Assessment of Detection and Treatment Response of Hepatitis C viral Infection in District Mardan Pakistan

Hepatitis C virus is known to be major public health issue around the globe. The aim was to investigate the treatment and detection of HCV infection in general population of District Mardan. Presently no standard treatment is available for the cure of Hepatitis C viral infection, attributed possibly to the hyper variations in HCV genome, expressing several distinct HCV genotypes. For a period of 5 months (June 2016 - November 2016), 270 suspected individuals visited the main hospital of Mardan Medical complex (MMC), were interviewed. Among them 100 individuals were diagnosed by ELISA and PCR for HCV detection at the diagnostic laboratory of MMC. A total of 170 HCV patients were treated at the MMC, with oral medicine or interferon vaccines and the response were monitored by PCR after treatments. Our result showed that high sensitivity for genome-based PCR detection of HCV in comparison to viral coat protein detection by ELISA. The assessment of treatment strategies for HCV showed high response for presently available medicines i.e., Sovaldi, Sofiget, Sofohil, Ocvir and sofosbuvir in comparison to interferon and pig interferon. The accurate and early diagnosis of the HCV infection is crucial for effective treatment strategies. Thereby PCR detection should be the proffered method for specific and accurate detection of HCV infection. The standard medicine available presently proved better treatment method for HCV infection in comparison to interferon vaccination. Keywords: Vaccine, Medication, Sovaldi, Mardan, Interferon, Sofohil, HCV.

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Predictors of Seroprevalence of Hepatitis C Infection among Health Care Workers in Nigeria; A Year after Post Implementation of Nigeria’s National Hepatitis Prevention Policy

Global Journal of Health Science ◽

10.5539/gjhs.v13n7p32 ◽

2021 ◽

Vol 13 (7) ◽

pp. 32

Author(s):

Theresa Nwagha ◽

Babatunde I Omotowo ◽

Uchenna N Ijoma ◽

Ijeoma A Meka ◽

Obinna D Onodugo ◽

...

Keyword(s):

Health Care ◽

At Risk ◽

Hepatitis C ◽

Mass Screening ◽

Health Care Workers ◽

Hcv Infection ◽

Public Health Issue ◽

Prevention Policy ◽

Care Workers ◽

Mode Of Transmission

BACKGROUND: Hepatitis C virus (HCV) infection is a global public health issue. Health care workers (HCWs) are particularly at risk. Nigeria hepatitis prevention policy aims to achieve country wide elimination of hepatitis through early detection using mass screening with life-style modifications of “at risk population” which are key preventive strategies. AIM: To determine the seroprevalence of HCV infection among HCWs in a large regional referral hospital in Nigeria METHODS: A hospital-based descriptive cross-sectional study (hepatitis mass screening) was done at the University of Nigeria Teaching Hospital, Enugu, Nigeria between July and August 2016. Non-randomised sampling was used. Blood samples were assayed for antibodies to HCV. Data on knowledge, risk factors and mode of transmission were collected using a structured, pre-validated, pretested, questionnaire and analysed using SPSS version 20. RESULTS: A total of 3132 out of 5144 (60.9%) HCWs participated in the study. The seroprevalence of hepatitis C among UNTH staff was 0.90% (28/3132). The mean knowledge score of 68.95% ± 24.23 and 56.70±17.25 translates to fair knowledge level about mode of transmission and risk of transmission of hepatitis C among HCWs, respectively. There was no reported case of hepatitis B and C co-infection. Females HCWs had highest sero-prevalence for HCV 17/5144 (0.33%) (P = 0.164, AOR= 1.76, 95%CI =0.431-2.413) CONCLUSION: This study found a low seropositivity of HCV among HCWs. A pointer to the possible success of the hospital-based education awareness programme, an implementation of Nigeria’s national hepatitis prevention policy.

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Identification of Hepatitis C Virus Inhibitors Targeting Different Aspects of Infection Using a Cell-Based Assay

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01413-12 ◽

2012 ◽

Vol 56 (12) ◽

pp. 6109-6120 ◽

Cited By ~ 6

Author(s):

Xuemei Yu ◽

Bruno Sainz ◽

Pavel A. Petukhov ◽

Susan L. Uprichard

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Viral Infection ◽

Treatment Options ◽

Hcv Infection ◽

Antiviral Compound ◽

Worldwide Population ◽

Dependent Inhibition ◽

Compound Screening ◽

A Cell

ABSTRACTWith 2 to 3% of the worldwide population chronically infected, hepatitis C virus (HCV) infection continues to be a major health care burden. Unfortunately, current interferon-based treatment options are not effective in all patients and are associated with significant side effects. Consequently, there is an ongoing need to identify and develop new anti-HCV therapies. Toward this goal, we previously developed a cell-based HCV infection assay for antiviral compound screening based on a low-multiplicity-of-infection approach that uniquely allows for the identification of antiviral compounds that target cell culture-derived HCV (HCVcc) at any step of the viral infection cycle. Using this assay, here we report the screening of the NCI Diversity Set II library, containing 1,974 synthesized chemical compounds, and the identification of compounds with specific anti-HCV activity. In combination with toxicity counterscreening, we identified 30 hits from the compound library, 13 of which showed reproducible and dose-dependent inhibition of HCV with mean therapeutic indices (50% cytotoxic concentration [CC50]/50% effective concentration [EC50]) of greater than 6. Using HCV pseudotype and replicon systems of multiple HCV genotypes, as well as infectious HCVcc-based assembly and secretion analysis, we determined that different compounds within this group of candidate inhibitors target different steps of viral infection. The compounds identified not only will serve as biological probes to study and further dissect the biology of viral infection but also should facilitate the development of new anti-HCV therapeutic treatments.

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PP110 Economic Impact Of Therapeutic Regime Reduction In The Hepatitis C Virus Infection

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462317002719 ◽

2017 ◽

Vol 33 (S1) ◽

pp. 124-124

Author(s):

Diego Antonio Barila ◽

Alessandra Bianco ◽

Susanna Bordignon ◽

Francesco Cattel ◽

Giulia Valinotti

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Healthcare Professionals ◽

Treatment Strategies ◽

Clinical History ◽

Hcv Infection ◽

Care Pathways ◽

Activity Based Costing ◽

Therapeutic Regime ◽

Abc Analysis

INTRODUCTION:Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide. The goal of HCV therapy is to eradicate the infection, which results in eliminating detectable circulating HCV after cessation of treatment, to prevent complications.METHODS:A prospective analysis was undertaken in the primary referral center in Turin. Throughout the use of questionnaries submitted to healthcare professionals, clinical and economic data from three different care pathways of HCV treatment were collected and processed. Costs were measured up to 8, 12, and 24-weeks treatment and based on time-driven activity-based costing (ABC) of the two main HCV treatments, Sovaldi and Harvoni. For the ABC analysis, three types of care pathways were considered, based on patient's clinical history resources used: patients treated for 8, 12, and 24 weeks. Gastroenterologists, pharmacists, administrative personel, and storemen were involved in the project. The aim of the analysis was to evaluate the organizational impact of the three different strategies for the treatment of HCV infection with Harvoni or Sovaldi and to estimate the differential cost.RESULTS:The data indicates that shortening treatment from 24 to 12 weeks and from 24 to 8 weeks leads to a saving of EUR192 and EUR766 for both treatment strategies. When drug costs are also taken into account, the reduction of treatment with shortening treatment from 12 to 8 weeks leads to a saving of EUR15,252.77, a reduction of EUR60,691.07 from 24 to 8 weeks for Harvoni treatment. The reduction of treatment with shortening from 24 to 12 weeks for Sovaldi leads to a saving of EUR37,668.30. The paths of 8 and 12 weeks are those associated with fewer resources in terms of professional's time, costs relating to laboratory tests, and cost of drugs.CONCLUSIONS:The reduction of the amount of time spent by healthcare professionals in the 12 weeks and in the 8 weeks strategies allows a reallocation of the resources employed.

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Mechanisms Underlying Hepatitis C Virus-Associated Hepatic Fibrosis

Cells ◽

10.3390/cells8101249 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1249 ◽

Cited By ~ 23

Author(s):

Mousumi Khatun ◽

Ratna B. Ray

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Liver Fibrosis ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Treatment Strategies ◽

Hcv Infection ◽

Direct Acting Antiviral ◽

Cytokines And Chemokines ◽

Chronic Hcv

Hepatitis C virus (HCV) infection often causes liver diseases, including fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Liver fibrosis is the outcome of the wound healing response to tissue damage caused by chronic HCV infection. This process is characterized by the excessive accumulation of extracellular matrix (ECM) proteins, such as collagen fibers secreted by activated hepatic stellate cells (HSCs). Activation of HSCs from the quiescent stage is mediated by different mechanisms, including pro-inflammatory cytokines and chemokines released from HCV-infected hepatocytes and liver macrophages. HCV infection modulates the expression of different microRNAs that can be transported and delivered to the HSCs via exosomes released from infected cells, also leading to the development of advanced disease pathogenesis. Although recent advancements in direct-acting antiviral (DAA) treatment can efficiently control viremia, there are very few treatment strategies available that can be effective at preventing pathogenesis in advanced liver fibrosis or cirrhosis in patients. Assessment of fibrosis is considered to be the major part of proper patient care and decision making in clinical practice. In this review, we highlighted the current knowledge of molecular mechanisms responsible for the progression of liver fibrosis in chronically HCV-infected patients, and currently available methods for evaluation of fibrosis in patients. A detailed understanding of these aspects at the molecular level may contribute to the development of new therapies targeting HCV-related liver fibrosis.

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Resistance Analysis and Characterization of a Thiazole Analogue, BP008, as a Potent Hepatitis C Virus NS5A Inhibitor

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00599-11 ◽

2011 ◽

Vol 56 (1) ◽

pp. 44-53 ◽

Cited By ~ 7

Author(s):

Hui-Mei Lin ◽

Jing-Chyi Wang ◽

Han-Shu Hu ◽

Pei-Shan Wu ◽

Chi-Chen Yang ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Small Molecule ◽

Synergistic Effects ◽

Treatment Strategies ◽

Small Molecule Inhibitor ◽

Hcv Infection ◽

Molecule Inhibitor ◽

Ns5b Polymerase Inhibitor ◽

Chronic Hcv

ABSTRACTHepatitis C virus (HCV) is a global health problem, affecting approximately 3% of the world's population. The standard treatment for HCV infection is often poorly tolerated and ineffective. Therefore, the development of novel or more effective treatment strategies to treat chronic HCV infection is urgently needed. In this report, BP008, a potent small-molecule inhibitor of HCV replication, was developed from a class of compounds with thiazol core structures by means of utilizing a cell-based HCV replicon system. The compound reduced the reporter expression of the HCV1b replicon with a 50% effective concentration (EC50) and selective index value of 4.1 ± 0.7 nM and >12,195, respectively. Sequencing analyses of several individual clones derived from BP008-resistant RNAs purified from cells harboring HCV1b replicon revealed that amino acid substitutions mainly within the N-terminal region (domain I) of NS5A were associated with decreased inhibitor susceptibility. Q24L, P58S, and Y93H are the key substitutions for resistance selection; F149L and V153M play the compensatory role in the replication and drug resistance processes. Moreover, BP008 displayed synergistic effects with alpha interferon (IFN-α), NS3 protease inhibitor, and NS5B polymerase inhibitor, as well as good oral bioavailability in SD rats and favorable exposure in rat liver. In summary, our results pointed to an effective small-molecule inhibitor, BP008, that potentially targets HCV NS5A. BP008 can be considered a part of a more effective therapeutic strategy for HCV in the future.

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Visualizing the Essential Role of Complete Virion Assembly Machinery in Efficient Hepatitis C Virus Cell-to-Cell Transmission by a Viral Infection-Activated Split-Intein-Mediated Reporter System

Journal of Virology ◽

10.1128/jvi.01720-16 ◽

2016 ◽

Vol 91 (2) ◽

Cited By ~ 12

Author(s):

Fanfan Zhao ◽

Ting Zhao ◽

Libin Deng ◽

Dawei Lv ◽

Xiaolong Zhang ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Viral Infection ◽

Hcv Infection ◽

Live Cell ◽

Reporter System ◽

Virion Assembly ◽

Split Intein ◽

Donor Cells ◽

Cell Transmission

ABSTRACT Hepatitis C virus (HCV) infects 2 to 3% of the world population and is a leading cause of liver diseases such as fibrosis, cirrhosis, and hepatocellular carcinoma. Many aspects of HCV study, ranging from molecular virology and antiviral drug development to drug resistance profiling, were supported by straightforward assays of HCV replication and infection. Among these assays, the HCV-dependent fluorescence relocalization (HDFR) system allowed live-cell visualization of infection without modifying the viral genome, but this strategy required careful recognition of the fluorescence relocalization pattern for its high fluorescence background in the cytoplasm. In this study, to achieve background-free visualization of HCV infection, a viral infection-activated split-intein-mediated reporter system (VISI) was devised. Uninfected Huh7.5.1-VISI cells show no background signal, while HCV infection specifically illuminates the nuclei of infected Huh7.5.1-VISI cells with either green fluorescent protein (GFP) or mCherry. Combining VISI-GFP and VISI-mCherry systems, we revisited HCV cell-to-cell transmission with clear-cut distinction of donor and recipient cells in a live-cell manner. Independently of virion assembly, exosomes have been reported to transfer HCV subgenomic RNA to initiate replication in uninfected cells, which suggested an assembly-free pathway. However, our data demonstrated that HCV structural genes and the p7 gene were essential for not only cell-free infectivity but also cell-to-cell transmission. Additionally, depletion of apolipoprotein E (ApoE) from donor cells but not from recipient cells significantly reduced HCV cell-to-cell transmission efficiency. In summary, we developed a background-free cell-based reporter system for convenient live-cell visualization of HCV infection, and our data indicate that complete HCV virion assembly machinery is essential for both cell-free and cell-to-cell transmission. IMPORTANCE Hepatitis C virus (HCV) infects hepatocytes via two pathways: cell-free infection and cell-to-cell transmission. Structural modules of the HCV genome are required for production of infectious cell-free virions; however, the role of specific genes within the structural module in cell-to-cell transmission is not clearly defined. Our data demonstrate that deletion of core, E1E2, and p7 genes individually results in no HCV cell-to-cell transmission and that ApoE knockdown from donor cells causes less-efficient cell-to-cell transmission. Thus, this work indicates that the complete HCV assembly machinery is required for HCV cell-to-cell transmission. At last, this work presents an optimized viral infection-activated split-intein-mediated reporter system for easy live-cell monitoring of HCV infection.

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Hepatitis C Virus-Induced Upregulation of MicroRNA miR-146a-5p in Hepatocytes Promotes Viral Infection and Deregulates Metabolic Pathways Associated with Liver Disease Pathogenesis

Journal of Virology ◽

10.1128/jvi.00619-16 ◽

2016 ◽

Vol 90 (14) ◽

pp. 6387-6400 ◽

Cited By ~ 56

Author(s):

Simonetta Bandiera ◽

Sophie Pernot ◽

Hussein El Saghire ◽

Sarah C. Durand ◽

Christine Thumann ◽

...

Keyword(s):

Hepatitis C Virus ◽

Liver Disease ◽

Hepatitis C ◽

Viral Infection ◽

Chronic Liver Disease ◽

Mirna Expression ◽

Liver Tissue ◽

Chronic Liver ◽

Hcv Infection ◽

Disease Pathogenesis

ABSTRACTHepatitis C virus (HCV)-induced chronic liver disease is a leading cause of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying HCC development following chronic HCV infection remain poorly understood. MicroRNAs (miRNAs) play an important role in homeostasis within the liver, and deregulation of miRNAs has been associated with liver disease, including HCC. While host miRNAs are essential for HCV replication, viral infection in turn appears to induce alterations of intrahepatic miRNA networks. Although the cross talk between HCV and liver cell miRNAs most likely contributes to liver disease pathogenesis, the functional involvement of miRNAs in HCV-driven hepatocyte injury and HCC remains elusive. Here we combined a hepatocyte-like cell-based model system, high-throughput small RNA sequencing, computational analysis, and functional studies to investigate HCV-miRNA interactions that may contribute to liver disease and HCC. Profiling analyses indicated that HCV infection differentially regulated the expression of 72 miRNAs by at least 2-fold, including miRNAs that were previously described to target genes associated with inflammation, fibrosis, and cancer development. Further investigation demonstrated that the miR-146a-5p level was consistently increased in HCV-infected hepatocyte-like cells and primary human hepatocytes, as well as in liver tissue from HCV-infected patients. Genome-wide microarray and computational analyses indicated that miR-146a-5p overexpression modulates pathways that are related to liver disease and HCC development. Furthermore, we showed that miR-146a-5p has a positive impact on late steps of the viral replication cycle, thereby increasing HCV infection. Collectively, our data indicate that the HCV-induced increase in miR-146a-5p expression both promotes viral infection and is relevant for pathogenesis of liver disease.IMPORTANCEHCV is a leading cause of chronic liver disease and cancer. However, how HCV induces liver cancer remains poorly understood. There is accumulating evidence that a viral cure does not eliminate the risk for HCC development. Thus, there is an unmet medical need to develop novel approaches to predict and prevent virus-induced HCC. miRNA expression is known to be deregulated in liver disease and cancer. Furthermore, miRNAs are essential for HCV replication, and HCV infection alters miRNA expression. However, how miRNAs contribute to HCV-driven pathogenesis remains elusive. Here we show that HCV induces miRNAs that may contribute to liver injury and carcinogenesis. The miR-146a-5p level was consistently increased in different cell-based models of HCV infection and in HCV patient-derived liver tissue. Furthermore, miR-146a-5p increased HCV infection. Collectively, our data are relevant to understanding viral pathogenesis and may open perspectives for novel biomarkers and prevention of virus-induced liver disease and HCC.

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