by human immunodeficiency virus (HIV, hepatitis B (HBV and C (HCV viruses pose a serious occupational risk for the healthcare workers especially those in emergency services, laboratories and surgery wards. Vaccination and establishment of the strict biosafety procedures are the main principles to prevent blood-borne infections in healthcare workers. Additionally, serological screening of the preoperative patients could decrease the risk for exposure. In this study, we aimed to determine the seroprevalence of HBsAg, anti-HCV, anti-HIV 1/2 in preoperative patients. Methods: Hospital automation records were evaluated retrospectively for 4.367 patients who were scheduled for surgery and scanned for anti-HIV 1/2, HBsAg and anti-HCV as preoperative procedures in the preparation period of operation between January 2012 and December 2012. Results: HBsAg positivity rate was found in 7.7% (n=336, anti-HCV positivity rate was found in 2.3% (n=101. A two (0.05% of five patients were positive for anti-HIV 1/2 was found positive verification test and the other three samples were accepted as false positive test results. Conclusion: All healthcare workers must be trained about occupational diseases and vaccinated against Hepatitis B. Universal precautions must be strictly followed particularly in the operating room. In addition, all patients should be considered as potential carriers regarded as a carrier of the potential for infection. J Clin Exp Invest 2013; 4 (4: 449-452

  7. Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease.

    Science.gov (United States)

    Charlton, Michael; Everson, Gregory T; Flamm, Steven L; Kumar, Princy; Landis, Charles; Brown, Robert S; Fried, Michael W; Terrault, Norah A; O'Leary, Jacqueline G; Vargas, Hugo E; Kuo, Alexander; Schiff, Eugene; Sulkowski, Mark S; Gilroy, Richard; Watt, Kymberly D; Brown, Kimberly; Kwo, Paul; Pungpapong, Surakit; Korenblat, Kevin M; Muir, Andrew J; Teperman, Lewis; Fontana, Robert J; Denning, Jill; Arterburn, Sarah; Dvory-Sobol, Hadas; Brandt-Sarif, Theo; Pang, Phillip S; McHutchison, John G; Reddy, K Rajender; Afdhal, Nezam

    2015-09-01

    There are no effective and safe treatments for chronic hepatitis C virus (HCV) infection of patients who have advanced liver disease. In this phase 2, open-label study, we assessed treatment with the NS5A inhibitor ledipasvir, the nucleotide polymerase inhibitor sofosbuvir, and ribavirin in patients infected with HCV genotypes 1 or 4. Cohort A enrolled patients with cirrhosis and moderate or severe hepatic impairment who had not undergone liver transplantation. Cohort B enrolled patients who had undergone liver transplantation: those without cirrhosis; those with cirrhosis and mild, moderate, or severe hepatic impairment; and those with fibrosing cholestatic hepatitis. Patients were assigned randomly (1:1) to receive 12 or 24 weeks of a fixed-dose combination tablet containing ledipasvir and sofosbuvir, once daily, plus ribavirin. The primary end point was sustained virologic response at 12 weeks after the end of treatment (SVR12). We enrolled 337 patients, 332 (99%) with HCV genotype 1 infection and 5 (1%) with HCV genotype 4 infection. In cohort A (nontransplant), SVR12 was achieved by 86%-89% of patients. In cohort B (transplant recipients), SVR12 was achieved by 96%-98% of patients without cirrhosis or with compensated cirrhosis, by 85%-88% of patients with moderate hepatic impairment, by 60%-75% of patients with severe hepatic impairment, and by all 6 patients with fibrosing cholestatic hepatitis. Response rates in the 12- and 24-week groups were similar. Thirteen patients (4%) discontinued the ledipasvir and sofosbuvir combination prematurely because of adverse events; 10 patients died, mainly from complications related to hepatic decompensation. The combination of ledipasvir, sofosbuvir, and ribavirin for 12 weeks produced high rates of SVR12 in patients with advanced liver disease, including those with decompensated cirrhosis before and after liver transplantation. ClinTrials.gov: NCT01938430. Copyright © 2015 AGA Institute. Published by Elsevier Inc

  8. HIV, HBV, and HCV molecular epidemiology among trans (transvestites, transsexuals, and transgender) sex workers in Argentina.

    Science.gov (United States)

    Carobene, Mauricio; Bolcic, Federico; Farías, María Sol Dos Ramos; Quarleri, Jorge; Avila, María Mercedes

    2014-01-01

    Commercial sex work is frequent among male-to-female transvestites, transsexuals and transgenders in Argentina, leading to high susceptibility to HIV, HBV, and HCV among other sexually transmitted infections. In a global context of scarce data on the trans sex workers population, this study was aimed to study the genomic characterization of these viruses. Plasma presence of HIV, HBV, and HCV genomic material was evaluated in samples from 273 trans sex workers. Genomic sequences of HIV-gag, pol, and vif-vpu genes, HBV-S gene, and HCV-5'UT and NS5B genes were obtained. Molecular characterization involved phylogenetic analysis and several in silico tools. Resistance-associated mutations in HIV and HBV pol genes were also analyzed. The HIV genomic characterization in 62 trans sex workers samples showed that 54.8% of the isolates corresponded to BF intersubtype recombinants, and 38.7% to subtype B. The remaining were classified as subtypes C (4.8%) and A (1.6%). HBV and HCV co-infection prevalence among HIV positive trans sex workers yielded rates of 3.2% and 6.5% respectively. Drug resistance-associated mutations were found in 12/62 (19%) HIV pol sequences, but none among HBV. Based on phylogenetic relationships, HIV isolates characterized as subtypes BF and B appeared intermingled with those from other high-risk groups. Despite trans sex workers declared not to have received antiviral treatment, complex drug resistance-associated mutation patterns were found in several HIV isolates. Planned prevention, screening, and treatment are needed to reduce further transmission and morbidity. © 2013 Wiley Periodicals, Inc.

  9. Detection of HCV-RNA in saliva of patients with chronic hepatitis C.

    OpenAIRE

    Couzigou, P; Richard, L; Dumas, F; Schouler, L; Fleury, H

    1993-01-01

    Previous studies have provided conflicting results on the presence of hepatitis C virus-RNA in saliva. In this study, 23 (62%) of 37 patients tested positive for hepatitis C virus-RNA in saliva, using polymerase chain reaction analysis. A slightly greater proportion had a sporadic rather than a parenteral origin of chronic hepatitis C. These results provide a biological basis for saliva as a possible source of hepatitis C virus (HCV) infection, but do not necessarily imply transmission by thi...

  10. Decreased tacrolimus plasma concentrations during HCV therapy: a drug-drug interaction or is there an alternative explanation?

    Science.gov (United States)

    Smolders, E J; Pape, S; de Kanter, C T M M; van den Berg, A P; Drenth, J P H; Burger, D M

    2017-03-01

    Chronic hepatitis C virus (HCV) infection can cause severe liver cirrhosis, for which liver transplantation is the only therapy. To prevent organ rejection, transplanted patients are treated with immunosuppressive agents. We describe two transplanted patients treated with tacrolimus who were simultaneously treated with direct-acting antivirals (DAAs) for their chronic HCV infection. No pharmacokinetic drug-drug interactions (DDIs) were expected between tacrolimus and the selected DAAs. However, in both patients, tacrolimus plasma concentrations decreased during HCV treatment. We hypothesise that decreased plasma concentrations were not caused by a DDI but were an indirect result of the clearance of the HCV infection. During chronic HCV infection, pro-inflammatory cytokines may inhibit cytochrome P450 (CYP) enzymes, which are primarily responsible for tacrolimus metabolism. If this is true, then with clearance of the virus the activity of these enzymes will normalise and tacrolimus metabolism will increase. These changes were clinically relevant because the tacrolimus dosage needed to be adjusted. Therefore, physicians should be aware that CYP substrates with narrow therapeutic ranges might require dose adaption during HCV therapy with DAAs. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  11. New Tools in HCV Diagnosis, in Light of the Enhanced Awareness and the New Drugs for Treatment: SMARTube and Stimmunology

    Directory of Open Access Journals (Sweden)

    Svetlana Gorodin

    2013-01-01

    Full Text Available With improved HCV therapy, challenges regarding HCV diagnosis, such as seronegative window period, false positive readings, and differentiation between recent, chronic, and resolved infections, are of increasing importance. To address these challenges an innovative device—SMARTube HIV & HCV—was used. Blood samples were tested for anti-HCV antibodies before and after incubation in the SMARTube, which promotes the in vitro stimulation of in vivo HCV primed lymphocytes, thus enhancing levels of anti-HCV antibodies. Comparing antibody levels, in concordant samples before and after SMARTube, yielded the Stimulation Index (SI. Among 5888 fresh blood samples, from various populations and regions worldwide, 641 were seropositive using plasma, while SMARTube processing (yielding enriched plasma, termed SMARTplasma enabled diagnosis of 10 additional carriers in high-risk cohorts, that is, earlier detection. Using SMARTplasma eliminated all false positive results, using the current assays. In addition we show that SI calculation may serve as an important tool for differentiating between those who recently seroconverted, carriers of long-term infection, and those who have cleared the virus. SMARTube and the SI could lead to better, more informative diagnosis of HCV infections and play an important role in changing the way we treat both the infected individuals and the epidemic as a whole.

  12. HBV and HCV Coinfection among HIV/AIDS Patients in the National Hospital of Tropical Diseases, Vietnam

    Directory of Open Access Journals (Sweden)

    Bùi Vũ Huy

    2014-01-01

    Full Text Available Aim. To examine prevalence and characterization of HBV and HCV coinfection among HIV/AIDS patients. Methods. This cross-sectional, retrospective study analyzed 724 HIV/AIDS patients in the HIV clinic at the National Hospital of Tropical Diseases (NHTD, from 5/2005 to 4/2011. Results. The prevalence of HBV, HCV, and HIV coinfection was 50.3% (364/724, of which HbsAg, HCV, and both of HbsAg, and HCV positivity were 8.4%, 35.4%, and 6.5%, respectively. The cohort (364 patients with HBV, HCV, and HIV coinfection live in the 30 provinces/cities in the North and Central area of Vietnam. We found statistically significant associations between heightened risk of coinfection with HIV and HCV in the age group 30–39 years (P<0.001, male gender (P<0.001, never married patients (P<0.001, patients with a history of injection drug use (P<0.001, and clinical stages 2–4 (P<0.001. Coinfection with HBV/HIV was statistically significant associations between heightened risk of marital status (never married (P<0.001 and those who reported transmission through sexual intercourse. Conclusion. Coinfection with viral hepatitis is common in HIV patients; further study of the impact and evolution of coinfection is necessary to find effective treatment algorithms.

  13. Label Free Inhibitor Screening of Hepatitis C Virus (HCV NS5B Viral Protein Using RNA Oligonucleotide

    Directory of Open Access Journals (Sweden)

    Sang Eun Kim

    2011-06-01

    Full Text Available Globally, over 170 million people (ca. 3% of the World’s population are infected with the hepatitis C virus (HCV, which can cause serious liver diseases such as chronic hepatitis, evolving into subsequent health problems. Driven by the need to detect the presence of HCV, as an essential factor in diagnostic medicine, the monitoring of viral protein has been of great interest in developing simple and reliable HCV detection methods. Despite considerable advances in viral protein detection as an HCV disease marker, the current enzyme linked immunosorbent assay (ELISA based detection methods using antibody treatment have several drawbacks. To overcome this bottleneck, an RNA aptamer become to be emerged as an antibody substitute in the application of biosensor for detection of viral protein. In this study, we demonstrated a streptavidin-biotin conjugation method, namely, the RNA aptamer sensor system that can quantify viral protein with detection level of 700 pg mL−1 using a biotinylated RNA oligonucleotide on an Octet optical biosensor. Also, we showed this method can be used to screen inhibitors of viral protein rapidly and simply on a biotinylated RNA oligonucleotide biosensor. Among the inhibitors screened, (−-Epigallocatechin gallate showed high binding inhibition effect on HCV NS5B viral protein. The proposed method can be considered a real-time monitoring method for inhibitor screening of HCV viral protein and is expected to be applicable to other types of diseases.

  14. Structure-based drug design of novel peptidomimetic cellulose derivatives as HCV-NS3 protease inhibitors.

    Science.gov (United States)

    Saleh, Noha A; Elshemey, Wael M

    2017-10-15

    Hepatitis C Virus (HCV) represents a global health threat not only due to the large number of reported worldwide HCV infections, but also due to the absence of a reliable vaccine for its prevention. HCV NS3 protease is one of the most important targets for drug design aiming at the deactivation of HCV. In the present work, molecular docking simulations are carried out for suggested novel NS3 protease inhibitors applied to the Egyptian genotype 4. These inhibitors are modifications of dimer cellulose by adding a hexa-peptide to the cellulose at one of the positions 2, 3, 6, 2', 3' or 6'. Results show that the inhibitor compound with the hexa-peptide at position 6 shows significantly higher simulation docking score with HCV NS3 protease active site. This is supported by low total energy value of docking system, formation of two H-bonds with HCV NS3 protease active site residues, high binding affinity and increased stability in the interaction system. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. The influence of HCV coinfection on clinical, immunological and virological responses to HAART in HIV-patients

    Directory of Open Access Journals (Sweden)

    Ricardo A. Carmo

    Full Text Available The potential impact of the hepatitis C virus (HCV on clinical, immunological and virological responses to initial highly active antiretroviral therapy (HAART of patients infected with human immunodeficiency virus (HIV is important to evaluate due to the high prevalence of HIV-HCV coinfection. A historical cohort study was conducted among 824 HIV-infected patients starting HAART at a public referral service in Belo Horizonte, Brazil, to assess the impact of HCV seropositivity on appearance of a new AIDS-defining opportunistic illness, AIDS-related death, suppression of viral load, and an increase in CD4-cell count. A total of 76 patients (9.2% had a positive HCV test, 26 of whom (34.2% had a history of intravenous drug use. In multivariate analysis, HCV seropositivity was associated with a smaller CD4-cell recovery (RH=0.68; 95% CI [0.49-0.92], but not with progression to a new AIDS-defining opportunistic illness or to AIDS-related death (RH=1.08; 95% CI [0.66-1.77], nor to suppression of HIV-1 viral load (RH=0.81; 95% CI [0.56-1.17] after starting HAART. These results indicate that although associated with a blunted CD4-cell recovery, HCV coinfection did not affect the morbidity or mortality related to AIDS or the virological response to initial HAART.

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

    Directory of Open Access Journals (Sweden)

    Wafaa M. Ezzat

    2013-12-01

    Full Text Available 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 2: fibrosis score: 4, 5, 6.The mean values of ATX in all studied patients with chronic HCV infection was 63.02 ± 36.29 while that of healthy controls was 65.31 ± 12.24 without any significant difference. Surprisingly, mean values of ATX were higher among patients with group 1 but it did not reach the significant level. In each group of them, the differences between mean values of ATX among different grades of liver fibrosis were insignificant. It was also noticed that the mean values of ATX were higher among men than in women .It was concluded that Autotoxin might not be used as a useful diagnostic marker for liver fibrosis in Egyptian chronic HCV patients.

  17. HVR1-mediated antibody evasion of highly infectious in vivo adapted HCV in humanised mice

    DEFF Research Database (Denmark)

    Prentoe, Jannick; Verhoye, Lieven; Moctezuma, Rodrigo Velazquez

    2016-01-01

    Objective HCV is a major cause of chronic liver disease worldwide, but the role of neutralising antibodies (nAbs) in its natural history remains poorly defined. We analysed the in vivo role of hypervariable region 1 (HVR1) for HCV virion properties, including nAb susceptibility. Design Analysis...... of HCV from human liver chimeric mice infected with cell-culture-derived prototype genotype 2a recombinant J6/JFH1 or HVR1-deleted variant J6/JFH1ΔHVR1 identified adaptive mutations, which were analysed by reverse genetics in Huh7.5 and CD81-deficient S29 cells. The increased in vivo genomic stability......-substitution resulted in a 4.7-fold increase in genomic stability. In vitro, NS2 substitutions enhanced infectivity 5–10-fold by increasing virus assembly. Mouse-derived mJ6/JFH1A876P and mJ6/JFH1ΔHVR1/A876P viruses displayed similar heterogeneous densities of 1.02–1.1 g/mL. Human liver chimeric mice loaded...

  18. A Framework for Prediction of Response to HCV Therapy Using Different Data Mining Techniques

    Directory of Open Access Journals (Sweden)

    Enas M. F. El Houby

    2014-01-01

    Full Text Available Hepatitis C which is a widely spread disease all over the world is a fatal liver disease caused by Hepatitis C Virus (HCV. The only approved therapy is interferon plus ribavirin. The number of responders to this treatment is low, while its cost is high and side effects are undesirable. Treatment response prediction will help in reducing the patients who suffer from the side effects and high costs without achieving recovery. The aim of this research is to develop a framework which can select the best model to predict HCV patients’ response to the treatment of HCV from clinical information. The framework contains three phases which are preprocessing phase to prepare the data for applying Data Mining (DM techniques, DM phase to apply different DM techniques, and evaluation phase to evaluate and compare the performance of the built models and select the best model as the recommended one. Different DM techniques had been applied which are associative classification, artificial neural network, and decision tree to evaluate the framework. The experimental results showed the effectiveness of the framework in selecting the best model which is the model built by associative classification using histology activity index, fibrosis stage, and alanine amino transferase.

  19. The treatment of HCV in patients with haemoglobinopathy in Kurdistan Region, Iraq: a single centre experience.

    Science.gov (United States)

    Hussein, N R; Tunjel, I; Basharat, Z; Taha, A; Irving, W

    2016-06-01

    Various variables that might influence the rapid and sustained virological response to recombinant PEG-IFN-α-2a were explored in Iraqi HCV-infected patients with haemoglobinopathy. Forty-three patients were evaluated for the relationship between rapid virological response (RVR), IL-28B polymorphism, viral load, liver enzyme levels, blood group, ultrasound findings, or HCV genotype and the sustained virological response (SVR) achievement. The overall RVR was 55·81% while the overall SVR was 53·49%. SVR in patients that achieved RVR was 82·61% (P = 0·0004). A significant association was found between initial alanine transaminase levels and viral load with SVR achievement (P = 0·025) and (P = 0·004), respectively. Thirty-two (74%) out of 43 of our samples were host genotyped at the IL-28B locus as CC, a significant association was found between CC group and SVR achievement (P = 0·04). Of our samples, 23/43 (53%) were typed as HCV genotype 4, 10/43 (23%) as genotype 1, 9/43 (20·9%) as genotype 3 and 1/43 (2·3%) as genotype 2. A significant association was found between genotype 3 and SVR achievement (P = 0·006). Multivariate analysis showed that only RVR achievement independently associated with SVR in the Iraqi population (P = 0·00). These results can be used to classify the patients requiring the more expensive new direct-acting antiviral drugs.

  20. Bidirectional Lipid Droplet Velocities Are Controlled by Differential Binding Strengths of HCV Core DII Protein

    Science.gov (United States)

    Lyn, Rodney K.; Hope, Graham; Sherratt, Allison R.; McLauchlan, John; Pezacki, John Paul

    2013-01-01

    Host cell lipid droplets (LD) are essential in the hepatitis C virus (HCV) life cycle and are targeted by the viral capsid core protein. Core-coated LDs accumulate in the perinuclear region and facilitate viral particle assembly, but it is unclear how mobility of these LDs is directed by core. Herein we used two-photon fluorescence, differential interference contrast imaging, and coherent anti-Stokes Raman scattering microscopies, to reveal novel core-mediated changes to LD dynamics. Expression of core protein’s lipid binding domain II (DII-core) induced slower LD speeds, but did not affect directionality of movement on microtubules. Modulating the LD binding strength of DII-core further impacted LD mobility, revealing the temporal effects of LD-bound DII-core. These results for DII-core coated LDs support a model for core-mediated LD localization that involves core slowing down the rate of movement of LDs until localization at the perinuclear region is accomplished where LD movement ceases. The guided localization of LDs by HCV core protein not only is essential to the viral life cycle but also poses an interesting target for the development of antiviral strategies against HCV. PMID:24223760

  1. Retreatment efficacy and predictors of ledipasvir plus sofosbuvir to HCV genotype 1 in Japan.

    Science.gov (United States)

    Akuta, Norio; Sezaki, Hitomi; Suzuki, Fumitaka; Fujiyama, Shunichiro; Kawamura, Yusuke; Hosaka, Tetsuya; Kobayashi, Masahiro; Kobayashi, Mariko; Saitoh, Satoshi; Suzuki, Yoshiyuki; Arase, Yasuji; Ikeda, Kenji; Kumada, Hiromitsu

    2017-02-01

    Predictors of treatment efficacy with ledipasvir plus sofosbuvir as direct-acting antiviral (DAA) regimen for HCV infection are still unclear. Retreatment efficacy of ledipasvir plus sofosbuvir for failures to prior DAA regimens, including NS5A inhibitors, are also unknown because resistance-associated variants (RAVs) in NS5A have been shown to persist up to the long-term of post-treatment. One hundred seventy-five patients with chronic HCV genotype 1 infection, without decompensated liver cirrhosis and hepatocellular carcinoma, were evaluated SVR12 by ledipasvir 90 mg plus sofosbuvir 400 mg once-daily for 12 weeks. Overall, SVR12 were 92%, based on intention to treat analysis. In failures to daclatasvir plus asunaprevir, SVR12 were 71%. The study using ultra-deep sequencing showed that ledipasvir plus sofosbuvir was effective to one case of failures to daclatasvir plus asunaprevir with multidrug RAVs (triple mutation in NS3-D168/NS5A-L31/NS5A-Y93). Multivariate analysis identified FIB4 index (ledipasvir plus sofosbuvir for HCV genotype 1 infection, including multidrug RAVs in Japan. Treatment efficacy could be predicted by the combination of viral and host factors. J. Med. Virol. 89:284-290, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Stability of liver fibrosis among HCV-infected injection drug users.

    Science.gov (United States)

    Mehta, Shruti H; Kirk, Gregory D; Astemborski, Jacquie; Sulkowski, Mark S; Afdhal, Nezam H; Thomas, David L

    2012-01-01

    There are few published data characterizing patterns of liver stiffness measurements (LSMs) among HCV-infected persons and their potential impact on clinical decisions (for example, deferring treatment and hepatocellular carcinoma surveillance). A total of 591 HCV-infected injection drug users in a community-based cohort had four LSMs. We used semi-parametric latent class growth modelling to identify patterns, which then became a gold standard against which we characterized validity of information from the initial measurements. Median age was 49, 68% were male, 92% African-American and 33% HIV-coinfected. The median LSM at visit 1 was 6.7 kPa (IQR 5.3-8.8). Over a median 1.75 years, LSM measures were stable; median change between visits was 0 kPa (IQR -1.4-1.7). Only 3% had evidence of fibrosis progression. Other groups included stable patterns of no fibrosis (59%), moderate fibrosis (21%), severe fibrosis (7%) and cirrhosis (9%). Individuals with fibrosis progression were more likely to be HIV-infected than those with stable low fibrosis (Pcancer surveillance (cirrhosis ≥12.3 kPa) was high (positive predictive value =97%). Although no single low LSM had high negative predictive value for significant fibrosis (metavir liver fibrosis in a cohort of predominantly African-American HCV-infected persons over 1.75 years, support using LSMs to monitor untreated persons at risk for progression and assess need for hepatocellular carcinoma surveillance.

  3. A framework for prediction of response to HCV therapy using different data mining techniques.

    Science.gov (United States)

    El Houby, Enas M F

    2014-01-01

    Hepatitis C which is a widely spread disease all over the world is a fatal liver disease caused by Hepatitis C Virus (HCV). The only approved therapy is interferon plus ribavirin. The number of responders to this treatment is low, while its cost is high and side effects are undesirable. Treatment response prediction will help in reducing the patients who suffer from the side effects and high costs without achieving recovery. The aim of this research is to develop a framework which can select the best model to predict HCV patients' response to the treatment of HCV from clinical information. The framework contains three phases which are preprocessing phase to prepare the data for applying Data Mining (DM) techniques, DM phase to apply different DM techniques, and evaluation phase to evaluate and compare the performance of the built models and select the best model as the recommended one. Different DM techniques had been applied which are associative classification, artificial neural network, and decision tree to evaluate the framework. The experimental results showed the effectiveness of the framework in selecting the best model which is the model built by associative classification using histology activity index, fibrosis stage, and alanine amino transferase.

  4. Phylogenetic analysis of HCV-4d in Turkey: the curious case of Kayseri province.

    Science.gov (United States)

    Ciccozzi, Massimo; Zehender, Gianguglielmo; Polat, Ceylan; Lai, Alessia; Kayman, Tuba; Sorrentino, Chiara; Ebranati, Erika; Cella, Eleonora; Lo Presti, Alessandra; Abacioglu, Hakan

    2014-03-01

    In Turkey, genotype 1, especially type 1b virus, causes approximately 90% of these infections, while types 2, 3, and 4 exist, albeit in low prevalences and are due to relatively recent and limited introductions. Two recent reports from Kayseri, a relatively large city in Central Anatolia, indicated unusually high prevalence for type 4 infections in the province reaching a 35% among patients admitted to hospitals for treatment of chronic hepatitis C. In this study, the origin, the demographic history, and the dynamic of the epidemic of unusual HCV genotype 4d in Turkey by using Bayesian coalescent-based method were investigated. A gene flow migration approach was also used to describe the synchronous geographical dispersal and genetic diversification of this unusual genotype in Kayseri province. The Turkish clade had a tMRCA of 44 years corresponding to the year 1967 and seems to have a different origin being completely segregated from the European one. Gene flow migration analysis indicated that Kayseri province appeared to be the epicenter of HCV-4d epidemic, exporting the infections. The demographic history of HCV-4d showed that the epidemic started in 1970s year then following a slow exponential growth until 1980s. The Turkish monophyletic clade suggests a segregate circulation of the epidemic in this region mostly due to unsafe parenteral medical procedures (with drug addiction playing a relatively negligible role). © 2013 Wiley Periodicals, Inc.

  5. Correlation between HIV and HCV in Brazilian prisoners: evidence for parenteral transmission inside prison

    Directory of Open Access Journals (Sweden)

    MN Burattini

    2000-10-01

    Full Text Available OBJECTIVE: It is an accepted fact that confinement conditions increase the risk of some infections related to sexual and/or injecting drugs practices. Mathematical techniques were applied to estimate time-dependent incidence densities of HIV infection among inmates. METHODS: A total of 631 prisoners from a Brazilian prison with 4,900 inmates at that time were interviewed and their blood drawn. Risky behavior for HIV infection was analyzed, and serological tests for HIV, hepatitis C and syphilis were performed, intended as surrogates for parenteral and sexual HIV transmission, respectively. Mathematical techniques were used to estimate the incidence density ratio, as related to the time of imprisonment. RESULTS: Prevalence were: HIV -- 16%; HCV -- 34%; and syphilis -- 18%. The main risk behaviors related to HIV infection were HCV prevalence (OR=10.49 and the acknowledged use of injecting drugs (OR=3.36. Incidence density ratio derivation showed that the risk of acquiring HIV infection increases with the time of imprisonment, peaking around three years after incarceration. CONCLUSIONS: The correlation between HIV and HCV seroprevalence and the results of the mathematical analysis suggest that HIV transmission in this population is predominantly due to parenteral exposure by injecting drug, and that it increases with time of imprisonment.

  6. 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.

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

    Science.gov (United States)

    2010-01-01

    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. PMID:20712912

  8. The roles of endoplasmic reticulum overload response induced by HCV and NS4B protein in human hepatocyte viability and virus replication.

    Directory of Open Access Journals (Sweden)

    Lingbao Kong

    Full Text Available Hepatitis C virus (HCV replication is associated with endoplasmic reticulum (ER and its infection triggers ER stress. In response to ER stress, ER overload response (EOR can be activated, which involves the release of Ca2+ from ER, production of reactive oxygen species (ROS and activation of nuclear factor κB (NF-κB. We have previously reported that HCV NS4B expression activates NF-κB via EOR-Ca2+-ROS pathway. Here, we showed that NS4B expression and HCV infection activated cancer-related NF-κB signaling pathway and induced the expression of cancer-related NF-κB target genes via EOR-Ca2+-ROS pathway. Moreover, we found that HCV-activated EOR-Ca2+-ROS pathway had profound effects on host cell viability and HCV replication. HCV infection induced human hepatocyte death by EOR-Ca2+-ROS pathway, whereas activation of EOR-Ca2+-ROS-NF-κB pathway in