Recombinant expression of the alternate reading frame protein (ARFP) of hepatitis C virus genotype 4a (HCV-4a) and detection of ARFP and anti-ARFP antibodies in HCV-infected patients.

PubMed

Shehat, Michael G; Bahey-El-Din, Mohammed; Kassem, Mervat A; Farghaly, Faten A; Abdul-Rahman, Medhat H; Fanaki, Nourhan H

2015-08-01

HCV is a single-stranded RNA virus with a single open reading frame (ORF) that is translated into a polyprotein that is then processed to form 10 viral proteins. An additional eleventh viral protein, the alternative reading frame protein (ARFP), was discovered relatively recently. This protein results from a translational frameshift in the core region during the expression of the viral proteins. Recombinant expression of different forms of ARFP was previously done for HCV genotypes 1 and 2, and more recently, genotype 3. However, none of the previous studies addressed the expression of ARFP of HCV genotype 4a, which is responsible for 80 % of HCV infections in the Middle East and Africa. Moreover, the direct detection of the ARFP antigen in HCV-infected patients was never studied before for any HCV genotype. In the present study, recombinant ARFP derived from HCV genotype 4a was successfully expressed in E. coli and purified using metal affinity chromatography. The recombinant ARFP protein and anti-ARFP antibodies were used for detection of ARFP antigen in patients' sera, employing competitive enzyme-linked immunosorbent assay (ELISA) procedures. Furthermore, the recombinant antigen was also used to detect and quantify anti-ARFP antibodies in HCV-infected Egyptian patients at different stages of pegylated interferon/ribavirin therapy, using an ELISA assay. The ARFP antigen was detectable in 69.4 % of RNA-positive sera, indicating that ARFP antigen is produced during the natural course of HCV infection. In addition, significant levels of anti-ARFP antibodies were present in 41 % of the serum samples tested. The important diagnostic value of the recombinant ARFP antigen was also demonstrated.

Chemiluminescent microparticle immunoassay based detection and prevalence of HCV infection in district Peshawar Pakistan

PubMed Central

2014-01-01

Background Due to the high rate of asymptomatic infections an advanced screening assay is of prompt importance to be used for the clinical diagnosis of HCV. Early detection of anti HCV is the first step in the management of chronic hepatitis and in the selection of patients needing treatments. In the current study we have first time used the advanced serological diagnostic technique i.e. Chemiluminescent Microparticle Immuno Assay (CMIA) for the detection of HCV infection in Peshawar Pakistan. Methods A total number of 982 samples were collected among the general public belongs to the different areas of district Peshawar. The samples were centrifuged at high speed to obtain a clear supernatant serum. All the samples were run on Architect system a fully automated immuno analyzer CMIA base technology. Results Out of 982 blood samples analyzed in this study, 160 (15.9%) were confirmed to be positive for active HCV infection. The overall prevalence was found to be 13.4%. Gender wise prevalence was recorded to be higher in male (19.1%) than female (12.7%). The age group 21-30 years was identified as the highest risk group among the studied population. Conclusion Among the tested samples, overall prevalence of active HCV infection was found to be 13.4% in the general population of Peshawar Pakistan. The young middle aged population of this region was at higher risk of HCV ailments compared to the other age groups. PMID:25016473

Comparison of a newly developed automated and quantitative hepatitis C virus (HCV) core antigen test with the HCV RNA assay for clinical usefulness in confirming anti-HCV results.

PubMed

Kesli, Recep; Polat, Hakki; Terzi, Yuksel; Kurtoglu, Muhammet Guzel; Uyar, Yavuz

2011-12-01

Hepatitis C virus (HCV) is a global health care problem. Diagnosis of HCV infection is mainly based on the detection of anti-HCV antibodies as a screening test with serum samples. Recombinant immunoblot assays are used as supplemental tests and for the final detection and quantification of HCV RNA in confirmatory tests. In this study, we aimed to compare the HCV core antigen test with the HCV RNA assay for confirming anti-HCV results to determine whether the HCV core antigen test may be used as an alternative confirmatory test to the HCV RNA test and to assess the diagnostic values of the total HCV core antigen test by determining the diagnostic specificity and sensitivity rates compared with the HCV RNA test. Sera from a total of 212 treatment-naive patients were analyzed for anti-HCV and HCV core antigen both with the Abbott Architect test and with the molecular HCV RNA assay consisting of a reverse transcription-PCR method as a confirmatory test. The diagnostic sensitivity, specificity, and positive and negative predictive values of the HCV core antigen assay compared to the HCV RNA test were 96.3%, 100%, 100%, and 89.7%, respectively. The levels of HCV core antigen showed a good correlation with those from the HCV RNA quantification (r = 0.907). In conclusion, the Architect HCV antigen assay is highly specific, sensitive, reliable, easy to perform, reproducible, cost-effective, and applicable as a screening, supplemental, and preconfirmatory test for anti-HCV assays used in laboratory procedures for the diagnosis of hepatitis C virus infection.

Declining Hepatitis C Virus (HCV) Incidence in Dutch Human Immunodeficiency Virus-Positive Men Who Have Sex With Men After Unrestricted Access to HCV Therapy.

PubMed

Boerekamps, Anne; van den Berk, Guido E; Lauw, Fanny N; Leyten, Eliane M; van Kasteren, Marjo E; van Eeden, Arne; Posthouwer, Dirk; Claassen, Mark A; Dofferhoff, Anton S; Verhagen, Dominique W M; Bierman, Wouter F; Lettinga, Kamilla D; Kroon, Frank P; Delsing, Corine E; Groeneveld, Paul H; Soetekouw, Robert; Peters, Edgar J; Hullegie, Sebastiaan J; Popping, Stephanie; van de Vijver, David A M C; Boucher, Charles A; Arends, Joop E; Rijnders, Bart J

2018-04-17

Direct-acting antivirals (DAAa) cure hepatitis C virus (HCV) infections in 95% of infected patients. Modeling studies predict that universal HCV treatment will lead to a decrease in the incidence of new infections but real-life data are lacking. The incidence of HCV among Dutch human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) has been high for >10 years. In 2015 DAAs became available to all Dutch HCV patients and resulted in a rapid treatment uptake in HIV-positive MSM. We assessed whether this uptake was followed by a decrease in the incidence of HCV infections. Two prospective studies of treatment for acute HCV infection enrolled patients in 17 Dutch HIV centers, having 76% of the total HIV-positive MSM population in care in the Netherlands. Patients were recruited in 2014 and 2016, the years before and after unrestricted DAA availability. We compared the HCV incidence in both years. The incidence of acute HCV infection decreased from 93 infections during 8290 person-years of follow-up (PYFU) in 2014 (11.2/1000 PYFU; 95% confidence interval [CI], 9.1-13.7) to 49 during 8961 PYFU in 2016 (5.5/1000 PYFU; 4.1-7.2). The incidence rate ratio of 2016 compared with 2014 was 0.49 (95% CI, .35-.69). Simultaneously, a significant increase in the percentage positive syphilis (+2.2%) and gonorrhea (+2.8%) tests in HIV-positive MSM was observed at sexual health clinics across the Netherlands and contradicts a decrease in risk behavior as an alternative explanation. Unrestricted DAA availability in the Netherlands was followed by a 51% decrease in acute HCV infections among HIV-positive MSM.

Is HCV core antigen a reliable marker of viral load? An evaluation of HCV core antigen automated immunoassay

PubMed Central

Hadziyannis, Emilia; Minopetrou, Martha; Georgiou, Anastasia; Spanou, Fotini; Koskinas, John

2013-01-01

Background Hepatitis C viral (HCV) load detection and quantification is routinely accomplished by HCV RNA measurement, an expensive but essential test, both for the diagnosis and treatment of chronic hepatitis C (CHC). HCV core antigen (Ag) testing has been suggested as an attractive alternative to molecular diagnostics. The aim of the study was to evaluate an automated chemiluminescent immunoassay (CLIA) for HCV core Ag measurement in comparison to quantitative HCV RNA determination. Methods HCV Ag was measured in 105 anti-HCV positive patients, from which 89 were HCV RNA positive with CHC and 16 HCV RNA negative after spontaneous HCV clearance. Viral load was quantified with branched DNA (bDNA, Versant, Siemens). Sera were stored at -70°C and then tested with the Architect HCV Ag test (Abbott Laboratories), a two-step CLIA assay, with high throughput and minimal handling of the specimens. Statistical analysis was performed on logarithmically transformed values. Results HCV-Ag was detectable and quantifiable in 83/89 and in grey zone in 4/89 HCV RNA positive sera. HCV-Ag was undetectable in all 16 HCV RNA negative samples. The sample with the lowest viral load that tested positive for HCV-Ag contained 1200 IU/mL HCV RNA. There was a positive correlation between HCV RNA and HCV-Ag (r=0.89). The HCV RNA/ HCV Ag ratio varied from 1.5 to 3.25. Conclusion The HCV core Ag is an easy test with comparable sensitivity (>90%) and satisfactory correlation with the HCV RNA bDNA assay. Its role in diagnostics and other clinical applications has to be determined based on cost effectiveness. PMID:24714621

Seroprevalence of HCV among Cairo University students in Egypt.

PubMed

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.

HCV RNA Genomic sequences and HCV-E2 glycoprotein in sural nerve biopsies from HCV-infected patients with peripheral neuropathy.

PubMed

Russi, S; Sansonno, D; Monaco, S; Mariotto, S; Ferrari, S; Pavone, F; Lauletta, G; Dammacco, F

2018-06-01

Peripheral neuropathy (PN), the major neurological complication of chronic HCV infection, is frequently associated with mixed cryoglobulinaemia (MC) and small-vessel systemic vasculitis. While humoral and cell-mediated immune mechanisms are suspected to act together in an aberrant immune response that results in peripheral nerve damage, the role of HCV remains largely speculative. The possible demonstration of HCV in peripheral nerve tissue would obviously assume important pathogenic implications. We studied sural nerve biopsies from 11 HCV-positive patients with neuropathic symptoms: five with and six without MC. In situ hybridization (ISH) and immunofluorescence studies were carried out to detect genomic and antigenomic HCV RNA sequences and HCV-encoded E2-glycoprotein, respectively. Epineurial vascular deposits of E2-glycoprotein were found in four (80%) MC and in two (33.3%) non-MC patients, respectively. These findings were enhanced by the perivascular deposition of positive-, though not negative-strand replicative RNA, as also found in the nerve extracts of all patients. Mild inflammatory cell infiltrates with no deposits of immunoglobulins and/or complement proteins were revealed around small vessels, without distinct vasculitis changes between MC and non-MC patients. These results indicate that nerve vascular HCV RNA/E2 deposits associated to perivascular inflammatory infiltrates were similar in chronically HCV-infected patients, regardless of cryoglobulin occurrence. Given the failure to demonstrate HCV productive infection in the examined sural nerve biopsies, nerve damage is likely to result from virus-triggered immune-mediated mechanisms. © 2017 British Neuropathological Society.

Maternal hepatitis C (HCV) infection and Anti-D immunoglobulin therapy: study testing antibodies, RNA and Genotype of HCV in Baghdad.

PubMed

Al-Kubaisy, Waqar; Daud, Suzanna; Al-Kubaisi, Mustafa Waseem; Al-Kubaisi, Omar Waseem; Abdullah, Nik Nairan

2018-04-30

Hepatitis C virus (HCV) infection is a serious health problem. It is a major contributor to end-stage liver disease. Worldwide, 1-8% of all pregnant women were infected. Women with viral hepatitis may be at an increased risk of pregnancy complications. There are several obstetrics intervention acts as risk factors, which are specific to women pertaining the HCV infection; anti-D immunoglobulin (Ig) therapy may be one of them. Our objectives were to estimate the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among women with anti-D Ig therapy. A cross sectional study was conducted. A sample of 154 Rhesus negative (Rh - ve) pregnant women regardless of the anti-D Ig therapy was collected. Anti-HCV were tested using third generation enzyme immunoassay (EIA-3) and immunoblot assay (Lia Tek-111), subsequently. In addition, 89 serum samples were subjected to molecular analysis using RT-PCR and DNA enzyme immunoassay (DEIA) method for the detection of HCV-RNA and genotypes. Anti-HCV, and HCV-RNA seroprevalence were significantly higher (17.1, 35.5%) among women with anti-D Ig than their counter group (6.4, 13.16%), p = .038, .018, respectively. Significant direct positive dose response correlation (r = 0.78, p = .005) had been seen between number of anti-D Ig therapy and anti-HCV seropositive rate. Anti-D Ig therapy act as a risk factor (odds ratio (OR) = 3.01, 95%CI: 1.01-8.9) especially from the third dose onward. Women with anti-D Ig therapy were at higher risk (3.6 times more) of positive HCV-RNA (OR =3.6, 95%CI =1.19-10.837). Genotype HCV-1b showed higher prevalent (52.9%) among the recipients of anti-D Ig therapy while genotype HCV-3a (6.6%) was the lowest. Our study showed that Anti-D immunoglobulin therapy acts as a risk factor for acquiring HCV infection. Screening for HCV should be recommended for all recipients of anti-D Ig. Not only HCV antibodies but HCV-RNA detection being recommended for the diagnosis of HCV

Immune Responses to HCV and Other Hepatitis Viruses

PubMed Central

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

Performance comparison of new generation HCV core antigen test versus HCV RNA test in management of hepatitis C virus infection.

PubMed

Çetiner, Salih; Çetin Duran, Alev; Kibar, Filiz; Yaman, Akgün

2017-06-01

The study has evaluated the performance of HCV core antigen (Cag) test by comparing HCV RNA PCR assay which is considered the gold standard for management of HCV infection. Totally, 132 samples sent for HCV RNA (real-time PCR) test were included in the study. Anti-HCV antibody test and HCV Cag test were performed by chemiluminescent enzyme immunoassay (CMEI). Anti-HCV test was positive in all samples. HCV RNA was detected in 112/132 (84.8%) samples, and HCV Cag in 105/132 (79.5%). The most common HCV genotype was genotype 1 (86%). Considering the HCV RNA test as gold standard; the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of Cag test were found to be 93.75%, 100%, 100%, 74.07% and 94.69%, respectively, and paired test results were detected as highly concordant. A high level of correlation was seen between HCV RNA and Cag tests, however, the concordance between the two tests appeared to be disrupted at viral loads lower than 10 3 IU/mL. On the contrary, the correlation reached significance for the values higher than 10 3 IU/mL. Viral loads were in the 17-2500IU/mL range for the negative results for Cag test. Pearson's correlation coefficient revealed a considerably high correlation. The concordance between HCV RNA and Cag tests was disrupted under a viral load lower than 10 3 IU/mL. Therefore, it would be appropriate to consider cost effectiveness, advantages and limitations of the HCV RNA and Cag tests during the decision on which method to use for patient management. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of the Abbott RealTime HCV assay for quantitative detection of hepatitis C virus RNA.

PubMed

Michelin, Birgit D A; Muller, Zsofia; Stelzl, Evelyn; Marth, Egon; Kessler, Harald H

2007-02-01

The Abbott RealTime HCV assay for quantitative detection of HCV RNA has recently been introduced. In this study, the performance of the Abbott RealTime HCV assay was evaluated and compared to the COBAS AmpliPrep/COBAS TaqMan HCV test. Accuracy, linearity, interassay and intra-assay variations were determined, and a total of 243 routine clinical samples were investigated. When accuracy of the new assay was tested, the majority of results were found to be within +/-0.5 log(10) unit of the results obtained by reference laboratories. Determination of linearity resulted in a quasilinear curve up to 1.0 x 10(6)IU/ml. The interassay variation ranged from 15% to 32%, and the intra-assay variation ranged from 5% to 8%. When clinical samples were tested by the Abbott RealTime HCV assay and the results were compared with those obtained by the COBAS AmpliPrep/COBAS TaqMan HCV test, the results for 93% of all samples with positive results by both tests were found to be within +/-1.0 log(10) unit. The viral loads for all patients measured by the Abbott and Roche assays showed a high correlation (R(2)=0.93); quantitative results obtained by the Abbott assay were found to be lower than those obtained by the Roche assay. The Abbott RealTime HCV assay proved to be suitable for use in the routine diagnostic laboratory. The time to results was similar for both of the assays.

[Contribution of HCV core antigen testing in HCV diagnosis by test from the company Abbott Laboratories].

PubMed

Trbusek, J

2009-11-01

Detection of HCV core antigen as direct marker of hepatitis C infection clearly improves diagnosis of this disease (especially reduction of window period) and brings broad clinical utilization. The company Abbott Laboratories offers fully automated laboratory test for measurement of HCV core antigen on ARCHITECT analyzers.

Diagnosis and monitoring of HCV infection using the cobas® HCV test for use on the cobas® 6800/8800 systems.

PubMed

Yao, Joseph D; Young, Stephen; Heilek, Gabrielle M; Marino, Enrique; Paxinos, Ellen E; Marins, Ed G; Valsamakis, Alexandra

2018-05-01

Accurate, sensitive, and specific tests for detection and monitoring of hepatitis C virus (HCV) RNA concentrations are essential for diagnosis and management of HCV infections. We evaluated the next-generation reverse-transcription real-time PCR test, cobas ® HCV test for use with the cobas ® 6800/8800 systems ("cobas HCV") by determining its analytical performance characteristics and clinical utility for the diagnosis and therapeutic monitoring of chronic HCV infections. The limit of detection (LOD), linearity, precision, specificity, matrix equivalence of plasma and serum, and quantitative agreement with the COBAS ® AmpliPrep/COBAS ® TaqMan ® HCV Test version 2.0 ("CAP/CTM HCV v2") were evaluated. Clinical utility for the diagnosis of chronic HCV infection was demonstrated by testing plasma from HCV seropositive individuals and comparing results to a nucleic acid amplification test (NAAT) approved for use in the diagnosis of chronic hepatitis C. Clinical specificity was investigated by testing plasma from HCV antibody negative subjects with non-HCV related liver diseases. Utility for monitoring treatment response was defined by testing plasma collected during treatment of HCV genotypes (GT) 1, 2, and 3 and determining positive predictive value (PPV), negative predictive value (NPV) and the odds ratio (OR) for predicting cure (sustained virologic response 12 weeks after treatment cessation, "SVR12"). The cobas HCV test demonstrated an LOD of at least 15 IU/mL and measurable range from 15 to at least 1.0E + 08 IU/mL (1.2-8.0 log 10 IU/mL) for GT 1-6, with high accuracy (≤0.16 log 10 difference) and precision (standard deviation 0.04-0.14 log 10 ) throughout the linear range. Paired plasma and serum samples showed highly correlated performance (R 2  = 0.97). Quantification was 100% specific for HCV in analytical studies. Correlation with CAP/CTM HCV v2 was high in patient samples (mean titer difference: 0.05 log 10 with a 95% CI: 0.03-0.06 log 10

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

PubMed

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.

HCV associated glomerulopathy in Egyptian patients: clinicopathological analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sabry, Alaa; E-Agroudy, Amgd; Sheashaa, Hussein

Background: Hepatitis C virus (HCV) infection in Egypt has reached an epidemic proportion and is associated with many extra hepatic manifestations; Glomerulonephritis (GN) is one of the most consequences of HCV infection often resulting in end stage renal disease in some cases. Detection of viral genome or particles within the kidney biopsies from HCV-infected patients has proven to be difficult. Histological characterization of renal lesions still represents a major challenge. The aim of our work was to describe the histological pattern of HCV-associated nephropathy. Methods: Fifty Patients - out of 233 - presented to Mansoura Urology and Nephrology clinic withmore » manifestations of glomerular disease were screened for HCV antibodies by a 3rd generation ELISA test. Those tested positive for HCV antibodies were confirmed by PCR for HCV-RNA and subjected to more detailed clinical, biochemical and histological study. Kidney biopsies and in appropriate cases liver biopsies were examined by LM and electron microscopy (EM). Results: Histological study of renal biopsies revealed membranoproliferative (MPGN) type 1 to be the most common lesion encountered (54%), followed by focal segmental glomerulosclerosis (FSGS) (24%), mesangioproliferative GN (18%), membranous nephropathy (MN) (4%) in that order. EM examinations of renal biopsies were successful in identifying HCV like particles in frozen renal tissue. Conclusion: HCV-associated glomerulopathy is a distinct category of glomerulonephritis. Results of LM showed some peculiar features. In addition, we were successful in location and detection of HCV particles in renal tissues by EM.« less

Usefulness of hepatitis C virus RNA counts by second generation HCV bDNA-probe in chronic hepatitis C based on the HCV genotype.

PubMed

Kobayashi, M; Kumada, H; Arase, Y; Chayama, K; Kobayashi, M; Tsubota, A; Koida, I; Saitoh, S; Suzuki, Y; Murashima, N; Ikeda, K; Miyano, Y; Mizoshita, K; Matsuda, M; Koike, H; Hashimoto, M

1998-04-01

Detection of hepatitis C virus (HCV) RNA by a second generation (ver 2) HCV bDNA-probe method (bDNA-probe) was compared with detection by the first generation (ver 1) assay. The two assays were performed simultaneously with the same serum samples of HCV genotypes 1b, 2a, 2b, 3a, and 3b. The positive rates with ver 1 were 82% for HCV genotype 1b (type 1b), 57.6% for HCV genotype 2a (type 2a), 75.0% for HCV genotype 2b (type 2b), 55.6% for HCV genotype 3a (type 3a), and 93.8% for HCV genotype 3b (type 3b). The positive rates with ver 2 were 95.0% for type 1b, 93.9% for type 2a, 83.3% for type 2b, 100% for type 3a, and 93.8% for type 3b. With Fisher's exact test, the detection rate for type 2a was significantly higher (P = 0.001) with ver 2 than with ver 1. We obtained regression lines using the HCV counts measured by bDNA-probe on the y axis and the HCV counts obtained by an HCV reverse transcriptase (RT)-competitive polymerase chain reaction method (competitive PCR) on the x axis. The gradients for types 1b, 2a, and 3b were greater with ver 2 compared to ver 1. The gradients for types 2a and 3b were the highest: for type 2a, y = 0.135x + 0.6 with ver 1 and y = 0.248x + 0.1 with ver 2; for type 3b, y = 0.366x + 0.1 with ver 1 and y = 0.727x + 0.3 for ver 2. In addition, HCV-RNA counts for all the genotypes tested in this study were significantly higher with ver 2 than with ver 1. Hence, we conclude that ver 2 of the bDNA-probe measures HCV-RNA counts closer to those obtained with competitive PCR than the ver 1 assay.

Comparison of the Abbott RealTime HCV and Roche COBAS Ampliprep/COBAS TaqMan HCV assays for the monitoring of sofosbuvir-based therapy.

PubMed

Ogawa, Eiichi; Furusyo, Norihiro; Murata, Masayuki; Shimizu, Motohiro; Toyoda, Kazuhiro; Hotta, Taeko; Uchiumi, Takeshi; Hayashi, Jun

2017-01-01

On-treatment HCV kinetics play an invaluable role in evaluating the efficacy of interferon-based therapies. However, the importance of HCV RNA monitoring has not been well discussed concerning treatment with sofosbuvir (SOF)-based regimens, especially for the utility of the Abbott RealTime HCV (ART) assay. This study consisted of 151 patients infected with HCV genotype-1 or -2, including patients with prior treatment-experience or cirrhosis. HCV genotype-1 patients were treated with SOF/ledipasvir and genotype-2 patients with SOF/ribavirin, both for 12 weeks. Serial measurements of HCV RNA were performed with both the ART and COBAS AmpliPrep/COBAS TaqMan v2.0 (CAP/CTM) assays simultaneously at weeks 0, 1, 2, 4, 6, 8, 10 and 12 of treatment. The rates of HCV RNA target not detected (TND) by ART were significantly lower than those by CAP/CTM between weeks 2 and 12 (end of treatment [EOT]), irrespective of prior treatment-experience or cirrhosis. 11 (11.6%) genotype-1 and 8 (14.3%) genotype-2 patients did not achieve HCV RNA TND by ART at EOT, in contrast to all having HCV RNA TND by CAP/CTM; however, all achieved sustained virological response. The time at which HCV RNA became TND or unquantifiable was not associated with treatment outcome by either the ART or CAP/CTM assay. Over 10% of the patients continued to have detectable HCV RNA by ART at EOT, irrespective of HCV genotype, prior treatment-experience and/or cirrhosis. However, prolonged residual HCV RNA was not associated with treatment failure.

Analytical characteristics and comparative evaluation of Aptima HCV quant Dx assay with the Abbott RealTime HCV assay and Roche COBAS AmpliPrep/COBAS TaqMan HCV quantitative test v2.0.

PubMed

Worlock, A; Blair, D; Hunsicker, M; Le-Nguyen, T; Motta, C; Nguyen, C; Papachristou, E; Pham, J; Williams, A; Vi, M; Vinluan, B; Hatzakis, A

2017-04-04

The Aptima HCV Quant Dx assay (Aptima assay) is a fully automated quantitative assay on the Panther® system. This assay is intended for confirmation of diagnosis and monitoring of HCV RNA in plasma and serum specimens. The purpose of the testing described in this paper was to evaluate the performance of the Aptima assay. The analytical sensitivity, analytical specificity, precision, and linearity of the Aptima assay were assessed. The performance of the Aptima assay was compared to two commercially available HCV assays; the Abbott RealTime HCV assay (Abbott assay, Abbott Labs Illinois, USA) and the Roche COBAS Ampliprep/COBAS Taqman HCV Quantitative Test v2.0 (Roche Assay, Roche Molecular Systems, Pleasanton CA, USA). The 95% Lower Limit of Detection (LoD) of the assay was determined from dilutions of the 2nd HCV WHO International Standard (NIBSC 96/798 genotype 1) and HCV positive clinical specimens in HCV negative human plasma and serum. Probit analysis was performed to generate the 95% predicted detection limits. The Lower Limit of Quantitation (LLoQ) was established for each genotype by diluting clinical specimens and the 2nd HCV WHO International Standard (NIBSC 96/798 genotype 1) in HCV negative human plasma and serum. Specificity was determined using 200 fresh and 536 frozen HCV RNA negative clinical specimens including 370 plasma specimens and 366 serum specimens. Linearity for genotypes 1 to 6 was established by diluting armored RNA or HCV positive clinical specimens in HCV negative serum or plasma from 8.08 log IU/mL to below 1 log IU/mL. Precision was tested using a 10 member panel made by diluting HCV positive clinical specimens or spiking armored RNA into HCV negative plasma and serum. A method comparison was conducted against the Abbott assay using 1058 clinical specimens and against the Roche assay using 608 clinical specimens from HCV infected patients. In addition, agreement between the Roche assay and the Aptima assay using specimens with low

Diagnostic Value of Anti-Hepatitis C Virus (HCV) Core Immunoglobulin M in Recurrence of HCV Infection after Orthotopic Liver Transplantation†

PubMed Central

Casino, Carmela; Lilli, Daniela; Rivanera, Daniela; Comanducci, Antonella; Rossi, Massimo; Casciaro, Giovanni; Pecorella, Irene; Alfani, Dario; Mancini, Carlo

1999-01-01

The significance of anti-hepatitis C virus (HCV) core immunoglobulin M (IgM) and its relationship with genotypes, alanine aminotransferase abnormality, and histological data were studied for 18 patients who had undergone orthotopic liver transplantation due to HCV-related end-stage disease. During follow-up, IgM response seemed to be associated with the recurrence of HCV infection but did not correlate with abnormal alanine aminotransferase levels and histological data. In addition, the results of this study indicated that the detection of HCV RNA is critical for diagnosis of reinfection in liver transplantation. PMID:10405433

Small molecule inhibitors of HCV replication from Pomegranate

NASA Astrophysics Data System (ADS)

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.

[Comparative sensitivity of different solid-phase immunoassays for detecting HBsAg and anti-HCV in blood].

PubMed

León, P; López, J A; Domingo, C J; Echevarría, J M

1992-10-01

The sensitivities of seven methods of enzyme-immunoassay for HBsAg detection, as well as of twelve immunoassays for detecting antibody to HCV, were compared, in an attempt to evaluate the need for an official technical validation of such methods prior to its commercialization in Spain. Significant differences were seen for the sensitivities of these methods, which may influence the proficiency of blood bank screening for HBsAg and anti-HCV for preventing cases of post-transfusional viral hepatitis. As a conclusion, it is recommended to establish legal regulations for pre-marketing validation of such assays in Spain, as well as to take the results obtained in these evaluation studies as the basis for selecting those tests which may be more convenient for screening purposes at the blood banks.

Torque Teno Midi Virus/Small Anellovirus in Sera of Healthy, HIV/HCV and HIV Infected Individuals in Lorestan Province, Iran

PubMed Central

Fatholahi, Maryam; Bouzari, Majid

2015-01-01

Background: Torque Teno Midi Virus/Small Anellovirus (TTMDV/SAV) is a member of the Gammatorquevirus genus within the family Anelloviridae. It is detected in healthy, Hepatitis B Virus, Hepatitis C Virus and HIV infected individuals and also patients with acute respiratory disease in different countries, but its role in clinical diseases and its full geographical distribution is still unclear. Objectives: The current study aimed to detect the frequency of infection with TTMDV/SAV in the sera of healthy blood donors, hepatitis C infected and HIV positive individuals in Lorestan province, Iran; and also investigate the possible role of TTMDV/SAV virus in liver diseases. Materials and Methods: Fifty two, 36, 4, and 110 serum samples from HIV positive, patients with HIV/HCV and HIV/HCV/HBV co-infections, and healthy individuals were collected in Khorramabad city, respectively. Nested-polymerase chain reaction was performed using SMAs/SMAr primers to detect TTMDV/SAV DNA. Serum aminotransferases were measured. Results: In the HIV/HCV, HIV/HCV/HBV, HIV, and control cases, 29 (80.5%), 3 (75%), 43 (82.7%), and 16 (14.5%) were positive for DNA of TTMDV/SAV, respectively. In the HIV/HCV infected cases and HIV positive cases the level of Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) were not significantly different in TTMDV/SAV infected and non-infected individuals (P > 0.05). Conclusions: Although significant differences (P < 0.01) were observed in the frequency of TTMDV/SAV between healthy controls and each of the HIV positive and HIV/HCV co-infected individuals, no significant difference was observed between HIV positive and HIV/HCV co-infected cases, which may be due to HIV associated immunodeficiency. This is the first time that TTMDV/SAV is reported in HIV infected individuals worldwide. Interpretation of the high frequency of the virus (82.7%) in HIV cases needs more detailed studies. PMID:26862377

Torque Teno Midi Virus/Small Anellovirus in Sera of Healthy, HIV/HCV and HIV Infected Individuals in Lorestan Province, Iran.

PubMed

Fatholahi, Maryam; Bouzari, Majid

2015-11-01

Torque Teno Midi Virus/Small Anellovirus (TTMDV/SAV) is a member of the Gammatorquevirus genus within the family Anelloviridae. It is detected in healthy, Hepatitis B Virus, Hepatitis C Virus and HIV infected individuals and also patients with acute respiratory disease in different countries, but its role in clinical diseases and its full geographical distribution is still unclear. The current study aimed to detect the frequency of infection with TTMDV/SAV in the sera of healthy blood donors, hepatitis C infected and HIV positive individuals in Lorestan province, Iran; and also investigate the possible role of TTMDV/SAV virus in liver diseases. Fifty two, 36, 4, and 110 serum samples from HIV positive, patients with HIV/HCV and HIV/HCV/HBV co-infections, and healthy individuals were collected in Khorramabad city, respectively. Nested-polymerase chain reaction was performed using SMAs/SMAr primers to detect TTMDV/SAV DNA. Serum aminotransferases were measured. In the HIV/HCV, HIV/HCV/HBV, HIV, and control cases, 29 (80.5%), 3 (75%), 43 (82.7%), and 16 (14.5%) were positive for DNA of TTMDV/SAV, respectively. In the HIV/HCV infected cases and HIV positive cases the level of Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) were not significantly different in TTMDV/SAV infected and non-infected individuals (P > 0.05). Although significant differences (P < 0.01) were observed in the frequency of TTMDV/SAV between healthy controls and each of the HIV positive and HIV/HCV co-infected individuals, no significant difference was observed between HIV positive and HIV/HCV co-infected cases, which may be due to HIV associated immunodeficiency. This is the first time that TTMDV/SAV is reported in HIV infected individuals worldwide. Interpretation of the high frequency of the virus (82.7%) in HIV cases needs more detailed studies.

Performance of the New Aptima HCV Quant Dx Assay in Comparison to the Cobas TaqMan HCV2 Test for Use with the High Pure System in Detection and Quantification of Hepatitis C Virus RNA in Plasma or Serum.

PubMed

Schalasta, Gunnar; Speicher, Andrea; Börner, Anna; Enders, Martin

2016-04-01

Quantitating the level of hepatitis C virus (HCV) RNA is the standard of care for monitoring HCV-infected patients during treatment. The performances of commercially available assays differ for precision, limit of detection, and limit of quantitation (LOQ). Here, we compare the performance of the Hologic Aptima HCV Quant Dx assay (Aptima) to that of the Roche Cobas TaqMan HCV test, version 2.0, using the High Pure system (HPS/CTM), considered a reference assay since it has been used in trials defining clinical decision points in patient care. The assays' performance characteristics were assessed using HCV RNA reference panels and plasma/serum from chronically HCV-infected patients. The agreement between the assays for the 3 reference panels was good, with a difference in quantitation values of <0.5 log. High concordance was demonstrated between the assays for 245 clinical samples (kappa = 0.80; 95% confidence interval [CI], 0.720 to 0.881); however, Aptima detected and/or quantitated 20 samples that HPS/CTM did not detect, while Aptima did not detect 1 sample that was quantitated by HPS/CTM. For the 165 samples quantitated by both assays, the values were highly correlated (R= 0.98;P< 0.0001). The linearity of quantitation from concentrations of 1.4 to 6 log was excellent for both assays for all HCV genotypes (GT) tested (GT 1a, 1b, 2b, and 3a) (R(2)> 0.99). The assays had similar levels of total and intra-assay variability across all genotypes at concentrations from 1,000 to 25 IU/ml. Aptima had a greater analytical sensitivity, quantitating more than 50% of replicates at 25-IU/ml target. Aptima showed performance characteristics comparable to those of HPS/CTM and increased sensitivity, making it suitable for use as a clinical diagnostic tool on the fully automated Panther platform. Copyright © 2016 Schalasta et al.

HCV IRES-Mediated Core Expression in Zebrafish

PubMed Central

Zhang, Jing-Pu; Hu, Zhan-Ying; Tong, Jun-Wei; Ding, Cun-Bao; Peng, Zong-Gen; Zhao, Li-Xun; Song, Dan-Qing; Jiang, Jian-Dong

2013-01-01

The lack of small animal models for hepatitis C virus has impeded the discovery and development of anti-HCV drugs. HCV-IRES plays an important role in HCV gene expression, and is an attractive target for antiviral therapy. In this study, we report a zebrafish model with a biscistron expression construct that can co-transcribe GFP and HCV-core genes by human hepatic lipase promoter and zebrafish liver fatty acid binding protein enhancer. HCV core translation was designed mediated by HCV-IRES sequence and gfp was by a canonical cap-dependent mechanism. Results of fluorescence image and in situ hybridization indicate that expression of HCV core and GFP is liver-specific; RT-PCR and Western blotting show that both core and gfp expression are elevated in a time-dependent manner for both transcription and translation. It means that the HCV-IRES exerted its role in this zebrafish model. Furthermore, the liver-pathological impact associated with HCV-infection was detected by examination of gene markers and some of them were elevated, such as adiponectin receptor, heparanase, TGF-β, PDGF-α, etc. The model was used to evaluate three clinical drugs, ribavirin, IFNα-2b and vitamin B12. The results show that vitamin B12 inhibited core expression in mRNA and protein levels in dose-dependent manner, but failed to impact gfp expression. Also VB12 down-regulated some gene transcriptions involved in fat liver, liver fibrosis and HCV-associated pathological process in the larvae. It reveals that HCV-IRES responds to vitamin B12 sensitively in the zebrafish model. Ribavirin did not disturb core expression, hinting that HCV-IRES is not a target site of ribavirin. IFNα-2b was not active, which maybe resulted from its degradation in vivo for the long time. These findings demonstrate the feasibility of the zebrafish model for screening of anti-HCV drugs targeting to HCV-IRES. The zebrafish system provides a novel evidence of using zebrafish as a HCV model organism. PMID:23469178

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacobs, Jon M.; Diamond, Deborah L.; Chan, Eric Y.

2005-06-01

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

Performance and diagnostic usefulness of commercially available enzyme linked immunosorbent assay and rapid kits for detection of HIV, HBV and HCV in India.

PubMed

Maity, Susmita; Nandi, Srijita; Biswas, Subrata; Sadhukhan, Salil Kumar; Saha, Malay Kumar

2012-11-26

HIV, HBV and HCV pose a major public health problem throughout the world. Detection of infection markers for these agents is a major challenge for testing laboratories in a resource poor setting. As blood transfusion is an important activity saving millions of live every year, it also carries a risk of transfusion transmissible infections caused by these fatal blood borne pathogens if the quality of testing is compromised. Conventional ELISA is regarded as the mostly used screening technique but due to limitations like high cost, unavailability in many blood banks and testing sites, involvement of costly instruments, time taking nature and requirement of highly skilled personnel for interpretation, rapid tests are gaining more importance and warrants comparison of performance. A comparative study between these two techniques has been performed using commercially available diagnostic kits to assess their efficacy for detection of HIV, HBV and HCV infections. Rapid kits were more efficient in specificity with synthetic antigens along with high PPV than ELISA in most cases. Comparison between different ELISA kits revealed that Microlisa HIV and Hepalisa (J. Mitra & Co. Pvt. Ltd.); ERBA LISA HIV1 + 2, ERBA LISA Hepatitis B and ERBA LISA HCV (Transasia Bio-medicals Ltd.) gives uniform result with good performance in terms of sensitivity, specificity, PPV, NPV and efficiency, whereas, Microlisa HCV (J. Mitra & Co. Pvt. Ltd.), Microscreen HBsAg ELISA and INNOVA HCV (Span Diagnostics Ltd.) did not perform well. Rapid kits were also having high degree of sensitivity and specificity (100%) except in HIV Comb and HCV Comb (J. Mitra & Co. Pvt. Ltd.). The kit efficiency didn't vary significantly among different companies and lots in all the cases except for HCV ELISA showing statistically significant variation (p < 0.01) among three kit types. ELISA is a good screening assay for markers of HIV, HBV and HCV infections. Rapid tests are useful for further detection of false

Performance and diagnostic usefulness of commercially available enzyme linked immunosorbent assay and rapid kits for detection of HIV, HBV and HCV in India

PubMed Central

2012-01-01

Background HIV, HBV and HCV pose a major public health problem throughout the world. Detection of infection markers for these agents is a major challenge for testing laboratories in a resource poor setting. As blood transfusion is an important activity saving millions of live every year, it also carries a risk of transfusion transmissible infections caused by these fatal blood borne pathogens if the quality of testing is compromised. Conventional ELISA is regarded as the mostly used screening technique but due to limitations like high cost, unavailability in many blood banks and testing sites, involvement of costly instruments, time taking nature and requirement of highly skilled personnel for interpretation, rapid tests are gaining more importance and warrants comparison of performance. Results A comparative study between these two techniques has been performed using commercially available diagnostic kits to assess their efficacy for detection of HIV, HBV and HCV infections. Rapid kits were more efficient in specificity with synthetic antigens along with high PPV than ELISA in most cases. Comparison between different ELISA kits revealed that Microlisa HIV and Hepalisa (J. Mitra & Co. Pvt. Ltd.); ERBA LISA HIV1 + 2, ERBA LISA Hepatitis B and ERBA LISA HCV (Transasia Bio-medicals Ltd.) gives uniform result with good performance in terms of sensitivity, specificity, PPV, NPV and efficiency, whereas, Microlisa HCV (J. Mitra & Co. Pvt. Ltd.), Microscreen HBsAg ELISA and INNOVA HCV (Span Diagnostics Ltd.) did not perform well. Rapid kits were also having high degree of sensitivity and specificity (100%) except in HIV Comb and HCV Comb (J. Mitra & Co. Pvt. Ltd.). The kit efficiency didn’t vary significantly among different companies and lots in all the cases except for HCV ELISA showing statistically significant variation (p < 0.01) among three kit types. Conclusions ELISA is a good screening assay for markers of HIV, HBV and HCV infections. Rapid tests are useful

HCV replication in gastrointestinal mucosa: Potential extra-hepatic viral reservoir and possible role in HCV infection recurrence after liver transplantation

PubMed Central

Pizzillo, Paola; Iannolo, Gioacchin; Barbera, Floriana; Liotta, Rosa; Traina, Mario; Vizzini, Giovanni; Gridelli, Bruno

2017-01-01

Purpose Hepatitis C virus (HCV) predominantly infects hepatocytes, although it is known that receptors for viral entry are distributed on a wide array of target cells. Chronic HCV infection is indeed characterized by multiple non-liver manifestations, suggesting a more complex HCV tropism extended to extrahepatic tissues and remains to be fully elucidated. In this study, we investigated the gastrointestinal mucosa (GIM) as a potential extrahepatic viral replication site and its contribution to HCV recurrence. Methods We analyzed GIM biopsies from a cohort of 76 patients, 11 of which were HCV-negative and 65 HCV-positive. Of these, 54 biopsies were from liver-transplanted patients. In 29 cases, we were able to investigate gastrointestinal biopsies from the same patient before and after transplant. To evaluate the presence of HCV, we looked for viral antigens and genome RNA, whilst to assess viral replicative activity, we searched for the replicative intermediate minus-strand RNA. We studied the genetic diversity and the phylogenetic relationship of HCV quasispecies from plasma, liver and gastrointestinal mucosa of HCV-liver-transplanted patients in order to assess HCV compartmentalization and possible contribution of gastrointestinal variants to liver re-infection after transplantation. Results Here we show that HCV infects and replicates in the cells of the GIM and that the favorite hosts were mostly enteroendocrine cells. Interestingly, we observed compartmentalization of the HCV quasispecies present in the gastrointestinal mucosa compared to other tissues of the same patient. Moreover, the phylogenetic analysis revealed a high similarity between HCV variants detected in gastrointestinal mucosa and those present in the re-infected graft. Conclusions Our results demonstrated that the gastrointestinal mucosa might be considered as an extrahepatic reservoir of HCV and that could contribute to viral recurrence. Moreover, the finding that HCV infects and replicates in

Characteristics of HCV positive patients in an Italian urban psychiatric unit

PubMed Central

2006-01-01

Objectives 1) to assess the prevalence of hepatitis C virus (HCV) infection in a population of acute psychiatric in-patients; 2) to find out relationships between HCV comorbidity and clinical features of psychiatric patients. Methods Prospective observational study in a 6-year period. Results 2396 cases (1492 patients) were admitted in the considered period. Forty-two patients (2.8%) were affected by HCV infection. HCV infection was more frequent in patients with less years of education, lower social class, lower last year best Global Assessment of Functioning score, more hostile or violent behavior in hospital, with a lifetime history of previous suicide attempt, and with substance-related disorders. Conclusion HCV infection in psychiatric patients constitutes a major threat to the health of psychiatric patients and is related with unfavorable social background, worse global functioning, hostile or violent behavior, substance-related disorders. It appears also to be a significant risk of suicidal behavior. PMID:17010216

Clearance of HCV RNA following acute hepatitis A superinfection.

PubMed

Cacopardo, B; Nunnari, G; Nigro, L

2009-05-01

A transient reduction of hepatitis C virus replication during the course of acute hepatitis A virus infection has already been reported in the literature. The present study reports the case study of a subject with chronic hepatitis due to hepatitis C virus who went on to develop an acute hepatitis A. From the early onset of acute disease, hepatitis C virus ribonucleic acid became undetectable. Following recovery from acute hepatitis, alanine amino-transferase levels became persistently normal and liver biopsy revealed a reduction in the Knodell histological activity index score. Hepatitis C virus ribonucleic acid clearance was maintained up to 4 years after the onset of acute hepatitis A. During the course of the acute disease, a sharp increase in interferon gamma levels was detected in serum and in the supernatant of both unstimulated and phytoemagglutinin/lipopolysaccharide-stimulated peripheral blood mononuclear cells. Interferon gamma levels were still high 3 months later. We hypothesize that acute hepatitis A virus superinfection during the course of chronic hepatitis C may lead to hepatitis C virus ribonucleic acid clearance through an immunological mechanism related to interferon gamma production.

Impedimetric genosensor for detection of hepatitis C virus (HCV1) DNA using viral probe on methylene blue doped silica nanoparticles.

PubMed

Singhal, Chaitali; Ingle, Aviraj; Chakraborty, Dhritiman; Pn, Anoop Krishna; Pundir, C S; Narang, Jagriti

2017-05-01

An impedimetric genosensor was fabricated for detection of hepatitis C virus (HCV) genotype 1 in serum, based on hybridization of the probe with complementary target cDNA from sample. To achieve it, probe DNA complementary to HCVgene was immobilized on the surface of methylene blue (MB) doped silica nanoparticles MB@SiNPs) modified fluorine doped tin oxide (FTO) electrode. The synthesized MB@SiNPs was characterized using scanning electron microscopy (SEM), high resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD) pattern. This modified electrode (ssDNA/MB@SiNPs/FTO) served both as a signal amplification platform (due to silica nanoparticles (SiNPs) as well as an electrochemical indicator (due to methylene blue (MB)) for the detection of the HCV DNA in patient serum sample. The genosensor was optimized and evaluated. The sensor showed a dynamic linear range 100-10 6 copies/mL, with a detection limit of 90 copies/mL. The sensor was applied for detection of HCV in sera of hepatitis patient and could be renewed. The half life of the sensor was 4 weeks. The MB@SiNPs/FTO electrode could be used for preparation of other gensensors also. Copyright © 2017 Elsevier B.V. All rights reserved.

Characteristics of hepatitis viruses among Egyptian children with acute hepatitis.

PubMed

Youssef, Ahmed; Yano, Yoshihiko; El-Sayed Zaki, Maysaa; Utsumi, Takako; Hayashi, Yoshitake

2013-04-01

Hepatitis viral infection is hyperendemic in Egypt, western Asia and Africa. However, little is known about the status of hepatitis viruses among rural Egyptian children. Therefore, this study sought to examine the prevalence and characteristics of hepatitis viruses among symptomatic Egyptian children. Serological and molecular analyses of hepatitis viral infection were conducted in 33 children hospitalised at Mansoura University with symptomatic hepatic dysfunction (mean ± standard deviation age, 9.7±3.4 years; alanine aminotransferase level, 130±68 IU/ml). Eleven children (33%) were positive for anti-haemagglutination-IgM and were diagnosed with acute hepatitis A. Hepatitis B surface antigen (HBsAg) and anti‑hepatitis C virus (HCV) were detected in 9 (27%) and 7 (21%) children, respectively, indicating acute-on-chronic infection with hepatitis viruses. None of the children was positive for anti‑hepatitis B core antigen-IgM. Phylogenetic analysis confirmed that all HBVs belonged to genotype D (subgenotype D1) and that HCV belonged to genotypes 4a and 1g. HBV-DNA was detected in 9 children (27%) in the pre-S/S region and in 16 children (48%) in the core promoter/precore region. The Y134F amino acid mutation in the 'α' determinant region was detected in all of the patients. The A1762T/G1764A double mutation, and the T1846A and G1896A single mutations were common in children with occult HBV infection. In conclusion, hepatitis viral infection, including acute-on-chronic infection with HCV and HBV, is common in Egyptian children hospitalised with acute hepatitis.

Clinical presentation and course of acute hepatitis C infection in HIV-infected patients.

PubMed

Luetkemeyer, Annie; Hare, C Bradley; Stansell, John; Tien, Phyllis C; Charlesbois, Edwin; Lum, Paula; Havlir, Diane; Peters, Marion

2006-01-01

Hepatitis C virus (HCV) has become a significant source of morbidity and mortality in HIV-infected patients. However, little is known about the clinical presentation and course of acute HCV infection in this population. This study reports the outcomes of acute HCV infection in 9 HIV-infected men. Sex with men was the only reported risk factor for HCV infection in 6 of the subjects. Clinical presentation of acute HCV ranged from incidentally discovered elevated transaminases to severe liver dysfunction requiring hospitalization. At the time of HCV diagnosis, 8 of 9 patients had CD4+ counts >250 cells/mm(3), and 6 had HIV viral loads of < or =5000 copies/mL. Eight patients were receiving antiretroviral therapy. Outcome of these acute HCV infections varied. Five patients experienced virologic clearance, 2 in whom virus cleared spontaneously and 3 who were treated with pegylated interferon and ribavirin. Four patients developed chronic infection, one of whom had a relapse during HCV treatment and 3 of whom were untreated. All 4 patients to whom HCV therapy was administered experienced significant anemia or neutropenia, necessitating dose reduction or support with growth factors. Prompt recognition of acute HCV infection may minimize antiretroviral treatment interruption and will allow early treatment, which may improve virologic clearance. Unexplained transaminase elevations in HIV-infected patients, including men who have sex with men, should trigger an evaluation for acute HCV infection.

HCV Diversity among Chinese and Burmese IDUs in Dehong, Yunnan, China

PubMed Central

Chen, Xin; Duo, Lin; Li, Peilu; Zheng, Yong-Tang; Zhang, Chiyu

2016-01-01

HCV transmission is closely associated with drug-trafficking routes in China. Dehong, a prefecture of Yunnan, is the important trade transfer station linking Southeast Asia and China, as well as the drug-trafficking channel linking “Golden triangle” and other regions of China and surrounding countries. In this study, we investigated the HCV genotype diversity among IDUs in Dehong based on 259 HCV positive samples from 118 Chinese and 141 Burmese IDUs. HCV genotypes were determined based on the phylogenies of C/E2 and NS5B genomic sequences. Six HCV subtypes, including 1a, 1b, 3a, 3b, 6n and 6u, were detected. Interestingly, 4 HCV sequences from Burmese IDUs did not cluster with any known HCV subtypes, but formed a well-supported independent clade in the phylogenetic trees of both C/E2 and NS5B, suggesting a potential new HCV subtype circulating in Dehong. Subtype 3b was the predominant subtype, followed by subtypes 6n and 6u. Comparison showed that Dehong had a unique pattern of HCV subtype distribution, obviously different from other regions of China. In particular, HCV subtypes 6u and the potential new HCV subtype had a relatively high prevalence in Dehong, but were rarely detected in other regions of China. There was no significant difference in HCV subtype distribution between Burmese and Chinese IDUs. Few HCV sequences from Burmese and Chinese IDUs clustered together to form transmission clusters. Furthermore, about half of HCV sequences from Burmese IDUs formed small transmission clusters, significantly higher than that from Chinese IDUs (p<0.01). These suggest that the Chinese and Burmese IDUs were relatively isolated from each other in injection drug use behavior and the Burmese IDUs might prefer to inject drugs themselves together. The unique genotype distribution and complex diversity of genotype 6 among IDUs may be associated with the special geographical position of Dehong. PMID:27657722

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

PubMed

Schønning, Kristian; Pedersen, Martin Schou; Johansen, Kim; Landt, Bodil; Nielsen, Lone Gilmor; Weis, Nina; Westh, Henrik

2017-10-01

Chronic hepatitis C virus (HCV) infection can be effectively treated with directly acting antiviral (DAA) therapy. Measurement of HCV RNA is used to evaluate patient compliance and virological response during and after treatment. To compare the analytical performance of the Aptima HCV Quant Dx Assay (Aptima) and the COBAS Ampliprep/COBAS TaqMan HCV Test v2.0 (CAPCTMv2) for the quantification of HCV RNA in plasma samples, and compare the clinical utility of the two tests in patients undergoing treatment with DAA therapy. Analytical performance was evaluated on two sets of plasma samples: 125 genotyped samples and 172 samples referred for quantification of HCV RNA. Furthermore, performance was evaluated using dilutions series of four samples containing HCV genotype 1a, 2b, 3a, and 4a, respectively. Clinical utility was evaluated on 118 plasma samples obtained from 13 patients undergoing treatment with DAAs. Deming regression of results from 187 plasma samples with HCV RNA >2 Log IU/mL indicated that the Aptima assay quantified higher than the CAPCTMv2 test for HCV RNA >4.9 Log IU/mL. The linearity of the Aptima assay was excellent across 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. The analytical performance of the Aptima assay makes it well suited for monitoring patients with chronic HCV infection undergoing antiviral treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

[Comparison of eight screening tests for ant-HCV antibody].

PubMed

Deguchi, Matsuo; Kagita, Masanori; Yamashita, Naoko; Nakano, Takasi; Tahara, Kazuko; Asari, Seishi; Iwatani, Yoshinori

2002-09-01

We compared eight HCV screening tests for detection of anti-HCV antibody; Ortho Quick Chaser HCV Ab (QC), Ortho HCV Ab ELISA III (ELISA), Ortho HVC Ab PA test III (PA), Lumipulse II Ortho HCV (LUMI), IMx HCV.DAINAPACKII (IMx), ARCHITECT HCV (ARCH), Immucheck.F-HCV C50 Ab (Immu), RANREAM HCV Ab Ex II (RAN). Sera from six hundred patients were examined by these eight screening tests. The positive rates of the eight screening tests were from 9.0% to 13.2%. Forty-five sera showed discrepant results between the eight screening tests, and about half of them showed weak positive reaction and/or false positive. Twenty-five of the forty-five sera were negative for ant-HCV antibody in the CHIRON RIBA III confirmatory test, and forty-four of them were negative for HCV-RNA in the PCR method. The agreement rates between the two reagents were from 95.5% to 99.2%, but were not always high between the two reagents that used similar antigen. The specificities and sensitivities evaluated by using the RIBA III confirmatory test were excellent in ELISA, LUMI, IMx, ARCH and Immu. Three BBI seroconversion panels were used to compare the positive readings in the initial stage of HCV infection by eight screening tests. ELISA and ARCH showed the earliest positive readings, and then IMx, LUMI = RAN, PA, QC and Immu in this order. These findings indicate that ELISA and ARCH were the most excellent in the sensitivity, specificity and early diagnosis of HCV infection. However, we must pay attention to the weak positive reaction in the screening tests, because there is a possibility of "false positive".

Geographical distribution of HCV genotypes in Mexico.

PubMed

Sánchez-Avila, Juan Francisco; González, Elizabeth; Vázquez, Victoria; Suárez, Susana; Uribe, Misael

2007-01-01

Chronic hepatitis C (CHC) is the second cause of endstage liver disease in our country and one of the main indications of liver transplantation. Hepatitis C virus (HCV) genotype is the principal prognostic factor and the determinant of the therapeutic scheme. In our country few data exist regarding the prevalence of HCV infection and genotype distribution in the Mexican Republic has not been determined. The aim of this study was to characterize the prevalence of the different HCV genotypes and to explore their geographical distribution. Mexican patients with hepatitis C infection, detected throughout the country between 2003 and 2006, were included. All samples were analyzed by a central laboratory and Hepatitis C genotype was identified by Line Immuno Probe Assay in PCR positive samples (Versant Line Probe Assay Quest Diagnostics Nichols Institute, San Juan Capistrano CA). Data were analyzed according to the four geographical areas in Mexico. One thousand three hundred and ninety CHC patients were included. The most frequent genotype detected was genotype 1 (69%) followed by genotype 2 (21.4%) and genotype 3 (9.2%). Genotype 4 and 5 were infrequent. There was no subject infected with genotype 6. Genotype 1 and 2 exhibit very similar distribution in all geographical areas. Genotype 3 infected patients were more frequent in the North region (52%) compared with other areas:center-western (30%), center (17%), South-South east (1%) (p < 0.001). The most prevalent HCV genotype in Mexico is genotype 1. Geographical distribution of HCV genotypes in the four geographical areas in Mexico is not homogenous with a greater frequency of genotype3 in the north region. This difference could be related to the global changes of risk factors for HCV infection.

Preclinical Evaluation of An Anti-HCV miRNA Cluster for Treatment of HCV Infection

PubMed Central

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

2013-01-01

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. PMID:23295950

Performance characteristics of the ARCHITECT anti-HCV assay.

PubMed

Jonas, Gesa; Pelzer, Claudia; Beckert, Christian; Hausmann, Michael; Kapprell, Hans-Peter

2005-10-01

The ARCHITECT Anti-HCV assay is a fully automated high throughput chemiluminescent microparticle immunoassay (CMIA) for the detection of antibodies to structural and nonstructural proteins of the hepatitis C virus (HCV). To further enhance the performance of this test, the assay was modified to improve the specificity for blood donor specimens. The specificity of the enhanced ARCHITECT Anti-HCV assay was evaluated by screening blood donor samples randomly collected from various German blood banks, as well as hospitalized patient samples derived from Germany and the US. Additionally, antibody sensitivity was determined on commercially available anti-HCV seroconversion panels and on a commercially available worldwide anti-HCV genotype performance panel. Apparent specificity of the modified ARCHITECT Anti-HCV assay in a blood donor population consisting of 3811 specimens was 99.92%, compared to 99.76% for the current on-market assay. Additionally, antibody sensitivity was determined on commercially available anti-HCV seroconversion panels. Seroconversion sensitivity equivalent to or better than the current on-market product was observed by testing 33 seroconversion panels. This study demonstrates that the modified version of the ARCHITECT Anti-HCV assay shows improved specificity for blood donor specimens compared to the current assay on market without compromising sensitivity. With the availability of the improved ARCHITECT Anti-HCV assay and the recent launch of the ARCHITECT HIV Ag/Ab Combo assay, the ARCHITECT system now offers a full hepatitis/retrovirus menu with excellent performance on a high throughput, random access, automated analyzer, ideally suited for blood screening and diagnostic applications.

Detection of HCV and HIV-1 antibody negative infections in Scottish and Northern Ireland blood donations by nucleic acid amplification testing.

PubMed

Jarvis, L M; Dow, B C; Cleland, A; Davidson, F; Lycett, C; Morris, K; Webb, B; Jordan, A; Petrik, J

2005-10-01

To reduce the risk of transfusion-transmissible viruses entering the blood supply, the nucleic acid amplification testing (NAT) was implemented to screen Scottish and Northern Irish blood donations in minipools. After 5 years of NAT for hepatitis C virus (HCV) and 2 years for human immunodeficiency virus-1 (HIV-1), the yield of serologically negative, nucleic acid positive 'window donations' and cost-benefit of NAT is under review. When the Scottish National Blood Transfusion Service (SNBTS) implemented NAT in 1999, a fully automated 'black box' system was not available. Therefore, an 'in-house' assimilated NAT assay was developed, validated and implemented. The system is flexible and allows testing for additional viral markers to be introduced with relative ease. The HCV and HIV NAT assays have 95% detection levels of 7.25 IU/ml and 39.8 IU/ml, respectively, as determined by probit analysis. One HCV (1 in 1.9 million) and one HIV (1 in 0.77 million) window donation have been detected in 5 and 2 years, respectively, of NAT. The SNBTS NAT assays are robust and have performed consistently over the last 5 years. The design of the in-house system allowed HIV NAT to be added in 2003 at a relatively small additional cost per sample, although for both assays, the royalty fee far exceeds the cost of the test itself. Clearly NAT has a benefit in improving the safety of the blood supply although the risks of transfusion-transmitted viral infections, as reported in the Serious Hazards of Transfusion (SHOT) report, are extremely low. Also, in UK the yield of HCV antibody negative, NAT positive donations is far lower than predicted although the early detection of an HIV window period donation and the increase of HIV in the blood donor and general populations may provide a stronger case for HIV NAT. SUMMARY SENTENCE: The yield of HCV and HIV NAT in UK is significantly less than that anticipated from statistical models.

[Eukaryotic expression and application of HCV Hebei strain E2 extracellular core region].

PubMed

Ye, Chuantao; Bian, Peiyu; Weng, Daihui; Zhang, Hui; Yang, Jing; Zhang, Ying; Lei, Yingfeng; Jia, Zhansheng

2016-06-01

Objective To express core region of HCV1b (Hebei strain) E2 protein (E2c) by eukaryotic system, and establish the detection method of specific anti-HCV E2 antibody in the sera from hepatitis C patients. Methods Based on the literature, the E2c gene was modified from the HCV1b gene and synthesized via overlapping PCR. Thereafter, the E2c gene including tissue-type plasminogen activator (tPA) signal peptide was cloned into the pCI-neo eukaryotic expression vector, and the product was named pCI-tpa-1bE2c. After HEK293T cells were transfected with pCI-tpa-1bE2c, the supernatant was collected, condensed and purified. Its specificity was identified by Western blotting. Galanthus nivalis agglutinin (GNA)-based ELISA was used to detect the antibody against HCVE2 in the sera from hepatitis C patients. Results Modified HCV E2c protein was successfully expressed in HEK293T cells and the GNA-based ELISA was developed for detecting the antibody against HCV E2 in the sera from hepatitis C patients. Conclusion HCV-1bE2c protein can be effectively expressed in HEK293T cells and applied clinically.

Evaluation of the COBAS Hepatitis C Virus (HCV) TaqMan analyte-specific reagent assay and comparison to the COBAS Amplicor HCV Monitor V2.0 and Versant HCV bDNA 3.0 assays.

PubMed

Konnick, Eric Q; Williams, Sheri M; Ashwood, Edward R; Hillyard, David R

2005-05-01

Performance characteristics of the COBAS hepatitis C virus (HCV) TaqMan analyte-specific reagent (TM-ASR) assay using the QIAGEN BioRobot 9604 for RNA extraction were evaluated and compared to the COBAS Amplicor HCV Monitor V2.0 (Amplicor) and Versant HCV bDNA 3.0 (Versant) assays using clinical samples. Calibration of TM-ASR using Armored RNA allowed determination of the distribution of HCV RNA in clinical samples, using 22,399 clinical samples. Limit of detection, linearity, and inter- and intraassay assay precision were determined for the TM-ASR assay using multiple clinical specimen panels across multiple determinations. Genotype specificity for the TM-ASR assay was determined using samples with different HCV RNA genotypes evaluated and compared against predetermined results. Contamination control of the TM-ASR assay was evaluated using pools of HCV RNA-positive and -negative samples tested in a checkerboard pattern over 12 runs of 96 samples. Correlation of the TM-ASR, Amplicor, and Versant assays was determined using 100 paired clinical samples and Deming regression analysis. The TM-ASR performed well with respect to linearity, precision, and contamination control. The correlation between TM-ASR and the Amplicor and Versant assays was poor, with large differences between assay results for individual samples. Calibration of the TM-ASR assay with Armored RNA allowed for a wide dynamic range and description of the distribution of HCV RNA in clinical samples.

Evaluation of the COBAS Hepatitis C Virus (HCV) TaqMan Analyte-Specific Reagent Assay and Comparison to the COBAS Amplicor HCV Monitor V2.0 and Versant HCV bDNA 3.0 Assays

PubMed Central

Konnick, Eric Q.; Williams, Sheri M.; Ashwood, Edward R.; Hillyard, David R.

2005-01-01

Performance characteristics of the COBAS hepatitis C virus (HCV) TaqMan analyte-specific reagent (TM-ASR) assay using the QIAGEN BioRobot 9604 for RNA extraction were evaluated and compared to the COBAS Amplicor HCV Monitor V2.0 (Amplicor) and Versant HCV bDNA 3.0 (Versant) assays using clinical samples. Calibration of TM-ASR using Armored RNA allowed determination of the distribution of HCV RNA in clinical samples, using 22,399 clinical samples. Limit of detection, linearity, and inter- and intraassay assay precision were determined for the TM-ASR assay using multiple clinical specimen panels across multiple determinations. Genotype specificity for the TM-ASR assay was determined using samples with different HCV RNA genotypes evaluated and compared against predetermined results. Contamination control of the TM-ASR assay was evaluated using pools of HCV RNA-positive and -negative samples tested in a checkerboard pattern over 12 runs of 96 samples. Correlation of the TM-ASR, Amplicor, and Versant assays was determined using 100 paired clinical samples and Deming regression analysis. The TM-ASR performed well with respect to linearity, precision, and contamination control. The correlation between TM-ASR and the Amplicor and Versant assays was poor, with large differences between assay results for individual samples. Calibration of the TM-ASR assay with Armored RNA allowed for a wide dynamic range and description of the distribution of HCV RNA in clinical samples. PMID:15872232

The New Aptima HCV Quant Dx Real-time TMA Assay Accurately Quantifies Hepatitis C Virus Genotype 1-6 RNA.

PubMed

Chevaliez, Stéphane; Dubernet, Fabienne; Dauvillier, Claude; Hézode, Christophe; Pawlotsky, Jean-Michel

2017-06-01

Sensitive and accurate hepatitis C virus (HCV) RNA detection and quantification is essential for the management of chronic hepatitis C therapy. Currently available platforms and assays are usually batched and require at least 5hours of work to complete the analyses. The aim of this study was to evaluate the ability of the newly developed Aptima HCV Quant Dx assay that eliminates the need for batch processing and automates all aspects of nucleic acid testing in a single step, to accurately detect and quantify HCV RNA in a large series of patients infected with different HCV genotypes. The limit of detection was estimated to be 2.3 IU/mL. The specificity of the assay was 98.6% (95% confidence interval: 96.1%-99.5%). Intra-assay and inter-assay coefficients of variation ranged from 0.09% to 5.61%, and 1.05% to 3.65%, respectively. The study of serum specimens from patients infected with HCV genotypes 1 to 6 showed a satisfactory relationship between HCV RNA levels measured by the Aptima HCV Quant Dx assay, and both real-time PCR comparators (Abbott RealTime HCV and Cobas AmpliPrep/Cobas TaqMan HCV Test, version 2.0, assays). the new Aptima HCV Quant Dx assay is rapid, sensitive, reasonably specific and reproducible and accurately quantifies HCV RNA in serum samples from patients with chronic HCV infection, including patients on antiviral treatment. The Aptima HCV Quant Dx assay can thus be confidently used to detect and quantify HCV RNA in both clinical trials with new anti-HCV drugs and clinical practice in Europe and the US. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2012-01-01

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

Hepatitis C virus RNA detection in serum and peripheral blood mononuclear cells of patients with hepatitis C

PubMed Central

Zhou, Ping; Cai, Qing; Chen, You-Chun; Zhang, Mu-Sen; Guan, Jian; Li, Xiao-Juan

1997-01-01

AIM: To investigate the existence and clinical significance of hepatitis C virus (HCV) RNA in the serum and peripheral blood mononuclear cells (PBMC) of patients with hepatitis C. METHODS: HCV RNA was detected by nested polymerase chain reaction (Nested PCR) in serum and in PBMC of 46 patients with acute hepatitis C (AHC) and in 42 patients with chronic hepatitis C (CHC). RESULTS: The positive rate of HCV RNA in PBMC of patients with CHC was markedly higher than that of patients with AHC (P < 0.01). The positive rates of HCV RNA in serum of patients with AHC and CHC and in PBMC of patients with CHC were significantly higher than those of anti-HCV positive patients with normal alanine aminotransferase (ALT) levels (P < 0.01). HCV RNA was negative in the serum of two patients, but could be detected in PBMC. In 12 patients, anti HCV was negative while HCV RNA was positive in serum. CONCLUSION: (1) detection of serum HCV RNA by nested PCR might be helpful in the early diagnosis of anti-HCV negative hepatitis C; (2) liver damage in patients with hepatitis C might be correlated with HCV-viremia; (3) infection of PBMC by HCV might play an important role in chronic liver damage in patients with HCV and in the chronicity of its clinical course; and (4) PBMC might be considered as a “reservoir” for HCV. PMID:27041960

Indeterminate RIBA results were associated with the absence of hepatitis C virus RNA (HCV-RNA) in blood donors.

PubMed

Pereira, Felicidade Mota; Zarife, Maria Alice Sant'ana; Reis, Eliana Almeida Gomes; G Reis, Mitermayer

2014-01-01

Hepatitis C virus (HCV) infection is diagnosed by the presence of antibodies and is supplemented by confirmatory testing methods, such as recombinant immunoblot assay (RIBA) and HCV-RNA detection. This study aimed to evaluate the efficacy of RIBA testing to diagnose HCV infection in blood donors positive for anti-HCV antibodies. A total of 102 subjects positive for anti-HCV determined by enzyme-linked immunosorbent assay (ELISA) at the Hematology and Hemotherapy Foundation of Bahia (HEMOBA) were later assessed with new samples using the Abbott Architect anti-HCV test (Abbott Diagnostics, Wiesbaden, Germany), the RIBA III test (Chiron RIBA HCV 3.0 SIA, Chiron Corp., Emeryville, CA, USA), the polymerase chain reaction (PCR; COBAS® AMPLICOR HCV Roche Diagnostics Corp., Indianapolis, IN, USA) and line probe assay (LiPA - Siemens, Tarrytown, NY, USA) genotyping for HCV diagnosis. Of these new samples, 38.2% (39/102) were positive, 57.8% (59/102) were negative and 3.9% (4/102) were indeterminate for anti-HCV; HCV-RNA was detected in 22.5% (23/102) of the samples. RIBA results were positive in 58.1% (25/43), negative in 9.3% (4/43) and indeterminate in 32.6% (14/43) of the samples. The prevailing genotypes were 1 (78.3%, 18/23), 3 (17.4%, 4/23) and 2 (4.3%, 1/23). All 14 samples with indeterminate RIBA results had undetectable viral loads (detection limit ≤50 IU/mL). Of these samples, 71.4% (10/14) were reevaluated six months later. Eighty percent (8/10) of these samples remained indeterminate by RIBA, and 20% (2/10) were negative. In this study, individuals with indeterminate RIBA results had no detectable HCV-RNA.

Diagnostic accuracy of APRI, FIB-4 and Forns for the detection of liver cirrhosis in HIV/HCV-coinfected patients.

PubMed

Merli, Marco; Galli, Laura; Castagna, Antonella; Salpietro, Stefania; Gianotti, Nicola; Messina, Emanuela; Poli, Andrea; Morsica, Giulia; Bagaglio, Sabrina; Cernuschi, Massimo; Bigoloni, Alba; Uberti-Foppa, Caterina; Lazzarin, Adriano; Hasson, Hamid

2016-04-01

We determined the diagnostic accuracy and optimal cut off of three indirect fibrosis biomarkers (APRI, FIB-4, Forns) compared with liver stiffness (LS) for the detection of liver cirrhosis in HIV/HCV-coinfected patients. An observational retrospective study on HIV/HCV-coinfected patients with concomitant LS measurement and APRI, FIB-4 and Forns was performed. The presence of liver cirrhosis was defined as a LS ≥13 KPa. The diagnostic accuracy and optimal cut-off values, compared with LS categorization (<13 vs ≥13 KPa), were determined by receiver operating characteristics (ROC) curves. The study sample included 646 patients. The area-under-the ROC curve (95% confidence interval) for the detection of liver cirrhosis were 0.84 (0.81-0.88), 0.87 (0.84-0.91) and 0.87 (0.84-0.90) for APRI, FIB-4 and Forns, respectively. According to the optimal cut off values for liver cirrhosis (≥0.97 for APRI, ≥2.02 for FIB-4 and ≥7.8 for Forns), 80%, 80% and 82% of subjects were correctly classified by the three indirect fibrosis biomarkers, respectively. Misclassifications were mostly due to false positive cases. The study suggests that indirect fibrosis biomarkers can help clinicians to exclude liver cirrhosis in the management of HIV/HCV co-infected patients, reducing the frequency of more expensive or invasive assessments.

Identification of a Novel Drug Lead That Inhibits HCV Infection and Cell-to-Cell Transmission by Targeting the HCV E2 Glycoprotein

DOE PAGES

Al Olaby, Reem R.; Cocquerel, Laurence; Zemla, Adam; ...

2014-10-30

We report that Hepatitis C Virus (HCV) infects 200 million individuals worldwide. Although several FDA approved drugs targeting the HCV serine protease and polymerase have shown promising results, there is a need for better drugs that are effective in treating a broader range of HCV genotypes and subtypes without being used in combination with interferon and/or ribavirin. Recently, two crystal structures of the core of the HCV E2 protein (E2c) have been determined, providing structural information that can now be used to target the E2 protein and develop drugs that disrupt the early stages of HCV infection by blocking E2’smore » interaction with different host factors. Using the E2c structure as a template, we have created a structural model of the E2 protein core (residues 421–645) that contains the three amino acid segments that are not present in either structure. Computational docking of a diverse library of 1,715 small molecules to this model led to the identification of a set of 34 ligands predicted to bind near conserved amino acid residues involved in the HCV E2: CD81 interaction. We used surface plasmon resonance detection to screen the ligand set for binding to recombinant E2 protein, and the best binders were subsequently tested to identify compounds that inhibit the infection of Huh-7 cells by HCV. One compound, 281816, blocked E2 binding to CD81 and inhibited HCV infection in a genotype-independent manner with IC50’s ranging from 2.2 µM to 4.6 µM. 281816 blocked the early and late steps of cell-free HCV entry and also abrogated the cell-to-cell transmission of HCV. Collectively the results obtained with this new structural model of E2c suggest the development of small molecule inhibitors such as 281816 that target E2 and disrupt its interaction with CD81 may provide a new paradigm for HCV treatment.« less

Identification of a Novel Drug Lead That Inhibits HCV Infection and Cell-to-Cell Transmission by Targeting the HCV E2 Glycoprotein

PubMed Central

Al Olaby, Reem R.; Cocquerel, Laurence; Zemla, Adam; Saas, Laure; Dubuisson, Jean; Vielmetter, Jost; Marcotrigiano, Joseph; Khan, Abdul Ghafoor; Catalan, Felipe Vences; Perryman, Alexander L.; Freundlich, Joel S.; Forli, Stefano; Levy, Shoshana; Balhorn, Rod; Azzazy, Hassan M.

2014-01-01

Hepatitis C Virus (HCV) infects 200 million individuals worldwide. Although several FDA approved drugs targeting the HCV serine protease and polymerase have shown promising results, there is a need for better drugs that are effective in treating a broader range of HCV genotypes and subtypes without being used in combination with interferon and/or ribavirin. Recently, two crystal structures of the core of the HCV E2 protein (E2c) have been determined, providing structural information that can now be used to target the E2 protein and develop drugs that disrupt the early stages of HCV infection by blocking E2’s interaction with different host factors. Using the E2c structure as a template, we have created a structural model of the E2 protein core (residues 421–645) that contains the three amino acid segments that are not present in either structure. Computational docking of a diverse library of 1,715 small molecules to this model led to the identification of a set of 34 ligands predicted to bind near conserved amino acid residues involved in the HCV E2: CD81 interaction. Surface plasmon resonance detection was used to screen the ligand set for binding to recombinant E2 protein, and the best binders were subsequently tested to identify compounds that inhibit the infection of Huh-7 cells by HCV. One compound, 281816, blocked E2 binding to CD81 and inhibited HCV infection in a genotype-independent manner with IC50’s ranging from 2.2 µM to 4.6 µM. 281816 blocked the early and late steps of cell-free HCV entry and also abrogated the cell-to-cell transmission of HCV. Collectively the results obtained with this new structural model of E2c suggest the development of small molecule inhibitors such as 281816 that target E2 and disrupt its interaction with CD81 may provide a new paradigm for HCV treatment. PMID:25357246

Identification of a novel drug lead that inhibits HCV infection and cell-to-cell transmission by targeting the HCV E2 glycoprotein.

PubMed

Al Olaby, Reem R; Cocquerel, Laurence; Zemla, Adam; Saas, Laure; Dubuisson, Jean; Vielmetter, Jost; Marcotrigiano, Joseph; Khan, Abdul Ghafoor; Vences Catalan, Felipe; Perryman, Alexander L; Freundlich, Joel S; Forli, Stefano; Levy, Shoshana; Balhorn, Rod; Azzazy, Hassan M

2014-01-01

Hepatitis C Virus (HCV) infects 200 million individuals worldwide. Although several FDA approved drugs targeting the HCV serine protease and polymerase have shown promising results, there is a need for better drugs that are effective in treating a broader range of HCV genotypes and subtypes without being used in combination with interferon and/or ribavirin. Recently, two crystal structures of the core of the HCV E2 protein (E2c) have been determined, providing structural information that can now be used to target the E2 protein and develop drugs that disrupt the early stages of HCV infection by blocking E2's interaction with different host factors. Using the E2c structure as a template, we have created a structural model of the E2 protein core (residues 421-645) that contains the three amino acid segments that are not present in either structure. Computational docking of a diverse library of 1,715 small molecules to this model led to the identification of a set of 34 ligands predicted to bind near conserved amino acid residues involved in the HCV E2: CD81 interaction. Surface plasmon resonance detection was used to screen the ligand set for binding to recombinant E2 protein, and the best binders were subsequently tested to identify compounds that inhibit the infection of Huh-7 cells by HCV. One compound, 281816, blocked E2 binding to CD81 and inhibited HCV infection in a genotype-independent manner with IC50's ranging from 2.2 µM to 4.6 µM. 281816 blocked the early and late steps of cell-free HCV entry and also abrogated the cell-to-cell transmission of HCV. Collectively the results obtained with this new structural model of E2c suggest the development of small molecule inhibitors such as 281816 that target E2 and disrupt its interaction with CD81 may provide a new paradigm for HCV treatment.

Identification of a Novel Drug Lead That Inhibits HCV Infection and Cell-to-Cell Transmission by Targeting the HCV E2 Glycoprotein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al Olaby, Reem R.; Cocquerel, Laurence; Zemla, Adam

We report that Hepatitis C Virus (HCV) infects 200 million individuals worldwide. Although several FDA approved drugs targeting the HCV serine protease and polymerase have shown promising results, there is a need for better drugs that are effective in treating a broader range of HCV genotypes and subtypes without being used in combination with interferon and/or ribavirin. Recently, two crystal structures of the core of the HCV E2 protein (E2c) have been determined, providing structural information that can now be used to target the E2 protein and develop drugs that disrupt the early stages of HCV infection by blocking E2’smore » interaction with different host factors. Using the E2c structure as a template, we have created a structural model of the E2 protein core (residues 421–645) that contains the three amino acid segments that are not present in either structure. Computational docking of a diverse library of 1,715 small molecules to this model led to the identification of a set of 34 ligands predicted to bind near conserved amino acid residues involved in the HCV E2: CD81 interaction. We used surface plasmon resonance detection to screen the ligand set for binding to recombinant E2 protein, and the best binders were subsequently tested to identify compounds that inhibit the infection of Huh-7 cells by HCV. One compound, 281816, blocked E2 binding to CD81 and inhibited HCV infection in a genotype-independent manner with IC50’s ranging from 2.2 µM to 4.6 µM. 281816 blocked the early and late steps of cell-free HCV entry and also abrogated the cell-to-cell transmission of HCV. Collectively the results obtained with this new structural model of E2c suggest the development of small molecule inhibitors such as 281816 that target E2 and disrupt its interaction with CD81 may provide a new paradigm for HCV treatment.« less

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

PubMed Central

De Giorgi, Valeria; Monaco, Alessandro; Worchech, Andrea; Tornesello, MariaLina; Izzo, Francesco; Buonaguro, Luigi; Marincola, Francesco M; Wang, Ena; Buonaguro, Franco M

2009-01-01

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, diagnosis, and classification

[Clinical benefit of HCV core antigen assay in patients receiving interferon and ribavirin combination therapy].

PubMed

Higashimoto, Makiko; Takahashi, Masahiko; Jokyu, Ritsuko; Saito, Hidetsugu

2006-02-01

A highly sensitive second generation HCV core antigen assay has recently been developed. We compared viral disappearance and kinetics data between commercially available core antigen assays, Lumipulse Ortho HCV Ag, and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor Test, Version 2 to estimate the predictive benefit of sustained viral response (SVR) and non-SVR in 59 patients treated with interferon and ribavirin combination therapy. We found a good correlation between HCV core Ag and HCV RNA level regardless of genotype. Although the sensitivity of the core antigen assay was lower than PCR, the dynamic range was broader than that of the PCR assay, so that we did not need to dilute the samples in 59 patients. We detected serial decline of core Ag levels in 24 hrs, 7 days and 14 days after interferon combination therapy. The decline of core antigen levels was significant in SVR patients compared to non-SVR as well as in genotype 2a, 2b patients compared to 1b. Core antigen-negative on day 1 could predict all 10 SVR patients (PPV = 100%), whereas RNA-negative could predict 22 SVR out of 25 on day 14 (PPV = 88.0%). None of the patients who had detectable serum core antigen on day 14 became SVR(NPV = 100%), although NPV was 91.2% on RNA negativity. An easy, simple, low cost new HCV core antigen detecting system seems to be useful for assessing and monitoring IFN treatment for HCV.

149 HCV AND lymphoma: Genetic and epigenetic factors

PubMed Central

Zignego, AL; Gragnani, L; Fognani, E; Piluso, A

2014-01-01

Over 180 million people worldwide are chronically infected with the hepatitis C virus (HCV). HCV infection is a major cause for hepatocellular carcinoma (HCC), moreover the association with B-cell lymphoproliferative disorders (LPDs) like mixed cryoglobulinemia (MC) or B-cell non-Hodgkin lymphoma (B-NHL) is undisputed. The mechanisms by which HCV contributes to LPD development are still poorly understood. Available data suggest that the viral infection may induce LPDs through a multifactorial and multistep process that involves the sustained activation of B cells, the abnormal and prolonged B cell survival, and genetic and/or epigenetic factors. Concerning genetic factors, different authors reported an association between specific HLA clusters or B-cell activating factor promoter genotype and a higher risk of developing MC and lymphoma. In addition, the results of a large, ongoing genome wide association study (GWAS) will probably allow the identification of specific genetic profile of HCV patients with LPDs. Furthermore, microRNAs (miRNAs) can give a major contribution to the pathogenesis of several neoplastic, lymphoproliferative diseases and it is conceivable their involvement in the pathogenesis of HCV-related LPDs. We recently showed that specific miRNAs were differently modulated in PBMCs from HCV patients who developed MC and/or NHL. In addition, HCV patients who developed HCC, showed a differential miRNAs regulation. In conclusion, available data suggest that the genetic/epigenetic analysis of HCV-related cancerogenesis is of great usefulness in both the pathogenetic and clinical/translational areas possibly allowing the definition of diagnostic/prognostic markers for early detection of lymphatic or hepatic cancer.

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

PubMed

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.

Comparison of the Bayer VERSANT HCV RNA 3.0 and the Roche COBAS Amplicor HCV Monitor, Version 2.0, assays in HCV genotype 4 infection.

PubMed

Jessner, W; Watkins-Riedel, T; Müller, C; Formann, E; Gschwantler, M; Ferenci, P

2007-11-01

Prediction of treatment response is clinically important in chronic hepatitis C virus (HCV) genotype 4 infection. Early viral kinetics is useful in this respect for genotype 1 but interpretation is dependent on assay linearity and reproducibility. The VERSANT HCV RNA 3.0 (bDNA-3.0) and the COBAS Amplicor HCV Monitor 2.0 (HCM-2.0) have been widely used quantitative assays. We wanted to comparatively evaluate the two tests in a large genotype 4 sample. Genotyping was performed by NS5b sequencing. Viral load was tested in parallel in 32 patients at least six times on antiviral therapy with interferon alpha (IFNalpha). Totally, 198 samples within a quantitative range from undetectable to about 7 x 10(6) IU/mL (bDNA-3.0) were obtained and compared. Twenty-two samples with viral load above 500 000 IU/mL tested by HCM-2.0 were 1:100 diluted and retested. Quantitative values were fitted to a third order polynomial (M = 0.118303 + 1.07503 x V+ 0.0112128 x V(2) - 0.0055504 x V(3); M...HCM-2.0, V...bDNA-3.0, both log IU/mL) showing progressive nonlinearity of HCM-2.0 above 100 000 IU/mL but better clinical sensitivity with respect to bDNA-3.0. Dilution lead to a gain of at least a factor of 2.7 and thus, overestimation compared with bDNA-3.0. Deviation from linearity and overestimation upon dilution by HCM-2.0 are similar with HCV genotype 4, compared with other HCV genotypes. Differences in test performance were not detected for subtypes but for individual patients possibly related to specific quasi-species patterns. The interpretation of viral kinetic data becomes difficult due to overestimation upon dilution of baseline values by HCM-2.0.

Effect of HCV, HIV and coinfection in kidney transplant recipients: mate kidney analyses.

PubMed

Xia, Y; Friedmann, P; Yaffe, H; Phair, J; Gupta, A; Kayler, L K

2014-09-01

Reports of kidney transplantation (KTX) in recipients with hepatitis C virus (HCV+), human immunodeficiency virus (HIV+) or coinfection often do not provide adequate adjustment for donor risk factors. We evaluated paired deceased-donor kidneys (derived from the same donor transplanted to different recipients) in which one kidney was transplanted into a patient with viral infection (HCV+, n = 1700; HIV+, n = 243) and the other transplanted into a recipient without infection (HCV- n = 1700; HIV- n = 243) using Scientific Registry of Transplant Recipients data between 2000 and 2013. On multivariable analysis (adjusted for recipient risk factors), HCV+ conferred increased risks of death-censored graft survival (DCGS) (adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.04-1.47) and patient survival (aHR 1.24, 95% CI 1.06-1.45) compared with HCV-. HIV+ conferred similar DCGS (aHR 0.85, 95% CI 0.48-1.51) and patient survival (aHR 0.80, 95% CI 0.39-1.64) compared with HIV-. HCV coinfection was a significant independent risk factor for DCGS (aHR 2.33; 95% CI 1.06, 5.12) and patient survival (aHR 2.88; 95% CI 1.35, 6.12). On multivariable analysis, 1-year acute rejection was not associated with HCV+, HIV+ or coinfection. Whereas KTX in HIV+ recipients were associated with similar outcomes relative to noninfected recipients, HCV monoinfection and, to a greater extent, coinfection were associated with poor patient and graft survival. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Genotype diversity of hepatitis C virus (HCV) in HCV-associated liver disease patients in Indonesia.

PubMed

Utama, Andi; Tania, Navessa Padma; Dhenni, Rama; Gani, Rino Alvani; Hasan, Irsan; Sanityoso, Andri; Lelosutan, Syafruddin A R; Martamala, Ruswhandi; Lesmana, Laurentius Adrianus; Sulaiman, Ali; Tai, Susan

2010-09-01

Hepatitis C virus (HCV) genotype distribution in Indonesia has been reported. However, the identification of HCV genotype was based on 5'-UTR or NS5B sequence. This study was aimed to observe HCV core sequence variation among HCV-associated liver disease patients in Jakarta, and to analyse the HCV genotype diversity based on the core sequence. Sixty-eight chronic hepatitis (CH), 48 liver cirrhosis (LC) and 34 hepatocellular carcinoma (HCC) were included in this study. HCV core variation was analysed by direct sequencing. Alignment of HCV core sequences demonstrated that the core sequence was relatively varied among the genotype. Indeed, 237 bases of the core sequence could classify the HCV subtype; however, 236 bases failed to differentiate several subtypes. Based on 237 bases of the core sequences, the HCV strains were classified into genotypes 1 (subtypes 1a, 1b and 1c), 2 (subtypes 2a, 2e and 2f) and 3 (subtypes 3a and 3k). The HCV 1b (47.3%) was the most prevalent, followed by subtypes 1c (18.7%), 3k (10.7%), 2a (10.0%), 1a (6.7%), 2e (5.3%), 2f (0.7%) and 3a (0.7%). HCV 1b was the most common in all patients, and the prevalence increased with the severity of liver disease (36.8% in CH, 54.2% in LC and 58.8% in HCC). These results were similar to a previous report based on NS5B sequence analysis. Hepatitis C virus core sequence (237 bases) could identify the HCV subtype and the prevalence of HCV subtype based on core sequence was similar to those based on the NS5B region.

Evaluation of third generation anti-HCV enzyme immunoassays.

PubMed

Panigrahi, A K; Nayak, B; Dixit, R; Acharya, S K; Panda, S K

1998-01-01

The Hepatitis C Virus (HCV) is a major cause of post transfusion hepatitis. The introduction of HCV antibody screening has reduced the risk of post transfusion hepatitis significantly. However, the test is yet to be used routinely in blood banks of several developing countries with limited resources. We have developed an Enzyme immunoassay using synthetic peptides. The test was compared to seven commercial tests available in the Indian market. The test was evaluated using a panel of 90 sera which were chosen from an earlier panel based on detection of HCV RNA by Reverse Transcription Polymerase Chain Reaction RT-PCR. In case of any discrepancy the sera were further analysed by Line immunoassay (LIA). The sensitivity of the in house EIA was 90%. The specificity of the commercial EIAs varied.

HCV knowledge among a sample of HCV positive Aboriginal Australians residing in New South Wales.

PubMed

Wilson, Hannah; Brener, Loren; Jackson, L Clair; Saunders, Veronica; Johnson, Priscilla; Treloar, Carla

2017-06-01

Australian Aboriginal and Torres Strait Islanders are overrepresented in both the prevalence and incidence of the hepatitis C (HCV). HCV knowledge has been associated with a range of positive health behaviours. HCV knowledge has previously been investigated as a single construct; however examining different knowledge domains (i.e. transmission, risk of complications, testing and treatment) separately may be beneficial. This study investigated whether having greater HCV knowledge in different domains is associated with self-reported positive health behaviours. 203 Aboriginal people living with HCV completed a survey assessing HCV knowledge, testing and care, lifestyle changes since diagnosis and treatment intent. Respondents' knowledge was relatively high. Greater knowledge of risk of health complications was associated with undertaking more positive lifestyle changes since diagnosis. Respondents testing and treatment knowledge was significantly associated with incarceration, lifestyle changes since diagnosis and future treatment intentions. This study illustrates the importance of ensuring that knowledge is high across different HCV domains to optimise a range of positive health behaviours of Aboriginal people living with HCV. Future health promotion campaigns targeted at Aboriginal people living with HCV could benefit from broadening their focus from prevention to other domains such as testing and treatment.

Hepatitis C virus acquisition among Egyptians: analysis of a 10-year surveillance of acute hepatitis C.

PubMed

Mohsen, Amira; Bernier, Adeline; LeFouler, Lenaig; Delarocque-Astagneau, Elisabeth; El-Daly, Mai; El-Kafrawy, Sherif; El-Mango, Salwa; Abdel-Hamid, Mohamed; Gadallah, Mohsen; Esmat, Gamal; Mohamed, Mostafa K; Fontanet, Arnaud

2015-01-01

To identify current risk factors for hepatitis C virus (HCV) acquisition among Egyptians. Patients with acute HCV were identified through a surveillance system of acute hepatitis in four fever hospitals in Egypt between 2002 and 2012. Case-control analysis was conducted, cases being incident acute symptomatic HCV and controls being acute hepatitis A identified at the same hospitals. The questionnaire covered iatrogenic, community and household exposures to HCV in the 1-6 months prior to onset of symptoms. Multivariate models were built to identify risk factors associated with HCV acquisition among non-drug users and drug users separately. Among non-drug users, hospital admission was independently associated with acute HCV infection (OR = 4.2, 95% CI = 1.7-10.5). Several iatrogenic procedures, for example admission in a surgery unit, sutures, IV injections and IV infusions, highly correlated with hospital admission, were also associated with acute HCV infection and could have been used in the final model instead of hospital admission. Among drug users, identified risk factors were multiple sexual relations (OR = 4.0, 95% CI = 1.1-14.7), intravenous drug use (OR = 3.9, 95% CI = 1.2-13.0) and shaving at the barbershops (OR = 8.7, 95% CI = 2.4-31.4). Illiteracy and marriage were significant risk factors in both groups. Invasive medical procedures are still a major risk for acquiring new HCV infections in Egypt, as is illicit drug use in spreading HCV infection. © 2014 John Wiley & Sons Ltd.

Quantification of HCV RNA in Clinical Specimens by Branched DNA (bDNA) Technology.

PubMed

Wilber, J C; Urdea, M S

1999-01-01

The diagnosis and monitoring of hepatitis C virus (HCV) infection have been aided by the development of HCV RNA quantification assays A direct measure of viral load, HCV RNA quantification has the advantage of providing information on viral kinetics and provides unique insight into the disease process. Branched DNA (bDNA) signal amplification technology provides a novel approach for the direct quantification of HCV RNA in patient specimens. The bDNA assay measures HCV RNA at physiological levels by boosting the reporter signal, rather than by replicating target sequences as the means of detection, and thus avoids the errors inherent in the extraction and amplification of target sequences. Inherently quantitative and nonradioactive, the bDNA assay is amenable to routine use in a clinical research setting, and has been used by several groups to explore the natural history, pathogenesis, and treatment of HCV infection.

Persistence of Circulating Hepatitis C Virus Antigens-Specific Immune Complexes in Patients with Resolved HCV Infection.

PubMed

Hu, Ke-Qin; Cui, Wei

2018-05-01

Our recent study indicated the possible presence of detectable hepatitis C virus antigens (HCV-Ags) after denaturation of sera with resolved HCV (R-HCV) infection. The present study determined and characterized persistent HCV-Ags-specific immune complexes (ICs) in these patients. Sixty-eight sera with R-HCV and 34 with viremic HCV (V-HCV) infection were tested for free and IC-bound HCV-Ags using HCV-Ags enzyme immunoassay (EIA), the presence of HCV-Ags-specific ICs by immunoprecipitation and Western blot (IP-WB), HCV ICs containing HCV virions using IP and HCV RNA RT-PCR, and correlation of HCV ICs with clinical presentation in these patients. Using HCV-Ags EIA, we found 57.4% of sera with R-HCV infection were tested positive for bound, but not free HCV-Ags. Using pooled or individual anti-HCV E1/E2, cAg, NS3, NS4b, and/or NS5a to precipitate HCV-specific-Ags, we confirmed persistent HCV-Ags ICs specific to various HCV structural and non-structural proteins not only in V-HCV infection, but also in R-HCV infection. Using IP and HCV RNA PCR, we then confirmed the presence of HCV virions within circulating ICs in V-HCV, but not in R-HCV sera. Multivariable analysis indicated significant and independent associations of persistent circulating HCV-Ags-specific ICs with both age and the presence of cirrhosis in patients with R-HCV infection. Various HCV-Ag-specific ICs, but not virions, persist in 57.4% of patients who had spontaneous or treatment-induced HCV clearance for 6 months to 20 years. These findings enriched our knowledge on HCV pathogenesis and support further study on its long-term clinical relevance, such as extrahepatic manifestation, transfusion medicine, and hepatocarcinogenesis.

Acute hepatitis A virus infection is associated with a limited type I interferon response and persistence of intrahepatic viral RNA.

PubMed

Lanford, Robert E; Feng, Zongdi; Chavez, Deborah; Guerra, Bernadette; Brasky, Kathleen M; Zhou, Yan; Yamane, Daisuke; Perelson, Alan S; Walker, Christopher M; Lemon, Stanley M

2011-07-05

Hepatitis A virus (HAV) is an hepatotropic human picornavirus that is associated only with acute infection. Its pathogenesis is not well understood because there are few studies in animal models using modern methodologies. We characterized HAV infections in three chimpanzees, quantifying viral RNA by quantitative RT-PCR and examining critical aspects of the innate immune response including intrahepatic IFN-stimulated gene expression. We compared these infection profiles with similar studies of chimpanzees infected with hepatitis C virus (HCV), an hepatotropic flavivirus that frequently causes persistent infection. Surprisingly, HAV-infected animals exhibited very limited induction of type I IFN-stimulated genes in the liver compared with chimpanzees with acute resolving HCV infection, despite similar levels of viremia and 100-fold greater quantities of viral RNA in the liver. Minimal IFN-stimulated gene 15 and IFIT1 responses peaked 1-2 wk after HAV challenge and then subsided despite continuing high hepatic viral RNA. An acute inflammatory response at 3-4 wk correlated with the appearance of virus-specific antibodies and apoptosis and proliferation of hepatocytes. Despite this, HAV RNA persisted in the liver for months, remaining present long after clearance from serum and feces and revealing dramatic differences in the kinetics of clearance in the three compartments. Viral RNA was detected in the liver for significantly longer (35 to >48 wk) than HCV RNA in animals with acute resolving HCV infection (10-20 wk). Collectively, these findings indicate that HAV is far stealthier than HCV early in the course of acute resolving infection. HAV infections represent a distinctly different paradigm in virus-host interactions within the liver.

Micro-RNA-122 levels in acute liver failure and chronic hepatitis C.

PubMed

Dubin, Perry H; Yuan, Hejun; Devine, Robert K; Hynan, Linda S; Jain, Mamta K; Lee, William M

2014-09-01

MicroRNA-122 (miR-122) is the foremost liver-related micro-RNA, but its role in the hepatocyte is not fully understood. To evaluate whether circulating levels of miR-122 are elevated in chronic-HCV for a reason other than hepatic injury, we compared serum level in patients with chronic hepatitis C to other forms of liver injury including patients with acute liver failure and healthy controls. MiR-122 was quantitated using sera from 35 acute liver failure patients (20 acetaminophen-induced, 15 other etiologies), 39 chronic-HCV patients and 12 controls. In parallel, human genomic DNA (hgDNA) levels were measured to reflect quantitatively the extent of hepatic necrosis. Additionally, six HIV-HCV co-infected patients, who achieved viral clearance after undergoing therapy with interferon and ribavirin, had serial sera miR-122 and hgDNA levels measured before and throughout treatment. Serum miR-122 levels were elevated approximately 100-fold in both acute liver failure and chronic-HCV sera as compared to controls (P < 0.001), whereas hgDNA levels were only elevated in acute liver failure patients as compared to both chronic-HCV and controls (P < 0.001). Subgroup analysis showed that chronic-HCV sera with normal aminotransferase levels showed elevated miR-122 despite low levels of hepatocyte necrosis. All successfully treated HCV patients showed a significant Log10 decrease in miR-122 levels ranging from 0.16 to 1.46, after sustained viral response. Chronic-HCV patients have very elevated serum miR-122 levels in the range of most patients with severe hepatic injury leading to acute liver failure. Eradication of HCV was associated with decreased miR-122 but not hgDNA. An additional mechanism besides hepatic injury may be active in chronic-HCV to explain the exaggerated circulating levels of miR-122 observed. © 2014 Wiley Periodicals, Inc.

Successful treatment of HCV/HBV/HDV-coinfection with pegylated interferon and ribavirin

PubMed Central

Hartl, Janine; Ott, Claudia; Kirchner, Gabriele; Salzberger, Bernd; Wiest, Reiner

2012-01-01

Dual and triple infections with hepatitis virus C (HCV), B (HBV) and D (HDV) frequently lead to severe liver damage. Hereby we describe a 38-year-old Caucasian male coinfected with HCV (genotype 3a), HBV [positive hepatitis B surface antigen (HbsAg) and antibody to hepatitis B core antigen; negative hepatitis B e antigen (HbeAg) and antibody to hepatitis B e antigen (anti-HBe)] and HDV. Laboratory diagnostics revealed increased liver enzymes and histological examination of the liver showed signs of fibrosis with moderate inflammation. On therapy with pegIFN-α2b and ribavirin HCV-RNA was undetectable at week 8. After week 24 the antiviral therapy was stopped because of a HBs-seroconversion, the loss of HbeAg and the detection of anti-HBe. Furthermore the HCV-RNA was negative. Six months after successful treatment of the triple-infection, HCV- and HDV-RNA and HbsAg remained negative and the liver enzymes had been completely normalized. In conclusion, pegylated-interferon plus ribavirin may be an effective therapy for HCV, HBV and HDV-coinfected patients. PMID:24765463

High false-negative rate of anti-HCV among Egyptian patients on regular hemodialysis.

PubMed

El-Sherif, Assem; Elbahrawy, Ashraf; Aboelfotoh, Atef; Abdelkarim, Magdy; Saied Mohammad, Abdel-Gawad; Abdallah, Abdallah Mahmoud; Mostafa, Sadek; Elmestikawy, Amr; Elwassief, Ahmed; Salah, Mohamed; Abdelbaseer, Mohamed Ali; Abdelwahab, Kouka Saadeldin

2012-07-01

Routine serological testing for hepatitis C virus (HCV) infection among hemodialysis (HD) patients is currently recommended. A dilemma existed on the value of serology because some investigators reported a high rate of false-negative serologic testing. In this study, we aimed to detect the false-negative rate of anti-HCV among Egyptian HD patients. Seventy-eight HD patients, negative for anti-HCV, anti-HIV, and hepatitis B surface antigen, were tested for HCV RNA by reverse transcriptase polymerase chain reaction (RT-PCR). In the next step, the viral load was quantified by real-time PCR in RT-PCR-positive patients. Risk factors for HCV infection, as well as clinical and biochemical indicators of liver disease, were compared between false-negative and true-negative anti-HCV HD patients. The frequency of false-negative anti-HCV was 17.9%. Frequency of blood transfusion, duration of HD, dialysis at multiple centers, and diabetes mellitus were not identified as risk factors for HCV infection. The frequency of false-negative results had a linear relation to the prevalence of HCV infection in the HD units. Timely identification of HCV within dialysis units is needed in order to lower the risk of HCV spread within the HD units. The high false-negative rate of anti-HCV among HD patients in our study justifies testing of a large scale of patients for precious assessment of effectiveness of nucleic acid amplification technology testing in screening HD patient. © 2012 The Authors. Hemodialysis International © 2012 International Society for Hemodialysis.

HCV Prevalence in Asian Americans in California.

PubMed

Lin, Oliver N; Chang, Christine; Lee, Joyce; Do, Ailinh; Martin, Marina; Martin, Andy; Nguyen, Mindie H

2017-02-01

The World Health Organization estimates that 170 million persons are infected with HCV worldwide, but only 22 million are from the Americas and Europe, compared to 94 million from Asia. HCV prevalence in the general US population is 1.6 %, but data for Asian Americans are limited. Our goal was to examine HCV prevalence in Asian Americans in a large ethnically diverse patient cohort seeking primary care at a free clinic in Northern California. A total of 1347 consecutive patients were seen from September 2009 to October 2012 and were studied via individual chart review using case report forms. HCV infection was defined as positive HCV antibody (anti-HCV) or HCV RNA by PCR. 699 out of 1347 patients were screened for HCV. Asian Americans comprised 57.2 % of these patients and 29 (4.1 %) patients tested positive for HCV. Of these 29 HCV-positive patients, 22 (75.9 %) were Asian, yielding a prevalence of 5.5 % for Asians and 2.3 % for non-Asians (P = 0.038). The highest HCV prevalence was seen in Vietnamese patients at 7.9 %, and 6.0 % in Chinese patients. Of the HCV-positive Asians, none had a history of intravenous drug use (IVDU), tattoos, or sexual exposure. On multivariate analysis, significant independent predictors for positive HCV infection were male gender (OR 2.53, P = 0.02) and presence of known risk factors (OR 21.1, P < 0.001). However, older age and Asian ethnicity were found to be significant predictors of HCV infection (OR 1.03, P = 0.05 and 2.31, P = 0.066, respectively). In our study, HCV prevalence in patients seeking routine primary care was 5.5 % in Asian Americans, which was over double the prevalence for non-Asians at 2.3 %. Known risk factors were also notably absent in Asian patients with HCV infection. The high prevalence of HCV in Asian-Americans is likely reflective of the higher prevalence of HCV in their countries of origin in Asia. Asian-Americans immigrants from endemic countries are at higher risk of HCV infection

Cost-effectiveness of rapid HCV testing and simultaneous rapid HCV and HIV testing in substance abuse treatment programs

PubMed Central

Schackman, Bruce R.; Leff, Jared A.; Barter, Devra M.; DiLorenzo, Madeline A.; Feaster, Daniel J.; Metsch, Lisa R.; Freedberg, Kenneth A.; Linas, Benjamin P.

2014-01-01

Aims To evaluate the cost-effectiveness of rapid hepatitis C virus (HCV) and simultaneous HCV/HIV antibody testing in substance abuse treatment programs. Design We used a decision analytic model to compare the cost-effectiveness of no HCV testing referral or offer, off-site HCV testing referral, on-site rapid HCV testing offer, and on-site rapid HCV and HIV testing offer. Base case inputs included 11% undetected chronic HCV, 0.4% undetected HIV, 35% HCV co-infection among HIV-infected, 53% linked to HCV care after testing antibody positive, and 67% linked to HIV care. Disease outcomes were estimated from established computer simulation models of HCV (HEP-CE) and HIV (CEPAC). Setting and Participants Data on test acceptance and costs were from a national randomized trial of HIV testing strategies conducted at 12 substance abuse treatment programs in the USA. Measurements Lifetime costs (2011 US dollars) and quality-adjusted life years (QALYs) discounted at 3% annually; incremental cost-effectiveness ratios (ICERs) Findings On-site rapid HCV testing had an ICER of $18,300/QALY compared with no testing, and was more efficient than (dominated) off-site HCV testing referral. On-site rapid HCV and HIV testing had an ICER of $64,500/QALY compared with on-site rapid HCV testing alone. In one and two-way sensitivity analyses, the ICER of on-site rapid HCV and HIV testing remained <$100,000/QALY, except when undetected HIV prevalence was <0.1% or when we assumed frequent HIV testing elsewhere. The ICER remained <$100,000/QALY in approximately 90% of probabilistic sensitivity analyses. Conclusions On-site rapid hepatitis C virus and HIV testing in substance abuse treatment programs is cost-effective at a <$100,000/ quality-adjusted life years threshold. PMID:25291977

HIV/HCV Coinfection in Taiwan.

PubMed

Hsu, Ching-Sheng; Kao, Jia-Horng

2016-01-01

Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection are important global public health problems with shared transmission routes. Although HIV/HCV coinfection is not uncommon, the prevalence rates vary significantly across different studies and regions. In Taiwan, injection drug users have become the major contributors to the HIV/AIDS epidemic since 2005. Because the prevalence of HCV infection is high in injection drug users, this HIV epidemic is also associated with a significant increase of HIV/HCV coinfection in Taiwan. To control Taiwan's HIV epidemic, Taiwan Centers for Disease Control (CDC) launched a harm-reduction program in 2006. The HIV epidemic, the percentage attributed to injection drug users, and the prevalence of HIV/HCV coinfection gradually declined thereafter. In this article, we aimed to thoroughly examine the current literatures of HIV/HCV coinfection in Taiwan and hope to provide a better understanding of the needs for the management of this coinfection. We conducted a narrative review and searched for literature from PubMed, Ovid MEDLINE, and the Cochrane Library database untill August 2015. Studies relevant to the epidemiology and associated risk factors of HIV/HCV coinfection in Taiwan were examined and discussed.

An OPTIMIZE study retrospective analysis for management of telaprevir-treated hepatitis C virus (HCV)-infected patients by use of the Abbott RealTime HCV RNA assay.

PubMed

Sarrazin, Christoph; Dierynck, Inge; Cloherty, Gavin; Ghys, Anne; Janssen, Katrien; Luo, Donghan; Witek, James; Buti, Maria; Picchio, Gaston; De Meyer, Sandra

2015-04-01

Protease inhibitor (PI)-based response-guided triple therapies for hepatitis C virus (HCV) infection are still widely used. Noncirrhotic treatment-naive and prior relapser patients receiving telaprevir-based treatment are eligible for shorter, 24-week total therapy if HCV RNA is undetectable at both weeks 4 and 12. In this study, the concordance in HCV RNA assessments between the Roche High Pure System/Cobas TaqMan and Abbott RealTime HCV RNA assays and the impacts of different HCV RNA cutoffs on treatment outcome were evaluated. A total of 2,629 samples from 663 HCV genotype 1 patients receiving telaprevir/pegylated interferon/ribavirin in OPTIMIZE were analyzed using the High Pure System and reanalyzed using Abbott RealTime (limits of detection, 15.1 IU/ml versus 8.3 IU/ml; limits of quantification, 25 IU/ml versus 12 IU/ml, respectively). Overall, good concordance was observed between the assays. Using undetectable HCV RNA at week 4, 34% of the patients would be eligible for shorter treatment duration with Abbott RealTime versus 72% with the High Pure System. However, using <12 IU/ml for Abbott RealTime, a similar proportion (74%) would be eligible. Of the patients receiving 24-week total therapy, 87% achieved a sustained virologic response with undetectable HCV RNA by the High Pure System or <12 IU/ml by Abbott RealTime; however, 92% of the patients with undetectable HCV RNA by Abbott RealTime achieved a sustained virologic response. Using undetectable HCV RNA as the cutoff, the more sensitive Abbott RealTime assay would identify fewer patients eligible for shorter treatment than the High Pure System. Our data confirm the <12-IU/ml cutoff, as previously established in other studies of the Abbott RealTime assay, to determine eligibility for shortened PI-based HCV treatment. (The study was registered with ClinicalTrials.gov under registration no. NCT01241760.). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Active co-infection with HBV and/or HCV in South African HIV positive patients due for cancer therapy.

PubMed

Musyoki, Andrew M; Msibi, Thembeni L; Motswaledi, Mojakgomo H; Selabe, Selokela G; Monokoane, Tshweu S; Mphahlele, M Jeffrey

2015-02-01

Human immunodeficiency virus (HIV), Hepatitis B virus (HBV) and Hepatitis C virus (HCV) share routes of transmission. There is limited data on the incidence of active co-infection with HBV and/or HCV in cancer patients infected with HIV in Africa. This was a prospective study based on 34 patients with varied cancer diagnosis, infected with HIV and awaiting cancer therapy in South Africa. HIV viral load, CD4+ cell counts, Alanine-aminotransferase and aspartate aminotransferase levels were tested. Exposure to HBV and HCV was assessed serologically using commercial kits. Active HBV and/or HCV co-infection was detected using viral specific nested PCR assays. HCV 5'-UTR PCR products were sequenced to confirm active HCV infection. Active viral infection was detected in 64.7% of patients for HBV, 38.2% for HCV, and 29.4% for both HBV and HCV. Occult HBV infection was observed in 63.6% of the patients, while seronegative HCV infection was found in 30.8% of patients. In addition, CD4+ cell count < 350 cells/µl was not a risk factor for increased active HBV, HCV or both HBV and HCV co-infections. A total of 72.7%, 18.2% and 9.1% of the HCV sequences were assigned genotype 5, 1 and 4 respectively.The study revealed for the first time a high active HBV and/or HCV co-infection rate in cancer patients infected with HIV. The findings call for HBV and HCV testing in such patients, and where feasible, appropriate antiviral treatment be indicated, as chemotherapy or radiotherapy has been associated with reactivation of viral hepatitis and termination of cancer therapy. © 2014 Wiley Periodicals, Inc.

[The epidemiological trends connected with detection of HIV, HCV, HBV and syphilis markers in blood donors in the years 2006-2009].

PubMed

Rudowska, Ewa; Basta, Lidia; Piwowarska, Grazyna; Drybańska, Bozena; Dylag, Stanisław

2011-03-01

In the recent years a great progress has been documented in infection prevention. There is more possibilities responsible for infection and its transmission. To analyze obtained epidemiological data concerned to detected infection in blood donors in the area of Blood Bank in Katowice in the years 2006-2009. Statistic calculations taking account of confirmed infections in the years 2006-2009 were analyzed in first-time donors and multiple donors, and for all donors. Tests confirming infection were performed in the IHiT in Warsaw, in RBC in Katowice, confirmation test for syphilis in the RBC in Warsaw. Only the positive confirmed results are taken into account and presented in summary. In first-time donors more frequently the markers of infection: HCV and HBV dozens of times, HIV and syphilis several times were detected. In the group of first-time donors a downward trend was detected in the number of detected infections HBV and HCV In the group of multiple donors the downward trend was documented in the number of detected antibodies associated to syphilis. In the group of multiple donors the number of detected HIV infections has been increased in the years 2008 and 2009. For monitoring trends of each type of infections, a period of four-years is not sufficiently long. This data needs a further observations.

Packaging of HCV-RNA into lentiviral vector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caval, Vincent; Piver, Eric; Service de Biochimie et Biologie Moleculaire, CHRU de Tours

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 andmore » 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.« less

Tim-3 expression on PD-1+ HCV-specific human CTLs is associated with viral persistence, and its blockade restores hepatocyte-directed in vitro cytotoxicity

PubMed Central

McMahan, Rachel H.; Golden-Mason, Lucy; Nishimura, Michael I.; McMahon, Brian J.; Kemper, Michael; Allen, Todd M.; Gretch, David R.; Rosen, Hugo R.

2010-01-01

Having successfully developed mechanisms to evade immune clearance, hepatitis C virus (HCV) establishes persistent infection in approximately 75%–80% of patients. In these individuals, the function of HCV-specific CD8+ T cells is impaired by ligation of inhibitory receptors, the repertoire of which has expanded considerably in the past few years. We hypothesized that the coexpression of the negative regulatory receptors T cell immunoglobulin and mucin domain–containing molecule 3 (Tim-3) and programmed death 1 (PD-1) in HCV infection would identify patients at risk of developing viral persistence during and after acute HCV infection. The frequency of PD-1–Tim-3– HCV-specific CTLs greatly outnumbered PD-1+Tim-3+ CTLs in patients with acute resolving infection. Moreover, the population of PD-1+Tim-3+ T cells was enriched for within the central memory T cell subset and within the liver. Blockade of either PD-1 or Tim-3 enhanced in vitro proliferation of HCV-specific CTLs to a similar extent, whereas cytotoxicity against a hepatocyte cell line that expressed cognate HCV epitopes was increased exclusively by Tim-3 blockade. These results indicate that the coexpression of these inhibitory molecules tracks with defective T cell responses and that anatomical differences might account for lack of immune control of persistent pathogens, which suggests their manipulation may represent a rational target for novel immunotherapeutic approaches. PMID:21084749

Anti-HCV immunoblot indeterminate results in blood donors: non-specific reactivity or past exposure to HCV?

PubMed

Kiely, P; Styles, C

2017-08-01

The significance of anti-HCV immunoblot (IB) indeterminate results can be difficult to determine. We analysed results for blood donors tested on the MP Diagnostics HCV Blot 3.0 IB assay to determine whether indeterminate results representing past exposure to HCV could be distinguished from those due to non-specific reactivity. Results for all donors tested by IB during the study period (July 2010 to December 2013) were included in this study. Of 131 donors tested by IB, 34 (26.0%) were negative, 38 (29.0%) were indeterminate, and 59 (45.0%) were positive. There was no significant difference in IB band reactivity strength between indeterminate and positive donors. The PRISM HCV chemiluminescent immunoassay (ChLIA) sample to cut-off (s/co) ratio distribution for the indeterminate donors was significantly higher than for those with biological false reactivity (P = 0·037), but significantly lower than for donors who were IB positive/HCV RNA negative (P < 0·001) or IB not tested/HCV RNA positive (P < 0·001). Of donors available for follow-up, 53.1% of the indeterminate group disclosed a putative risk factor for HCV infection compared to 39.4% (P < 0·001) for the IB-negative group, 76.6% (P = 0·065) for the IB-positive group and 83.4% (P < 0·001) for the HCV RNA-positive group. The results of this study indicate that PRISM ChLIA s/co ratios >2·00 with IB indeterminate results predict exposure to HCV, particularly in the presence of putative risk factors for HCV infection. These findings may be applied to optimizing counselling of donors with indeterminate HCV results. © 2017 International Society of Blood Transfusion.

Utility of the Abbott RealTime HCV Genotype Plus RUO assay used in combination with the Abbott RealTime HCV Genotype II assay.

PubMed

He, Chao; Germer, Jeffrey J; Ptacek, Elizabeth R; Bommersbach, Carl E; Mitchell, P Shawn; Yao, Joseph D C

Hepatitis virus C (HCV) genotype (GT) determination and subtype (ST) differentiation (1a versus 1b) remain important for the selection of appropriate direct-acting antiviral (DAA) therapy. This study is a retrospective comparison of HCV GT and ST result distribution when using the Abbott RealTime HCV Genotype II assay (HCVGT II) alone and in combination with the Abbott RealTime HCV Genotype Plus RUO assay (HCVGT Plus) for routine testing of clinical serum specimens at a reference laboratory. HCVGT II results of specimens tested from June 2014 through January 2016 (period 1) were compared with combined results from HCVGT II and HCVGT Plus (HCVGT II/Plus) performed from January 2016 through January 2017 (period 2). A total of 44,127 and 25,361 specimens were tested during periods 1 and 2, respectively. Use of HCVGT II/Plus significantly reduced the frequency of GT 1 results without ST (0.4%) when compared to preliminary HCVGT II results during period 2 (5.3%; p < 0.01) and final HCVGT II results in period 1 (5.5%; p < 0.01). HCVGT II/Plus also resulted in GT 6 reactivity in 38 specimens with results of "HCV detected" (n = 17) or GT 1 (n = 21) following initial HCVGT II testing during period 2. When compared to the use of HCVGT II alone, HCVGT II/Plus significantly reduced the frequency of GT 1 without ST results observed in a large reference laboratory, while also enabling the identification of HCV GT 6. Copyright © 2018 Elsevier B.V. All rights reserved.

Performance evaluation of the Abbott RealTime HCV Genotype II for hepatitis C virus genotyping.

PubMed

Sohn, Yong-Hak; Ko, Sun-Young; Kim, Myeong Hee; Oh, Heung-Bum

2010-04-01

The Abbott RealTime hepatitis C virus (HCV) Genotype II (Abbott Molecular Inc.) for HCV genotyping, which uses real-time PCR technology, has recently been developed. Accuracy and sensitivity of detection were assessed using the HCV RNA PHW202 performance panel (SeraCare Life Sciences). Consistency with restriction fragment mass polymorphism (RFMP) data, cross-reactivity with other viruses, and the ability to detect minor strains in mixtures of genotypes 1 and 2 were evaluated using clinical samples. All performance panel viruses were correctly genotyped at levels of >500 IU/mL. Results were 100% concordant with RFMP genotypic data (66/66). However, 5% (3/66) of the samples examined displayed probable genotypic cross reactivity. No cross reactivity with other viruses was evident. Minor strains in the mixtures were not effectively distinguished, even at quantities higher than the detection limit. The Abbott RealTime HCV Genotype II assay was very accurate and yielded results consistent with RFMP data. Although the assay has the advantages of automation and short turnaround time, we suggest that further improvements are necessary before it is used routinely in clinical practice. Efforts are needed to decrease cross reactivity among genotypes and to improve the ability to detect minor genotypes in mixed infections.

European Multicenter Study on Analytical Performance of DxN Veris System HCV Assay.

PubMed

Braun, Patrick; Delgado, Rafael; Drago, Monica; Fanti, Diana; Fleury, Hervé; Gismondo, Maria Rita; Hofmann, Jörg; Izopet, Jacques; Kühn, Sebastian; Lombardi, Alessandra; Marcos, Maria Angeles; Sauné, Karine; O'Shea, Siobhan; Pérez-Rivilla, Alfredo; Ramble, John; Trimoulet, Pascale; Vila, Jordi; Whittaker, Duncan; Artus, Alain; Rhodes, Daniel W

2017-04-01

The analytical performance of the Veris HCV Assay for use on the new and fully automated Beckman Coulter DxN Veris Molecular Diagnostics System (DxN Veris System) was evaluated at 10 European virology laboratories. Precision, analytical sensitivity, specificity, and performance with negative samples, linearity, and performance with hepatitis C virus (HCV) genotypes were evaluated. Precision for all sites showed a standard deviation (SD) of 0.22 log 10 IU/ml or lower for each level tested. Analytical sensitivity determined by probit analysis was between 6.2 and 9.0 IU/ml. Specificity on 94 unique patient samples was 100%, and performance with 1,089 negative samples demonstrated 100% not-detected results. Linearity using patient samples was shown from 1.34 to 6.94 log 10 IU/ml. The assay demonstrated linearity upon dilution with all HCV genotypes. The Veris HCV Assay demonstrated an analytical performance comparable to that of currently marketed HCV assays when tested across multiple European sites. Copyright © 2017 American Society for Microbiology.

Distribution of Hepatitis C virus (HCV) genotypes in seropositive patients in the state of Alagoas, Brazil

PubMed Central

Gonzaga, Rosa Maria S.; Rodart, Itatiana F.; Reis, Mitermayer Galvão; Ramalho Neto, Cícero Eduardo; Silva, Denise Wanderlei

2008-01-01

We determined the frequency of hepatitis C virus (HCV) genotypes in anti-HCV seropositive patients in the state of Alagoas, Brazil, by means of nested-reverse transcription-polymerase chain reaction (RT-nested-PCR) followed by restriction fragment length polymorphism (RFLP) of amplified fragments of the 5´NCR. The nested-PCR with genotype-specific primers from the core region was carried out when detection was not possible by the first approach. Detectable HCV-RNA was present in 115 (74.7%) of 154 serum samples. Genotype 1 was the most frequent (77.4%), against 20.9% of genotype 3 and 0.8% of genotype 2. Subtype 1b was predominant (65.2%), followed by subtypes 1a (8.7%), and 3a (6.1%). Coinfection (1a/3a) was detected in 0.8% of the samples. Indeed, there was no significant differences in the prevalence of genotype 1 compared to what has been obtained from anti-HCV seropositive patients from other locations in Brazil. Here we report for the first time the genotype 2 in the state of Alagoas. PMID:24031281

Synthetic lipophilic antioxidant BO-653 suppresses HCV replication.

PubMed

Yasui, Fumihiko; Sudoh, Masayuki; Arai, Masaaki; Kohara, Michinori

2013-02-01

The influence of the intracellular redox state on the hepatitis C virus (HCV) life cycle is poorly understood. This study demonstrated the anti-HCV activity of 2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran (BO-653), a synthetic lipophilic antioxidant, and examined whether BO-653's antioxidant activity is integral to its anti-HCV activity. The anti-HCV activity of BO-653 was investigated in HuH-7 cells bearing an HCV subgenomic replicon (FLR3-1 cells) and in HuH-7 cells infected persistently with HCV (RMT-tri cells). BO-653 inhibition of HCV replication was also compared with that of several hydrophilic and lipophilic antioxidants. BO-653 suppressed HCV replication in FLR3-1 and RMT-tri cells in a concentration-dependent manner. The lipophilic antioxidants had stronger anti-HCV activities than the hydrophilic antioxidants, and BO-653 displayed the strongest anti-HCV activity of all the antioxidants examined. Therefore, the anti-HCV activity of BO-653 was examined in chimeric mice harboring human hepatocytes infected with HCV. The combination treatment of BO-653 and polyethylene glycol-conjugated interferon-α (PEG-IFN) decreased serum HCV RNA titer more than that seen with PEG-IFN alone. These findings suggest that both the lipophilic property and the antioxidant activity of BO-653 play an important role in the inhibition of HCV replication. Copyright © 2012 Wiley Periodicals, Inc.

CD8+ T cells of chronic HCV-infected patients express multiple negative immune checkpoints following stimulation with HCV peptides.

PubMed

Barathan, Muttiah; Mohamed, Rosmawati; Vadivelu, Jamuna; Chang, Li Yen; Vignesh, Ramachandran; Krishnan, Jayalakshmi; Sigamani, Panneer; Saeidi, Alireza; Ram, M Ravishankar; Velu, Vijayakumar; Larsson, Marie; Shankar, Esaki M

2017-03-01

Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease. Accumulation of exhausted HCV-specific T cells during chronic infection results in considerable loss of protective functional immune responses. The role of T-cell exhaustion in chronic HCV disease remains poorly understood. Here, we studied the frequency of HCV peptide-stimulated T cells expressing negative immune checkpoints (PD-1, CTLA-4, TRAIL, TIM-3 and BTLA) by flow cytometry, and measured the levels of Th1/Th2/Th17 cytokines secreted by T cells by a commercial Multi-Analyte ELISArray™ following in vitro stimulation of T cells using HCV peptides and phytohemagglutinin (PHA). HCV peptide-stimulated CD4+ and CD8+ T cells of chronic HCV (CHC) patients showed significant increase of CTLA-4. Furthermore, HCV peptide-stimulated CD4+ T cells of CHC patients also displayed relatively higher levels of PD-1 and TRAIL, whereas TIM-3 was up-regulated on HCV peptide-stimulated CD8+ T cells. Whereas the levels of IL-10 and TGF-β1 were significantly increased, the levels of pro-inflammatory cytokines IL-2, TNF-α, IL-17A and IL-6 were markedly decreased in the T cell cultures of CHC patients. Chronic HCV infection results in functional exhaustion of CD4+ and CD8+ T cells likely contributing to viral persistence. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2004-05-01

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

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

PubMed

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

2015-01-01

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 efficient infectious cell culture systems for these genotype 1a strains by using the HCV-1/SF9_A and H77C in vivo infectious clones. We initially adapted a genome with the HCV-1 5'UTR-NS5A (where UTR stands for untranslated region) and the JFH1 NS5B-3'UTR (5-5A recombinant), including the genotype 2a-derived mutations F1464L/A1672S/D2979G (LSG), to grow efficiently in Huh7.5 cells, thus identifying the E2 mutation S399F. The combination of LSG/S399F and reported TNcc(1a)-adaptive mutations A1226G/Q1773H/N1927T/Y2981F/F2994S promoted adaptation of the full-length HCV-1 clone. An HCV-1 recombinant with 17 mutations (HCV1cc) replicated efficiently in Huh7.5 cells and produced supernatant infectivity titers of 10(4.0) focus-forming units (FFU)/ml. Eight of these mutations were identified from passaged HCV-1 viruses, and the A970T/I1312V/C2419R/A2919T mutations were essential for infectious particle production. Using CD81-deficient Huh7 cells, we further demonstrated the importance of A970T/I1312V/A2919T or A970T/C2419R/A2919T for virus assembly and that the I1312V/C2419R combination played a major role in virus release. Using a similar approach, we found that NS5B mutation F2994R, identified here from culture-adapted full-length TN viruses and a common NS3 helicase mutation (S1368P) derived from viable H77C and HCV-1 5-5A recombinants, initiated replication and culture adaptation of H77C containing LSG and TNcc(1a)-adaptive mutations. An H77C recombinant harboring 19 mutations (H77Ccc) replicated and spread efficiently after transfection and subsequent infection of naive Huh7.5 cells, reaching titers of 10(3.5) and 10(4.4) FFU/ml, respectively. Hepatitis C virus (HCV) was discovered in 1989 with

HCV genotype 3 and squamous cell carcinoma antigen (SCCA)-IgM are independently associated with histological features of NASH in HCV-infected patients.

PubMed

Martini, A; Fattovich, G; Guido, M; Bugianesi, E; Biasiolo, A; Ieluzzi, D; Gallotta, A; Fassina, G; Merkel, C; Gatta, A; Negro, F; Pontisso, P

2015-10-01

Nonalcoholic steatohepatitis (NASH) enhances the risk of progressive liver disease. In chronic hepatitis C (CHC), liver steatosis is frequent, especially in genotype 3, but its clinical significance is debated. As squamous cell carcinoma antigen (SCCA)-IgM has been associated with advanced liver disease and risk of tumour development, we evaluated its occurrence in CHC and the possible relation with NASH at liver biopsy. Using a validated ELISA, serum SCCA-IgM was measured in 91 patients with CHC at the time of liver biopsy performed before antiviral treatment, at the end of treatment and 6 months thereafter, and in 93 HCV-negative patients with histological diagnosis of nonalcoholic fatty liver disease, as controls. SCCA-IgM was detected in 33% of CHC patients and in 4% of controls. This biomarker was found more elevated in CHC patients with histological NASH, and at multivariate analysis, SCCA-IgM and HCV genotype 3 were independently associated with NASH [OR (95% CI): 6.94 (1.21-40) and 27.02 (4.44-166.6)]. As predictors of NASH, HCV genotype 3 and SCCA-IgM had a specificity and a sensitivity of 97% and 44%, and of 95% and 27%, respectively. PPV and NPV were 80% and 86% for HCV genotype 3 vs 73% and 72% for SCCA-IgM. In patients with sustained virologic response to therapy, SCCA-IgM levels decreased significantly, while these remained unchanged in nonresponders. In conclusion, SCCA-IgM is detectable in one-third of patients with CHC and significantly correlates with histological NASH. © 2015 John Wiley & Sons Ltd.

Review of HIV and HCV infection among drug users in China.

PubMed

Bao, Yan-ping; Liu, Zhi-min; Lu, Lin

2010-05-01

Drug abuse has resulted in a huge public health and economic burden in China, especially the rapid spread of HIV/AIDS and hepatitis C virus (HCV) infection. Multiple HIV and HCV subtypes were detected among drug users in China, this study reviews the molecular distribution of HIV and HCV among injection drug users (IDUs) and explores new epidemiologic trends of HIV and HCV among drug users in China. The 2009 National Narcotic Control Commission report showed that the percentage of users of 'new-type drugs', including amphetamine-type stimulants (ATS: methamphetamine and MDMA/ecstasy) and ketamine, was about 27% of total drug users. The pooled data from published papers showed that CRF07BC was the predominant HIV-1 subtype, which accounted for 38.8%, and it was followed by AE, which accounted for 22.7% among HIV-positive IDUs. Following these, the CRF08BC, B' and C subtypes accounted for about 10.8%, 9.9% and 9.2%, respectively. Subtype 6a was the predominant HCV subtype, accounting for 36.7%, and subtypes 3b, 1a, 3a and 1b were the next most predominant subtypes. With the increase of 'new-type drugs' use and AE HIV-1 subtype infection among IDUs, the situation regarding HIV/AIDS and HCV infection has become complicated. More comprehensive prevention and intervention strategies should be instigated for the extensive high-risk populations in China.

Prevalence of HCV among the young male blood donors of Quetta region of Balochistan, Pakistan

PubMed Central

2013-01-01

Background Hepatitis C, caused by hepatitis C virus (HCV) is a contagious disease of the liver which infects more than 170 million people world-wide and around 16 million in Pakistan. HCV associated infection spreads mainly by blood-to-blood contact. In recent years, many studies have been conducted to determine the prevalence of HCV infection in Pakistan; however, no data is available on HCV infection from the largest province of Pakistan. Therefore, the present study focuses on the prevalence of HCV infection in the young male blood donor population of Quetta region of Balochistan, Pakistan. Methods A total of 356 blood samples were collected from blood donors (age range 17–25 years) at Combined Military Hospital (CMH), Quetta, Balochistan, Pakistan. Blood samples were screened for HCV positivity by Immunochromatographic test (ICT) and Enzyme Linked Immunosorbant Assay (ELISA). Results Out of 356 blood samples, the overall HCV prevalence was 20.8%. Among the HCV positive cases, the age group with 25 years was more frequently infected with a prevalence of 26.3%. Conclusions The present study provides the preliminary information about high HCV prevalence among the young male donor population in Balochistan province. This data may be helpful in formulating public health strategy for the prevention of risk factors associated with spreading of the disease. Furthermore, we recommend that in public sector hospitals and health care units ELISA should be preferred for anti-HCV detection over ICT. PMID:23497435

Prevalence of HCV among the young male blood donors of Quetta region of Balochistan, Pakistan.

PubMed

Khan, Ayesha; Tareen, Abdul Malik; Ikram, Aamer; Rahman, Hazir; Wadood, Abdul; Qasim, Muhammad; Khan, Kalimullah

2013-03-13

Hepatitis C, caused by hepatitis C virus (HCV) is a contagious disease of the liver which infects more than 170 million people world-wide and around 16 million in Pakistan. HCV associated infection spreads mainly by blood-to-blood contact. In recent years, many studies have been conducted to determine the prevalence of HCV infection in Pakistan; however, no data is available on HCV infection from the largest province of Pakistan. Therefore, the present study focuses on the prevalence of HCV infection in the young male blood donor population of Quetta region of Balochistan, Pakistan. A total of 356 blood samples were collected from blood donors (age range 17-25 years) at Combined Military Hospital (CMH), Quetta, Balochistan, Pakistan. Blood samples were screened for HCV positivity by Immunochromatographic test (ICT) and Enzyme Linked Immunosorbant Assay (ELISA). Out of 356 blood samples, the overall HCV prevalence was 20.8%. Among the HCV positive cases, the age group with 25 years was more frequently infected with a prevalence of 26.3%. The present study provides the preliminary information about high HCV prevalence among the young male donor population in Balochistan province. This data may be helpful in formulating public health strategy for the prevention of risk factors associated with spreading of the disease. Furthermore, we recommend that in public sector hospitals and health care units ELISA should be preferred for anti-HCV detection over ICT.

Utilization of Signal-to-Cutoff Ratio of Hepatitis C Virus Antibody Assay in Predicting HCV Viremia among Hemodialysis Patients.

PubMed

Kao, Hao-Hsi; Chen, Kuo-Su; Lin, Chih-Lang; Chang, Jia-Jang; Lee, Chien-Hung

2015-01-01

Hepatitis C virus (HCV) infection is a common cause of acute and chronic hepatitis among the hemodialysis population. To prevent cross infection between hemodialysis patients during the hemodialysis procedure, routine screening of anti-HCV antibody is recommended. However, a reactive anti-HCV EIA test is not equal to active HCV infection. An expensive RT-PCR study is required to confirm HCV viremia. This will significantly increase the cost burden because payment for each hemodialysis treatment is very low in Taiwan. Thus, it is useful to identify parameters that could predict HCV viremia among anti-HCV-reactive patients. In this study, we examined the usefulness of signal-to-cut (S/CO) ratio of anti-HCV antibody in discriminating HCV viremia from non-viremia among the anti-HCV-reactive hemodialysis population. In a cross-sectional measurement of anti-HCV antibody among 369 chronic hemodialysis patients, 44 showed reactive and 9 grey zone reaction for anti-HCV. These 53 patients underwent further blood tests for the measurement of AST, ALT and HCV RNA (by RT-PCR). The results of RT-PCR were used as a dependent variable. Then, S/CO ratios of anti-HCV, serum AST, ALT levels, age and duration of hemodialysis were used as independent variables to undergo ROC curve and logistic regression analysis. Thirty-six of the 53 reactive and grey zone patients were positive for HCV RNA in the RT-PCR study. Patients who were positive for HCV RNA had a higher S/CO ratio (p < 0.01), higher AST and ALT levels (p < 0.01), and longer duration on hemodialysis (p < 0.05) than those negative for HCV RNA. Logistic regression revealed that only S/CO ratio was a significant predictor for HCV viremia (p = 0.004). ROC curve analysis showed that S/CO ratio had a highest area under curve (0.967, p < 0.001), followed by ALT (0.826, p < 0.001), AST (0.778, p = 0.001), duration on hemodialysis (0.606, p = 0.215) and age (0.426, p = 0.386) in discriminating HCV viremia from non-viremia. Using a

[Improvement of sensitivity in the second generation HCV core antigen assay by a novel concentration method using polyethylene glycol (PEG)].

PubMed

Higashimoto, Makiko; Takahashi, Masahiko; Jokyu, Ritsuko; Syundou, Hiromi; Saito, Hidetsugu

2007-11-01

A HCV core antigen (Ag) detection assay system, Lumipulse Ortho HCV Ag has been developed and is commercially available in Japan with a lower detection level limit of 50 fmol/l, which is equivalent to 20 KIU/ml in PCR quantitative assay. HCV core Ag assay has an advantage of broader dynamic range compared with PCR assay, however the sensitivity is lower than PCR. We developed a novel HCV core Ag concentration method using polyethylene glycol (PEG), which can improve the sensitivity five times better than the original assay. The reproducibility was examined by consecutive five-time measurement of HCV patients serum, in which the results of HCV core Ag original and concentrated method were 56.8 +/- 8.1 fmol/l (mean +/- SD), CV 14.2% and 322.9 +/- 45.5 fmol/l CV 14.0%, respectively. The assay results of HCV negative samples in original HCV core Ag were all 0.1 fmol/l and the results were same even in the concentration method. The results of concentration method were 5.7 times higher than original assay, which was almost equal to theoretical rate as expected. The assay results of serially diluted samples were also as same as expected data in both original and concentration assay. We confirmed that the sensitivity of HCV core Ag concentration method had almost as same sensitivity as PCR high range assay in the competitive assay study using the serially monitored samples of five HCV patients during interferon therapy. A novel concentration method using PEG in HCV core Ag assay system seems to be useful for assessing and monitoring interferon treatment for HCV.

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

PubMed Central

2011-01-01

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. PMID:21457561

PML tumor suppressor protein is required for HCV production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuroki, Misao; Research Fellow of the Japan Society for the Promotion of Science; Center for AIDS Research, Kumamoto University, Kumamoto 860-0811

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.more » 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.« less

Acute pancreatitis associated with pegylated interferon-alpha-2a therapy in chronic hepatitis C.

PubMed

Choi, Jong Wook; Lee, June Sung; Paik, Woo Hyun; Song, Tae Jun; Kim, Jung Wook; Bae, Won Ki; Kim, Kyung-Ah; Kim, Jung Gon

2016-03-01

Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea.

Patient-to-patient transmission of hepatitis C virus (HCV) during colonoscopy diagnosis

PubMed Central

2010-01-01

Background No recognized risk factors can be identified in 10-40% of hepatitis C virus (HCV)-infected patients suggesting that the modes of transmission involved could be underestimated or unidentified. Invasive diagnostic procedures, such as endoscopy, have been considered as a potential HCV transmission route; although the actual extent of transmission in endoscopy procedures remains controversial. Most reported HCV outbreaks related to nosocomial acquisition have been attributed to unsafe injection practices and use of multi-dose vials. Only a few cases of likely patient-to-patient HCV transmission via a contaminated colonoscope have been reported to date. Nosocomial HCV infection may have important medical and legal implications and, therefore, possible transmission routes should be investigated. In this study, a case of nosocomial transmission of HCV from a common source to two patients who underwent colonoscopy in an endoscopy unit is reported. Results A retrospective epidemiological search after detection of index cases revealed several potentially infective procedures: sample blood collection, use of a peripheral catheter, anesthesia and colonoscopy procedures. The epidemiological investigation showed breaches in colonoscope reprocessing and deficiencies in the recording of valuable tracing data. Direct sequences from the NS5B region were obtained to determine the extent of the outbreak and cloned sequences from the E1-E2 region were used to establish the relationships among intrapatient viral populations. Phylogenetic analyses of individual sequences from viral populations infecting the three patients involved in the outbreak confirmed the patient pointed out by the epidemiological search as the source of the outbreak. Furthermore, the sequential order in which the patients underwent colonoscopy correlates with viral genetic variability estimates. Conclusions Patient-to-patient transmission of HCV could be demonstrated although the precise route of

The natural history of acute hepatitis C: clinical presentation, laboratory findings and treatment outcomes.

PubMed

Loomba, R; Rivera, M M; McBurney, R; Park, Y; Haynes-Williams, V; Rehermann, B; Alter, H J; Herrine, S K; Liang, T J; Hoofnagle, J H; Heller, T

2011-03-01

Acute hepatitis C has variable modes of presentation and frequently results in chronic infection. Its optimal management has yet to be defined. To establish natural history and complications of treatment of acute hepatitis C. Data from all patients presenting with acute hepatitis C to the National Institutes of Health between 1994 and 2007 were reviewed. Twenty-five patients were identified. Symptoms were reported by 80% and jaundice by 40%. Aminotransferase levels and hepatitis C virus (HCV) RNA levels fluctuated greatly; 18% of patients were intermittently negative for HCV RNA. Five patients recovered spontaneously whereas 20 developed chronicity or received interferon-based therapy during the acute phase. Among 15 patients treated during the acute phase with peginterferon with or without ribavirin for 24 weeks, all became HCV RNA negative within 4-8 weeks, and all except two (HIV-positive) achieved a sustained virological response. Side effects (particularly psychiatric) were common and limited treatment in 30%. Among 25 patients with acute HCV infection, fluctuating illness was common and spontaneous recovery occurred in only 20%. Anti-viral treatment with a 24-week course of peginterferon and ribavirin was highly effective, but marked by frequent and severe side effects. Published 2010. This article is a US Government work and is in the public domain in the USA.

The natural history of acute hepatitis C: clinical presentation, laboratory findings, and treatment outcomes

PubMed Central

Loomba, R.; Rivera, M. M.; McBurney, R.; Park, Y.; Haynes-Williams, V.; Rehermann, B.; Alter, H. J.; Herrine, S. K.; Liang, T. J.; Hoofnagle, J. H.; Heller, T.

2017-01-01

Summary Background Acute hepatitis C has variable modes of presentation and frequently results in chronic infection. Its optimal management has yet to be defined. Aims To establish natural history and complications of treatment of acute hepatitis C. Methods Data from all patients presenting with acute hepatitis C to the National Institutes of Health between 1994 and 2007 were reviewed. Results Twenty-five patients were identified. Symptoms were reported by 80% and jaundice by 40%. Aminotransferase levels and HCV RNA levels fluctuated greatly; 18% of patients were intermittently negative for HCV RNA. Five patients recovered spontaneously whereas 20 developed chronicity or received interferon-based therapy during the acute phase. Among 15 patients treated during the acute phase with peginterferon with or without ribavirin for 24 weeks, all became HCV RNA negative within 4 to 8 weeks, and all except two (HIV-positive) achieved a sustained virological response. Side effects (particularly psychiatric) were common and limited treatment in 30%. Conclusion Thus, among 25 patients with acute HCV infection, fluctuating illness was common and spontaneous recovery occurred in only 20%. Antiviral treatment with a 24-week course of peginterferon and ribavirin was highly effective but marked by frequent and severe side effects. PMID:21198704

HCV Core Antigen Testing for Diagnosis of HCV Infection: A systematic review and meta-analysis

PubMed Central

Freiman, J. Morgan; Tran, Trang M.; Schumacher, Samuel G; White, Laura F.; Ongarello, Stefano; Cohn, Jennifer; Easterbrook, Philippa J.; Linas, Benjamin P.; Denkinger, Claudia M.

2017-01-01

Background Diagnosis of chronic Hepatitis C Virus (HCV) infection requires both a positive HCV antibody screen and confirmatory nucleic acid test (NAT). HCV core antigen (HCVcAg) is a potential alternative to NAT. Purpose This systematic review evaluated the accuracy of diagnosis of active HCV infection among adults and children for five HCVcAg tests compared to NAT. Data Sources EMBASE, PubMed, Web of Science, Scopus, and Cochrane from 1990 through March 31, 2016. Study Selection Cohort, cross-sectional, and randomized controlled trials were included without language restriction Data Extraction Two independent reviewers extracted data and assessed quality using an adapted Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Data Synthesis 44 studies evaluated 5 index tests. Studies for the ARCHITECT had the highest quality, while those for Ortho ELISA were the lowest. From bivariate analyses, the sensitivity and specificity with 95% CI were: ARCHITECT 93.4% (90.1, 96.4) and 98.8% (97.4, 99.5), Ortho ELISA 93.2% (81.6, 97.7) and 99.2% (87.9, 100), and Hunan Jynda 59.5% (46.0, 71.7) and 82.9% (58.6, 94.3). Insufficient data were available for a meta-analysis for Lumipulse and Lumispot. In three quantitative studies using ARCHITECT, HCVcAg correlated closely with HCV RNA above 3000 IU/mL. Limitations There was insufficient data on covariates such as HIV or HBV status for sub-group analyses. Few studies reported genotypes of isolates and there were scant data for genotypes 4, 5, and 6. Most studies were conducted in high resource settings within reference laboratories. Conclusions HCVcAg assays with signal amplification have high sensitivity, high specificity, and good correlation with HCV RNA above 3000 IU/mL. HCVcAg assays have the potential to replace NAT in high HCV prevalence settings. PMID:27322622

Numerical detection, measuring and analysis of differential interferon resistance for individual HCV intra-host variants and its influence on the therapy response.

PubMed

Skums, Pavel; Campo, David S; Dimitrova, Zoya; Vaughan, Gilberto; Lau, Daryl T; Khudyakov, Yury

Hepatitis C virus (HCV) is a major cause of liver disease world-wide. Current interferon and ribavirin (IFN/RBV) therapy is effective in 50%-60% of patients. HCV exists in infected patients as a large viral population of intra-host variants (quasispecies), which may be differentially resistant to interferon treatment. We present a method for measuring differential interferon resistance of HCV quasispecies based on mathematical modeling and analysis of HCV population dynamics during the first hours of interferon therapy. The mathematical models showed that individual intra-host HCV variants have a wide range of resistance to IFN treatment in each patient. Analysis of differential IFN resistance among intra-host HCV variants allows for accurate prediction of response to IFN therapy. The models strongly suggest that resistance to interferon may vary broadly among closely related variants in infected hosts and therapy outcome may be defined by a single or a few variants irrespective of their frequency in the intra-host HCV population before treatment.

HCV proteins and immunoglobulin variable gene (IgV) subfamilies in HCV-induced type II mixed cryoglobulinemia: a concurrent pathogenetic role.

PubMed

Sautto, Giuseppe; Mancini, Nicasio; Solforosi, Laura; Diotti, Roberta A; Clementi, Massimo; Burioni, Roberto

2012-01-01

The association between hepatitis C virus (HCV) infection and type II mixed cryoglobulinemia (MCII) is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV) gene subfamilies frequently endowed with rheumatoid factor (RF) activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved.

Acute pancreatitis associated with pegylated interferon-alpha-2a therapy in chronic hepatitis C

PubMed Central

Choi, Jong Wook; Lee, June Sung; Paik, Woo Hyun; Song, Tae Jun; Kim, Jung Wook; Bae, Won Ki; Kim, Kyung-Ah; Kim, Jung Gon

2016-01-01

Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea. PMID:27044768

Direct anti-HCV agents

PubMed Central

Zhang, Xingquan

2015-01-01

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. PMID:26904396

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

PubMed

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.

HCV Proteins and Immunoglobulin Variable Gene (IgV) Subfamilies in HCV-Induced Type II Mixed Cryoglobulinemia: A Concurrent Pathogenetic Role

PubMed Central

Sautto, Giuseppe; Mancini, Nicasio; Solforosi, Laura; Diotti, Roberta A.; Clementi, Massimo; Burioni, Roberto

2012-01-01

The association between hepatitis C virus (HCV) infection and type II mixed cryoglobulinemia (MCII) is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV) gene subfamilies frequently endowed with rheumatoid factor (RF) activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved. PMID:22690241

Performance of the New Bayer VERSANT HCV RNA 3.0 assay for quantitation of hepatitis C virus RNA in plasma and serum: conversion to international units and comparison with the Roche COBAS Amplicor HCV Monitor, Version 2.0, assay.

PubMed

Beld, Marcel; Sentjens, Roel; Rebers, Sjoerd; Weegink, Christine; Weel, Jan; Sol, Cees; Boom, René

2002-03-01

We have evaluated the VERSANT HCV RNA 3.0. Assay (HCV 3.0 bDNA assay) (Bayer Diagnostics, Berkeley, Calif.), which is an improved signal amplification procedure for the HCV 2.0 bDNA assay for the quantitation of hepatitis C virus (HCV) RNA in serum or plasma of HCV-infected individuals. The HCV 3.0 bDNA assay has a linear dynamic range of 2.5 x 10(3) to 4.0 x 10(7) HCV RNA copies per ml (c/ml). The performance of the HCV 3.0 bDNA assay was evaluated using three different test panels. An overall specificity of 96.8% relative to the detection limit of the HCV 3.0 bDNA assay was found. The intra- and interrun reproducibilities for both the dilution panel and the NAP (AcroMetrix, Benicia, Calif.) panel were consistent with coefficients of variation of less than 9%. Quantitation with the HCV 3.0 bDNA assay was linear over the entire range of both panels (ranges of 4.4 x 10(3) to 3.5 x 10(6) c/ml and 5 x 10(3) to 2 x 10(6) IU/ml, respectively), with correlation coefficients of 0.999, slopes close to one, and intercepts close to zero. The regression equation indicated that 1 IU corresponded to about 4.8 copies of HCV RNA. A correlation coefficient of 0.941 was found for HCV RNA values (in international units per milliliter) obtained from the HCV 3.0 bDNA assay and the HCV Monitor version 2.0 assay (HCV Monitor 2.0 assay) (Roche Diagnostic Systems, Branchburg, N.J.). Quantitative results obtained close to the lower limit of the HCV 3.0 bDNA assay might imply that its lower limit should be reconsidered and raised, if necessary. It appeared that quantitation values obtained from the HCV Monitor 2.0 assay of between 5 x 10(2) and 10(5) IU/ml were in general higher than those obtained from the HCV 3.0 bDNA assay, whereas values obtained from the HCV Monitor 2.0 assay were underestimated for samples with HCV RNA levels above 10(5) IU/ml.

Performance of the New Bayer VERSANT HCV RNA 3.0 Assay for Quantitation of Hepatitis C Virus RNA in Plasma and Serum: Conversion to International Units and Comparison with the Roche COBAS Amplicor HCV Monitor, Version 2.0, Assay

PubMed Central

Beld, Marcel; Sentjens, Roel; Rebers, Sjoerd; Weegink, Christine; Weel, Jan; Sol, Cees; Boom, René

2002-01-01

We have evaluated the VERSANT HCV RNA 3.0. Assay (HCV 3.0 bDNA assay) (Bayer Diagnostics, Berkeley, Calif.), which is an improved signal amplification procedure for the HCV 2.0 bDNA assay for the quantitation of hepatitis C virus (HCV) RNA in serum or plasma of HCV-infected individuals. The HCV 3.0 bDNA assay has a linear dynamic range of 2.5 × 103 to 4.0 × 107 HCV RNA copies per ml (c/ml). The performance of the HCV 3.0 bDNA assay was evaluated using three different test panels. An overall specificity of 96.8% relative to the detection limit of the HCV 3.0 bDNA assay was found. The intra- and interrun reproducibilities for both the dilution panel and the NAP (AcroMetrix, Benicia, Calif.) panel were consistent with coefficients of variation of less than 9%. Quantitation with the HCV 3.0 bDNA assay was linear over the entire range of both panels (ranges of 4.4 × 103 to 3.5 × 106 c/ml and 5 × 103 to 2 × 106 IU/ml, respectively), with correlation coefficients of 0.999, slopes close to one, and intercepts close to zero. The regression equation indicated that 1 IU corresponded to about 4.8 copies of HCV RNA. A correlation coefficient of 0.941 was found for HCV RNA values (in international units per milliliter) obtained from the HCV 3.0 bDNA assay and the HCV Monitor version 2.0 assay (HCV Monitor 2.0 assay) (Roche Diagnostic Systems, Branchburg, N.J.). Quantitative results obtained close to the lower limit of the HCV 3.0 bDNA assay might imply that its lower limit should be reconsidered and raised, if necessary. It appeared that quantitation values obtained from the HCV Monitor 2.0 assay of between 5 × 102 and 105 IU/ml were in general higher than those obtained from the HCV 3.0 bDNA assay, whereas values obtained from the HCV Monitor 2.0 assay were underestimated for samples with HCV RNA levels above 105 IU/ml. PMID:11880394

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

PubMed

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.

New insights into HCV replication in original cells from Aedes mosquitoes.

PubMed

Fallecker, Catherine; Caporossi, Alban; Rechoum, Yassine; Garzoni, Frederic; Larrat, Sylvie; François, Olivier; Fender, Pascal; Morand, Patrice; Berger, Imre; Petit, Marie-Anne; Drouet, Emmanuel

2017-08-22

The existing literature about HCV association with, and replication in mosquitoes is extremely poor. To fill this gap, we performed cellular investigations aimed at exploring (i) the capacity of HCV E1E2 glycoproteins to bind on Aedes mosquito cells and (ii) the ability of HCV serum particles (HCVsp) to replicate in these cell lines. First, we used purified E1E2 expressing baculovirus-derived HCV pseudo particles (bacHCVpp) so we could investigate their association with mosquito cell lines from Aedes aegypti (Aag-2) and Aedes albopictus (C6/36). We initiated a series of infections of both mosquito cells (Ae aegypti and Ae albopictus) with the HCVsp (Lat strain - genotype 3) and we observed the evolution dynamics of viral populations within cells over the course of infection via next-generation sequencing (NGS) experiments. Our binding assays revealed bacHCVpp an association with the mosquito cells, at comparable levels obtained with human hepatocytes (HepaRG cells) used as a control. In our infection experiments, the HCV RNA (+) were detectable by RT-PCR in the cells between 21 and 28 days post-infection (p.i.). In human hepatocytes HepaRG and Ae aegypti insect cells, NGS experiments revealed an increase of global viral diversity with a selection for a quasi-species, suggesting a structuration of the population with elimination of deleterious mutations. The evolutionary pattern in Ae albopictus insect cells is different (stability of viral diversity and polymorphism). These results demonstrate for the first time that natural HCV could really replicate within Aedes mosquitoes, a discovery which may have major consequences for public health as well as in vaccine development.

Increased CD56(bright) NK cells in HIV-HCV co-infection and HCV mono-infection are associated with distinctive alterations of their phenotype.

PubMed

Bhardwaj, Suvercha; Ahmad, Fareed; Wedemeyer, Heiner; Cornberg, Marcus; Schulze Zur Wiesch, Julian; van Lunzen, Jan; Sarin, Shiv K; Schmidt, Reinhold E; Meyer-Olson, Dirk

2016-04-18

HIV-HCV co-infection is associated with accelerated progression to hepatic fibrosis, cirrhosis and hepatocellular carcinoma than HCV mono-infection. The contribution of innate immunity during HIV-HCV co-infection has been a relatively under-investigated area. Natural killer (NK) cells are pivotal sentinels of innate immunity against viruses and tumour cells. In this study we evaluated the effect of HIV-HCV co-infection on peripheral blood NK cell subsets with emphasis on the phenotype of CD56(bright) NK cells. Sixty patients were included in the study; HIV mono-infected (n = 12), HCV mono-infected (n = 15), HCV-HIV co-infected (n = 21) and healthy controls (n = 16). PBMCs were isolated and immunophenotyping of NK cells was performed by flowcytometry. We observed an expansion of CD56(bright) NK cell subset in HIV-HCV co-infection as compared to healthy controls and HIV mono-infected group. All the infected groups had an upregulated expression of the activating receptor NKG2D on CD56(bright) NK cells in comparison to healthy controls while not differing amongst themselves. The expression of NKp46 in HIV-HCV co-infected group was significantly upregulated as compared to both HIV as well as HCV mono-infections while NKp30 expression in the HIV-HCV co-infected group significantly differed as compared to HIV mono-infection. The CD56(bright) NK cell subset was activated in HIV-HCV co-infection as assessed by the expression of CD69 as compared to healthy controls but was significantly downregulated in comparison to HIV mono-infection. CD95 expression on CD56(bright) NK cells followed the same pattern where there was an increased expression of CD95 in HIV mono-infection and HIV-HCV co-infection as compared to healthy controls. In contrast to CD69 expression, CD95 expression in HCV mono-infection was decreased when compared to HIV mono-infection and HIV-HCV co-infection. Finally, expression of CXCR3 on CD56(bright) NK cells was increased in HIV-HCV co-infection in comparison

Stability of hepatitis C virus RNA and anti-HCV antibody in air-dried and freeze-dried human plasma samples.

PubMed

Poe, Amanda; Duong, Ngocvien Thi; Bedi, Kanwar; Kodani, Maja

2018-03-01

Diagnosis of hepatitis C virus (HCV) infection is based on testing for antibodies to HCV (anti-HCV), hepatitis C core antigen (HCV cAg) and HCV RNA. To ensure quality control (QC) and quality assurance (QA), proficiency panels are provided by reference laboratories and various international organizations, requiring costly dry ice shipments to maintain specimen integrity. Alternative methods of specimen preservation and transport can save on shipping and handling and help in improving diagnostics by facilitating QA/QC of various laboratories especially in resource limited countries. Plasma samples positive for anti-HCV and HCV RNA were either dried using dried tube specimens (DTS) method or lyophilization for varying durations of time and temperature. Preservation of samples using DTS method resulted in loss of anti-HCV reactivity for low-positive samples and did not generate enough volume for HCV RNA testing. Lyophilized samples tested positive for anti-HCV even after storage at 4 °C and 25 °C for 12 weeks. Further, HCV RNA was detectable in 5 of 5 (100%) samples over the course of 12 week storage at 4, 25, 37 and 45 °C. In conclusion, lyophilization of specimens maintains integrity of plasma samples for testing for markers of HCV infection and can be a potent mode of sharing proficiency samples without incurring huge shipping costs and avoids challenges with dry ice shipments between donor and recipient laboratories. Copyright © 2017. Published by Elsevier B.V.

Understanding the molecular mechanism(s) of hepatitis C virus (HCV) induced interferon resistance.

PubMed

Qashqari, Hanadi; Al-Mars, Amany; Chaudhary, Adeel; Abuzenadah, Adel; Damanhouri, Ghazi; Alqahtani, Mohammed; Mahmoud, Maged; El Sayed Zaki, Maysaa; Fatima, Kaneez; Qadri, Ishtiaq

2013-10-01

Hepatitis C virus (HCV) is one of the foremost causes of chronic liver disease affecting over 300 million globally. HCV contains a positive-stranded RNA of ~9600 nt and is surrounded by the 5' and 3'untranslated regions (UTR). The only successful treatment regimen includes interferon (IFN) and ribavirin. Like many other viruses, HCV has also evolved various mechanisms to circumvent the IFN response by blocking (1) downstream signaling actions via STAT1, STAT2, IRF9 and JAK-STAT pathways and (2) repertoire of IFN Stimulatory Genes (ISGs). Several studies have identified complex host demographic and genetic factors as well as viral genetic heterogeneity associated with outcomes of IFN therapy. The genetic predispositions of over 2000 ISGS may render the patients to become resistant, thus identification of such parameters within a subset of population are necessary for management corollary. The ability of various HCV genotypes to diminish IFN antiviral responses plays critical role in the establishment of chronic infection at the acute stage of infection, thus highlighting importance of the resistance in HCV treated groups. The recently defined role of viral protein such as C, E2, NS3/NS4 and NS5A proteins in inducing the IFN resistance are discussed in this article. How the viral and host genetic composition and epistatic connectivity among polymorphic genomic sites synchronizes the evolutionary IFN resistance trend remains under investigation. However, these signals may have the potential to be employed for accurate prediction of therapeutic outcomes. In this review article, we accentuate the significance of host and viral components in IFN resistance with the aim to determine the successful outcome in patients. Copyright © 2013 Elsevier B.V. All rights reserved.

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

PubMed

Ndjoyi-Mbiguino, Angélique; Kombe Kombe, Arnaud John; Bivigou-Mboumba, Berthold; Zoa-Assoumou, Samira; Akombi, Falone Larissa; Nzengui Nzengui, Francis; M'boyis Kamdem, Hervé; François-Souquière, Sandrine

2018-01-01

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.

Use of HCV+ Donors Does Not Affect HCV Clearance With Directly Acting Antiviral Therapy But Shortens the Wait Time to Kidney Transplantation.

PubMed

Sawinski, Deirdre; Patel, Nikunjkumar; Appolo, Brenda; Bloom, Roy

2017-05-01

Hepatitis C virus (HCV) infection is prevalent in the renal transplant population but direct acting antiviral agents (DAA) provide an effective cure of HCV infection without risk of allograft rejection. We report our experience treating 43 renal transplant recipients with 4 different DAA regimens. One hundred percent achieved a sustained viral response by 12 weeks after therapy, and DAA regimens were well tolerated. Recipients transplanted with a HCV+ donor responded equally well to DAA therapy those transplanted with a kidney from an HCV- donor, but recipients of HCV+ organs experienced significantly shorter wait times to transplantation, 485 days (interquartile range, 228-783) versus 969 days (interquartile range, 452-2008; P = 0.02). On this basis, we advocate for a strategy of early posttransplant HCV eradication to facilitate use of HCV+ organs whenever possible. Additional studies are needed to identify the optimal DAA regimen for kidney transplant recipients, accounting for efficacy, timing relative to transplant, posttransplant clinical outcomes, and cost.

HCV mono-infected and HIV/HCV co-infected individuals treated with direct-acting antivirals: to what extent do they differ?

PubMed

Bruno, Giuseppe; Saracino, Annalisa; Scudeller, Luigia; Fabrizio, Claudia; Dell'Acqua, Raffaele; Milano, Eugenio; Milella, Michele; Ladisa, Nicoletta; Monno, Laura; Angarano, Gioacchino

2017-09-01

Direct-acting antiviral (DAA)-based treatment of hepatitis C virus (HCV) has been associated with high sustained virological response (SVR) rates and good tolerability in randomized clinical trials. This study was performed to assess the safety and effectiveness of DAAs in both HCV mono-infected and HIV/HCV co-infected patients. All consecutive HCV-infected patients, including HIV/HCV co-infected patients, receiving DAA-based treatment from February 2015 to September 2016 at the study clinic were included. Clinical, virological, and biochemical data were retrieved. The primary end-point was the SVR12 (HCV RNA undetectable 12 weeks after the end of treatment) is commonly used worldwide. The secondary end-point was the safety profile of DAAs during the treatment period. A total of 382 patients were included; 62 were HIV/HCV co-infected. Cirrhosis was found in 256 patients (67.4%). SVR12 was achieved in 365/382 (95.5%) individuals (58/62 HIV/HCV co-infected, 93.5%) in the intention-to-treat (ITT) analysis. A platelet count <90×10 9 /l (odds ratio (OR) 4.12, 95% confidence interval (CI) 1.5-11.3, p=0.006), HCV genotype 3 infection (OR 5.49, 95% CI 1.9-15.7, p=0.002), liver stiffness >20kPa (OR 3.05, 95% CI 1.03-8.96, p=0.04), and Model for End-Stage Liver Disease (MELD) score >10 (OR 5.27, 95% CI 1.16-23.8, p=0.03) were associated with lower SVR rates. On multivariate analysis, only genotype 3 infection remained a negative predictor of SVR (OR 21.6, 95% CI 3.81-123, p=0.001). Treatment discontinuation was observed in 10 subjects. Severe adverse events (SAEs) occurred in 17 patients (4.5%). High SVR12 rates were observed in both HCV mono-infected and HIV/HCV co-infected individuals. Overall, DAA-based treatment was safe and there were no differences in terms of SAEs and treatment discontinuation between the two groups. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Functional restoration of HCV-specific CD8 T cells by PD-1 blockade is defined by PD-1 expression and compartmentalization.

PubMed

Nakamoto, Nobuhiro; Kaplan, David E; Coleclough, Jennifer; Li, Yun; Valiga, Mary E; Kaminski, Mary; Shaked, Abraham; Olthoff, Kim; Gostick, Emma; Price, David A; Freeman, Gordon J; Wherry, E John; Chang, Kyong-Mi

2008-06-01

The immunoinhibitory receptor programmed death-1 (PD-1) is up-regulated on dysfunctional virus-specific CD8 T cells during chronic viral infections, and blockade of PD-1/PD-ligand (PD-L) interactions can restore their function. As hepatitis C virus (HCV) persists in the liver with immune-mediated disease pathogenesis, we examined the role of PD-1/PD-L pathway in antigen-specific CD8 T-cell dysfunction in the liver and blood of HCV-infected patients. PD-1 expression and function of circulating CD8 T cells specific for HCV, Epstein-Barr virus, and influenza virus were examined ex vivo and following antigenic stimulation in vitro in patients with acute, chronic, and resolved HCV infection using class I tetramers and flow cytometry. Intrahepatic CD8 T cells were examined from liver explants of chronically HCV-infected transplant recipients. Intrahepatic HCV-specific CD8 T cells from chronically HCV-infected patients were highly PD-1 positive, profoundly dysfunctional, and unexpectedly refractory to PD-1/PD-L blockade, contrasting from circulating PD-1-intermediate HCV-specific CD8 T cells with responsiveness to PD-1/PD-L blockade. This intrahepatic functional impairment was HCV-specific and directly associated with the level of PD-1 expression. Highly PD-1-positive intrahepatic CD8 T cells were more phenotypically exhausted with increased cytotoxic T-lymphocyte antigen 4 and reduced CD28 and CD127 expression, suggesting that active antigen-specific stimulation in the liver induces a profound functional exhaustion not reversible by PD-1/PD-L blockade alone. HCV-specific CD8 T-cell dysfunction and responsiveness to PD-1/PD-L blockade are defined by their PD-1 expression and compartmentalization. These findings provide new and clinically relevant insight to differential antigen-specific CD8 T-cell exhaustion and their functional restoration.

Functional restoration of HCV-specific CD8 T-cells by PD1 blockade is defined by PD1 expression and compartmentalization

PubMed Central

Nakamoto, Nobuhiro; Kaplan, David E.; Coleclough, Jennifer; Li, Yun; Kaminski, Mary; Shaked, Abraham; Olthoff, Kim; Gostick, Emma; Price, David A.; Freeman, Gordon J.; Wherry, E. John; Chang, Kyong-Mi

2008-01-01

Background & Aims The immuno-inhibitory receptor Programmed Death-1 (PD-1) is upregulated on dysfunctional virus-specific CD8 T-cells during chronic viral infections and blockade of PD-1:PD-ligand (PD-L) interactions can restore their function. As hepatitis C virus (HCV) persists in the liver with immune-mediated disease pathogenesis, we examined the role of PD1/PD-L pathway in antigen-specific CD8 T-cell dysfunction in the liver and blood of HCV-infected patients. Methods PD-1 expression and function of circulating CD8 T-cells specific for HCV, EBV and Flu were examined ex vivo and following antigenic stimulation in vitro in patients with acute, chronic and resolved HCV infection using class I tetramers and flow cytometry. Intrahepatic CD8 T-cells were examined from liver explants of chronically HCV-infected transplant recipients. Results Intrahepatic HCV-specific CD8 T-cells from chronically HCV-infected patients were highly PD-1-positive, profoundly dysfunctional and unexpectedly refractory to PD-1:PD-L blockade, contrasting from circulating PD-1-intermediate HCV-specific CD8 T-cells with responsiveness to PD-1:PD-L blockade. This intrahepatic functional impairment was HCV-specific and directly associated with the level of PD-1 expression. Highly PD-1-positive intrahepatic CD8 T-cells were more phenotypically exhausted with increased cytotoxic T-lymphocyte antigen 4 (CTLA-4) and reduced CD28 and CD127 expression, suggesting that active antigen-specific stimulation in the liver induces a profound functional exhaustion not reversible by PD-1:PD-L blockade alone. Conclusion HCV-specific CD8 T-cell dysfunction and responsiveness to PD-1:PD-L blockade are defined by their PD-1 expression and compartmentalization. These findings provide new and clinically relevant insight to differential antigen-specific CD8 T-cell exhaustion and their functional restoration. PMID:18549878

Clinical performance of the novel DiaSorin LIAISON(®) XL murex: HBsAg Quant, HCV-Ab, HIV-Ab/Ag assays.

PubMed

Krawczyk, Adalbert; Hintze, Christian; Ackermann, Jessica; Goitowski, Birgit; Trippler, Martin; Grüner, Nico; Neumann-Fraune, Maria; Verheyen, Jens; Fiedler, Melanie

2014-01-01

The fully automated and closed LIAISON(®)XL platform was developed for reliable detection of infection markers like hepatitis B virus (HBV) surface antigen (HBsAg), hepatitis C virus (HCV) antibodies (Ab) or human immunodeficiency virus (HIV)-Ag/Ab. To date, less is known about the diagnostic performance of this system in direct comparison to the common Abbott ARCHITECT(®) platform. We compared the diagnostic performance and usability of the DiaSorin LIAISON(®)XL with the commonly used Abbott ARCHITECT(®) system. The qualitative performance of the above mentioned assays was compared in about 500 sera. Quantitative tests were performed for HBsAg-positive samples from patients under therapy (n=289) and in vitro expressed mutants (n=37). For HCV-Ab, a total number of 155 selected samples from patients chronically infected with different HCV genotypes were tested. The concordance between both systems was 99.4% for HBsAg, 98.81% for HCV-Ab, and 99.6% for HIV-Ab/Ag. The quantitative LIAISON(®)XL murex HBsAg assay detected all mutants in comparable amounts to the HBsAg wild type and yielded highly reliable HBsAg kinetics in patients treated with antiviral drugs. Dilution experiments using the 2nd International Standard for HBsAg (WHO) showed a high accuracy of this test. HCV-Ab from patients infected with genotypes 1-3 were equally detected in both systems. Interestingly, S/CO levels of HCV-Ab from patients infected with genotype 3 seem to be relatively low using both systems. The LIAISON(®)XL platform proved to be an excellent system for diagnostics of HBV, HCV, and HIV with equal performance compared to the ARCHITECT(®) system. Copyright © 2013 Elsevier B.V. All rights reserved.

Mechanisms of accelerated liver fibrosis in HIV-HCV coinfection.

PubMed

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.

[Study of neutralization antibodie induced by DNA vaccine of HCV envelope protein 2 in mice].

PubMed

Shao, Shengwen; Zhou, Hongchang; Tong, Yimin; Ren, Yanli; Chen, Zhihui

2011-05-01

To explore the feasibility of induction of neutralization antibodies against hepatitis C virus (HCV) infection by HCV envelope 2 protein (E2) DNA vaccines immunization. Two kinds of expression plasmids of HCV envelope 2 protein, plasmid pCI-1b661 Delta encoding hydrophobic carboxyl terminal truncated E2 and pCI-1b661 Delta encoding E2 with deletion of hypervariable region 1 (HVR1) and carboxyl terminal, were constructed and respectively transfeted 293T cells, and truncated E2 protein in whole cell lysate and supernatant of 293T cells were analyzed by Western blot. After BALB/c mouse were intramuscularly immunized by the plasmids, sera antibodies against HVR1 were detected by ELISA and the neutralization activity of the antibodies were assayed with HCV pseudotype particle (HCVpp). Both plasmids could express secretary truncated E2 protein. All the mice immunized with plasmid pCI-1b661 produced HVR1 antibodies,while no HVR1 antibodies were detected in pCI-1b661 Delta immunized mice. The sera neutralization percentages against HCVpp in pCI1lb661 Delta and pCI-lb661 Delta immunized mice were (78.5 +/- 13.8)% and (38.7 +/- 6.5)%, respectively (P <0.01). Sera neutralization activity against HCVpp was positive correlated with the level of HVR1 antibodies in pCI-1b661 immunized mice (r = 0.967, P<0.01). DNA vaccines expressing truncated E2 protein could induce neutralization antibodies against HCV, and neutralization antibodies mainly was consisted of the antibodies against HVR1.

Epidemiological profile and risk factors of HIV and HBV/HCV co-infection in Fujian Province, southeastern China.

PubMed

Wu, Shouli; Yan, Pingping; Yang, Tianfei; Wang, Zhenghua; Yan, Yansheng

2017-03-01

This study aimed to investigate the epidemiological features of HIV-infected subjects co-infected with HBV/HCV in Fujian Province, southeastern China, and identify the risk factors. Blood samples were collected from 2,028 HIV antibody-positive subjects in Fujian Province. Serum HBsAg and anti-HCV antibody were detected, and CD4 + T cell count was measured. Of the 2,028 subjects, the prevalence of HIV-HBV, HIV-HCV, and HIV-HBV-HCV co-infections was 16.22%, 3.7%, and 0.79%, respectively. Man (OR = 1.912, 95% CI: 1.371-2.667), key population (OR = 0.756, 95% CI: 0.57-0.976) and detainee (OR = 0.486, 95% CI: 0.259-0.909) were risk factors of HIV-HBV co-infection, and man (OR = 2.227, 95% CI: 1.096-4.525), minority (OR = 5.04, 95% CI: 1.696-14.98), junior high school or lower education (OR = 2.32, 95% CI: 1.071-5.025), intravenous drug use (OR = 38.46, 95% CI: 11.46-129.11) and detainee (OR = 5.687, 95% CI: 2.44-13.25) were risk factors of HIV-HCV co-infection. In addition, a lower mean CD4 + T cell count was measured in HIV/HBV and HIV/HCV co-infected subjects than in HIV-infected subjects among the untreated individuals, while in the treated populations, a higher mean CD4 + T cell count was detected in HIV/HBV and HIV/HCV co-infected subjects than in HIV-infected subjects. HIV co-infection with HBV or HCV, notably HIV-HBV co-infection, is widespread in southeastern China. Hepatitis virus screening should be included in monitoring of HIV infection, and HIV and hepatitis virus co-infection should be considered during the development of HIV antiretroviral therapy scheme. J. Med. Virol. 89:443-449, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Expression of human factors CD81, claudin-1, scavenger receptor, and occludin in mouse hepatocytes does not confer susceptibility to HCV entry.

PubMed

Hikosaka, Keisuke; Noritake, Hidenao; Kimura, Wataru; Sultana, Nishat; Sharkar, Mohammad T K; Tagawa, Yoh-Ichi; Uezato, Tadayoshi; Kobayashi, Yoshimasa; Wakita, Takaji; Miura, Naoyuki

2011-04-01

No suitable mouse model is available for studying chronic liver disease caused by hepatitis C virus (HCV). CD81, claudin-1, scavenger receptor class B type I, and occludin were recently reported to be the important factors in HCV entry into hepatocytes. We made transgenic mice (Alb-CCSO) expressing the four human proteins and examined whether HCV from a patient serum or HCV pseudoparticles (HCVpp) were capable of infecting them. HCV was not detected in the mouse serum after injecting the mice with HCV from a patient serum. We also found no indications of HCVpp entry into primary hepatocytes from Alb-CCSO mice. In addition, HCV-infectible Hep3B cells were fused with HCV-resistant primary mouse hepatocytes and the fused cells showed 35-fold lower infectivity compared to wild-type Hep3B cells, indicating that primary mouse hepatocytes have the inhibitory factor(s) in HCVpp entry. Our results suggest that the expression of the human factors does not confer susceptibility to HCV entry into the liver.

Demographics, socio-behavioral factors, and drug use patterns: what matters in spontaneous HCV clearance?

PubMed

Shah, Dimpy P; Grimes, Carolyn Z; Brown, Eric; Hwang, Lu-Yu

2012-02-01

Hepatitis C virus (HCV), an emerging bloodborne pathogen, causes chronic liver disease frequently except in about 10-20% of infections which undergo spontaneous resolution. Investigating factors that influence viral clearance is essential to understand the natural history of this infection and establishing novel strategies for prevention and treatment. HCV clearance was estimated in a unique cohort of 1,260 HIV and HBV negative current drug users enrolled for a hepatitis B vaccination study. It was defined as the inability to detect viral RNA using a PCR method in presence of serum anti-HCV antibody EIA. Associated demographic and socio-behavioral factors including drug use patterns were identified from the enrolled subjects using multivariate regression analysis. 33.3% (420/1260) of drug users were found positive for anti-HCV antibodies and 14.8% (62/420) of these individuals achieved viral clearance (negative PCR test). Race or ethnicity of the participants was the only significant factor associated with HCV clearance. Hispanics (OR = 3.4, 95% CI: 1.3-8.5, P = 0.01) and Caucasians (OR = 3.1, 95% CI: 1.5-6.6, P = 0.003) had significantly higher odds of clearing the virus compared to African Americans when adjusted for age and gender. None of the socio-behavioral factors including alcohol intake and drug use patterns were significant determinants of HCV clearance. Racial or ethnic differences in HCV clearance were observed in this study suggesting an important role of host genetic susceptibility factors in determining the clinical course of this disease. Further research is needed to examine these genetic associations of host-virus relationships. Copyright © 2011 Wiley Periodicals, Inc.

Clinical application of the Quantiplex HCV RNA 2.0 and Amplicor HCV Monitor assays for quantifying serum hepatitis C virus RNA.

PubMed

Yu, M L; Chuang, W L; Chen, S C; Lin, Z Y; Hsieh, M Y; Wang, L Y; Chang, W Y

1999-11-01

To compare the performance characteristics and clinical application of two different technologies for quantifying serum hepatitis C virus (HCV) RNA levels. HCV RNA was quantified by Amplicor HCV Monitor assay (Amplicor) and Quantiplex HCV RNA 2.0 assay (bDNA-2) in 119 sera from 107 HCV infected patients. Both assays had similar sensitivity (79.4% for Amplicor; 86.0% for bDNA-2), acceptable coefficients of variation (5.3% in Amplicor; 2.6% in bDNA-2), and good linearity (r2 > or = 0.98). There was a positive correlation between quantification values of both methods (r = 0.683, p < 0.001). The Amplicor values were on an average 1.76 log lower than bDNA-2 results. Male subjects and HCV genotype 1b were significantly associated with higher viral load determined by Amplicor, but not with viral load measured by bDNA-2. In 70 chronic HCV infected patients treated with interferon alfa, mean (SD) pretreatment viral load in 27 complete responders (3.47 (0.84) logs for Amplicor, 5.63 (0.58) for bDNA-2) was significantly lower than in non-responders (4.43 (1.01) logs for Amplicor, 6.10 (0.67) logs for bDNA-2; p < 0.001). Cut off points of 3.9 logs for Amplicor and 5.8 logs for bDNA-2 were determined to be the best for predicting response to interferon alfa, giving acceptable sensitivity (70.4%, 74.1%), specificity (72.1%, 65.1%), and accuracy (71.4%, 68.6%), respectively. Both the Amplicor and bDNA-2 assays are clinically useful methods for HCV RNA quantification and are reliable for predicting the outcome of treatment, despite differences in absolute quantification values and in the correlation between HCV genotypes and viral load.

Genetic variations of the NPC1L1 gene associated with hepatitis C virus (HCV) infection and biochemical characteristics of HCV patients in China.

PubMed

Zhang, A-Mei; Zhang, Cheng-Lin; Song, Yuzhu; Zhao, Ping; Feng, Yue; Wang, Binghui; Li, Zheng; Liu, Li; Xia, Xueshan

2016-12-01

About 2% of the world population is infected with hepatitis C virus (HCV), a leading cause of hepatic cirrhosis and hepatocellular carcinoma. The Niemann-Pick C1-like 1 cholesterol absorption receptor (NPC1L1) was recently identified to be an important factor for HCV entry into host cells. Whether genetic variations of the NPC1L1 gene are associated with HCV infection is unknown. In this study, five single nucleotide polymorphisms (SNPs) of the NPC1L1 gene were analyzed in 261 HCV-infected individuals and 265 general controls from Yunnan Province, China. No significant differences were identified in genotypes or alleles of the SNPs between the two groups. After constructing haplotypes based on the five SNPs, a significant difference between HCV-infected individuals and general controls was shown for two haplotypes. Haplotype GCCTT appeared to be a protective factor and haplotype GCCCT was a risk factor for HCV-infected individuals. Genotypes of four SNPs correlated with biochemical characteristics of HCV-infected persons. Genotypes of SNPs rs799444 and rs2070607 were correlated with total bilirubin. Genotype TT of rs917098 was a risk factor for the gamma-glutamyltransferase level. Furthermore, HCV-infected individuals carrying genotype GG of rs41279633 showed statistically higher gamma-glutamyltransferase levels than HCV-infected persons with GT and TT. The results of this study identified the association between genetic susceptibility of the NPC1L1 gene and HCV infection, as well as biochemical characteristics of HCV-infected persons in Yunnan, China. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

According to Hepatitis C Virus (HCV) Infection Stage, Interleukin-7 Plus 4-1BB Triggering Alone or Combined with PD-1 Blockade Increases TRAF1low HCV-Specific CD8+ Cell Reactivity.

PubMed

Moreno-Cubero, Elia; Subirá, Dolores; Sanz-de-Villalobos, Eduardo; Parra-Cid, Trinidad; Madejón, Antonio; Miquel, Joaquín; Olveira, Antonio; González-Praetorius, Alejandro; García-Samaniego, Javier; Larrubia, Juan-Ramón

2018-01-15

Hepatitis C virus (HCV)-specific CD8 + T cells suffer a progressive exhaustion during persistent infection (PI) with HCV. This process could involve the positive immune checkpoint 4-1BB/4-1BBL through the loss of its signal transducer, TRAF1. To address this issue, peripheral HCV-specific CD8 + T cells (pentamer-positive [pentamer + ]/CD8 + T cells) from patients with PI and resolved infection (RI) after treatment were studied. The duration of HCV infection and the liver fibrosis progression rate inversely correlated with the likelihood of detection of peripheral pentamer + /CD8 + cells. In PI, pentamer + /CD8 + cells had impaired antigen-specific reactivity that worsened when these cells were not detectable ex vivo Short/midduration PI was characterized by detectable peripheral PD-1 + CD127 low TRAF1 low cells. After triggering of T cell receptors (TCR), the TRAF1 level positively correlated with the levels of CD127, Mcl-1, and CD107a expression and proliferation intensity but negatively with PD-1 expression, linking TRAF1 low to exhaustion. In vitro treatment with interleukin-7 (IL-7) upregulated TRAF1 expression, while treatment with transforming growth factor-β1 (TGF-β1) did the opposite, suggesting that the IL-7/TGF-β1 balance, besides TCR stimulation, could be involved in TRAF1 regulation. In fact, the serum TGF-β1 concentration was higher in patients with PI than in patients with RI, and it negatively correlated with TRAF1 expression. In line with IL-7 increasing the level of TRAF1 expression, IL-7 plus 4-1BBL treatment in vitro enhanced T cell reactivity in patients with short/midduration infection. However, in patients with long-lasting PI, anti-PD-L1, in addition to the combination of IL-7 and 4-1BBL, was necessary to reestablish T cell proliferation in individuals with slowly progressing liver fibrosis (slow fibrosers) but had no effect in rapid fibrosers. In conclusion, a peripheral hyporeactive TRAF1 low HCV-specific CD8 + T cell response

SUMO1 depletion prevents lipid droplet accumulation and HCV replication.

PubMed

Akil, Abdellah; Wedeh, Ghaith; Zahid Mustafa, Mohammad; Gassama-Diagne, Ama

2016-01-01

Infection by hepatitis C virus (HCV) is a major public-health problem. Chronic infection often leads to cirrhosis, steatosis, and hepatocellular carcinoma. The life cycle of HCV depends on the host cell machinery and involves intimate interaction between viral and host proteins. However, the role of host proteins in the life cycle of HCV remains poorly understood. Here, we identify the small ubiquitin-related modifier (SUMO1) as a key host factor required for HCV replication. We performed a series of cell biology and biochemistry experiments using the HCV JFH-1 (Japanese fulminate hepatitis 1) genotype 2a strain, which produces infectious particles and recapitulates all the steps of the HCV life cycle. We observed that SUMO1 is upregulated in Huh7.5 infected cells. Reciprocally, SUMO1 was found to regulate the expression of viral core protein. Moreover, knockdown of SUMO1 using specific siRNA influenced the accumulation of lipid droplets and reduced HCV replication as measured by qRT-PCR. Thus, we identify SUMO1 as a key host factor required for HCV replication. To our knowledge, this is the first report showing that SUMO1 regulates lipid droplets in the context of viral infection. Our report provides a meaningful insight into how HCV replicates and interacts with host proteins and is of significant importance for the field of HCV and RNA viruses.

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

PubMed

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 14 th 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.

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

PubMed Central

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.

2017-01-01

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. PMID:28266565

Characterization of miR-122-independent propagation of HCV

PubMed Central

Motooka, Daisuke; Nakamura, Shota; Yamamoto, Satomi; Mori, Hiroyuki; Sato, Asuka; Uemura, Kentaro; Fauzyah, Yuzy; Suda, Takahiro; Nishio, Akira; Hmwe, Su Su; Okamoto, Toru; Tatsumi, Tomohide; Takehara, Tetsuo; Chayama, Kazuaki; Wakita, Takaji; Koike, Kazuhiko

2017-01-01

miR-122, a liver-specific microRNA, is one of the determinants for liver tropism of hepatitis C virus (HCV) infection. Although miR-122 is required for efficient propagation of HCV, we have previously shown that HCV replicates at a low rate in miR-122-deficient cells, suggesting that HCV-RNA is capable of propagating in an miR-122-independent manner. We herein investigated the roles of miR-122 in both the replication of HCV-RNA and the production of infectious particles by using miR-122-knockout Huh7 (Huh7-122KO) cells. A slight increase of intracellular HCV-RNA levels and infectious titers in the culture supernatants was observed in Huh7-122KO cells upon infection with HCV. Moreover, after serial passages of HCV in miR-122-knockout Huh7.5.1 cells, we obtained an adaptive mutant, HCV122KO, possessing G28A substitution in the 5’UTR of the HCV genotype 2a JFH1 genome, and this mutant may help to enhance replication complex formation, a possibility supported by polysome analysis. We also found the introduction of adaptive mutation around miR-122 binding site in the genotype 1b/2a chimeric virus, which originally had an adenine at the nucleotide position 29. HCV122KO exhibited efficient RNA replication in miR-122-knockout cells and non-hepatic cells without exogenous expression of miR-122. Competition assay revealed that the G28A mutant was dominant in the absence of miR-122, but its effects were equivalent to those of the wild type in the presence of miR-122, suggesting that the G28A mutation does not confer an advantage for propagation in miR-122-rich hepatocytes. These observations may explain the clinical finding that the positive rate of G28A mutation was higher in miR-122-deficient PBMCs than in the patient serum, which mainly included the hepatocyte-derived virus from HCV-genotype-2a patients. These results suggest that the emergence of HCV mutants that can propagate in non-hepatic cells in an miR-122-independent manner may participate in the induction of

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

PubMed

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%, p<0.01), achieve an HCV-specific evaluation (40.8% vs. 21.3%, p<0.05), be offered HCV treatment (22.4% vs. 8.5%, p<0.05), and initiate HCV treatment (9.2% vs. 6.4%, p=0.6). Given the current opioid epidemic in the US and the growing number of people receiving buprenorphine 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.

Retention in Buprenorphine Treatment is Associated with Improved HCV Care Outcomes

PubMed Central

Norton, BL; Beitin, A; Glenn, M; DeLuca, J; Litwin, AH; Cunningham, CO

2018-01-01

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-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%, p<0.01), achieve an HCV-specific evaluation (40.8% vs. 21.3%, p<0.05), be offered HCV treatment (22.4% vs. 8.5%, p<0.05), and initiate HCV treatment (9.2% vs. 6.4%, p=0.6). Given the current opioid epidemic in the US and the growing number of people receiving buprenorphine 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. PMID:28237052

The Cobas AmpliPrep/Cobas TaqMan HCV test, version 2.0, real-time PCR assay accurately quantifies hepatitis C virus genotype 4 RNA.

PubMed

Chevaliez, Stéphane; Bouvier-Alias, Magali; Rodriguez, Christophe; Soulier, Alexandre; Poveda, Jean-Dominique; Pawlotsky, Jean-Michel

2013-04-01

Accurate hepatitis C virus (HCV) RNA quantification is mandatory for the management of chronic hepatitis C therapy. The first-generation Cobas AmpliPrep/Cobas TaqMan HCV test (CAP/CTM HCV) underestimated HCV RNA levels by >1-log10 international units/ml in a number of patients infected with HCV genotype 4 and occasionally failed to detect it. The aim of this study was to evaluate the ability of the Cobas AmpliPrep/Cobas TaqMan HCV test, version 2.0 (CAP/CTM HCV v2.0), to accurately quantify HCV RNA in a large series of patients infected with different subtypes of HCV genotype 4. Group A comprised 122 patients with chronic HCV genotype 4 infection, and group B comprised 4 patients with HCV genotype 4 in whom HCV RNA was undetectable using the CAP/CTM HCV. Each specimen was tested with the third-generation branched DNA (bDNA) assay, CAP/CTM HCV, and CAP/CTM HCV v2.0. The HCV RNA level was lower in CAP/CTM HCV than in bDNA in 76.2% of cases, regardless of the HCV genotype 4 subtype. In contrast, the correlation between bDNA and CAP/CTM HCV v2.0 values was excellent. CAP/CTM HCV v2.0 accurately quantified HCV RNA levels in the presence of an A-to-T substitution at position 165 alone or combined with a G-to-A substitution at position 145 of the 5' untranslated region of HCV genome. In conclusion, CAP/CTM HCV v2.0 accurately quantifies HCV RNA in genotype 4 clinical specimens, regardless of the subtype, and can be confidently used in clinical trials and clinical practice with this genotype.

Osteopontin Regulates Hepatitis C Virus (HCV) Replication and Assembly by Interacting with HCV Proteins and Lipid Droplets and by Binding to Receptors αVβ3 and CD44.

PubMed

Iqbal, Jawed; Sarkar-Dutta, Mehuli; McRae, Steven; Ramachandran, Akshaya; Kumar, Binod; Waris, Gulam

2018-07-01

Hepatitis C virus (HCV) replication and assembly occur at the specialized site of endoplasmic reticulum (ER) membranes and lipid droplets (LDs), respectively. Recently, several host proteins have been shown to be involved in HCV replication and assembly. In the present study, we demonstrated the important relationship among osteopontin (OPN), the ER, and LDs. OPN is a secreted phosphoprotein, and overexpression of OPN in hepatocellular carcinoma (HCC) tissue can lead to invasion and metastasis. OPN expression is also enhanced in HCV-associated HCC. Our recent studies have demonstrated the induction, proteolytic cleavage, and secretion of OPN in response to HCV infection. We also defined the critical role of secreted OPN in human hepatoma cell migration and invasion through binding to receptors integrin αVβ3 and CD44. However, the role of HCV-induced OPN in the HCV life cycle has not been elucidated. In this study, we showed a significant reduction in HCV replication, assembly, and infectivity in HCV-infected cells transfected with small interfering RNA (siRNA) against OPN, αVβ3, and CD44. We also observed the association of endogenous OPN with HCV proteins (NS3, NS5A, NS4A/B, NS5B, and core). Confocal microscopy revealed the colocalization of OPN with HCV NS5A and core in the ER and LDs, indicating a possible role for OPN in HCV replication and assembly. Interestingly, the secreted OPN activated HCV replication, infectivity, and assembly through binding to αVβ3 and CD44. Collectively, these observations provide evidence that HCV-induced OPN is critical for HCV replication and assembly. IMPORTANCE Recently, our studies uncovered the critical role of HCV-induced endogenous and secreted OPN in migration and invasion of hepatocytes. However, the role of OPN in the HCV life cycle has not been elucidated. In this study, we investigated the importance of OPN in HCV replication and assembly. We demonstrated that endogenous OPN associates with HCV NS3, NS5A, NS5B, and

[The velocity of HCV subtype 6a transmission in southwest China].

PubMed

Hong, Guo-hu; Tan, Zhao-xia; Guo, Yan; Mao, Qing

2011-07-01

To estimate the velocity of HCV subtype 6a transmission in Southwest China. The HCV CE1 region from 61 patients infected with HCV genotype 6 were amplificated by RT-PCR and sequenced. The subtypes were identified, and the period of HCV 6a strains originated in southwest china was estimated by using molecular clock phylogenetic analysis. The velocity of HCV subtype 6a transmission in southwest China was estimated by BEAST v1.6.1 and Tracer v1.5 software theoretically. Most of HCV 6a strains distributed in Southwest China origine around the year 1968 and at last 4 epidemic strains existed. The earlier origine strains could be isolated both in intravenous drug users (IDU) and non-IDU patients. After 1997, the HCV 6a strains transmission in southwest China accelerated and the trend intensified in 2007. HCV 6a strains spread fastly both in IDU and non-IDU patients, which might be the main HCV subtype distributed in Southwest China in the future.

High burden of HCV disease and poor access to HCV services among people who inject drugs in India: A cross-sectional study among 14,481 drug users across India

PubMed Central

Solomon, Sunil Suhas; Mehta, Shruti H; Srikrishnan, Aylur K; Solomon, Suniti; McFall, Allison M.; Laeyendecker, Oliver; Celentano, David D; Iqbal, Syed H; Anand, Santhanam; Vasudevan, Canjeevaram K; Saravanan, Shanmugam; Lucas, Gregory M; Kumar, Muniratnam S; Sulkowski, Mark S; Quinn, Thomas C

2014-01-01

Background Globally, 90% of HCV-infected individuals reside in resource-limited settings (RLS). We characterized the prevalence of HCV, HIV/HCV co-infection, and the HCV care continuum among people who inject drugs (PWID) in India. Methods 14,481 PWID were sampled from 15 cities throughout India using respondent-driven sampling (RDS) from January–December 2013. HCV prevalence was estimated by the presence of anti-HCV antibodies incorporating RDS weights. HCV care continuum outcomes were self-reported except for viral clearance among treatment-experienced participants. Findings Median age was 30 years and 13,608/14,449 (92·4%) were male. Overall weighted HCV prevalence was 37·2% (5,777/14,447); HIV/HCV co-infection prevalence was 13·2% (2,085/14,435). Correlates of HCV infection included higher lifetime injection frequency, HIV positivity, and a higher prevalence of persons with HIV RNA > 1000 copies/ml in the community. Of 5,777 HCV antibody positive PWID, 440 (5·5%) were aware of their status, 225 (3·0%) had seen a doctor for their HCV, 79 (1·4%) had taken HCV treatment, and 18 (0·4%) had undetectable HCV RNA. Overall, 6,138/12,128 (50·5%) did not get tested for HCV because they had never heard of HCV. Among the 5,777 HCV antibody positives, 2,086 (34·4%) reported harmful/hazardous alcohol use of whom 1,082 (50·4%) were dependent; 3,007 (52.9%) reported recent needle sharing. Awareness of HCV positive status was significantly associated with higher education, HIV testing history, awareness of HIV positive status, and higher community antiretroviral therapy coverage. Interpretation The high burden of HCV and HIV/HCV co-infection coupled with low-access to HCV services highlights an urgent need to include RLS in the global HCV agenda. While newer treatments will become available globally in the near future, programs to improve awareness, and reduce disease progression and transmission need to be scaled-up without further delay. Failure to do so could

Dynamics of HCV epidemiology in Aydin province of Turkey and the associated factors.

PubMed

Kirdar, Sevin; Aydin, Neriman; Tiryaki, Yasin; Ertugrul, Bulent; Coskun, Adil; Bilgen, Mehmet

2018-02-01

This paper gives an update on the local distributions of HCV genotypes in Aydin province of Turkey, provides a comparison with the previous records, and discusses the potential causal reasons shaping the evolving genotype profiles. Patient files from 2011 to 2016 were retrospectively analyzed, and newly detected cases were documented. Out of 286 patients, male and female ratios were determined to remain nearly the same (~50%). Genotype 1 was still the most common (90.2%), followed by genotype 3 (5.9%), genotype 2 (2.1%), and genotype 4 (1.4%) in frequency. There were international patients (4.50%). One patient had genotyped 2+3 together. Genotypes 4 and 2+3 were detected for the first time, and the patients with genotype 4 were interestingly all male and also domestic individuals. However, these patients traveled or lived abroad in the past due to occupational reasons, thereby likely acquired the infection while abroad. HCV surveillance system is currently inadequate and some infected patients may go undetected in the province. Remapping the regional distribution of HCV genotypes from time-to-time is required for identifying the local dynamics and causes leading to it. This process enhances the clinical preparation and readiness for the better management of the disease. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Consensus statement on the management of patients with HCV infection in Romania

PubMed Central

Ancuța, Ioan

2017-01-01

Background HCV direct-acting antivirals (DAAs) have made treatment easier for both patients and healthcare practitioners, but have also brought new challenges in terms of patient management and monitoring prior to, during, and after treatment. Methods To sum up and unify the clinical experience of Romanian DAA prescribing physicians, we have organized a Consensus Meeting in November 2016 in Bucharest, Romania. Consensus Statement The Consensus Meeting has provided expert answers to ten significant questions regarding HCV infection, namely: How do we diagnose patients with HCV infection? How do we stage liver disease in patients with HCV infection? How do we monitor patients with HCV infection prior to treatment? Which patients with HCV infection do we treat? When do we start treatment for HCV infection? What regimens do we use for treating HCV infection? How do we monitor patients with HCV infection during treatment? What adverse events should we expect during treatment of HCV infection and how do we prevent/manage them? How do we monitor patients with HCV infection after treatment? How do we expect the landscape of HCV to change in the following years? PMID:28331840

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ishida, Hisashi; Tatsumi, Tomohide; Hosui, Atsushi

2011-08-19

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

Rates of sustained virological response 12 weeks after the scheduled end of direct-acting antiviral (DAA)-based hepatitis C virus (HCV) therapy from the National German HCV registry: does HIV coinfection impair the response to DAA combination therapy?

PubMed

Bischoff, J; Mauss, S; Cordes, C; Lutz, T; Scholten, S; Moll, A; Jäger, H; Cornberg, M; Manns, M P; Baumgarten, A; Rockstroh, J K

2018-04-01

The European Association for the Study of the Liver (EASL) treatment recommendations for hepatitis C no longer discriminate between HIV/hepatitis C virus (HCV)-coinfected and HCV-monoinfected patients. However, recent data from Spain are questioning these recommendations on the basis of the findings of higher relapse rates and lower cure rates in HIV/HCV-infected subjects. The aim of our study was to compare HCV cure rates in monoinfected and coinfected patients from Germany. Data acquired from the Deutsches Hepatitis C-Registry were analysed. A total of 5657 HCV-monoinfected subjects and 488 HIV/HCV-coinfected patients were included in the study. Rates of sustained virological response 12 weeks after the scheduled end of therapy (SVR12) were collected in both subgroups and in cirrhotic and noncirrhotic patients. HIV/HCV-coinfected patients were more frequently male (84.6% vs. 56.4%, respectively; P < 0.001) and younger than HCV-monoinfected subjects (46.5 ± 9 vs. 53.8 ± 12.5 years, respectively; P < 0.001). The CD4 blood cell count was > 350 cells/μL in 63.1% of HIV-positive subjects and 88.7% were on antiretroviral therapy. SVR12 rates were 90.3% (5111 of 5657) in our HCV-monoinfected cohort and 91.2% (445 of 488) in our coinfected patients. Liver cirrhosis was confirmed in 1667 of 5657 (29.5%) monoinfected patients and 84 of 488 (17.2%; P < 0.001) coinfected patients. SVR12 rates did not differ between HCV-monoinfected and HIV/HCV-coinfected patients with liver cirrhosis (87.8% vs. 89.3%, respectively; P = 0.864). A treatment duration of 8 weeks did not reduce the percentage of patients with SVR12 in either subgroup (93.7% in both groups). We found high SVR12 rates in monoinfected as well as coinfected individuals. No differences were detected between the two subgroups regardless of whether there was accompanying liver cirrhosis or a shortened treatment duration. © 2018 British HIV Association.

Comparative evaluation of the VERSANT HCV RNA 3.0, QUANTIPLEX HCV RNA 2.0, and COBAS AMPLICOR HCV MONITOR version 2.0 Assays for quantification of hepatitis C virus RNA in serum.

PubMed

Germer, Jeffrey J; Heimgartner, Paul J; Ilstrup, Duane M; Harmsen, W Scott; Jenkins, Greg D; Patel, Robin

2002-02-01

A comparison of quantitative results expressed in hepatitis C virus (HCV) international units per milliliter, obtained from the VERSANT HCV RNA 3.0 (bDNA-3.0) assay, the QUANTIPLEX HCV RNA 2.0 (bDNA-2.0) assay, and the COBAS AMPLICOR HCV MONITOR version 2.0 (HCM-2.0) test was performed. A total of 168 patient specimens submitted to the Mayo Clinic Molecular Microbiology Laboratory for HCV quantification or HCV genotyping were studied. Of the specimens tested, 97, 88, and 79% yielded quantitative results within the dynamic range of the bDNA-3.0, bDNA-2.0, and HCM-2.0 assays, respectively. Overall, there was substantial agreement between the results generated by all three assays. A total of 15 out of 29 (52%) of the specimens determined to contain viral loads of <31,746 IU/ml by the bDNA-3.0 assay were categorized as containing viral loads within the range of 31,746 to 500,000 IU/ml by the bDNA-2.0 assay. Although substantial agreement was noted between the results generated by the bDNA-2.0 and bDNA-3.0 assays, a bias toward higher viral titer by the bDNA-2.0 assay was noted (P = 0.001). Likewise, although substantial agreement was noted between the results generated by the HCM-2.0 and bDNA-3.0 assays, a bias toward higher viral titer by the bDNA-3.0 assay was noted (P < or = 0.001). The discrepancy between the HCM-2.0 and bDNA-3.0 results was more pronounced when viral loads were >500,000 IU/ml and resulted in statistically significant differences (P < or = 0.001) in determining whether viral loads were above or below 800,000 IU/ml of HCV RNA, the proposed threshold value for tailoring the duration of combination therapy. The expression of quantitative values in HCV international units per milliliter was a strength of both the bDNA-3.0 and HCM-2.0 assays.

Comparative Evaluation of the VERSANT HCV RNA 3.0, QUANTIPLEX HCV RNA 2.0, and COBAS AMPLICOR HCV MONITOR Version 2.0 Assays for Quantification of Hepatitis C Virus RNA in Serum

PubMed Central

Germer, Jeffrey J.; Heimgartner, Paul J.; Ilstrup, Duane M.; Harmsen, W. Scott; Jenkins, Greg D.; Patel, Robin

2002-01-01

A comparison of quantitative results expressed in hepatitis C virus (HCV) international units per milliliter, obtained from the VERSANT HCV RNA 3.0 (bDNA-3.0) assay, the QUANTIPLEX HCV RNA 2.0 (bDNA-2.0) assay, and the COBAS AMPLICOR HCV MONITOR version 2.0 (HCM-2.0) test was performed. A total of 168 patient specimens submitted to the Mayo Clinic Molecular Microbiology Laboratory for HCV quantification or HCV genotyping were studied. Of the specimens tested, 97, 88, and 79% yielded quantitative results within the dynamic range of the bDNA-3.0, bDNA-2.0, and HCM-2.0 assays, respectively. Overall, there was substantial agreement between the results generated by all three assays. A total of 15 out of 29 (52%) of the specimens determined to contain viral loads of <31,746 IU/ml by the bDNA-3.0 assay were categorized as containing viral loads within the range of 31,746 to 500,000 IU/ml by the bDNA-2.0 assay. Although substantial agreement was noted between the results generated by the bDNA-2.0 and bDNA-3.0 assays, a bias toward higher viral titer by the bDNA-2.0 assay was noted (P = 0.001). Likewise, although substantial agreement was noted between the results generated by the HCM-2.0 and bDNA-3.0 assays, a bias toward higher viral titer by the bDNA-3.0 assay was noted (P ≤ 0.001). The discrepancy between the HCM-2.0 and bDNA-3.0 results was more pronounced when viral loads were >500,000 IU/ml and resulted in statistically significant differences (P ≤ 0.001) in determining whether viral loads were above or below 800,000 IU/ml of HCV RNA, the proposed threshold value for tailoring the duration of combination therapy. The expression of quantitative values in HCV international units per milliliter was a strength of both the bDNA-3.0 and HCM-2.0 assays. PMID:11825962

Characterization of Samples Identified as Hepatitis C Virus Genotype 1 without Subtype by Abbott RealTime HCV Genotype II Assay Using the New Abbott HCV Genotype Plus RUO Test.

PubMed

Mokhtari, Camelia; Ebel, Anne; Reinhardt, Birgit; Merlin, Sandra; Proust, Stéphanie; Roque-Afonso, Anne-Marie

2016-02-01

Hepatitis C virus (HCV) genotyping continues to be relevant for therapeutic strategies. Some samples are reported as genotype 1 (gt 1) without subtype by the Abbott RealTime HCV Genotype II (GT II) test. To characterize such samples further, the Abbott HCV Genotype Plus RUO (Plus) assay, which targets the core region for gt 1a, gt 1b, and gt 6 detection, was evaluated as a reflex test in reference to NS5B or 5'-untranslated region (UTR)/core region sequencing. Of 3,626 routine samples, results of gt 1 without subtype were received for 171 samples (4.7%), accounting for 11.5% of gt 1 specimens. The Plus assay and sequencing were applied to 98 of those samples. NS5B or 5'-UTR/core region sequencing was successful for 91/98 specimens (92.9%). Plus assay and sequencing results were concordant for 87.9% of specimens (80/91 samples). Sequencing confirmed Plus assay results for 82.6%, 85.7%, 100%, and 89.3% of gt 1a, gt 1b, gt 6, and non-gt 1a/1b/6 results, respectively. Notably, 12 gt 6 samples that had been identified previously as gt 1 without subtype were assigned correctly here; for 25/28 samples reported as "not detected" by the Plus assay, sequencing identified the samples as gt 1 with subtypes other than 1a/1b. The genetic variability of HCV continues to present challenges for the current genotyping platforms regardless of the applied methodology. Samples identified by the GT II assay as gt 1 without subtype can be further resolved and reliably characterized by the new Plus assay. Copyright © 2016 Mokhtari et al.

HCV core protein represses the apoptosis and improves the autophagy of human hepatocytes

PubMed Central

Liu, Changhong; Qu, Aihua; Han, Xiaochun; Wang, Yiguo

2015-01-01

Objectives: This study aims to investigate the influence on human hepatocytes apoptosis and autophagy by the hepatitis C virus (HCV) core protein. Methods: QSG-7701, a human-derived non-neoplastic liver cell line, was transfected with PIRES-core vector that was a eukaryotic vector to express HCV core protein. Fluorescence microscope was used to observe the changes of nuclei in apoptosis cells by Annex in V-FITC/PI double staining. Flow cytometry was applied to detect the rate of cell apoptosis. Western blotting was used to detect the expression of HCV core protein, transcription factor nuclear factor-kappa B (NF-κB), autophagic biomarker microtubule associated protein 1 light chain 3 (LC3), and Beclin-1. Results: The apoptosis rate was significantly lower (P < 0.05) in QSG7701/core group (transfected with PIRES-core vector, (1.34±0.07)%) than in QSG7701 group (no transfection, (2.35±0.11)%) and in QSG7701 QSG7701/pcDNA3.1 group (transfected with pcDNA3.1 vector, (2.58±0.1)%). NF-κB expression was up-expressed in QSG7701/core group than in QSG7701/pcDNA3.1 group and QSG7701 group (P < 0.05). LC3-II expression and Beclin-1 expression was significant higher in QSG7701/core group than in the QSG7701/pcDNA3.1 group and QSG7701 group (P < 0.05). Conclusion: HCV core protein can repress the apoptosis and improve the autophagy of QSG7701 through up-regulating NF-κB and Beclin-1 expression. PMID:26629077

HCV RNA traffic and association with NS5A in living cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fiches, Guillaume N.; Eyre, Nicholas S.; Aloia, Amanda L.

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.more » 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.« less

Entry inhibitors: New advances in HCV treatment

PubMed Central

Qian, Xi-Jing; Zhu, Yong-Zhe; Zhao, Ping; Qi, Zhong-Tian

2016-01-01

Hepatitis C virus (HCV) infection affects approximately 3% of the world's population and causes chronic liver diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. Although current antiviral therapy comprising direct-acting antivirals (DAAs) can achieve a quite satisfying sustained virological response (SVR) rate, it is still limited by viral resistance, long treatment duration, combined adverse reactions, and high costs. Moreover, the currently marketed antivirals fail to prevent graft reinfections in HCV patients who receive liver transplantations, probably due to the cell-to-cell transmission of the virus, which is also one of the main reasons behind treatment failure. HCV entry is a highly orchestrated process involving initial attachment and binding, post-binding interactions with host cell factors, internalization, and fusion between the virion and the host cell membrane. Together, these processes provide multiple novel and promising targets for antiviral therapy. Most entry inhibitors target host cell components with high genetic barriers and eliminate viral infection from the very beginning of the viral life cycle. In future, the addition of entry inhibitors to a combination of treatment regimens might optimize and widen the prevention and treatment of HCV infection. This review summarizes the molecular mechanisms and prospects of the current preclinical and clinical development of antiviral agents targeting HCV entry. PMID:26733381

HBV Bypasses the Innate Immune Response and Does Not Protect HCV From Antiviral Activity of Interferon.

PubMed

Mutz, Pascal; Metz, Philippe; Lempp, Florian A; Bender, Silke; Qu, Bingqian; Schöneweis, Katrin; Seitz, Stefan; Tu, Thomas; Restuccia, Agnese; Frankish, Jamie; Dächert, Christopher; Schusser, Benjamin; Koschny, Ronald; Polychronidis, Georgios; Schemmer, Peter; Hoffmann, Katrin; Baumert, Thomas F; Binder, Marco; Urban, Stephan; Bartenschlager, Ralf

2018-05-01

Hepatitis C virus (HCV) infection is sensitive to interferon (IFN)-based therapy, whereas hepatitis B virus (HBV) infection is not. It is unclear whether HBV escapes detection by the IFN-mediated immune response or actively suppresses it. Moreover, little is known on how HBV and HCV influence each other in coinfected cells. We investigated interactions between HBV and the IFN-mediated immune response using HepaRG cells and primary human hepatocytes (PHHs). We analyzed the effects of HBV on HCV replication, and vice versa, at the single-cell level. PHHs were isolated from liver resection tissues from HBV-, HCV-, and human immunodeficiency virus-negative patients. Differentiated HepaRG cells overexpressing the HBV receptor sodium taurocholate cotransporting polypeptide (dHepaRGNTCP) and PHHs were infected with HBV. Huh7.5 cells were transfected with circular HBV DNA genomes resembling viral covalently closed circular DNA (cccDNA), and subsequently infected with HCV; this served as a model of HBV and HCV coinfection. Cells were incubated with IFN inducers, or IFNs, and antiviral response and viral replication were analyzed by immune fluorescence, reverse-transcription quantitative polymerase chain reaction, enzyme-linked immunosorbent assays, and flow cytometry. HBV infection of dHepaRGNTCP cells and PHHs neither activated nor inhibited signaling via pattern recognition receptors. Incubation of dHepaRGNTCP cells and PHHs with IFN had little effect on HBV replication or levels of cccDNA. HBV infection of these cells did not inhibit JAK-STAT signaling or up-regulation of IFN-stimulated genes. In coinfected cells, HBV did not prevent IFN-induced suppression of HCV replication. In dHepaRGNTCP cells and PHHs, HBV evades the induction of IFN and IFN-induced antiviral effects. HBV infection does not rescue HCV from the IFN-mediated response. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Distribution of HCV genotypes in Poland.

PubMed

Panasiuk, Anatol; Flisiak, Robert; Mozer-Lisewska, Iwona; Adamek, Agnieszka; Tyczyno, Małgorzata; Halota, Waldemar; Pawłowska, Małgorzata; Stańczak, Janusz; Berak, Hanna; Wawrzynowicz-Syczewska, Marta; Boroń-Kaczmarska, Anna; Łapiński, Tadeusz Wojciech; Grzeszczuk, Anna; Piekarska, Anna; Tomasiewicz, Krzysztof; Jabłkowski, Maciej; Kryczka, Wiesław; Zarebska-Michaluk, Dorota; Stepień, Piotr; Garlicki, Aleksander Michał; Kozłowska, Joanna; Wiercińska-Drapało, Alicja; Zasik, Ewelina; Mazur, Waldemar; Dobracka, Bozena; Dobracki, Witold; Simon, Krzysztof; Ryzko, Józef; Pawłowska, Joanna; Dzierzanowska-Fangrat, Katarzyna; Januszkiewicz-Lewandowska, Danuta; Szenborn, Leszek; Zaleska, Izabela; Rokitka, Maria; Strawińska, Elzbieta; Balinowska, Katarzyna; Smiatacz, Tomasz; Stalke, Piotr; Sikorska, Katarzyna; Lakomy, Anna; Zdrojewski, Maciej; Lachowicz, Anna

2013-01-01

Available data on prevalence of HCV genotypes in Poland are insufficient. The aim of the study was the analysis of distribution of HCV genotypes in Poland over the period of recent 10 years regarding the age of patients and the regions of the country. Analysis of HCV genotypes in Poland was carried out between 2003 and 2012, and included 14 651 patients from 22 centers where patients with chronic viral hepatitis C are diagnosed and treated. Genotypes were analyzed in age groups (< 20 years of age, 20-40 years of age, > 40 years of age) as well as in populations of HBV and HIV co-infections. Genotype (G) 1 infection was demonstrated in 79.4%, G2 -0.1%, G3- 13.8%, G4- 4.9%, G6-0.09% and mixed infections in 1.6%. There was no infection with genotype 5. The highest prevalence of G1 was observed in the Łódzkie voivodship (89.2%) and the Slaskie voivodship (86.7%) while the lowest one in the Warmińsko-mazurskie (62.0%) and the Podlaskie voivodships (68.2%). Genotype 3 most commonly occurs in the Warmińsko-mazurskie (28.1%), and the Podlaskie voivodships (23.0%) and is least common in the Małopolskie (7.9%) and the Łódzkie voivodships (9.0%). Genotype 4 is more common in the Kujawsko-pomorskie (11.7%) and the Podlaskie voivodships (8.6%) and relatively less common in the Lubelskie (1.1%) and the Łódzkie voivodships (1.8%). Prevalence of G1 infection in 2003-2004 was 72% and increased up to 85.6% in 2011-2012, that was accompanied by decrease of G3 prevalence from 17% to 8% in this period. In HBV co-infected (n = 83), G1 infection was demonstrated in 85.5%, G3 - in 7.2%, G4 -4.8%, and mixed genotypes in 6%. Among HIV co-infected (n = 391), a much lower prevalence of G1 (33.0%) and a high of G3 (40.4%) as well as G4 (24.0%) were observed. There is a geographic variability of HCV genotypes prevalence in Poland. Increase of HCV G1 infections and decrease of G3 and G4 were observed in the last 10 years. Genotypes G3 and G4 occur more often in HCV/HIV co-infected than

Liver transplantation for HCV cirrhosis at Karolinska University Hospital Huddinge, Stockholm.

PubMed

Gjertsen, H; Weiland, O; Oksanen, A; Söderdahl, G; Broomé, U; Ericzon, B-G

2006-10-01

Hepatitis C virus (HCV)-induced cirrhosis is the major indication for liver transplantation globally, and an increasing indication for liver transplantation in Sweden. We have retrospectively examined the 120 patients transplanted for HCV cirrhosis from 1987 through 2005, including 11 who received more than one graft. The 1-, 3-, and 5-year postoperative survivals for all patients transplanted for HCV with or without hepatocellular cancer (HCC) were 77%, 66%, and 53%, respectively. HCV patients without HCC had a 1-, 3-, and 5-year survivals of 78%, 73%, and 61%, compared with 84%, 79% and 74%, respectively, for patients transplanted with chronic liver diseases without cancer or HCV. The number of patients with HCV cirrhosis transplanted in our center is increasing. Compared with patients transplanted for other chronic liver diseases, we experienced inferior results among patients with HCV cirrhosis.

A comparative evaluation between real time Roche COBas TAQMAN 48 HCV and bDNA Bayer Versant HCV 3.0.

PubMed

Giraldi, Cristina; Noto, Alessandra; Tenuta, Robert; Greco, Francesca; Perugini, Daniela; Spadafora, Mario; Bianco, Anna Maria Lo; Savino, Olga; Natale, Alfonso

2006-10-01

The HCV virus is a common human pathogen made of a single stranded RNA genome with 9600nt. This work compared two different commercial methods used for HCV viral load, the bDNA Bayer Versant HCV 3.0 and the RealTime Roche COBAS TaqMan 48 HCV. We compared the reproducibility and linearity of the two methods. Seventy-five plasma samples with genotypes 1 to 4, which represent the population (45% genotype 1; 24% genotype 2; 13% genotype 3; 18% genotype 4) were directly processed with the Versanto method based upon signal amplification; the same samples were first extracted (COBAS Ampliprep - TNAI) and then amplified using RealTime PCR (COBAS TaqMan 48). The results obtained indicate the same performance for both methods if they have genotype 1, but in samples with genotypes 2, 3 and 4 the RealTime PCR Roche method gave an underestimation in respect to the Bayer bDNA assay.

A novel anticancer agent ARC antagonizes HIV-1 and HCV.

PubMed

Nekhai, S; Bhat, U G; Ammosova, T; Radhakrishnan, S K; Jerebtsova, M; Niu, X; Foster, A; Layden, T J; Gartel, A L

2007-05-31

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) pose major public health concerns worldwide. HCV is clearly associated with the occurrence of hepatocellular carcinoma, and recently HIV infection has also been linked to the development of a multitude of cancers. Previously, we identified a novel nucleoside analog transcriptional inhibitor ARC (4-amino-6-hydrazino-7-beta-D-ribofuranosyl-7H-pyrrolo[2,3-d]-pyrimidine-5-carboxamide) that exhibited proapoptotic and antiangiogenic properties in vitro. Here, we evaluated the effect of ARC on HIV-1 transcription and HCV replication. Using reporter assays, we found that ARC inhibited HIV-1 Tat-based transactivation in different cell systems. Also, using hepatoma cells that harbor subgenomic and full-length replicons of HCV, we found that ARC inhibited HCV replication. Together, our data indicate that ARC could be a promising candidate for the development of antiviral therapeutics against HIV and HCV.

Linkage and retention in HCV care for HIV-infected populations: early data from the DAA era.

PubMed

Sacks-Davis, Rachel; Doyle, Joseph S; Rauch, Andri; Beguelin, Charles; Pedrana, Alisa E; Matthews, Gail V; Prins, Maria; van der Valk, Marc; Klein, Marina B; Saeed, Sahar; Lacombe, Karine; Chkhartishvili, Nikoloz; Altice, Frederick L; Hellard, Margaret E

2018-04-01

There is currently no published data on the effectiveness of DAA treatment for elimination of HCV infection in HIV-infected populations at a population level. However, a number of relevant studies and initiatives are emerging. This research aims to report cascade of care data for emerging HCV elimination initiatives and studies that are currently being evaluated in HIV/HCV co-infected populations in the context of implementation science theory. HCV elimination initiatives and studies in HIV co-infected populations that are currently underway were identified. Context, intervention characteristics and cascade of care data were synthesized in the context of implementation science frameworks. Seven HCV elimination initiatives and studies were identified in HIV co-infected populations, mainly operating in high-income countries. Four were focused mainly on HCV elimination in HIV-infected gay and bisexual men (GBM), and three included a combination of people who inject drugs (PWID), GBM and other HIV-infected populations. None were evaluating treatment delivery in incarcerated populations. Overall, HCV RNA was detected in 4894 HIV-infected participants (range within studies: 297 to 994): 48% of these initiated HCV treatment (range: 21% to 85%; within studies from a period where DAAs were broadly available the total is 57%, range: 36% to 74%). Among studies with treatment completion data, 96% of 1109 initiating treatment completed treatment (range: 94% to 99%). Among those who could be assessed for sustained virological response at 12 weeks (SVR12), 1631 of 1757 attained SVR12 (93%, range: 86% to 98%). Early results from emerging research on HCV elimination in HIV-infected populations suggest that HCV treatment uptake is higher than reported levels prior to DAA treatment availability, but approximately half of patients remain untreated. These results are among diagnosed populations and additional effort is required to increase diagnosis rates. Among those who have

Prevalence of hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus and hepatitis E virus as causes of acute viral hepatitis in North India: a hospital based study.

PubMed

Jain, P; Prakash, S; Gupta, S; Singh, K P; Shrivastava, S; Singh, D D; Singh, J; Jain, A

2013-01-01

Acute viral hepatitis (AVH) is a major public health problem and is an important cause of morbidity and mortality. The aim of the present study is to determine the prevalence of hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV) as causes of AVH in a tertiary care hospital of North India. Blood samples and clinical information was collected from cases of AVH referred to the Grade I viral diagnostic laboratory over a 1-year period. Samples were tested for hepatitis B surface antigen, anti-HCV total antibodies, anti-HAV immunoglobulin M (IgM) and anti-HEV IgM by the enzyme-linked immunosorbent assay. PCR for nucleic acid detection of HBV and HCV was also carried out. Those positive for HBV infection were tested for anti-HDV antibodies. Fisher's exact test was used and a P < 0.05 was considered to be statistically significant. Of the 267 viral hepatitis cases, 62 (23.22%) patients presented as acute hepatic failure. HAV (26.96%) was identified as the most common cause of acute hepatitis followed by HEV (17.97%), HBV (16.10%) and HCV (11.98%). Co-infections with more than one virus were present in 34 cases; HAV-HEV co-infection being the most common. HEV was the most important cause of acute hepatic failure followed by co-infection with HAV and HEV. An indication towards epidemiological shift of HAV infection from children to adults with a rise in HAV prevalence was seen. To the best of our knowledge, this is the first report indicating epidemiological shift of HAV in Uttar Pradesh.

Detection and genotyping of torque teno virus (TTV) in healthy blood donors and patients infected with HBV or HCV in Qatar.

PubMed

AbuOdeh, Raed; Al-Mawlawi, Naema; Al-Qahtani, Ahmed A; Bohol, Marie Fe F; Al-Ahdal, Mohammed N; Hasan, Haydar A; AbuOdeh, Lamees; Nasrallah, Gheyath K

2015-07-01

Torque Teno virus (TTV) has been associated with non A-G hepatitis. The goal of this study was to estimate the infection rates and genotypic characteristics of TTV in the State of Qatar. A total of 644 blood samples representing different nationalities: (i) Qatari (118) and (ii) non-Qatari (526) nationals (mostly from Arab and South Eeast Asia countries) were tested for the presence of TTV DNA by nested PCR. The majority (573) of the blood samples belonged to healthy blood donors, whereas 54 and 53 of the blood samples belonged to patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV), respectively. The results obtained showed that the TTV infection rates in the healthy blood donors, and those infected with HBV or HCV patients were 81.4, 90.75 and 84.9%, respectively. Significant association between TTV viremia and age, or nationality was observed. Sequence analysis of PCR fragments amplified from the 5'-untranslated region (5'-UTR) of all (531) TTV positive samples showed that 65.5% (348/531) of the PCR fragment sequences were classified into main genogroup 3, followed by main genogroups 5 (24%), 2 (5.8%), and 1 (4.7%). Genogroup 4 was not detected among the our studied subjects. Phylogenetic and pairwise analyses using sequences from TTV viremic samples also showed an overall close similarity to the main genogroup 3. In conclusion, there was no significant difference in the rates of TTV detection among Qataris and non-Qataris and several genotypes, mainly genotype 3, were isolated. © 2015 Wiley Periodicals, Inc.

Effect of genotypes on the quantification of hepatitis C virus (HCV) RNA in clinical samples using the Amplicor HCV Monitor Test and the Quantiplex HCV RNA 2.0 assay (bDNA).

PubMed

Tong, C Y; Hollingsworth, R C; Williams, H; Irving, W L; Gilmore, I T

1998-07-01

The Amplicor HCV Monitor test and the Quantiplex HCV RNA 2.0 (bDNA) assay are two commercially available assays for the quantification of hepatitis C virus (HCV) RNA in clinical samples. A direct comparison of the two assays was carried out using sera frozen previously from patients known to be chronically infected with HCV. Overall, 61 samples from 51 patients were tested simultaneously by the two methods: 67% (28/42) of the patients were infected by HCV genotype/serotype 1, 10% (4/42) with type 2, and 24% (10/42) with type 3. When the absolute value from each assay was examined, the Quantiplex assay gave a consistently higher reading and the mean logarithmic difference between the two assays was 1.4 (1.0 in type 1, 2.0 in type 2, and 2.2 in type 3). When analyzed according to genotype, strong correlation was observed between the two assays for type 1 (r = 0.83, 95% CI 0.63-0.93, P < 0.01), but not for nontype 1 samples. Despite the difference in absolute level reported by the two assays, there was a consistent trend of change in HCV RNA concentration by both assays in patients whose consecutive samples were analyzed and the differences between the two assays in consecutive samples were within 0.4 log of each other. The results suggested that with samples containing genotype 1, the Amplicor assay was more sensitive than the Quantiplex assay by about one log. However, the sensitivities of the two assays with nontype 1 samples were much closer probably due to the failure of the Amplicor assay to quantify nontype 1 genotypes effectively.

Natural history of acute and chronic hepatitis C.

PubMed

Maasoumy, Benjamin; Wedemeyer, Heiner

2012-08-01

Hepatitis C virus (HCV) infection remains a major global health burden. Hepatitis C causes significant liver-related morbidity and mortality due to hepatic decompensation and development of hepatocellular carcinoma. In addition, extra-hepatic manifestations of hepatitis C are frequent. There is a very large interindividual variability in the natural history of both acute and chronic hepatitis C which can be explained in part by a combination of various host, viral and environmental factors. Successful antiviral treatment can prevent short- and long-term complications of HCV infection in many patients. Still, the relative contribution of distinct risk factors for disease progression in different phases of HCV infection needs to be better defined. Personalized treatment approaches for HCV infection should consider individual risk profiles to avoid both under- and over-treatment - which will remain important also in upcoming era of interferon-free treatment of hepatitis C. Copyright © 2012. Published by Elsevier Ltd.

Induction of humoural and cellular immunity by immunisation with HCV particle vaccine in a non-human primate model.

PubMed

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/.

Interferon-free therapy in hepatitis C virus (HCV) monoinfected and HCV/HIV coinfected patients: effect on cognitive function, fatigue, and mental health.

PubMed

Kleefeld, Felix; Heller, Sophie; Ingiliz, Patrick; Jessen, Heiko; Petersen, Anders; Kopp, Ute; Kraft, Antje; Hahn, Katrin

2018-05-21

The efficacy and safety of interferon-free therapies for hepatitis C virus (HCV) infection have been reported. Considering the accumulating evidence for a direct central nervous system infection by HCV, we aim to evaluate the effect of direct acting antivirals (DAA) therapy on cognitive function in HCV patients. We conducted a longitudinal analysis of the cognitive performance of 22 patients (8 HCV+, 14 HCV+/HIV+) who completed neuropsychological testing at baseline and at week 12 after DAA therapy. In 20 patients, we analyzed specific attention parameters derived from an experimental testing based on the Theory of Visual Attention (TVA). Depression, fatigue, and mental health were assessed as patient reported outcomes. At baseline, 54.5% of the patients met the criteria for cognitive impairment and 40% showed impairment in TVA parameters. Follow-up analysis revealed significant improvements in the domains of visual memory/learning, executive functions, verbal fluency, processing speed, and motor skills but not in verbal learning and attention/working memory. We did not observe significant improvement in visual attention measured by TVA. Fatigue and mental health significantly improved at follow-up. Our findings indicate that successful DAA treatment leads to cognitive improvements in several domains measured by standard neuropsychological testing. The absence of improvement in TVA parameters and of significant improvement in the domain of attention/working memory might reflect the persistence of specific cognitive deficits after HCV eradication. In summary, DAA treatment seems to have a positive effect on some cognitive domains and leads to an improvement in mental health and fatigue in HCV-infected patients.

Amino acid substitutions in the hepatitis C virus core region predict hepatocarcinogenesis following eradication of HCV RNA by all-oral direct-acting antiviral regimens.

PubMed

Ogata, Fumihiro; Akuta, Norio; Kobayashi, Masahiro; Fujiyama, Shunichiro; Kawamura, Yusuke; Sezaki, Hitomi; Hosaka, Tetsuya; Kobayashi, Mariko; Saitoh, Satoshi; Suzuki, Yoshiyuki; Suzuki, Fumitaka; Arase, Yasuji; Ikeda, Kenji; Kumada, Hiromitsu

2018-06-01

Impact of substitution of aa70 in the core region (Core aa70) in HCV genotype 1b (HCV-1b) on hepatocarcinogenesis following eradication of HCV RNA by direct-acting antiviral therapy is not clear. In a retrospective study, 533 patients with HCV-related chronic liver disease, with sustained virological response defined as negative HCV RNA at 12 weeks after cessation of direct-acting antiviral therapy, were examined to evaluate the relationship between Core aa70 substitution and hepatocarcinogenesis. Twelve patients developed hepatocellular carcinoma during the follow-up period. The cumulative hepatocarcinogenesis rates were 1.7% and 2.4% at the end of 1 and 2 years, respectively. Overall, multivariate analysis identified HCV subgroup (HCV-1b with Gln70(His70); P = 0.003) and age (>65 years; P = 0.049), as pretreatment predictors of hepatocarcinogenesis. In HCV-1b patients, multivariate analysis identified post-treatment Wisteria floribunda agglutinin positive Mac-2 binding protein (>1.8 COI; P = 0.042) and HCV subgroup (HCV-1b with Gln70(His70); P = 0.071), as predictors of hepatocarcinogenesis, including post-treatment parameter. In conclusion, Core aa70 substitution in HCV-1b at the start of direct-acting antiviral therapy is an important predictor of hepatocarcinogenesis following eradication of HCV RNA. This study emphasizes the importance of detection of Core aa70 substitution before initiating antiviral therapy. © 2018 Wiley Periodicals, Inc.

Treatment of chronic hepatitis C in patients with HIV/HCV coinfection

PubMed Central

Coppola, Nicola; Martini, Salvatore; Pisaturo, Mariantonietta; Sagnelli, Caterina; Filippini, Pietro; Sagnelli, Evangelista

2015-01-01

Hepatitis C virus (HCV) infection is one of the most frequent causes of comorbidity and mortality in the human immunodeficiency virus (HIV) population, and liver-related mortality is now the second highest cause of death in HIV-positive patients, so HCV infection should be countered with adequate antiviral therapy. In 2011 began the era of directly acting antivirals (DAAs) and the HCV NS3/4A protease inhibitors telaprevir and boceprevir were approved to treat HCV-genotype-1 infection, each one in combination with pegylated interferon alfa (Peg-IFN) + ribavirin (RBV). The addition of the first generation DAAs, strongly improved the efficacy of antiviral therapy in patients with HCV-genotype 1, both for the HCV-monoinfected and HIV/HCV coinfected, and the poor response to Peg-IFN + RBV in HCV/HIV coinfection was enhanced. These treatments showed higher rates of sustained virological response than Peg-IFN + RBV but reduced tolerability and adherence due to the high pill burden and the several pharmacokinetic interactions between HCV NS3/4A protease inhibitors and antiretroviral drugs. Then in 2013 a new wave of DAAs arrived, characterized by high efficacy, good tolerability, a low pill burden and shortened treatment duration. The second and third generation DAAs also comprised IFN-free regimens, which in small recent trials on HIV-positive patients have shown comforting preliminary results in terms of efficacy, tolerability and adherence. PMID:25674512

Universal opt-out screening for hepatitis C virus (HCV) within correctional facilities is an effective intervention to improve public health.

PubMed

Morris, Meghan D; Brown, Brandon; Allen, Scott A

2017-09-11

Purpose Worldwide efforts to identify individuals infected with the hepatitis C virus (HCV) focus almost exclusively on community healthcare systems, thereby failing to reach high-risk populations and those with poor access to primary care. In the USA, community-based HCV testing policies and guidelines overlook correctional facilities, where HCV rates are believed to be as high as 40 percent. This is a missed opportunity: more than ten million Americans move through correctional facilities each year. Herein, the purpose of this paper is to examine HCV testing practices in the US correctional system, California and describe how universal opt-out HCV testing could expand early HCV detection, improve public health in correctional facilities and communities, and prove cost-effective over time. Design/methodology/approach A commentary on the value of standardizing screening programs across facilities by mandating all facilities (universal) to implement opt-out testing policies for all prisoners upon entry to the correctional facilities. Findings Current variability in facility-level testing programs results in inconsistent testing levels across correctional facilities, and therefore makes estimating the actual number of HCV-infected adults in the USA difficult. The authors argue that universal opt-out testing policies ensure earlier diagnosis of HCV among a population most affected by the disease and is more cost-effective than selective testing policies. Originality/value The commentary explores the current limitations of selective testing policies in correctional systems and provides recommendations and implications for public health and correctional organizations.

The HCV and HIV coinfected patient: what have we learned about pathophysiology?

PubMed

Talal, Andrew H; Canchis, P Wilfredo; Jacobson, Ira

2002-02-01

Hepatitis C virus (HCV) infection is an important problem in individuals who are also infected with HIV. HCV infection is very common in HIV-infected individuals, occurring in approximately one quarter to one third of this group, presumably as a consequence of shared routes of transmission related to virologic and pathogenic aspects of the viral infections. Although both are single-stranded RNA viruses and share similar epidemiologic properties, there are many important differences. Although the quantity of HIV RNA in plasma is an important prognostic determinant of HIV infection, this has not been shown with HCV. A direct relationship is apparent between HIV-related destruction of CD4 cells and the clinical consequences of the disease resulting from immunodeficiency. The pathogenesis of HCV, which occurs as a consequence of hepatic fibrosis, is much more complex. The hepatic stellate cell, the major producer of the extracellular matrix protein, is the main contributor to hepatic fibrosis, but the mechanism by which HCV induces hepatic fibrosis remains unclear. Treatment of HCV is increasingly important in HIV-infected patients due to improved HIV-associated morbidity and mortality and due to the frequency with which HCV occurs in patients with HIV-HCV coinfection. Timing of treatment initiation, management of side effects, and possible effects of anti-HCV therapy on HIV are among the issues that need consideration. Also, because several issues concerning HCV are unique to coinfected patients, further research is needed to determine optimal management of HCV in this setting.

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

PubMed Central

2012-01-01

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. PMID:22409788

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

PubMed

Salmon-Ceron, Dominique; Cohen, Julien; Winnock, Maria; Roux, Perrine; Sadr, Firouze Bani; Rosenthal, Eric; Martin, Isabelle Poizot; Loko, Marc-Arthur; Mora, Marion; Sogni, Philippe; Spire, Bruno; Dabis, François; Carrieri, Maria Patrizia

2012-03-12

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. 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. 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. 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.

Modelling the impact of incarceration and prison‐based hepatitis C virus (HCV) treatment on HCV transmission among people who inject drugs in Scotland

PubMed Central

Martin, Natasha K.; Hickman, Matthew; Hutchinson, Sharon J.; Aspinall, Esther; Taylor, Avril; Munro, Alison; Dunleavy, Karen; Peters, Erica; Bramley, Peter; Hayes, Peter C.; Goldberg, David J.; Vickerman, Peter

2017-01-01

Abstract Background and Aims People who inject drugs (PWID) experience high incarceration rates, and previous incarceration is associated with elevated hepatitis C virus (HCV) transmission risk. In Scotland, national survey data indicate lower HCV incidence in prison than the community (4.3 versus 7.3 per 100 person‐years), but a 2.3‐fold elevated transmission risk among recently released (< 6 months) PWID. We evaluated the contribution of incarceration to HCV transmission among PWID and the impact of prison‐related prevention interventions, including scaling‐up direct‐acting antivirals (DAAs) in prison. Design Dynamic mathematical modelling of incarceration and HCV transmission, using approximate Bayesian computation for model calibration. Setting Scotland, UK. Participants A simulated population of PWID. Measurements Population‐attributable fraction (PAF) of incarceration to HCV transmission among PWID. Decrease in HCV incidence and chronic prevalence due to current levels of prison opiate substitution therapy (OST; 57% coverage) and HCV treatment, as well as scaling‐up DAAs in prison and/or preventing the elevated risk associated with prison release. Findings Incarceration contributes 27.7% [PAF; 95% credible interval (CrI) –3.1 to 51.1%] of HCV transmission among PWID in Scotland. During the next 15 years, current HCV treatment rates (10.4/6.8 per 1000 incarcerated/community PWID annually), with existing prison OST, could reduce incidence and chronic prevalence among all PWID by a relative 10.7% (95% CrI = 8.4–13.3%) and 9.7% (95% CrI = 7.7–12.1%), respectively. Conversely, without prison OST, HCV incidence and chronic prevalence would decrease by 3.1% (95% CrI = –28.5 to 18.0%) and 4.7% (95% CrI = –11.3 to 14.5%). Additionally, preventing the heightened risk among recently released PWID could reduce incidence and chronic prevalence by 45.0% (95% CrI = 19.7–57.5%) and 33.3% (95% CrI = 15.6–43.6%) or scaling‐up prison

The design of drugs for HIV and HCV.

PubMed

De Clercq, Erik

2007-12-01

Since the discovery of the human immunodeficiency virus (HIV) in 1983, dramatic progress has been made in the development of novel antiviral drugs. The HIV epidemic fuelled the development of new antiviral drug classes, which are now combined to provide highly active antiretroviral therapies. The need for the treatment of hepatitis C virus (HCV), which was discovered in 1989, has also provided considerable impetus for the development of new classes of antiviral drugs, and future treatment strategies for chronic HCV might involve combination regimens that are analogous to those currently used for HIV. By considering the drug targets in the different stages of the life cycle of these two viruses, this article presents aspects of the history, medicinal chemistry and mechanisms of action of approved and investigational drugs for HIV and HCV, and highlights general lessons learned from anti-HIV-drug design that could be applied to HCV.

HBV or HCV Coinfection in HIV-1-Infected Pregnant Women in France: Prevalence and Pregnancy Outcomes.

PubMed

Benhammou, Valérie; Tubiana, Roland; Matheron, Sophie; Sellier, Pierre; Mandelbrot, Laurent; Chenadec, Jérôme Le; Marel, Emmanuelle; Khoshnood, Babak; Warszawski, Josiane

2018-04-15

Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is frequent in HIV-infected persons but their impact on pregnant HIV-infected women is understudied. We explored whether these coinfections are associated with adverse pregnancy outcomes and lower response to antiretroviral therapy (ART). Pregnancies in HIV-1-infected women included in the ANRS French Perinatal Cohort between 2005 and 2013 were analyzed if HBV and HCV infection statuses were available. Among 4236 women, the prevalence of HBV (HBs Ag+) and HCV (RNA+) were 6.2% (95% confidence interval: 5.4 to 6.8) and 1.7% (1.3 to 2.1), respectively. HCV coinfection was strongly associated with a history of drug use; HBV coinfection was 6 times more frequent in women born in Sub-Saharan Africa than in European France. Baseline HIV viral load, CD4 count, and HIV care during pregnancy were similar in coinfected and monoinfected HIV mothers, except that 90% of HBV/HIV women were receiving tenofovir and/or lamivudine or emtricitabine. HCV coinfection was significantly associated with cholestasis [adjusted odds ratio: 4.1 (1.5-10.8), P = 0.005], preterm delivery [3.0 (1.6-5.7), P < 0.001], lower CD4 [2.6 (1.0-6.4), P < 0.001], and detectable viral load [2.3 (1.0-5.5), P = 0.06] at the end of pregnancy. HBV coinfection was not associated with any of these outcomes. In HIV-infected women, chronic HBV infection, mostly treated using targeted ART, had no major impact on the course of pregnancy. By contrast, chronic HCV infection was associated with a higher risk of obstetrical complications and a poorer immune-virological response to ART. It is yet unknown whether cure of HCV infection before conception can limit these adverse outcomes.

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

PubMed

Agrawal, Babita; Singh, Shakti; Gupta, Nancy; Li, Wen; Vedi, Satish; Kumar, Rakesh

2017-07-27

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.

HOMA-AD in Assessing Insulin Resistance in Lean Noncirrhotic HCV Outpatients.

PubMed

Michalczuk, Matheus Truccolo; Kappel, Camila Rippol; Birkhan, Oscar; Bragança, Ana Carolina; Alvares-da-Silva, Mário Reis

2012-01-01

Introduction. There is an association between HCV and insulin resistance (IR), which is currently assessed by HOMA-IR. There is evidence that HOMA-adiponectin (HOMA-AD) is more accurate, but its role in HCV patients is unknown. The purpose of this study was to evaluate IR in an HCV sample and controls, in order to compare the accuracy of HOMA-IR and HOMA-AD. Methods. Ninety-four HCV outpatients aged <60 years who met the criteria of nondiabetic, nonobese, noncirrhotic, and nonalcohol abusers were included and compared to 29 controls. Fasting glucose, insulin, adiponectin, and lipid profiles were determined. IR was estimated by HOMA-IR and HOMA-AD. Results. The groups were similar regarding sex and BMI, but the HCV patients were older. The median insulin level was higher in the HCV group (8.6 mU/mL (6.5-13.7) versus 6.5 (4.3-10.7), P = 0.004), as was median HOMA-IR (1.94 (1.51 to 3.48) versus 1.40 (1.02 to 2.36), P = 0.002) and the prevalence of IR (38.3% versus 10.3% (P = 0.009)). No differences were found in adiponectin levels (P = 0.294) and HOMA-AD (P = 0.393). Conclusion. IR is highly prevalent even in low-risk HCV outpatients. Adiponectin is not influenced by the presence of HCV. HOMA-AD does not seem to be useful in assessing IR in HCV patients.

Impact of HCV treatment and depressive symptoms on adherence to HAART among coinfected HIV-HCV patients: results from the ANRS-CO13-HEPAVIH cohort

PubMed Central

Roux, Perrine; Lions, Caroline; Cohen, Julien; Winnock, Maria; Salmon-Céron, Dominique; Bani-Sadr, Firouzé; Sogni, Philippe; Spire, Bruno; Dabis, François; Carrieri, Maria Patrizia

2014-01-01

Background The additional burden of HCV infection in HIV-HCV coinfected individuals may have some consequences on adherence to highly active antiretroviral therapy (HAART). Few studies have explored the pattern of correlates of non-adherence to HAART while simultaneously considering the impact of HCV treatment and depressive symptoms on adherence to HAART. We used longitudinal data to assess factors associated with non-adherence to HAART. Methods The French national prospective cohort ANRS-CO-13-HEPAVIH is a multi-center cohort which recruited 1175 HIV-HCV coinfected patients in 17 hospital outpatient units delivering HIV and HCV care in France between October 2006 and June 2008. For this analysis, we selected participants on HAART with self-reported data for adherence to HAART (n = 727 patients, 1190 visits). Data were collected using self-administered questionnaires and medical records. A mixed logistic regression model based on an exchangeable correlation matrix was used to identify factors associated with non-adherence to HAART. Results Patients reported non-adherence to HAART in 808 (68%) of the 1190 visits. Four variables remained associated with non-adherence to HAART after multivariate analysis: hazardous alcohol consumption, cocaine use and depressive symptoms, regardless of whether treatment for depression was being received. Finally, patients being treated for HCV infection were less likely to be non-adherent to HAART. Conclusions Besides the problem of polydrug use, two other dimensions deserve special attention when considering adherence to HAART in HIV-HCV coinfected patients. Access to HCV treatment should be encouraged as well adequate treatment for depression in this population to improve adherence and response to HAART. PMID:24166726

Accidental exposure to HCV antibody-positive blood in hospital and pre-emptive one-shot interferon alpha-2b treatment.

PubMed

Nukaya, Haruhiko; Ohno, Tomoyoshi; Sakakibara, Kenji; Kato, Atunaga; Hasegawa, Izumi; Matunaga, Seijiro; Endo, Masayuki; Tanaka, Yoshito; Hirashima, Noboru; Tanaka, Yasuhito; Orito, Etsuro; Joh, Takashi; Mizokami, Masashi

2007-03-01

Infection with hepatitis viruses following blood exposure accidents, such as needle stick injuries, is a serious issue for medical staff. In particular, although accidental exposure to hepatitis C virus (HCV) occurs frequently, postexposure prophylactic measures have not been established yet. In this study we investigate the efficacy of recombinant alpha-2b interferon (IFN) as a single, 10 MU intramuscular injection for preventing transmission. 264 incidents of accidental blood to HCV antibody-positive blood, occurring between 1993 and 2003 in the Social Insurance Chukyo Hospital, were surveyed. Accident reports, which described in detail the circumstances and the presence or absence of infectious disease in the blood, and accidental exposure to HCV antibody-positive blood was investigated. Pre-emptive IFN treatment was given in 115 out of 157 cases occurring between 1993 and 1998. One case developed acute HCV. Phylogenetic analysis provided evidence that the accident caused the infection and the patient was cured by immediate IFN therapy. Between 1999 and 2003, the exposed were in principle followed-up without IFN treatment; IFN treatment was only given when requested. As a result, IFN was given in 14 of 107 cases. During this period, no transmission was observed. Taken together, the benefits of pre-emptive IFN treatment were considered unremarkable and a follow-up without treatment, or immediate IFN therapy after confirmation of the onset, was recommended.

Induction of multispecific Th-1 type immune response against HCV in mice by protein immunization using CpG and Montanide ISA 720 as adjuvants

PubMed Central

Qiu, Qi; Wang, Richard Yuan-Hu; Jiao, Xuanmao; Jin, Bo; Sugauchi, Fuminaka; Grandinetti, Teresa; Alter, Harvey J.; Shih, J. Wai-Kuo

2017-01-01

Recent studies demonstrate that Th1-type immune responses against a broad spectrum of hepatitis C virus (HCV) gene products are crucial to the resolution of acute HCV infection. We investigated new vaccine approaches to augment the strength of HCV-specific Th1-type immune responses. ELISPOT assay revealed that single or multiple protein immunization using both CpG ODN and Montanide ISA 720 as adjuvants induced much stronger IFN-γ-producing Th1 responses against core, NS3 and NS5b targets than did the formulation without these adjuvants. Protein vaccination using CpG ODN and Montanide ISA 720 as adjuvants also greatly enhanced humoral responses to HCV core, E1/E2 and NS3. When specific IgG isotypes were assayed, protein immunization using CpG ODN and Montanide ISA 720 as adjuvants produced higher titers of IgG2a dominant antibodies than did protein immunization alone, indicating a more Th1-biasedpathway. This increase in IgG2a is consistent with the induction of Th1 cells secreting IFN-γ demonstrated by ELISPOT assay. In conclusion, protein immunization using CpG ODN and Montanide ISA 720 as adjuvants greatly enhanced cellular (Th1 type) as well as humoral immune responses against HCV in Balb/c mice. The use of adjuvants appears critical to the induction of Th1 immune responses during HCV vaccination with recombinant proteins. PMID:18675871

Induction of multispecific Th-1 type immune response against HCV in mice by protein immunization using CpG and Montanide ISA 720 as adjuvants.

PubMed

Qiu, Qi; Wang, Richard Yuan-Hu; Jiao, Xuanmao; Jin, Bo; Sugauchi, Fuminaka; Grandinetti, Teresa; Alter, Harvey J; Shih, J Wai-Kuo

2008-10-09

Recent studies demonstrate that Th1-type immune responses against a broad spectrum of hepatitis C virus (HCV) gene products are crucial to the resolution of acute HCV infection. We investigated new vaccine approaches to augment the strength of HCV-specific Th1-type immune responses. ELISPOT assay revealed that single or multiple protein immunization using both CpG ODN and Montanide ISA 720 as adjuvants induced much stronger IFN-gamma-producing Th1 responses against core, NS3 and NS5b targets than did the formulation without these adjuvants. Protein vaccination using CpG ODN and Montanide ISA 720 as adjuvants also greatly enhanced humoral responses to HCV core, E1/E2 and NS3. When specific IgG isotypes were assayed, protein immunization using CpG ODN and Montanide ISA 720 as adjuvants produced higher titers of IgG2a dominant antibodies than did protein immunization alone, indicating a more Th1-biased pathway. This increase in IgG2a is consistent with the induction of Th1 cells secreting IFN-gamma demonstrated by ELISPOT assay. In conclusion, protein immunization using CpG ODN and Montanide ISA 720 as adjuvants greatly enhanced cellular (Th1 type) as well as humoral immune responses against HCV in Balb/c mice. The use of adjuvants appears critical to the induction of Th1 immune responses during HCV vaccination with recombinant proteins.

Seroprevalence of anti-HCV antibodies among blood donors of north India

PubMed Central

Makroo, R.N.; Walia, Rimpreet Singh; Chowdhry, Mohit; Bhatia, Aakanksha; Hegde, Vikas; Rosamma, N.L.

2013-01-01

Background & objectives: Transfusion of blood and blood products although considered as a life saving treatment modality, but may lead to certain infectious and non-infectious complications in the recipients. The purpose of this analysis was to monitor the seroprevalence of anti-HCV antibody in the blood donor population in a hospital based blood bank in north India, to evaluate the trends over the years (2001-2011). Methods: Relevant information of all the blood donors who donated whole blood at the department of Transfusion Medicine, Indraprastha Apollo Hospitals, New Delhi from the January 1, 2001 to December 31, 2011 was retrieved from the departmental records. The number of donors who were found reactive for anti-HCV anatibodies was calculated. Results: Of the 2,06,022 blood donors, 1,93,661 were males and 12,361 were females. The percentage of whole blood donors found seroreactive for anti-HCV antibodies was 0.39 per cent (n=795). The seroprevalence of anti-HCV in male blood donors was 0.38 per cent (n=750) and the respective seroprevalence in female blood donors was 0.36 per cent (n=45). No significant change in the trend of HCV seroprevalence was observed over the period under consideration. Maximum seroprevalence of anti-HCV was observed in the age group of 18 to 30 yr (0.41%) and the minimum in the age group of 51 to 60 yr (0.26%). Interpretation & conclusion: HCV seroprevalence in our study was 0.39 per cent and a decreasing trend with age was observed. No significant change in the trend of anti-HCV seroprevalence was seen over a decade. Since, no vaccine is presently available for immunization against HCV infection, transfusion transmitted HCV infection remains a potential threat to the safety of the blood supply. PMID:24056566

Analysis of resistance-associated substitutions in acute hepatitis C virus infection by deep sequencing across six genotypes and three continents.

PubMed

Eltahla, A A; Rodrigo, C; Betz-Stablein, B; Grebely, J; Applegate, T; Luciani, F; Schinkel, J; Dore, G J; Page, K; Bruneau, J; Morris, M D; Cox, A L; Kim, A Y; Shoukry, N H; Lauer, G M; Maher, L; Hellard, M; Prins, M; Lloyd, A R; Bull, R A

2017-01-01

Several direct-acting antivirals (DAAs) have been approved for the treatment of chronic hepatitis C virus (HCV) infections, opening the door to highly effective interferon-free treatment regimens. Resistance-associated substitutions (RASs) have been reported both in treatment-naïve patients and following treatment with protease (NS3), phosphoprotein (NS5A) and polymerase (NS5B) inhibitors. The prevalence of naturally occurring RASs in untreated HCV-infected individuals has mostly been analysed in those infected with genotype 1 (GT1), in the late phase of infection, and only within limited regions of the genome. Furthermore, the geographic distribution of RASs remains poorly characterized. In this study, we used next-generation sequencing to analyse full-length HCV genomes for the prevalence of RASs in acute HCV infections identified in nine international prospective cohorts. RASs were analysed in 179 participants infected with all six major HCV genotypes (GT1-GT6), and the geographic distribution of RASs was assessed in 107 GT1a and GT3a samples. While RASs were detected at varied frequencies across the three genomic regions, and between genotypes, RASs relevant to multiple DAAs in the leading IFN-free regimens were rarely detected in combination. Low-frequency RASs (<10% of the viral population) were also shown to have a GT-specific distribution. The main RASs with geographic associations were NS3 Q80K in GT1a samples and NS5B N142T in GT3a. These data provide the backdrop for prospective surveillance of RASs during DAA treatment scale-up. © 2016 John Wiley & Sons Ltd.

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

PubMed Central

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

2014-01-01

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

HCV core protein promotes hepatocyte proliferation and chemoresistance by inhibiting NR4A1

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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 withmore » 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

Occult HCV Infection: The Current State of Knowledge

PubMed Central

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

Interferon-free treatment for HCV-infected patients with decompensated cirrhosis.

PubMed

Kanda, Tatsuo

2017-01-01

Progress in interferon-free treatment against hepatitis C virus (HCV) has remained a challenge in patients with decompensated cirrhosis due to a paucity of information on efficacy and safety profiles. This review illustrates that interferon-free treatment could result in greater than 85 % sustained virological response (SVR) rates in patients with HCV genotype 1 and decompensated cirrhosis. The combination of pangenotypic HCV NS5A inhibitor velpatasvir and HCV NS5B inhibitor sofosbuvir has demonstrated high SVR rates in patients with HCV genotypes 1, 2, 3, 4 or 6 and decompensated cirrhosis. Certain patients discontinued treatment due to adverse events, death or having liver transplantation. Taken together, interferon-free treatment could produce higher SVR rates in decompensated hepatic cirrhosis. However, as adverse events were occasionally observed, liver transplantation should always be considered as well. Further improvements in treatment are called for in patients with decompensated cirrhosis.

Engineered Toxins “Zymoxins” Are Activated by the HCV NS3 Protease by Removal of an Inhibitory Protein Domain

PubMed Central

Shapira, Assaf; Gal-Tanamy, Meital; Nahary, Limor; Litvak-Greenfeld, Dana; Zemel, Romy; Tur-Kaspa, Ran; Benhar, Itai

2011-01-01

The synthesis of inactive enzyme precursors, also known as “zymogens,” serves as a mechanism for regulating the execution of selected catalytic activities in a desirable time and/or site. Zymogens are usually activated by proteolytic cleavage. Many viruses encode proteases that execute key proteolytic steps of the viral life cycle. Here, we describe a proof of concept for a therapeutic approach to fighting viral infections through eradication of virally infected cells exclusively, thus limiting virus production and spread. Using the hepatitis C virus (HCV) as a model, we designed two HCV NS3 protease-activated “zymogenized” chimeric toxins (which we denote “zymoxins”). In these recombinant constructs, the bacterial and plant toxins diphtheria toxin A (DTA) and Ricin A chain (RTA), respectively, were fused to rationally designed inhibitor peptides/domains via an HCV NS3 protease-cleavable linker. The above toxins were then fused to the binding and translocation domains of Pseudomonas exotoxin A in order to enable translocation into the mammalian cells cytoplasm. We show that these toxins exhibit NS3 cleavage dependent increase in enzymatic activity upon NS3 protease cleavage in vitro. Moreover, a higher level of cytotoxicity was observed when zymoxins were applied to NS3 expressing cells or to HCV infected cells, demonstrating a potential therapeutic window. The increase in toxin activity correlated with NS3 protease activity in the treated cells, thus the therapeutic window was larger in cells expressing recombinant NS3 than in HCV infected cells. This suggests that the “zymoxin” approach may be most appropriate for application to life-threatening acute infections where much higher levels of the activating protease would be expected. PMID:21264238

Improving HCV cure rates in HIV-coinfected patients - a real-world perspective.

PubMed

Lakshmi, Seetha; Alcaide, Maria; Palacio, Ana M; Shaikhomer, Mohammed; Alexander, Abigail L; Gill-Wiehl, Genevieve; Pandey, Aman; Patel, Kunal; Jayaweera, Dushyantha; Del Pilar Hernandez, Maria

2016-05-01

To study rates and predictors of hepatitis C virus (HCV) cure among human immunodeficiency virus (HIV)/HCV-coinfected patients, and then to evaluate the effect of attendance at clinic visits on HCV cure. Retrospective cohort study of adult HIV/HCV-coinfected patients who initiated and completed treatment for HCV with direct-acting antivirals (DAAs) between January 1, 2014, and June 30, 2015. Eighty-four participants reported completing treatment. The median age was 58 years (interquartile ratio, 50-66); 88% were male and 50% were black. One-third were cirrhotic and half were HCV-treatment-experienced. The most commonly used regimen was sofosbuvir/ledipasvir (40%) followed by simeprevir/sofosbuvir (30%). Cure was achieved in 83.3%, 11.9% relapsed, and 2.3% experienced virological breakthrough. Two patients (2.3%) did not complete treatment based on pill counts and follow-up visit documentation. In multivariable analysis, cure was associated with attendance at follow-up clinic visits (odds ratio [OR], 9.0; 95% CI, 2.91-163) and with use of an integrase-based HIV regimen versus other non-integrase regimens, such as non-nucleoside analogues or protease inhibitors (OR, 6.22; 95% CI 1.81-141). Age, race, genotype, presence of cirrhosis, prior HCV treatment, HCV regimen, and pre-treatment CD4 counts were not associated with cure. Real-world HCV cure rates with DAAs in HCV/HIV coinfection are lower than those seen in clinical trials. Cure is associated with attendance at follow-up clinic visits and with use of an integrase-based HIV regimen. Future studies should evaluate best antiretroviral regimens, predictors of attendance at follow-up visits, impact of different monitoring protocols on medication adherence, and interventions to ensure adequate models of HIV/HCV care.

HCV core protein induces hepatic lipid accumulation by activating SREBP1 and PPAR{gamma}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Kook Hwan; Hong, Sung Pyo; Kim, KyeongJin

2007-04-20

Hepatic steatosis is a common feature in patients with chronic hepatitis C virus (HCV) infection. HCV core protein plays an important role in the development of hepatic steatosis in HCV infection. Because SREBP1 (sterol regulatory element binding protein 1) and PPAR{gamma} (peroxisome proliferators-activated receptor {gamma}) are involved in the regulation of lipid metabolism of hepatocyte, we sought to determine whether HCV core protein may impair the expression and activity of SREBP1 and PPAR{gamma}. In this study, it was demonstrated that HCV core protein increases the gene expression of SREBP1 not only in Chang liver, Huh7, and HepG2 cells transiently transfectedmore » with HCV core protein expression plasmid, but also in Chang liver-core stable cells. Furthermore, HCV core protein enhanced the transcriptional activity of SREBP1. In addition, HCV core protein elevated PPAR{gamma} transcriptional activity. However, HCV core protein had no effect on PPAR{gamma} gene expression. Finally, we showed that HCV core protein stimulates the genes expression of lipogenic enzyme and fatty acid uptake associated protein. Therefore, our finding provides a new insight into the mechanism of hepatic steatosis by HCV infection.« less

An Outbreak of Acute Hepatitis in a Medical Facility of Bangladesh

PubMed Central

Mohammad Fazle Akbar, Sheikh; chandra Podder, Dulal; Kumar Saha, Paban; Jahan, Munira; Begum, Lovely; Afrose, Tanjina; chowdhury, Farzana; Rahman, Salimur

2014-01-01

ABSTRACT A total of 45 patients with acute hepatitis were detected in a medical facility of Bangladesh over a period of 6 months. All of them were physicians, nurses, students or employees of the hospital. About 50% of these patients suffered from acute hepatitis within a period of 2 months. All of them had clinical and biochemical evidences of acute hepatitis. All of them shared common working places as well as common dining and cooking facilities. Although the disease was supposed to be caused by hepatitis viruses, none of them were expressing IgM type antibody to hepatitis B core antigen (IgM anti-HBc) or hepatitis C virus (IgM anti-HCV). IgM type antibody to hepatitis A virus (IgM HAV) was detected in one patient and IgM type antibody to hepatitis E virus (anti-HEV IgM) were found in 14 patients. In conclusion, diagnosis of etiological agent of viral acute hepatitis constitutes a formidable challenge to the existing health care delivery system in developing countries as available serological and routine screening fails to find the proper etiological agent. How to cite this article: Mahtab MA, Akbar SMF, Podder DC, Saha PK, Jahan M, Begum L, Afrose T, Chowdhury F, Rahman S. An Outbreak of Acute Hepatitis in a Medical Facility of Bangladesh. Euroasian J Hepato-Gastroenterol 2014;4(1):66-67. PMID:29264325

An Outbreak of Acute Hepatitis in a Medical Facility of Bangladesh.

PubMed

Al Mahtab, Mamun; Mohammad Fazle Akbar, Sheikh; Chandra Podder, Dulal; Kumar Saha, Paban; Jahan, Munira; Begum, Lovely; Afrose, Tanjina; Chowdhury, Farzana; Rahman, Salimur

2014-01-01

A total of 45 patients with acute hepatitis were detected in a medical facility of Bangladesh over a period of 6 months. All of them were physicians, nurses, students or employees of the hospital. About 50% of these patients suffered from acute hepatitis within a period of 2 months. All of them had clinical and biochemical evidences of acute hepatitis. All of them shared common working places as well as common dining and cooking facilities. Although the disease was supposed to be caused by hepatitis viruses, none of them were expressing IgM type antibody to hepatitis B core antigen (IgM anti-HBc) or hepatitis C virus (IgM anti-HCV). IgM type antibody to hepatitis A virus (IgM HAV) was detected in one patient and IgM type antibody to hepatitis E virus (anti-HEV IgM) were found in 14 patients. In conclusion, diagnosis of etiological agent of viral acute hepatitis constitutes a formidable challenge to the existing health care delivery system in developing countries as available serological and routine screening fails to find the proper etiological agent. How to cite this article: Mahtab MA, Akbar SMF, Podder DC, Saha PK, Jahan M, Begum L, Afrose T, Chowdhury F, Rahman S. An Outbreak of Acute Hepatitis in a Medical Facility of Bangladesh. Euroasian J Hepato-Gastroenterol 2014;4(1):66-67.

Real-World Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir/+Dasabuvir±Ribavirin (OBV/PTV/r/+DSV±RBV) Therapy in Recurrent Hepatitis C Virus (HCV) Genotype 1 Infection Post-Liver Transplant: AMBER-CEE Study.

PubMed

Tronina, Olga; Durlik, Magdalena; Wawrzynowicz-Syczewska, Marta; Buivydiene, Arida; Katzarov, Krum; Kupcinskas, Limas; Tolmane, Ieva; Karpińska, Ewa; Pisula, Arkadiusz; Karwowska, Kornelia Magdalena; Bolewska, Beata; Jabłkowski, Maciej; Rostkowska, Karolina; Jakutiene, Jolita; Simonova, Marieta; Flisiak, Robert

2017-04-07

BACKGROUND The introduction of direct-acting antivirals (DAAs) has considerably improved therapeutic outcomes for patients with chronic hepatitis C virus (HCV) infections. The AMBER-CEE study aimed to assess real-world efficacy and safety of ombitasvir/paritaprevir/ritonavir/+ dasabuvir ±ribavirin (OBV/PTV/r/ +DSV±RBV) in the treatment of post-transplant recurrence of HCV infection. MATERIAL AND METHODS Liver transplant recipients with recurrent HCV genotype 1 infection, scheduled for OBV/PTV/r/+DSV±RBV according to therapeutic guidelines, were eligible. The primary efficacy endpoint was sustained virologic response (SVR) 12 weeks after the end of treatment (FU12). Clinical and laboratory adverse events (AEs) were recorded from baseline to FU12. RESULTS A total of 35 patients were included: 91.4% genotype 1b-infected, 94.3% treatment-experienced, and 77.1% at fibrosis stage ≥F2. SVR12 was achieved by all patients (35/35, 100%) including one patient with genotype 1a, one patient with detectable HCV RNA at the end of treatment, two patients with a history of first-generation DAA therapy, and two patients who prematurely discontinued the regimen. AEs were experienced by 22 patients (62.9%) and were mostly mild. No death, graft loss, or acute graft rejections were reported during the therapy. On-treatment hepatic decompensation occurred in three patients (8.6%). Anemia was observed in 29 patients (83.9%), with 21 (60%) requiring RBV dose reduction or discontinuation. CONCLUSIONS OBV/PTV/r/+DSV±RBV has excellent efficacy in post-transplant recurrence of HCV genotype 1-infection treated under real-world conditions. Excellent virologic outcomes were observed irrespective of prior treatment history or the degree of fibrosis, and AEs were mostly mild and transient.

Occult HCV Infection (OCI) Diagnosis in Cirrhotic and Non-cirrhotic Naïve Patients by Intra-PBMC Nested Viral RNA PCR.

PubMed

Abd Alla, Mohamed Darwish Ahmed; Elibiary, Saleh Ahmed; Wu, George Y; El-Awady, Mostafa Kamel

2017-12-28

.003). HCV-RNA seroconversion was associated with intra-PBMC infection when both sense and antisense strands were detected ( p = 0.047). Conclusions: Intracellular HCV-RNA evaluation is crucial for diagnosing OCIs and addressing relapse probability.

A multifaceted computational report on the variants effect on KIR2DL3 and IFNL3 candidate gene in HCV clearance.

PubMed

Singh, Pratichi; Dass, J Febin Prabhu

2016-10-01

HCV infection causes acute and chronic liver diseases including, cirrhosis and hepatocellular carcinoma. Following HCV infection, spontaneous clearance occurs in approximately 20 % of the population dependant upon HCV genotype. In this study, functional and non-functional variant analysis was executed for the classical and the latest HCV clearance candidate genes namely, KIR2DL3 and IFNL3. Initially, the functional effects of non-synonymous SNPs were assigned on exposing to homology based tools, SIFT, PolyPhen-2 and PROVEAN. Further, UTR and splice sites variants were scanned for the gene expression and regulation changes. Subsequently, the haplotype and CNV were also identified. The mutation H77Y of KIR2DL3 and R157Q, H156Y, S63L, R157W, F179V, H128R, T101M, R180C, and F176I of IFNL3 results in conservation, RMSD, total energy, stability, and secondary structures revealed a negative impact on the structural fitness. UTRscan and the splice site result indicate functional change, which may affect gene regulation and expression. The graphical display of selected population shows alleles like rs270779, rs2296370, rs10423751, rs12982559, rs9797797, and rs35987710 of KIR2DL3 and rs12972991, rs12980275, rs4803217, rs8109886, and rs8099917 of IFNL3 are in high LD with a measure of [Formula: see text] broadcasting its protective effect in HCV clearance. Similarly, CNV report suggests major DNA fragment loss that could have a profound impact on the gene expression affecting the overall phenotype. This roundup report specifies the effect of NK cell receptor, KIR2DL3 and IFNL3 variants that can have a better prospect in GWAS and immunogenetic studies leading to better understanding of HCV clearance and progression.

Update on epidemiology of HCV in Italy: focus on the Calabria Region

PubMed Central

2014-01-01

The epidemiological profile of HCV infection is evolving in Europe, as well as in Italy. We have previously showed genotype distributions and their dynamics in 2,153 HCV RNA positive patients living in Calabria, Southern Italy, over 11 years. In this study, we extend and update this information by evaluating a hospital-based cohort of 945 HCV RNA positive patients attending five hospitals in the Calabria Region from January 2011 to August 2013. We assessed rates of HCV genotypes according to age and gender and the dynamics of HCV genotype distribution over the 3-year period studied. Data showed that genotype 1b is the most prevalent, followed by subtypes 2a/2c and genotype 3. Genotype 4 exhibited an increase between 2011 and 2013. Also, we found a significant decrease in the median age of subjects infected with HCV genotype 3 and 4 during the period studied. Since HCV genotypes are important in epidemiology, pathogenesis and response to antiviral therapy, a continuous epidemiological surveillance is needed. PMID:25236184

Efficacy and Safety of Sofosbuvir Plus Daclatasvir for Treatment of HCV-Associated Cryoglobulinemia Vasculitis.

PubMed

Saadoun, David; Pol, Stanislas; Ferfar, Yasmina; Alric, Laurent; Hezode, Christophe; Si Ahmed, Si Nafa; de Saint Martin, Luc; Comarmond, Cloé; Bouyer, Anne Sophie; Musset, Lucile; Poynard, Thierry; Resche Rigon, Matthieu; Cacoub, Patrice

2017-07-01

Circulating mixed cryoglobulins are detected in 40%-60% of patients with hepatitis C virus (HCV) infection, and overt cryoglobulinemia vasculitis (CryoVas) develops in approximately 15% of patients. Remission of vasculitis has been associated with viral clearance, but few studies have reported the effectiveness of direct-acting antiviral drugs in these patients. We performed an open-label, prospective, multicenter study of the effectiveness and tolerance of an all-oral, interferon- and ribavirin-free regimen of sofosbuvir plus daclatasvir in patients with HCV-associated CryoVas. Forty-one consecutive patients with active HCV-associated CryoVas (median age, 56 y; 53.6% women) were recruited from hospitals in Paris, France, from 2014 through 2016. They received sofosbuvir (400 mg/day) plus daclatasvir (60 mg/day) for 12 weeks (n = 32) or 24 weeks (n = 9), and were evaluated every 4 weeks until week 24 and at week 36. Blood samples were analyzed for complete blood count, serum chemistry profile, level of alanine aminotransferase, rheumatoid factor activity, C4 fraction of complement, and cryoglobulin; peripheral blood mononuclear cells were isolated for flow cytometry analysis. Thirty-seven patients (90.2%) had a complete clinical response (defined by improvement of all the affected organs involved at baseline and no clinical relapse) after a median time of 12 weeks of therapy; all had a sustained virologic response (no detectable serum HCV RNA 12 weeks after the end of antiviral therapy). Patients' mean cryoglobulin level decreased from 0.56 ± 0.18 at baseline to 0.21 ± 0.14 g/L at week 36, and no cryoglobulin was detected in 50% of patients at this time point. After antiviral therapy, patients had increased numbers of T-regulatory cells, IgM+CD21-/low-memory B cells, CD4+CXCR5+ interleukin 21+ cells, and T-helper 17 cells, compared with before therapy. After a median follow-up period of 26 months (interquartile range, 20-30 mo), no patients had a serious adverse

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

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 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...

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

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 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...

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true 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...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 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...

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

Code of Federal Regulations, 2010 CFR

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...

Geographic differences in the epidemiological features of HCV infection in Korea

PubMed Central

Kim, Kyung-Ah; Jang, Eun Sun; Kim, Young Seok; Lee, Youn Jae; Jung, Eun Uk; Kim, In Hee; Cho, Sung Bum; Kee, Mee-Kyung; Kang, Chun

2014-01-01

Background/Aims The prevalence of hepatitis C virus (HCV) infection in Korea exhibits significant geographic variation, with it being higher in Busan and Jeonam than in other areas. The reason for this intranational geographic difference was investigated in this study by conducting a comparative analysis of the risk factors related to HCV infection among three geographic areas: the capital (Seoul), Busan, and the province of Jeolla. Methods In total, 990 patients with chronic HCV infection were prospectively enrolled at 5 university hospitals located in Seoul (n=374), Busan (n=264), and Jeolla (n=352). A standardized questionnaire survey on the risk factors for HCV infection was administered to these three groups of patients, and a comparative analysis of the findings was performed. Results The analysis revealed significant regional differences in exposure to the risk factors of HCV infection. By comparison with patients in Seoul as a control group in the multivariate analysis, patients in Busan had significantly more experience of invasive medical procedures, acupuncture, cosmetic procedures, and multiple sex partners. In contrast, patients in Jeolla were significantly older, and they had a higher prevalence of hepatocellular carcinoma, a lower prevalence of multiple sex partners, and had experienced fewer invasive procedures. Conclusions There was a significant geographic difference in the exposure to potential risk factors of HCV infection between patients from the three studied regions. This may explain the regional variation of the prevalence of HCV infection in Korea, and should be taken into account when planning strategies for the prevention and management of HCV infection. PMID:25548742

Is diabetes mellitus a risk factor for HCV infection?

PubMed

Picerno, I; Di Pietro, A; Spataro, P; Di Benedetto, A; Romano, G; Scoglio, M E

2002-01-01

The aim of this study was to investigate whether or not the diabetes mellitus may be considered a risk factor for the HCV infection. The HCV seroprevalence was evaluated in 254 diabetic subjects, whose anamnestic data and risk factors are known, in comparison to 223 first-time blood donors, carefully age- and gender-matched. The statistical analysis showed that the studied groups belonged to the same population (Mann-Whitney U test) and that there were no significant differences between cases and controls as regards HCV prevalence (Yates corrected chi 2 test). The obtained data underline the importance of the control group selection, especially in the studies considering age-related pathologies. The authors disprove type 2 diabetes as a risk factor for the HCV infection and consider that this is a valid hypothesis only when the hepatitis C was unknown and not adequate prevention was used.

Hepatitis C virus (HCV) induces formation of stress granules whose proteins regulate HCV RNA replication and virus assembly and egress.

PubMed

Garaigorta, Urtzi; Heim, Markus H; Boyd, Bryan; Wieland, Stefan; Chisari, Francis V

2012-10-01

Stress granules (SGs) are cytoplasmic structures that are induced in response to environmental stress, including viral infections. Here we report that hepatitis C virus (HCV) triggers the appearance of SGs in a PKR- and interferon (IFN)-dependent manner. Moreover, we show an inverse correlation between the presence of stress granules and the induction of IFN-stimulated proteins, i.e., MxA and USP18, in HCV-infected cells despite high-level expression of the corresponding MxA and USP18 mRNAs, suggesting that interferon-stimulated gene translation is inhibited in stress granule-containing HCV-infected cells. Finally, in short hairpin RNA (shRNA) knockdown experiments, we found that the stress granule proteins T-cell-restricted intracellular antigen 1 (TIA-1), TIA1-related protein (TIAR), and RasGAP-SH3 domain binding protein 1 (G3BP1) are required for efficient HCV RNA and protein accumulation at early time points in the infection and that G3BP1 and TIA-1 are required for intracellular and extracellular infectious virus production late in the infection, suggesting that they are required for virus assembly. In contrast, TIAR downregulation decreases extracellular infectious virus titers with little effect on intracellular RNA content or infectivity late in the infection, suggesting that it is required for infectious particle release. Collectively, these results illustrate that HCV exploits the stress granule machinery at least two ways: by inducing the formation of SGs by triggering PKR phosphorylation, thereby downregulating the translation of antiviral interferon-stimulated genes, and by co-opting SG proteins for its replication, assembly, and egress.

[Acute outbreak of hepatitis C in human immunodeficiency virus-infected patients].

PubMed

Martínez-Rebollar, Maria; Mallolas, Josep; Pérez, Iñaki; González-Cordón, Ana; Loncà, Montserrat; Torres, Berta; Rojas, Jhon-Fredy; Monteiro, Polyana; Blanco, José-Luis; Martínez, Esteban; Gatell, José-María; Laguno, Montserrat

2015-01-01

Recent studies suggest an increased incidence of acute infection with hepatitisC virus (AHC) in men who have sex with men (MSM) co-infected with HIV. Early treatment with interferon-alpha, alone or in combination with ribavirin, significantly reduces the risk of chronic evolution. This retrospective study includes all HIV patients with AHC in our centre from 2003 to March 2013. AHC was defined by seroconversion of HCV antibodies and detection of serum HCV RNA. 93 episodes of AHC were diagnosed in 89 patients. All but three were MSM with a history of unprotected sex. Thirty-seven (40%) patients had other associated sexually transmitted disease. The 29% (27) had any symptoms suggestive of AHC. HCV genotype 4 was the most common (41%), followed by genotype1. Seventy patients started treatment with interferon-alfa and weight-adjusted ribavirin. Currently 46 have completed treatment and follow-up, reaching 26 of them (56.5%) sustained viral response. The incidence of AHC in HIV MSM patients from our centre has increased exponentially in recent years; sexual transmission remains the main route of infection. Early treatment with interferon-alpha and ribavirin achieved a moderate response in these patients. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Infection with hepatitis A, B, C, and delta viruses among patients with acute hepatitis in Mongolia.

PubMed

Tsatsralt-Od, Bira; Takahashi, Masaharu; Endo, Kazunori; Buyankhuu, Osorjin; Baatarkhuu, Oidov; Nishizawa, Tsutomu; Okamoto, Hiroaki

2006-05-01

One hundred ten consecutive patients (60 males and 50 females; age, mean +/- standard deviation [SD], 22.6 +/- 6.4 years; range 16-48 years) who were clinically diagnosed with sporadic acute hepatitis between December 2004 and January 2005 in Ulaanbaatar, Mongolia, were studied. IgM antibodies to hepatitis A virus were detected in 18 patients (16.4%), IgM antibodies to hepatitis B core (anti-HBc IgM) in 38 patients (34.5%) including two patients with concurrent hepatitis delta virus (HDV) infection, and hepatitis C virus RNA in nine patients (8.2%). There were 30 hepatitis B virus (HBV) carriers who had detectable hepatitis B surface antigen and antibodies to HDV but were negative for anti-HBc IgM, suggesting that they acquired type D acute hepatitis due to superinfection of HDV on a background of chronic HBV infection. None had IgM antibodies to hepatitis E virus (HEV). Consequently, 16.4, 32.7, 6.4, 1.8, and 27.3% of the patients were diagnosed as having acute hepatitis of type A, B, C, type B + D (HBV/HDV coinfection), and type D (superinfection of HDV), respectively. The cause of hepatitis was not known in the remaining 17 patients (15.5%). All 18 HAV isolates were genotyped as IA, all 9 HCV isolates were genotyped as 1b, and all 32 HDV isolates were classified into genotype I. The distribution of HBV genotypes among the 67 HBV isolates was A (1.5%, n = 1) and D (98.5%, n = 66). The present study indicates that de novo infections of HAV, HBV, HCV, and HDV are prevalent among young adults in Mongolia. Copyright 2006 Wiley-Liss, Inc.

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

PubMed

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

2015-01-01

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

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.

PubMed

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.

Modeling HCV cure after an ultra-short duration of therapy with direct acting agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goyal, Ashish; Lurie, Yoav; Meissner, Eric G.

In cases of sustained-virological response (SVR or cure) after an ultra-short duration (≤ 27 days) of direct-acting antiviral (DAA)-based therapy, despite HCV being detected at end of treatment (EOT), have been reported. Established HCV mathematical models that predict the treatment duration required to achieve cure do not take into account the possibility that the infectivity of virus produced during treatment might be reduced. The aim of this study was to develop a new mathematical model that considers the fundamental and critical concept that HCV RNA in serum represents both infectious virus (V i) and non-infectious virus (V ni) in ordermore » to explain the observation of cure with ultrashort DAA therapy. Established HCV models were compared to the new mathematical model to retrospectively explain cure in 2 patients who achieved cure after 24 or 27 days of paritaprevir, ombitasvir, dasabuvir, ritonavir and ribavirin or sofosbuvir plus ribavirin, respectively. Fitting established models with measured longitudinal HCV viral loads indicated that in both cases, cure would not have been expected without an additional 3–6 weeks of therapy after the actual EOT. In contrast, the new model fits the observed outcome by considering that in addition to blocking V i and V ni production (ε~0.998), these DAA + ribavirin treatments further enhanced the ratio of V ni to V i, thus increasing the log (V ni/V i) from 1 at pretreatment to 6 by EOT, which led to <1 infectious-virus particle in the extracellular body fluid (i.e., cure) prior to EOT. This new model can explain cure after short duration of DAA + ribavirin therapy by suggesting that a minimum 6-fold increase of log (V ni/V i) results from drug-induced enhancement of the V ni/V i.« less

Modeling HCV cure after an ultra-short duration of therapy with direct acting agents

DOE PAGES

Goyal, Ashish; Lurie, Yoav; Meissner, Eric G.; ...

2017-06-30

In cases of sustained-virological response (SVR or cure) after an ultra-short duration (≤ 27 days) of direct-acting antiviral (DAA)-based therapy, despite HCV being detected at end of treatment (EOT), have been reported. Established HCV mathematical models that predict the treatment duration required to achieve cure do not take into account the possibility that the infectivity of virus produced during treatment might be reduced. The aim of this study was to develop a new mathematical model that considers the fundamental and critical concept that HCV RNA in serum represents both infectious virus (V i) and non-infectious virus (V ni) in ordermore » to explain the observation of cure with ultrashort DAA therapy. Established HCV models were compared to the new mathematical model to retrospectively explain cure in 2 patients who achieved cure after 24 or 27 days of paritaprevir, ombitasvir, dasabuvir, ritonavir and ribavirin or sofosbuvir plus ribavirin, respectively. Fitting established models with measured longitudinal HCV viral loads indicated that in both cases, cure would not have been expected without an additional 3–6 weeks of therapy after the actual EOT. In contrast, the new model fits the observed outcome by considering that in addition to blocking V i and V ni production (ε~0.998), these DAA + ribavirin treatments further enhanced the ratio of V ni to V i, thus increasing the log (V ni/V i) from 1 at pretreatment to 6 by EOT, which led to <1 infectious-virus particle in the extracellular body fluid (i.e., cure) prior to EOT. This new model can explain cure after short duration of DAA + ribavirin therapy by suggesting that a minimum 6-fold increase of log (V ni/V i) results from drug-induced enhancement of the V ni/V i.« less

Ultrasensitive HCV RNA Quantification in Antiviral Triple Therapy: New Insight on Viral Clearance Dynamics and Treatment Outcome Predictors

PubMed Central

Garbuglia, Anna Rosa; Visco-Comandini, Ubaldo; Lionetti, Raffaella; Lapa, Daniele; Castiglione, Filippo; D’Offizi, Gianpiero; Taibi, Chiara; Montalbano, Marzia; Capobianchi, Maria Rosaria; Paci, Paola

2016-01-01

Objectives Identifying the predictive factors of Sustained Virological Response (SVR) represents an important challenge in new interferon-based DAA therapies. Here, we analyzed the kinetics of antiviral response associated with a triple drug regimen, and the association between negative residual viral load at different time points during treatment. Methods Twenty-three HCV genotype 1 (GT 1a n = 11; GT1b n = 12) infected patients were included in the study. Linear Discriminant Analysis (LDA) was used to establish possible association between HCV RNA values at days 1 and 4 from start of therapy and SVR. Principal component analysis (PCA) was applied to analyze the correlation between HCV RNA slope and SVR. A ultrasensitive (US) method was established to measure the residual HCV viral load in those samples which resulted “detected <12IU/ml” or undetectable with ABBOTT standard assay, and was retrospectively used on samples collected at different time points to establish its predictive power for SVR. Results According to LDA, there was no association between SVR and viral kinetics neither at time points earlier than 1 week (days 1 and 4) after therapy initiation nor later. The slopes were not relevant for classifying patients as SVR or no-SVR. No significant differences were observed in the median HCV RNA values at T0 among SVR and no-SVR patients. HCV RNA values with US protocol (LOD 1.2 IU/ml) after 1 month of therapy were considered; the area under the ROC curve was 0.70. Overall, PPV and NPV of undetectable HCV RNA with the US method for SVR was 100% and 46.7%, respectively; sensitivity and specificity were 38.4% and 100% respectively. Conclusion HCV RNA “not detected” by the US method after 1 month of treatment is predictive of SVR in first generation Protease inhibitor (PI)-based triple therapy. The US method could have clinical utility for advanced monitoring of virological response in new interferon based DAA combination regimens. PMID:27560794

Independent, parallel pathways to CXCL10 induction in HCV-infected hepatocytes.

PubMed

Brownell, Jessica; Wagoner, Jessica; Lovelace, Erica S; Thirstrup, Derek; Mohar, Isaac; Smith, Wesley; Giugliano, Silvia; Li, Kui; Crispe, I Nicholas; Rosen, Hugo R; Polyak, Stephen J

2013-10-01

The pro-inflammatory chemokine CXCL10 is induced by HCV infection in vitro and in vivo, and is associated with outcome of IFN (interferon)-based therapy. We studied how hepatocyte sensing of early HCV infection via TLR3 (Toll-like receptor 3) and RIG-I (retinoic acid inducible gene I) led to expression of CXCL10. CXCL10, type I IFN, and type III IFN mRNAs and proteins were measured in PHH (primary human hepatocytes) and hepatocyte lines harboring functional or non-functional TLR3 and RIG-I pathways following HCV infection or exposure to receptor-specific stimuli. HuH7 human hepatoma cells expressing both TLR3 and RIG-I produced maximal CXCL10 during early HCV infection. Neutralization of type I and type III IFNs had no impact on virus-induced CXCL10 expression in TLR3+/RIG-I+ HuH7 cells, but reduced CXCL10 expression in PHH. PHH cultures were positive for monocyte, macrophage, and dendritic cell mRNAs. Immunodepletion of non-parenchymal cells (NPCs) eliminated marker expression in PHH cultures, which then showed no IFN requirement for CXCL10 induction during HCV infection. Immunofluorescence studies also revealed a positive correlation between intracellular HCV Core and CXCL10 protein expression (r(2) = 0.88, p ≤ 0.001). While CXCL10 induction in hepatocytes during the initial phase of HCV infection is independent of hepatocyte-derived type I and type III IFNs, NPC-derived IFNs contribute to CXCL10 induction during HCV infection in PHH cultures. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Association between depressive symptoms, CD4 count and HIV viral suppression among HIV-HCV co-infected people.

PubMed

Aibibula, Wusiman; Cox, Joseph; Hamelin, Anne-Marie; Moodie, Erica E M; Anema, Aranka; Klein, Marina B; Brassard, Paul

2018-05-01

Depressive symptoms are associated with poor HIV viral control and immune recovery among people living with HIV. However, no prior studies assessed this association exclusively among people co-infected with HIV-hepatitis C virus (HCV). While people with HIV only and those with HIV-HCV co-infection share many characteristics, co-infected people may become more susceptible to the effects of depressive symptoms on health outcomes. We assessed this association exclusively among people co-infected with HIV-HCV in Canada using data from the Food Security & HIV-HCV Sub-Study (FS Sub-Study) of the Canadian Co-Infection Cohort (CCC). Stabilized inverse probability weighted marginal structural model was used to account for potential time-varying confounders. A total of 725 participants were enrolled between 2012 and 2015. At baseline, 52% of participants reported depressive symptoms, 75% had undetectable HIV viral load, and median CD4 count was 466 (IQR 300-665). People experiencing depressive symptoms had 1.32 times (95% CI: 1.07, 1.63) the risk of having detectable HIV viral load, but had comparable CD4 count to people who did not experience depressive symptoms (fold change of CD4 = 0.96, 95% CI: 0.91, 1.03). Presence of depressive symptoms is a risk factor for incomplete short-term HIV viral suppression among people co-infected with HIV-HCV. Therefore, depressive symptoms screening and related counseling may improve HIV related health outcomes and reduce HIV transmission.

CD81 expression on CD19+ peripheral blood lymphocytes is associated with chronic HCV disease and increased risk for HCV infection: a putative role for inflammatory cytokines.

PubMed

D'Agosto, G; Trento, E; Nosotti, L; Bordignon, V; Battista, M; Prignano, G; Pimpinelli, F; Biolcati, G; Macrì, A; Palamara, G; Miglioresi, L; Morrone, A; Di Carlo, A; Cordiali-Fei, P; Ensoli, F

2009-01-01

The level of CD81 cell surface expression, a cellular co-receptor for hepatitis C virus (HCV), is critical for productive HCV infection of host cells. In addition, the cross-linking of HCV-E2 protein to CD81 can alter the function of T and B lymphocytes as well as that of NK cells by interfering with the activation signalling pathway. The down-regulation of CD81 expression on peripheral blood lymphocytes (PBL) has been associated to effective therapy of HCV infection. The aim of the present study is to quantitatively assess the levels of CD81 expression in PBL from HCV-infected patients compared to subjects at high risk for HCV infection such as HIV-infected individuals or patients with Porphyria Cutanea Tarda (PCT). The expression of CD81 was quantified by flow-cytometry using Phycoerythrin-labelled standard beads. Determination of CD81 was performed on CD3+ and CD19+ lymphocytes from 34 healthy controls, 51 patients with HCV infection and different clinical outcomes [these included HCV-RNA-negative subjects (8), patients with chronic active hepatitis (16), recipients of liver transplantation under immunosuppressive therapy (12), a subgroup with concomitant HIV infection (9) or concomitant PCT (6)]. In addition, 60 HIV-infected subjects and 4 patients with PCT were studied. The putative role of inflammatory cytokines in modulating CD81 was explored in vitro by assessing the effect of IL-6 or IFN-gamma on cultured human hepatocytes. A significant increase of the CD81 expression was found on CD19+ lymphocytes in association with either HIV or HCV infection, as compared to the control group. Immunosuppressive therapy with FK506, subsequent to liver transplantation, restored CD81 expression at normal levels. Data gathered in vitro using the WRL 68 hepatocytic cell line confirmed that inflammatory cytokines can up-regulate CD81 expression in liver cell inclusion. Our data suggest that CD81 up-regulation can increase the risk of HCV infection, particularly in HIV

How physicians describe outcomes to HCV therapy: prevalence and meaning of "cure" during provider-patient in-office discussions of HCV.

PubMed

Hamilton, Heidi E; Gordon, Cynthia; Nelson, Meaghan; Cotler, Scott J; Martin, Paul

2008-04-01

How physicians convey information about hepatitis C virus (HCV) impacts patients' perceptions of treatment outcomes and informed therapy decisions. However, HCV patients reported difficulties communicating with their physicians in a recent study. Another study showed that 45% of patients did not understand projected response rates conveyed by providers, and patients with unfavorable projected treatment outcomes were more likely to lack understanding. This article analyzes naturally occurring patient-provider interactions to evaluate physicians' use of the word 'cure', and framing of HCV response as optimistic, pessimistic, or neutral, to suggest possible reasons why patients with unfavorable projected sustained virologic response rates might perceive their odds as more favorable than they are. Gastroenterologists, allied health professionals, and HCV patients were video and audio-recorded during regular scheduled visits. Recordings were transcribed and analyzed using validated sociolinguistic techniques. Sixty-three percent of physicians used the word 'cure' in 38% of visits involving response discussions. 'Cure' most frequently meant 'absolute cure' and occurred more commonly in visits conducted before therapy initiation, and with patients having favorable genotypes. Physicians hedged the meaning of 'cure' in 29% of visits. Moreover, 69.5% of response-related utterances were framed optimistically. HCV dialogs are characterized by the prevalence of 'cure' and optimistic framing. These positive language attributes could potentially contribute to the misunderstanding regarding the projected response rates. During treatment outcome discussions, the physicians should attempt to (1) operate using the same definition of the therapy outcome as the patient, (2) balance medically accurate information with patient comprehension, and (3) consider possible consequences of discussing treatment options on the basis of message framing.

The management of HCV-infected pregnant women.

PubMed

Valladares, Guillermo; Chacaltana, Alfonso; Sjogren, Maria H

2010-01-01

Hepatitis C is, at present, a worldwide health problem and is the most common cause of liver transplantation. Its prevalence in pregnant women is similar to that of the general population. In the absence of cirrhosis and portal hypertension, most HCV-infected pregnant women do not have obstetric complications. Screening of pregnant women that are asymptomatic and do not have risk factors is not cost effective. A high hepatitis C viral load reportedly increases vertical transmission and is higher in women who are coinfected with HIV or who are intravenous drug users. Prolonged rupture of the membrane for more than 6 h, amniocentesis, and perineal lacerations increase the potential risk of perinatal transmission. Although the hepatitis C virus can be transmitted intrapartum, prevention by caesarean delivery is not generally indicated. The HCV virus can be found in maternal milk; however, breast feeding is not contraindicated. In conclusion, there are no antiviral treatment recommendations for HCV-infected women during pregnancy, or guidelines for the prevention of vertical transmission.

Use of 2'-spirocyclic ethers in HCV nucleoside design.

PubMed

Du, Jinfa; Chun, Byoung-Kwon; Mosley, Ralph T; Bansal, Shalini; Bao, Haiying; Espiritu, Christine; Lam, Angela M; Murakami, Eisuke; Niu, Congrong; Micolochick Steuer, Holly M; Furman, Phillip A; Sofia, Michael J

2014-03-13

Conformationally restricted 2'-spironucleosides and their prodrugs were synthesized as potential anti-HCV agents. Although the replicon activity of the new agents containing pyrimidine bases was modest, the triphosphate of a 2'-oxetane cytidine analogue demonstrated potent intrinsic biochemical activity against the NS5B polymerase, with IC50 = 8.48 μM. Activity against NS5B bearing the S282T mutation was reduced. Phosphoramidate prodrugs of a 2'-oxetane 2-amino-6-O-methyl-purine nucleoside demonstrated potent anti-HCV activity in vitro, and the corresponding triphosphate retained similar potent activity against both wild-type and S282T HCV NS5B polymerase.

Interferon lambda: opportunities, risks, and uncertainties in the fight against HCV.

PubMed

Laidlaw, Stephen M; Dustin, Lynn B

2014-01-01

Innate immunity is key to the fight against the daily onslaught from viruses that our bodies are subjected to. Essential to this response are the interferons (IFNs) that prime our cells to block viral pathogens. Recent evidence suggests that the Type III (λ) IFNs are intimately associated with the immune response to hepatitis C virus (HCV) infection. Genome-wide association studies have identified polymorphisms within the IFN-λ gene locus that correlate with response to IFNα-based antiviral therapy and with spontaneous clearance of HCV infection. The mechanisms for these correlations are incompletely understood. Restricted expression of the IFN-λ receptor, and the ability of IFN-λ to induce IFN-stimulated genes in HCV-infected cells, suggest potential roles for IFN-λ in HCV therapy even in this era of directly acting antivirals. This review summarizes our current understanding of the IFN-λ family and the role of λ IFNs in the natural history of HCV infection.

Insulin-resistance HCV infection-related affects vascular stiffness in normotensives.

PubMed

Perticone, Maria; Maio, Raffaele; Tassone, Eliezer Joseph; Tripepi, Giovanni; Di Cello, Serena; Miceli, Sofia; Caroleo, Benedetto; Sciacqua, Angela; Licata, Anna; Sesti, Giorgio; Perticone, Francesco

2015-01-01

BACKGROUND AND AIMS. Arterial stiffness evaluated as pulse wave velocity, is an early marker of vascular damage and an independent predictor for cardiovascular events. We investigated if the insulin resistance/hyperinsulinemia chronic hepatitis C virus infection-related could influence arterial stiffness. METHODS. We enrolled 260 outpatients matched for age, body mass index, gender, ethnicity: 52 with never-treated uncomplicated chronic hepatitis C virus infection (HCV(+)), 104 never-treated hypertensives (HT) and 104 healthy subjects (NT). Pulse wave velocity was evaluated by a validated system employing high-fidelity applanation tonometry. We also measured: fasting plasma glucose and insulin, total, LDL- and HDL-cholesterol, triglyceride, creatinine, e-GFR-EPI, HOMA, quantitative HCV-RNA. RESULTS. HCV(+) patients with respect to NT had an increased pulse wave velocity (7.9 ± 2.1 vs 6.4 ± 2.1 m/s; P < 0.0001), similar to that observed in HT group (8.8 ± 3.2 m/s). HCV(+) patients, in comparison with NT, had higher triglyceride, creatinine, fasting insulin and HOMA (3.2 ± 1.3 vs 2.5 ± 1.0; P < 0.0001). At linear regression analysis, the correlation between pulse wave velocity and HOMA was similar in HT (r = 0.380, P < 0.0001) and HCV(+) (r = 0.369, P = 0.004) groups. At multiple regression analysis, HOMA resulted the major determinant of pulse wave velocity in all groups, explaining respectively 11.8%, 14.4% and 13.6% of its variation in NT, HT and HCV(+). At correlational analysis hepatitis C virus-RNA and HOMA demonstrated a strong and linear relationship between them, explaining the 72.4% of their variation (P = 0.022). CONCLUSIONS. We demonstrated a significant and direct correlation between HOMA and pulse wave velocity in HCV(+) patients, similar to that observed in hypertensives. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Management of HCV-Related Liver Disease in Hemophilia and Thalassemia.

PubMed

Rumi, Maria Grazia; Di Marco, Vito; Colombo, Massimo

2018-05-01

Chronic infection with the hepatitis C virus (HCV) has long been the dominant complication of substitution therapy in patients with inherited blood disorders and the cause of anticipated death due to end-stage liver disease. In hemophilia, transmission of HCV with clotting factors concentrates started to be curbed in the mid-1980s following the adoption of procedures of virus inactivation of concentrates based on heat, whereas in the 1990s treatment of HCV infection with interferon monotherapy was attempted, however, with little success. The advent of combination therapy of interferon with ribavirin led to a substantial improvement of treatment outcome (40% rate of cure), that however was still of limited efficacy in patients with advanced liver disease, those with high load of HCV genotype 1, and patients coinfected with the human immunodeficiency virus. In this latter population, while the course of hepatitis C was accelerated as a consequence of immunodeficiency, the advent of highly active antiretroviral therapy led acquired immunodeficiency syndrome (AIDS) to decline and hepatitis C to progressively emerge as a dominant cause of mortality, in parallel. In patients with thalassemia, transfusion-related transmission of HCV was efficiently interrupted in 1992 with the advent of sensitive screening tests for testing donors for HCV, whereas treatment with interferon and ribavirin of infected thalassemics was constrained by an increased risk of anemia due to the hemolytic properties of ribavirin coupled with interferon-induced bone marrow suppression. The advent of safe and potent regimens based on the oral administration of direct antiviral agents has revolutionized therapy of HCV in patients with congenital blood diseases, providing substantial clinical benefits and making elimination of infection in these populations, possible. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Biochemical non-invasive assessment of liver fibrosis cannot replace biopsy in HIV-HCV coinfected patients.

PubMed

Kliemann, Dimas A; Wolff, Fernando H; Tovo, Cristiane V; Alencastro, Paulo R; Ikeda, Maria L R; Brandão, Ajácio B M; Barcellos, Nêmora; Fuchs, Sandra C

2016-01-01

The liver biopsy has been considered the gold standard for the diagnosis and quantification of fibrosis. However, this method presents limitations. In addition, the non-invasive evaluation of liver fibrosis is a challenge. The aim of this study was to validate the fibrosis cirrhosis index (FCI) index in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients, and compare to AST/ALT ratio (AAR), AST to platelet ratio index (APRI) and FIB-4 scores, as a tool for the assessment of liver fibrosis in coinfected patients. Retrospective cross sectional study including 92 HIV-HCV coinfected patients evaluated in two reference centers for HIV treatment in the Public Health System in Southern Brazil. Patients who underwent liver biopsy for any indication and had concomitant laboratory data in the 3 months prior to liver biopsy, to allow the calculation of studied noninvasive markers (AAR, APRI, FIB-4 and FCI) were included. APRI < 0.5 presents the higher specificity to detect no or minimal fibrosis, whereas APRI > 1.5 presents the best negative predictive value and FCI > 1.25 the best specificity to detect significant fibrosis. The values of noninvasive markers for each Metavir fibrosis stage showed statistically significant differences only for APRI. In conclusion, until better noninvasive markers for liver fibrosis are developed and validated for HIV-HCV coinfected patients, noninvasive serum markers should be used carefully in this population.

Acute pancreatitis associated with interferon and ribavirin therapy in patients with chronic hepatitis C.

PubMed

Chaudhari, Swati; Park, James; Anand, Bhupinderjit S; Pimstone, Neville R; Dieterich, Douglas T; Batash, Steven; Bini, Edmund J

2004-06-01

Acute pancreatitis is a rare complication of interferon (IFN) and ribavirin (RBV) therapy. The aim of this study was to determine the incidence, clinical presentation, and outcome of acute pancreatitis in patients with chronic hepatitis C virus (HCV) infection treated with IFN and RBV combination therapy. We conducted a retrospective review of 1706 HCV-infected patients treated with IFN alpha-2b and RBV. The diagnosis of drug-induced acute pancreatitis was made based on the presence of epigastric pain, elevated amylase and lipase levels, and the absence of other identifiable causes of pancreatitis. Acute pancreatitis was diagnosed in 7 of 1706 HCV-infected patients (0.4%; 95% CI, 0.2 to 0.8%) who were treated with IFN alpha-2b and RBV. The mean age of the patients (four males and three females) was 51.4 +/- 4.7 years and the median duration of therapy prior to development of pancreatitis was 12.0 weeks (range, 4.0-21.0 weeks). All patients presented with epigastric pain associated with nausea, vomiting, and/or fever. The median amylase and lipase values at the time of diagnosis of pancreatitis were 330.0 U/L (range, 182.0-1813.0 U/L) and 500.0 U/L (range, 171.0-2778.0 U/L), respectively. IFN and RBV were discontinued in all patients at the time of diagnosis and six of the seven patients were hospitalized; one patient refused hospital admission. Pancreatitis resolved in all seven patients and none of these individuals had recurrent pancreatitis during a median follow-up of 18.0 months (range, 3.0-27.0 months). In conclusion, IFN and RBV combination therapy is a potential cause of drug-induced pancreatitis in patients with chronic HCV. In these individuals, pancreatitis is often severe enough to warrant hospital admission, although symptoms resolve promptly after discontinuation of antiviral therapy.

In vitro antigen-specific induction of IL-22 in human subjects that resolved HCV infection

PubMed Central

Cusick, Matthew F; Libbey, Jane E; Fujinami, Robert S; Eckels, David D

2012-01-01

Aims To determine if in vitro production of IL-22 and IL-17 correlated with resolution of HCV infection. Materials & methods Human peripheral blood cells isolated from a well-defined cohort of resolved and chronic HCV-infected subjects were used to measure HCV-, influenza- and mitogen-activated T-cell proliferation. In addition, IL-22 and IL-17 production was measured via ELISAs and flow cytometry. Results Resolved HCV subjects had a significantly higher T-cell proliferative response to recombinant NS3 protein compared with chronic HCV subjects. Resolved subjects had a dose-dependent IL-22 response to recombinant NS3 compared with chronic HCV subjects. Conclusion IL-22 production is associated with antigen-specific induction of CD4 + T cells in individuals that resolved HCV infection, suggesting a potential role for IL-22 in HCV clearance. PMID:23185211

Several Human Liver Cell Expressed Apolipoproteins Complement HCV Virus Production with Varying Efficacy Conferring Differential Specific Infectivity to Released Viruses.

PubMed

Hueging, Kathrin; Weller, Romy; Doepke, Mandy; Vieyres, Gabrielle; Todt, Daniel; Wölk, Benno; Vondran, Florian W R; Geffers, Robert; Lauber, Chris; Kaderali, Lars; Penin, François; Pietschmann, Thomas

2015-01-01

Apolipoprotein E (ApoE), an exchangeable apolipoprotein, is necessary for production of infectious Hepatitis C virus (HCV) particles. However, ApoE is not the only liver-expressed apolipoprotein and the role of other apolipoproteins for production of infectious HCV progeny is incompletely defined. Therefore, we quantified mRNA expression of human apolipoproteins in primary human hepatocytes. Subsequently, cDNAs encoding apolipoproteins were expressed in 293T/miR-122 cells to explore if they complement HCV virus production in cells that are non-permissive due to limiting endogenous levels of human apolipoproteins. Primary human hepatocytes expressed high mRNA levels of ApoA1, A2, C1, C3, E, and H. ApoA4, A5, B, D, F, J, L1, L2, L3, L4, L6, M, and O were expressed at intermediate levels, and C2, C4, and L5 were not detected. All members of the ApoA and ApoC family of lipoproteins complemented HCV virus production in HCV transfected 293T/miR-122 cells, albeit with significantly lower efficacy compared with ApoE. In contrast, ApoD expression did not support production of infectious HCV. Specific infectivity of released particles complemented with ApoA family members was significantly lower compared with ApoE. Moreover, the ratio of extracellular to intracellular infectious virus was significantly higher for ApoE compared to ApoA2 and ApoC3. Since apolipoproteins complementing HCV virus production share amphipathic alpha helices as common structural features we altered the two alpha helices of ApoC1. Helix breaking mutations in both ApoC1 helices impaired virus assembly highlighting a critical role of alpha helices in apolipoproteins supporting HCV assembly. In summary, various liver expressed apolipoproteins with amphipathic alpha helices complement HCV virus production in human non liver cells. Differences in the efficiency of virus assembly, the specific infectivity of released particles, and the ratio between extracellular and intracellular infectivity point to

Several Human Liver Cell Expressed Apolipoproteins Complement HCV Virus Production with Varying Efficacy Conferring Differential Specific Infectivity to Released Viruses

PubMed Central

Doepke, Mandy; Vieyres, Gabrielle; Todt, Daniel; Wölk, Benno; Vondran, Florian W. R.; Geffers, Robert; Lauber, Chris; Kaderali, Lars; Penin, François; Pietschmann, Thomas

2015-01-01

Apolipoprotein E (ApoE), an exchangeable apolipoprotein, is necessary for production of infectious Hepatitis C virus (HCV) particles. However, ApoE is not the only liver-expressed apolipoprotein and the role of other apolipoproteins for production of infectious HCV progeny is incompletely defined. Therefore, we quantified mRNA expression of human apolipoproteins in primary human hepatocytes. Subsequently, cDNAs encoding apolipoproteins were expressed in 293T/miR-122 cells to explore if they complement HCV virus production in cells that are non-permissive due to limiting endogenous levels of human apolipoproteins. Primary human hepatocytes expressed high mRNA levels of ApoA1, A2, C1, C3, E, and H. ApoA4, A5, B, D, F, J, L1, L2, L3, L4, L6, M, and O were expressed at intermediate levels, and C2, C4, and L5 were not detected. All members of the ApoA and ApoC family of lipoproteins complemented HCV virus production in HCV transfected 293T/miR-122 cells, albeit with significantly lower efficacy compared with ApoE. In contrast, ApoD expression did not support production of infectious HCV. Specific infectivity of released particles complemented with ApoA family members was significantly lower compared with ApoE. Moreover, the ratio of extracellular to intracellular infectious virus was significantly higher for ApoE compared to ApoA2 and ApoC3. Since apolipoproteins complementing HCV virus production share amphipathic alpha helices as common structural features we altered the two alpha helices of ApoC1. Helix breaking mutations in both ApoC1 helices impaired virus assembly highlighting a critical role of alpha helices in apolipoproteins supporting HCV assembly. In summary, various liver expressed apolipoproteins with amphipathic alpha helices complement HCV virus production in human non liver cells. Differences in the efficiency of virus assembly, the specific infectivity of released particles, and the ratio between extracellular and intracellular infectivity point to

Simultaneous Runs of the Bayer VERSANT HIV-1 Version 3.0 and HCV bDNA Version 3.0 Quantitative Assays on the System 340 Platform Provide Reliable Quantitation and Improved Work Flow

PubMed Central

Elbeik, Tarek; Markowitz, Norman; Nassos, Patricia; Kumar, Uday; Beringer, Scott; Haller, Barbara; Ng, Valerie

2004-01-01

Branched DNA (bDNA) assays to quantify human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) consist of three distinct steps, including sample processing, hybridization, and detection, and utilize the System 340 platform for plate incubation and washing. Sample processing differs: HIV-1 from 1 ml of plasma is concentrated by high-speed centrifugation, whereas HCV plasma or serum samples are used without concentration. The first step of hybridization involves viral lysis at 63°C: HIV-1 is performed in a heat block, whereas HCV is performed in System 340. The remaining hybridization and detection steps are similar for HIV-1 and HCV and executed on System 340. In the present study, the HIV-1 bDNA assay was adapted for viral lysis in the System 340 platform. The adaptation, test method 2, includes a 20-s vortex of concentrated viral pellet and lysis working solution, transfer of viral lysate to the 96-well capture plate, and transfer to System 340 programmed for HCV assay specifications. With test method 2, specificity and quantification were within assay specifications. HCV bDNA methodology remains unchanged. Hence, an HIV-1 and an HCV bDNA can be run simultaneously on System 340. With simultaneous testing, laboratories can run full plates, as well as combinations of full and partial plates. Also, simultaneous HIV-1 and HCV bDNA permits labor consolidation and improved workflow while maintaining multitasking and rapid patient result turnaround. PMID:15243070

Simultaneous runs of the Bayer VERSANT HIV-1 version 3.0 and HCV bDNA version 3.0 quantitative assays on the system 340 platform provide reliable quantitation and improved work flow.

PubMed

Elbeik, Tarek; Markowitz, Norman; Nassos, Patricia; Kumar, Uday; Beringer, Scott; Haller, Barbara; Ng, Valerie

2004-07-01

Branched DNA (bDNA) assays to quantify human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) consist of three distinct steps, including sample processing, hybridization, and detection, and utilize the System 340 platform for plate incubation and washing. Sample processing differs: HIV-1 from 1 ml of plasma is concentrated by high-speed centrifugation, whereas HCV plasma or serum samples are used without concentration. The first step of hybridization involves viral lysis at 63 degrees C: HIV-1 is performed in a heat block, whereas HCV is performed in System 340. The remaining hybridization and detection steps are similar for HIV-1 and HCV and executed on System 340. In the present study, the HIV-1 bDNA assay was adapted for viral lysis in the System 340 platform. The adaptation, test method 2, includes a 20-s vortex of concentrated viral pellet and lysis working solution, transfer of viral lysate to the 96-well capture plate, and transfer to System 340 programmed for HCV assay specifications. With test method 2, specificity and quantification were within assay specifications. HCV bDNA methodology remains unchanged. Hence, an HIV-1 and an HCV bDNA can be run simultaneously on System 340. With simultaneous testing, laboratories can run full plates, as well as combinations of full and partial plates. Also, simultaneous HIV-1 and HCV bDNA permits labor consolidation and improved workflow while maintaining multitasking and rapid patient result turnaround.

Environmental Stability and Infectivity of Hepatitis C Virus (HCV) in Different Human Body Fluids.

PubMed

Pfaender, Stephanie; Helfritz, Fabian A; Siddharta, Anindya; Todt, Daniel; Behrendt, Patrick; Heyden, Julia; Riebesehl, Nina; Willmann, Wiebke; Steinmann, Joerg; Münch, Jan; Ciesek, Sandra; Steinmann, Eike

2018-01-01

Background: Hepatitis C virus (HCV) is a hepatotropic, blood-borne virus, but in up to one-third of infections of the transmission route remained unidentified. Viral genome copies of HCV have been identified in several body fluids, however, non-parental transmission upon exposure to contaminated body fluids seems to be rare. Several body fluids, e.g., tears and saliva, are renowned for their antimicrobial and antiviral properties, nevertheless, HCV stability has never been systematically analyzed in those fluids. Methods: We used state of the art infectious HCV cell culture techniques to investigate the stability of HCV in different body fluids to estimate the potential risk of transmission via patient body fluid material. In addition, we mimicked a potential contamination of HCV in tear fluid and analyzed which impact commercially available contact lens solutions might have in such a scenario. Results: We could demonstrate that HCV remains infectious over several days in body fluids like tears, saliva, semen, and cerebrospinal fluid. Only hydrogen-peroxide contact lens solutions were able to efficiently inactivate HCV in a suspension test. Conclusion: These results indicate that HCV, once it is present in various body fluids of infected patients, remains infective and could potentially contribute to transmission upon direct contact.

Prevalence of hepatitis C virus (HCV) genotypes in Balochistan.

PubMed

Afridi, Sarwat; Naeem, Muhammad; Hussain, Abid; Kakar, Naseebullah; Babar, Masroor Ellahi; Ahmad, Jamil

2009-07-01

A molecular study was conducted to investigate the prevalence of Hepatitis C virus genotypes in HCV infected population of Balochistan. Forty HCV seropositive samples belonging to seven different locations of Balochistan were collected from different health care centres. Qualitative analysis of these samples using PCR resulted in 28 positive samples. The PCR positive samples were subjected to genotyping using the method described by Ohno et al (J Clin Microbiol 35:201-202, 1997) with minor modifications. Genotyping of 28 samples revealed three different genotypes including 3a, 3b and 1a. The most prevalent genotype was 3a with rate of 50% followed by genotype 3b and 1a, respectively. Nine samples remained untyped, suggesting the need of further investigation of genotypes in this region. It has been proposed that sequencing of these samples may be helpful to unreveal these genotypes and further epidemiology of HCV genotypes. Further more, extensive and large scale studies are needed to understand the epidemiology of HCV genotypes, as no such study has been carried in this province.

Detection of hepatitis "C" virus in formalin-fixed liver tissue by nested polymerase chain reaction.

PubMed

Sallie, R; Rayner, A; Portmann, B; Eddleston, A L; Williams, R

1992-08-01

Interpretation of antibody to hepatitis C virus (HCV) in patients with liver disease is difficult due to false-positive reactivity in some conditions. To evaluate the feasibility of HCV in archival material, HCV was sought in formalin-fixed, paraffin-embedded liver biopsy specimens. Nested polymerase chain reaction was used to detect hepatitis C virus in formalin-fixed, paraffin-embedded liver biopsy specimens after total RNA was extracted from tissue by proteinase K digestion and phenol/chloroform purification. The relative efficiency of amplification of HCV RNA from formalin-fixed material was estimated semiquantitatively by serial dilution of cDNA synthesised from RNA extracted from fresh and formalin-fixed sections from the same liver. Although HCV RNA could be detected in formalin-fixed liver tissue by nested PCR in 5/5 cases in which HCV was detected in serum, amplification was approximately 5-fold less efficient than when HCV was amplified from fresh tissue. Nevertheless, nested PCR of HCV from formalin-fixed liver tissue represents a useful technique in addressing some important questions related to the pathogenesis of liver disease.

HCV upregulates Bim through the ROS/JNK signalling pathway, leading to Bax-mediated apoptosis.

PubMed

Deng, Lin; Chen, Ming; Tanaka, Motofumi; Ku, Yonson; Itoh, Tomoo; Shoji, Ikuo; Hotta, Hak

2015-09-01

We previously reported that hepatitis C virus (HCV) infection induces Bax-triggered, mitochondrion-mediated apoptosis by using the HCV J6/JFH1 strain and Huh-7.5 cells. However, it was still unclear how HCV-induced Bax activation. In this study, we showed that the HCV-induced activation and mitochondrial accumulation of Bax were significantly attenuated by treatment with a general antioxidant, N-acetyl cysteine (NAC), or a specific c-Jun N-terminal kinase (JNK) inhibitor, SP600125, with the result suggesting that the reactive oxygen species (ROS)/JNK signalling pathway is upstream of Bax activation in HCV-induced apoptosis. We also demonstrated that HCV infection transcriptionally activated the gene for the pro-apoptotic protein Bim and the protein expression of three major splice variants of Bim (BimEL, BimL and BimS). The HCV-induced increase in the Bim mRNA and protein levels was significantly counteracted by treatment with NAC or SP600125, suggesting that the ROS/JNK signalling pathway is involved in Bim upregulation. Moreover, HCV infection led to a marked accumulation of Bim on the mitochondria to facilitate its interaction with Bax. On the other hand, downregulation of Bim by siRNA (small interfering RNA) significantly prevented HCV-mediated activation of Bax and caspase 3. Taken together, these observations suggest that HCV-induced ROS/JNK signalling transcriptionally activates Bim expression, which leads to Bax activation and apoptosis induction.

The Changing Face of Hepatitis C: Recent Advances on HCV Inhibitors Targeting NS5A

PubMed

Rai, Diwakar; Wang, Liu; Jiang, Xuemei; Zhan, Peng; Jia, Haiyong; De Clercq, Erik; Liu, Xinyong

2015-05-05

Current treatment for HCV infections consists of approved direct acting antivirals (DAAs), viz. the protease inhibitors (boceprevir, telaprevir, and simeprevir), NS5B polymerase inhibitors (sofosbuvir) and NS5A inhibitor (ledipasvir) in combination with pegylated interferon α and ribavirin). These treatments have made a great improvement in the treatment of chronic HCV infections in recent years, but their adverse side effects, emergence of resistant mutants, high cost, and increased pill burden have limited their clinical use. Recently, with the increasing knowledge in understanding the HCV life cycle, more targets have been recognized. NS5A protein plays a critical role in assembly of infectious HCV particles and offering potential for HCV therapies. Therefore, discovery and development of novel DAAs targeting NS5A with novel mechanisms of action, is of great necessity to improve the quality of existing HCV treatments. In the present review, we discuss recent advances with NS5A inhibitors with potent anti-HCV activity, and the potential for the development of HCV NS5A inhibitors to combat HCV infections.

Statin Utilization and Recommendations Among HIV- and HCV-infected Veterans: A Cohort Study

PubMed Central

Clement, Meredith E.; Park, Lawrence P.; Navar, Ann Marie; Okeke, Nwora Lance; Pencina, Michael J.; Douglas, Pamela S.; Naggie, Susanna

2016-01-01

Background. Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections are associated with increased risk of cardiovascular disease (CVD). The potential impact of recently updated cholesterol guidelines on treatment of HIV- and HCV-infected veterans is unknown. Methods. We performed a retrospective cohort study to assess statin use and recommendations among 13 579 HIV-infected, 169 767 HCV-infected, and 6628 HIV/HCV-coinfected male veterans aged 40–75 years. Prior 2004 Adult Treatment Panel (ATP-III) guidelines were compared with current 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines and 2014 US Department of Veterans Affairs (VA)/US Department of Defense (DoD) joint clinical practice guidelines using laboratory, medication, and comorbidity data from the VA Clinical Case Registry from 2008 through 2010. Results. Using risk criteria delineated by the ATP-III guidelines, 50.6% of HIV-infected, 45.9% of HCV-infected, and 33.8% of HIV/HCV-coinfected veterans had an indication for statin therapy. However, among those eligible, 22.7%, 30.5%, and 31.5%, respectively, were not receiving ATP-III recommended statin therapy. When current cholesterol guidelines were applied by VA/DoD and ACC/AHA criteria, increases in recommendations for statins were found in all groups (57.3% and 66.1% of HIV-infected, 64.4% and 73.7% of HCV-infected, 49.1% and 58.5% of HIV/HCV-coinfected veterans recommended). Conclusions. Statins were underutilized among veterans infected with HIV, HCV, and HIV/HCV according to previous ATP-III guidelines. Current VA/DoD and ACC/AHA guidelines substantially expand statin recommendations and widen the gap of statin underutilization in all groups. These gaps in care present an opportunity to improve CVD prevention efforts in these at-risk populations. PMID:27143663

Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus.

PubMed

Llibre, Alba; Shimakawa, Yusuke; Mottez, Estelle; Ainsworth, Shaun; Buivan, Tan-Phuc; Firth, Rick; Harrison, Elliott; Rosenberg, Arielle R; Meritet, Jean-François; Fontanet, Arnaud; Castan, Pablo; Madejón, Antonio; Laverick, Mark; Glass, Allison; Viana, Raquel; Pol, Stanislas; McClure, C Patrick; Irving, William Lucien; Miele, Gino; Albert, Matthew L; Duffy, Darragh

2018-04-03

Recently approved direct acting antivirals provide transformative therapies for chronic hepatitis C virus (HCV) infection. The major clinical challenge remains to identify the undiagnosed patients worldwide, many of whom live in low-income and middle-income countries, where access to nucleic acid testing remains limited. The aim of this study was to develop and validate a point-of-care (PoC) assay for the qualitative detection of HCV RNA. We developed a PoC assay for the qualitative detection of HCV RNA on the PCR Genedrive instrument. We validated the Genedrive HCV assay through a case-control study comparing results with those obtained with the Abbott RealTi m e HCV test. The PoC assay identified all major HCV genotypes, with a limit of detection of 2362 IU/mL (95% CI 1966 to 2788). Using 422 patients chronically infected with HCV and 503 controls negative for anti-HCV and HCV RNA, the Genedrive HCV assay showed 98.6% sensitivity (95% CI 96.9% to 99.5%) and 100% specificity (95% CI 99.3% to 100%) to detect HCV. In addition, melting peak ratiometric analysis demonstrated proof-of-principle for semiquantification of HCV. The test was further validated in a real clinical setting in a resource-limited country. We report a rapid, simple, portable and accurate PoC molecular test for HCV, with sensitivity and specificity that fulfils the recent FIND/WHO Target Product Profile for HCV decentralised testing in low-income and middle-income countries. This Genedrive HCV assay may positively impact the continuum of HCV care from screening to cure by supporting real-time treatment decisions. NCT02992184. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Naturally occurring mutations associated with resistance to HCV NS5B polymerase and NS3 protease inhibitors in treatment-naïve patients with chronic hepatitis C.

PubMed

Costantino, Angela; Spada, Enea; Equestre, Michele; Bruni, Roberto; Tritarelli, Elena; Coppola, Nicola; Sagnelli, Caterina; Sagnelli, Evangelista; Ciccaglione, Anna Rita

2015-11-14

The detection of baseline resistance mutations to new direct-acting antivirals (DAAs) in HCV chronically infected treatment-naïve patients could be important for their management and outcome prevision. In this study, we investigated the presence of mutations, which have been previously reported to be associated with resistance to DAAs in HCV polymerase (NS5B) and HCV protease (NS3) regions, in sera of treatment-naïve patients. HCV RNA from 152 naïve patients (84 % Italian and 16 % immigrants from various countries) infected with different HCV genotypes (21,1a; 21, 1b; 2, 2a; 60, 2c; 22, 3a; 25, 4d and 1, 4k) was evaluated for sequence analysis. Amplification and sequencing of fragments in the NS5B (nt 8256-8640) and NS3 (nt 3420-3960) regions of HCV genome were carried out for 152 and 28 patients, respectively. The polymorphism C316N/H in NS5B region, associated with resistance to sofosbuvir, was detected in 9 of the 21 (43 %) analysed sequences from genotype 1b-infected patients. Naturally occurring mutations V36L, and M175L in the NS3 protease region were observed in 100 % of patients infected with subtype 2c and 4. A relevant proportion of treatment naïve genotype 1b infected patients evaluated in this study harboured N316 polymorphism and might poorly respond to sofosbuvir treatment. As sofosbuvir has been approved for treatment of HCV chronic infection in USA and Europe including Italy, pre-treatment testing for N316 polymorphism on genotype 1b naïve patients should be considered for this drug.

3D cultured immortalized human hepatocytes useful to develop drugs for blood-borne HCV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aly, Hussein Hassan; Shimotohno, Kunitada; Hijikata, Makoto

2009-02-06

Due to the high polymorphism of natural hepatitis C virus (HCV) variants, existing recombinant HCV replication models have failed to be effective in developing effective anti-HCV agents. In the current study, we describe an in vitro system that supports the infection and replication of natural HCV from patient blood using an immortalized primary human hepatocyte cell line cultured in a three-dimensional (3D) culture system. Comparison of the gene expression profile of cells cultured in the 3D system to those cultured in the existing 2D system demonstrated an up-regulation of several genes activated by peroxisome proliferator-activated receptor alpha (PPAR{alpha}) signaling. Furthermore,more » using PPAR{alpha} agonists and antagonists, we also analyzed the effect of PPAR{alpha} signaling on the modulation of HCV replication using this system. The 3D in vitro system described in this study provides significant insight into the search for novel anti-HCV strategies that are specific to various strains of HCV.« less

A polymorphism near IL28B is associated with spontaneous clearance of acute hepatitis C virus and jaundice.

PubMed

Tillmann, Hans L; Thompson, Alex J; Patel, Keyur; Wiese, Manfred; Tenckhoff, Hannelore; Nischalke, Hans D; Lokhnygina, Yuliya; Kullig, Ulrike; Göbel, Uwe; Capka, Emanuela; Wiegand, Johannes; Schiefke, Ingolf; Güthoff, Wolfgang; Grüngreiff, Kurt; König, Ingrid; Spengler, Ulrich; McCarthy, Jeanette; Shianna, Kevin V; Goldstein, David B; McHutchison, John G; Timm, Jörg; Nattermann, Jacob

2010-11-01

A single nucleotide polymorphism (SNP) upstream of the IL28B gene has been associated with response of patients with chronic hepatitis C to therapy with pegylated interferon and ribavirin and also with spontaneous clearance of acute hepatitis C in a heterogeneous population. We analyzed the association between IL28B and the clinical presentation of acute hepatitis C virus (HCV) infection in a homogeneous population. We analyzed the SNP rs12979860 in 190 women from the German anti-D cohort (infected with HCV genotype 1b via contaminated rhesus prophylaxis) and its association with spontaneous clearance. Clinical data were available in 136 women with acute infection who were also evaluated for IL28B genotype. Based on results of a TaqMan polymerase chain reaction assay, the rs12979860 SNP genotypes studied were C/C, C/T, or T/T. Spontaneous clearance was more common in patients with the C/C genotype (43/67; 64%) compared with C/T (22/90; 24%) or T/T (2/33; 6%) (P < .001). Jaundice during acute infection was more common among patients with C/C genotype (32.7%) than non-C/C patients (with C/T or T/T) (16.1%; P = .032). In C/C patients, jaundice during acute infection was not associated with an increased chance of spontaneous clearance (56.3%) compared with those without jaundice (60.6%). In contrast, in non-C/C patients, jaundice was associated with a higher likelihood of spontaneous clearance (42.9%) compared with those without jaundice (13.7%). The SNP rs12979860 upstream of IL28B is associated with spontaneous clearance of HCV. Women with the C/T or T/T genotype who did not develop jaundice had a lower chance of spontaneous clearance of HCV infection. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Detection of hepatitis C virus RNA using ligation-dependent polymerase chain reaction in formalin-fixed, paraffin-embedded liver tissues.

PubMed Central

Park, Y. N.; Abe, K.; Li, H.; Hsuih, T.; Thung, S. N.; Zhang, D. Y.

1996-01-01

Reverse transcription polymerase chain reaction (RT-PCR) has been used to detect hepatitis C virus (HCV) sequences in liver tissue. However, RT-PCR has a variable detection sensitivity, especially on routinely processed formalin-fixed, paraffin-embedded (FFPE) specimens. RNA-RNA and RNA-protein cross-links formed during formalin fixation is the major limiting factor preventing reverse trans criptase from extending the primers. To overcome this problem, we applied the ligation-dependent PCR (LD-PCR) for the detection of HCV RNA in FFPE liver tissue. This method uses two capture probes for RNA isolation and two hemiprobes for the subsequent PCR. Despite cross-links, the capture probes and the hemiprobes are able to form hybrids with HCV RNAs released from the FFPE tissue. The hybrids are isolated through binding of the capture probes to paramagnetic beads. The hemiprobes are then ligated by a T4 DNA ligase to form a full probe that serves as a template for the Taq DNA polymerase. A total of 22 FFPE liver specimens, 21 with hepatocellular carcinoma (HCC) and 1 with biliary cirrhosis secondary to bile duct atresia were selected for this study, of which 13 patients were HCV seropositive and 9 seronegative. HCV RNA was detectable by ID-PCR from all 13 HCV-seropositive HCCs and from 5 of 8 HCV-seronegative HCCs but not from the HCV-seronegative liver with biliary atresia. By contrast, RT-PCR detected HCV sequences in only 5 of the HCV-sero-positive and in 1 of the HCV-seronegative HCCs. To resolve the discordance between the LD-PCR and RT-PCR results, RT-PCR was performed on frozen liver tissue of the discrepant specimens, which confirmed the LD-PCR positive results. In conclusion, LD-PCR is a more sensitive method than RT-PCR for the detection of HCV sequences in routinely processed liver tissues. A high rate of HCV infection (86%) is found in HCC specimens, indicating a previously underestimated role of HCV in HCC pathogenesis. Images Figure 2 PMID:8909238

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

PubMed

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

2015-05-08

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

Seroprevalence and diagnosis of HIV, HBV, HCV and syphilis infections among blood donors.

PubMed

Tafesse, Tadesse Bekele; Gebru, Addis Adera; Gobalee, Semgne; Belay, Gosaye Degu; Belew, Molla Teferi; Ataro, Demelash; Ebrahim, Belay Ali; Shebeshi, Getachew Mekonnon; Yimam, Yonas

2017-01-01

Blood transfusion is one of the most important therapeutic options of life-saving intervention for recipients who are in diseased or non-diseased conditions with severe blood loss. However, it is associated with certain risks which can lead to adverse consequences that may cause acute or delayed complications and bring the risk of transfusion-transmissible infections including HIV, Hepatitis B & C and Syphilis. So, there might be a fatal risk instead of life saving. This paper aims to provide a comprehensive and reliable tabulation of available data on seroprevalence and diagnosis of HIV, HBV, HCV and Syphilis infections among blood donors. We searched studies reporting the prevalence rate of HIV, HBV, HCV and Syphilis infections among blood donors that were published between October 2009 and June 2016, using databases of PubMed, Scopus, MEDLINE, Elsevier, ScienceDirect, EBSCO, Google Scholar, EMBASE, and Web of Science with keywords: ``Hepatitis C Virus'', ``Hepatitis B Virus'', ``HIV'', ``Syphilis'', ``Seroprevalence'', and ``blood donor''. The seroprevalence of HBV and HCV was highest in African countries as compared to others continents, predominantly the West African region with a range of 10.0% to 14.96% and 1.5% to 8.69%, respectively, while the overall seropositivity of HIV and syphilis infection show a significant declining pattern through successive years globally, even though relatively higher prevalence rate was observed among older age and those with low level of education. There is a problem during selection, diagnoses and screening process in developing nations primarily due to shortage of sensitive screening test kits, highly qualified human resource and lack of proper standard operating procedures and hence, the safety of blood and blood products are the primary threats in the region. Proper clinical diagnosis and screening method should be applied during blood donation and therefore, all the donated blood should be screened properly for

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.

PubMed

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

2016-05-01

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). 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. 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. 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. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Classical and emerging roles of vitamin D in hepatitis C virus (HCV) infection

PubMed Central

Gutierrez, Julio A.; Parikh, Neil; Branch, Andrea D.

2014-01-01

The risk of clinically-significant vitamin D deficiency increases at 25-hydroxyvitamin D levels below 20 ng/mL, according to the Institute of Medicine. By this standard, most cirrhotic hepatitis C virus (HCV)-positive patients and many non-cirrhotic patients are vitamin D deficient. The high prevalence of vitamin D deficiency among HCV patients is a cause for concern for several specific reasons. Classic studies established the importance of vitamin D and calcium in maintaining bone. Vitamin D's beneficial effects on bone are likely to be vital for HCV-infected patients because these individuals have a high prevalence of low bone mineral density. Many pharmaceutical agents reduce bone density and exposure to these drugs may increase bone disease in HCV-positive patients. Bone loss occurs following liver transplantation and bone density is often low in patients with HIV/HCV co-infection who are on combination antiretroviral therapy. Some evidence suggests that ribavirin reduces bone density, underscoring the special need to monitor vitamin D in patients receiving HCV treatment and to prescribe supplements, as appropriate. In addition to its role in calcium metabolism, vitamin D is also an immune modulator that reduces inflammation while enhancing protective immune responses. Higher vitamin D levels are associated with less liver fibrosis and less inflammation in HCV patients. Recent studies show that low vitamin D levels are associated with treatment failure among HCV-infected patients receiving pegylated-interferon and ribavirin. If confirmed, these findings will provide an additional reason to ensure adequate levels of vitamin D. The article concludes with information about how to monitor vitamin D status and how to use vitamin D supplements most effectively in HCV-infected patients. PMID:22189978

Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection.

PubMed

Foster, Graham R; Afdhal, Nezam; Roberts, Stuart K; Bräu, Norbert; Gane, Edward J; Pianko, Stephen; Lawitz, Eric; Thompson, Alex; Shiffman, Mitchell L; Cooper, Curtis; Towner, William J; Conway, Brian; Ruane, Peter; Bourlière, Marc; Asselah, Tarik; Berg, Thomas; Zeuzem, Stefan; Rosenberg, William; Agarwal, Kosh; Stedman, Catherine A M; Mo, Hongmei; Dvory-Sobol, Hadas; Han, Lingling; Wang, Jing; McNally, John; Osinusi, Anu; Brainard, Diana M; McHutchison, John G; Mazzotta, Francesco; Tran, Tram T; Gordon, Stuart C; Patel, Keyur; Reau, Nancy; Mangia, Alessandra; Sulkowski, Mark

2015-12-31

In phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic response in patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3. We conducted two randomized, phase 3, open-label studies involving patients who had received previous treatment for HCV genotype 2 or 3 and those who had not received such treatment, including patients with compensated cirrhosis. In one trial, patients with HCV genotype 2 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir, in a once-daily, fixed-dose combination tablet (134 patients), or sofosbuvir plus weight-based ribavirin (132 patients) for 12 weeks. In a second trial, patients with HCV genotype 3 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir for 12 weeks (277 patients) or sofosbuvir-ribavirin for 24 weeks (275 patients). The primary end point for the two trials was a sustained virologic response at 12 weeks after the end of therapy. Among patients with HCV genotype 2, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 99% (95% confidence interval [CI], 96 to 100), which was superior to the rate of 94% (95% CI, 88 to 97) in the sofosbuvir-ribavirin group (P=0.02). Among patients with HCV genotype 3, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 95% (95% CI, 92 to 98), which was superior to the rate of 80% (95% CI, 75 to 85) in the sofosbuvir-ribavirin group (P<0.001). The most common adverse events in the two studies were fatigue, headache, nausea, and insomnia. Among patients with HCV genotype 2 or 3 with or without previous treatment, including those with compensated cirrhosis, 12 weeks of treatment with sofosbuvir-velpatasvir resulted in rates of sustained virologic response that were superior to those with standard treatment with sofosbuvir-ribavirin. (Funded by Gilead Sciences

A New Signaling Pathway for HCV Inhibition by Estrogen: GPR30 Activation Leads to Cleavage of Occludin by MMP-9.

PubMed

Ulitzky, Laura; Lafer, Manuel M; KuKuruga, Mark A; Silberstein, Erica; Cehan, Nicoleta; Taylor, Deborah R

2016-01-01

Poor outcome in response to hepatitis C virus, including higher viral load, hepatocellular carcinoma and cirrhosis, is more associated with men and postmenopausal women than with premenopausal women and women receiving hormone replacement therapy, suggesting that β-estradiol plays an innate role in preventing viral infection and liver disease. Consequently, most research in the field has concluded that estrogen affects HCV replication through viral interactions with estrogen receptor-α. Previously, estrogen-like antagonists, including Tamoxifen, were shown to reduce HCV RNA production and prevent viral entry, although the authors did not identify host factors involved. Estrogen can act alternatively through the membrane-bound G-protein-coupled estrogen receptor, GPR30. Here, human hepatoma Huh7.5 cells were infected with HCV J6/JFH-1 and treated with estrogen or Tamoxifen, resulting in a marked decrease in detectable virus. The effect was mimicked by G1, a GPR30-specific agonist, and was reversed by the GPR30-specific antagonist, G15. While previous studies have demonstrated that estrogen down-regulated occludin in cervical cancer cells, its action on liver cells was unknown. Occludin is a tight junction protein and HCV receptor and here we report that activation and cellular export of MMP-9 led to the cleavage of occludin upon estrogen treatment of liver cells. This is the first report of the cleavage of an HCV receptor in response to estrogen. We also identify the occludin cleavage site in extracellular Domain D; the motif required for HCV entry and spread. This pathway gives new insight into a novel innate antiviral pathway and the suboptimal environment that estrogen provides for the proliferation of the virus. It may also explain the disparate host-virus responses to HCV demonstrated by the two sexes. Moreover, these data suggest that hormone replacement therapy may have beneficial antiviral enhancement properties for HCV-infected postmenopausal women and

Acute hepatitis B in a patient with OLT during treatment with peg-interferon and ribavirin for hepatitis C recurrence.

PubMed

Biliotti, Elisa; Zacharia, Sabu; Grieco, Stefania; Spaziante, Martina; Giusto, Michela; Merli, Manuela; Gallinaro, Valentina; Taliani, Gloria

2012-12-01

The course and outcome of acute viral hepatitis in liver transplanted patients with hepatitis C recurrence are unknown. Here we describe a patient who presented with acute hepatitis B infection while on treatment with peg-interferon and ribavirin for hepatitis C recurrence after liver transplantation. A nucleoside analogue was added (entecavir) and the patient cleared hepatitis C virus (HCV) infection and seroconverted to anti-HBs. In this case, the acute hepatitis B virus (HBV) infection might have contributed to the clearance of HCV, the concomitant immunosuppression might have lead to the slow clearance of HBV infection, and the combined antiviral therapy has helped in the resolution of both infections. Hepatitis B vaccination should be recommended in susceptible patients waiting for liver transplantation.

Hepatitis C virus genotyping of organ donor samples to aid in transplantation of HCV-positive organs.

PubMed

Gentile, Caren; Van Deerlin, Vivianna M; Goldberg, David S; Reese, Peter P; Hasz, Richard D; Abt, Peter; Blumberg, Emily; Farooqi, Midhat S

2018-02-01

Given the availability of new highly efficacious anti-HCV therapies, some clinicians have advocated for wider use of kidneys from hepatitis C virus-positive (HCV+) donors, including transplanting them into HCV-negative recipients. As treatment regimens for HCV are commonly guided by genotype, pretransplant HCV genotyping of tissue donors would be beneficial. To our knowledge, donor HCV genotyping has never been reported. We retrieved archived frozen plasma samples for 17 previous organ donors through a local organ procurement organization. We performed HCV genotyping using the eSensor HCVg Direct Test (GenMark Diagnostics) and also by Sanger sequencing, for confirmation (Retrogen). In addition, viral loads were measured using the COBAS AmpliPrep/TaqMan system (Roche Diagnostics). We found that most of the samples (n = 14) were HCV Genotype 1a with the remainder being Genotype 2b (n = 1) or Genotype 3 (n = 2). All genotyping results were concordant with Sanger sequencing. The average HCV viral load in the sample group was ~ 1.6 million IU/mL (range: ~16 000 IU/mL to 7 million IU/mL). We demonstrate that viral RNA from organ donor plasma can be successfully genotyped for HCV. This ability suggests that transplantation of HCV+ kidneys into HCV-negative recipients, followed by genotype-guided antiviral therapy, could be feasible. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Detection of hepatitis C viral sequences in formalin-fixed, paraffin-embedded liver tissue: effect of interferon alpha therapy.

PubMed

Diamond, D A; Davis, G L; Qian, K P; Lau, J Y

1994-03-01

To determine the effect of interferon-alpha (IFN) therapy on hepatitis C virus (HCV) in liver, reverse transcription "nested" polymerase chain reaction (RT-PCR) was applied to detect HCV RNA in formalin-fixed, paraffin-embedded liver biopsy specimens obtained before and at the end of IFN therapy in 42 patients with chronic HCV infection. Results were correlated with the clinical and biochemical outcome in 36 cases. Fifteen patients were nonresponders to IFN; 13 patients had a complete response to IFN but relapsed shortly after IFN was stopped (responders who relapsed); and 8 patients showed a complete and sustained response to IFN therapy (sustained responders). Total RNA was extracted using proteinase K digestion and phenol/chloroform/isoamyl alcohol extraction, and HCV RNA was detected by standard RT-PCR using primers from the highly conserved 5' untranslated region. HCV RNA was detected in 41 of the 42 pretreatment specimens. Of the 36 patients with paired posttreatment samples, HCV RNA was detected in all 15 patients who did not respond to IFN and 9 of 13 who responded to IFN but relapsed shortly after IFN was stopped. In contrast, only one of the eight patients who had a sustained response to IFN therapy had HCV RNA detected by RT-PCR (P < 0.04). These data confirm 1) the feasibility of detecting HCV RNA in formalin-fixed, paraffin-embedded tissue from patients with chronic HCV infection, 2) show that sustained response to IFN is associated with loss of liver HCV RNA at the end of IFN therapy, and 3) offer an explanation for recurrence in patients who relapse.

Statin Utilization and Recommendations Among HIV- and HCV-infected Veterans: A Cohort Study.

PubMed

Clement, Meredith E; Park, Lawrence P; Navar, Ann Marie; Okeke, Nwora Lance; Pencina, Michael J; Douglas, Pamela S; Naggie, Susanna

2016-08-01

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections are associated with increased risk of cardiovascular disease (CVD). The potential impact of recently updated cholesterol guidelines on treatment of HIV- and HCV-infected veterans is unknown. We performed a retrospective cohort study to assess statin use and recommendations among 13 579 HIV-infected, 169 767 HCV-infected, and 6628 HIV/HCV-coinfected male veterans aged 40-75 years. Prior 2004 Adult Treatment Panel (ATP-III) guidelines were compared with current 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines and 2014 US Department of Veterans Affairs (VA)/US Department of Defense (DoD) joint clinical practice guidelines using laboratory, medication, and comorbidity data from the VA Clinical Case Registry from 2008 through 2010. Using risk criteria delineated by the ATP-III guidelines, 50.6% of HIV-infected, 45.9% of HCV-infected, and 33.8% of HIV/HCV-coinfected veterans had an indication for statin therapy. However, among those eligible, 22.7%, 30.5%, and 31.5%, respectively, were not receiving ATP-III recommended statin therapy. When current cholesterol guidelines were applied by VA/DoD and ACC/AHA criteria, increases in recommendations for statins were found in all groups (57.3% and 66.1% of HIV-infected, 64.4% and 73.7% of HCV-infected, 49.1% and 58.5% of HIV/HCV-coinfected veterans recommended). Statins were underutilized among veterans infected with HIV, HCV, and HIV/HCV according to previous ATP-III guidelines. Current VA/DoD and ACC/AHA guidelines substantially expand statin recommendations and widen the gap of statin underutilization in all groups. These gaps in care present an opportunity to improve CVD prevention efforts in these at-risk populations. © 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.

Report: Study is about the prevalence of the HCV disease and survival of HCV patients with associated factors in the population of district Multan.

PubMed

Tabassum, Hina; Amin, Muhammad; Amanullah, Muhammad; Tabassum, Sana

2015-09-01

To find out the significant factors associated with HCV disease and evaluate the impact of these factors on the survival pattern of HCV patients in district Multan. The study was conducted in Nishter Hospital of Multan district from 1st January 2011 to 1st October 2012. To see a significant difference between the survival rates of patients with associated factors, non-parametric Cox- proportional hazard model with their graphical results were used. All the patients above 11 years old of both sexes were included in the study. All those who were surviving with HCV disease were studied with their associated factors such as age, family history (FH) barber/parlor services, blood group (BG) types weight loss (WL), Gender and drug use were collected from Nishter Hospital Multan. Results indicated that age, blood group types and gender are the most significant factors in the patients who are surviving with HCV disease. It was also observed that survival rate of female patients is high as compare to male patients.

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

PubMed

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

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

PubMed

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

2016-01-01

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

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

PubMed

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

2015-08-20

Effective treatment for hepatitis C virus (HCV) in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains an unmet medical need. 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. 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 virologic rebound. The most common adverse events were headache (25%), fatigue (21%), and diarrhea (11%). No patient discontinued treatment because of adverse events. 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.).

Vitamin D and Osteoporosis in HIV/HCV Coinfected Patients: A Literature Review.

PubMed

Di Carlo, Paola; Siracusa, Lucia; Mazzola, Giovanni; Colletti, Piero; Soresi, Maurizio; Giannitrapani, Lydia; Li Vecchi, Valentina; Montalto, Giuseppe

2015-01-01

Vitamin D deficiency further increases the risk of osteoporosis in HIV-positive patients coinfected with hepatitis C virus (HCV); however, it is still unclear whether HCV-related increased fracture risk is a function of the severity of liver disease. The aim of this review was to identify studies on associative vitamin D deficiency patterns in high-risk populations such as HIV/HCV coinfected patients. We did this by searching MEDLINE and EMBASE databases, from inception to August 2014, and included bibliographies. The final 12 articles selected are homogeneous in terms of age but heterogeneous in terms of sample size, participant recruitment, and data source. Most of the HIV/HCV coinfected patients have less than adequate levels of vitamin D. After reviewing the selected articles, we concluded that vitamin D deficiency should be regarded as a continuum and that the lower limit of the ideal range is debatable. We found that vitamin D deficiency might influence liver disease progression in HIV/HCV coinfected patients. Methodological issues in evaluating vitamin D supplementation as a relatively inexpensive therapeutic option are discussed, as well as the need for future research, above all on its role in reducing the risk of HCV-related fracture by modifying liver fibrosis progression.

Use of versant TMA and bDNA 3.0 assays to detect and quantify hepatitis C virus in semen.

PubMed

Pekler, Vyacheslav A; Robbins, Wendie A; Nyamathi, Adeline; Yashina, Tatyana L; Leak, Barbara; Robins, Terry A

2003-01-01

Previous findings of hepatitis C virus (HCV) in human semen have been inconsistent. This study attempted to elucidate the presence of HCV in semen from 80 HCV RNA blood plasma positive homeless men using two novel non-PCR based techniques. Semen was frozen immediately upon ejaculation in order to preserve virus quantity. This study demonstrated that 36% of the study population had HCV in semen. Bayer's Versant HCV RNA Qualitative Assay (Bayer Diagnostics, Emeryville, CA) based on transcription mediated amplification (TMA) assay detected 29 positive semen samples and Versant HCV RNA 3.0 Assay (bDNA) (Bayer Diagnostics, Emeryville, CA) detected only six. This demonstrated that TMA was more sensitive than the bDNA in detecting HCV in semen (P<0.002). HCV blood plasma viral load was positively correlated with the presence of HCV in semen (Spearman's Rho=0.40, P<0.0002), while the presence of leukocytes in semen was not (Spearman's Rho=0.19, P<0.12). This supports the hypothesis that HCV is "leaked out" from the peripheral circulation into semen. Three semen samples had a viral load of >5000 IU/mL. The presence of a high viral load in semen in certain men suggests that sexual transmission of the virus is possible. Laboratory capability to accurately detect HCV positive semen is an important step in establishing the risk of sexual transmission and in identifying strategies for protecting uninfected partners. Copyright 2003 Wiley-Liss, Inc.

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

PubMed Central

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

Rapid and sensitive approach to simultaneous detection of genomes of hepatitis A, B, C, D and E viruses.

PubMed

Kodani, Maja; Mixson-Hayden, Tonya; Drobeniuc, Jan; Kamili, Saleem

2014-10-01

Five viruses have been etiologically associated with viral hepatitis. Nucleic acid testing (NAT) remains the gold standard for diagnosis of viremic stages of infection. NAT methodologies have been developed for all hepatitis viruses; however, a NAT-based assay that can simultaneously detect all five viruses is not available. We designed TaqMan card-based assays for detection of HAV RNA, HBV DNA, HCV RNA, HDV RNA and HEV RNA. The performances of individual assays were evaluated on TaqMan Array Cards (TAC) for detecting five viral genomes simultaneously. Sensitivity and specificity were determined by testing 329 NAT-tested clinical specimens. All NAT-positive samples for HCV (n = 32), HDV (n = 28) and HEV (n = 14) were also found positive in TAC (sensitivity, 100%). Forty-three of 46 HAV-NAT positive samples were also positive in TAC (sensitivity, 94%), while 36 of 39 HBV-NAT positive samples were positive (sensitivity, 92%). No false-positives were detected for HBV (n = 32), HCV (n = 36), HDV (n = 30), and HEV (n = 31) NAT-negative samples (specificity 100%), while 38 of 41 HAV-NAT negative samples were negative by TAC (specificity 93%). TAC assay was concordant with corresponding individual NATs for hepatitis A-E viral genomes and can be used for their detection simultaneously. The TAC assay has potential for use in hepatitis surveillance, for screening of donor specimens and in outbreak situations. Wider availability of TAC-ready assays may allow for customized assays, for improving acute jaundice surveillance and for other purposes for which there is need to identify multiple pathogens rapidly. Published by Elsevier B.V.

Trouble with bleeding: risk factors for acute hepatitis C among HIV-positive gay men from Germany--a case-control study.

PubMed

Schmidt, Axel J; Rockstroh, Jürgen K; Vogel, Martin; An der Heiden, Matthias; Baillot, Armin; Krznaric, Ivanka; Radun, Doris

2011-03-08

To identify risk factors for hepatitis C among HIV-positive men who have sex with men (MSM), focusing on potential sexual, nosocomial, and other non-sexual determinants. Outbreaks of hepatitis C virus (HCV) infections among HIV-positive MSM have been reported by clinicians in post-industrialized countries since 2000. The sexual acquisition of HCV by gay men who are HIV positive is not, however, fully understood. Between 2006 and 2008, a case-control study was embedded into a behavioural survey of MSM in Germany. Cases were HIV-positive and acutely HCV-co-infected, with no history of injection drug use. HIV-positive MSM without known HCV infection, matched for age group, served as controls. The HCV-serostatus of controls was assessed by serological testing of dried blood specimens. Univariable and multivariable regression analyses were used to identify factors independently associated with HCV-co-infection. 34 cases and 67 controls were included. Sex-associated rectal bleeding, receptive fisting and snorting cocaine/amphetamines, combined with group sex, were independently associated with case status. Among cases, surgical interventions overlapped with sex-associated rectal bleeding. Sexual practices leading to rectal bleeding, and snorting drugs in settings of increased HCV-prevalence are risk factors for acute hepatitis C. We suggest that sharing snorting equipment as well as sharing sexual partners might be modes of sexual transmission. Condoms and gloves may not provide adequate protection if they are contaminated with blood. Public health interventions for HIV-positive gay men should address the role of blood in sexual risk behaviour. Further research is needed into the interplay of proctosurgery and sex-associated rectal bleeding.

Liver stiffness is not associated with short- and long-term plasma HIV RNA replication in immunocompetent patients with HIV infection and with HIV/HCV coinfection

PubMed Central

Parisi, Saverio Giuseppe; Basso, Monica; Mengoli, Carlo; Scaggiante, Renzo; Andreis, Samantha; Franzetti, Marzia Maria; Cattelan, Anna Maria; Zago, Daniela; Cruciani, Mario; Andreoni, Massimo; Piovesan, Sara; Palù, Giorgio; Alberti, Alfredo

2017-01-01

Background Human immunodeficiency virus (HIV) may be directly responsible for liver damage but there are contrasting data regarding the influence of detectable plasma viremia. We analyzed the influence of plasma HIV RNA (pHIV) detectability and of other clinical and viro-immunological variables on liver stiffness (LS) measurement in adult immunocompetent HIV-monoinfected patients and in patients coinfected with hepatitis C virus (HCV). Methods Logistic regression analysis was performed using the value of LS>7.1 kPa as the dependent variable. A linear regression model was applied using LS measurement after log10 transformation (lkpa) as the dependent variable and we analyzed the predicted values versus the observed lkpa values; pHIV was classified as detectable or undetectable in the 12- and 36-month study periods before LS measurement. Results We studied 251 patients (178 with HIV monoinfection), most of whom were on antiviral treatment; 36-month study time was available for 154 subjects. The mean CD4+ cell count was 634 cells/mm3 in HIV-monoinfected patients and 606 cells/mm3 in coinfected patients. No difference in LS was found between patients with detectable or undetectable pHIV in either the 12- or the 36-month study period before transient elastography. The mean LS was higher in HIV/HCV coinfected patients (P<0.0001) than in the HIV-monoinfected subjects; lkpa was positively correlated with HCV coinfection (P<0.0001) and aspartate aminotransferase levels (P<0.0001). Detectable pHIV failed to reach significance. Eight HIV-monoinfected patients had a predicted LS measurement lower than the observed one, while eight patients had the opposite result. Conclusion LS was not correlated with ongoing HIV replication during the 12- and 36-month study periods in immunocompetent HIV-monoinfected and HIV/HCV-coinfected patients. PMID:28845109

Shortened therapy of eight weeks with paritaprevir/ritonavir/ombitasvir and dasabuvir is highly effective in people with recent HCV genotype 1 infection.

PubMed

Martinello, M; Bhagani, S; Gane, E; Orkin, C; Cooke, G; Dore, G J; Petoumenos, K; Applegate, T L; Tu, E; Marks, P; Pagani, N; Grebely, J; Nelson, M; Matthews, G V

2018-04-16

Paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 12 weeks are approved for treatment of chronic HCV genotype 1 infection. This study assessed the efficacy of shortened duration paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 8 weeks among people with recent HCV infection. In this open-label single-arm trial conducted in Australia, England and New Zealand, adults with recent HCV (duration of infection <12 months) received paritaprevir/ritonavir/ombitasvir and dasabuvir (with weight-based ribavirin for genotypes 1a and 1, no subtype) for 8 weeks. The primary endpoint was sustained virological response at 12 weeks post-treatment (SVR12) in the intention-to-treat (ITT) population. Thirty people (median age 38 years, male 93%) commenced treatment (with ribavirin, 97%), of whom 77% (n = 23) were HIV-positive, 93% (n = 28) had genotype 1a infection and 53% (n = 16) had ever injected drugs. Median maximum ALT in the preceding 12 months was 433 IU/L (IQR 321, 1012). Acute clinical hepatitis with ALT > 10 x ULN was documented in 83% (n = 25); one participant (3%) had jaundice. At baseline, median estimated duration of infection was 30 weeks (range 11, 51), and median HCV RNA was 5.7 log 10 IU/mL (range 2.7, 7.3). SVR12 was achieved in 97% (29/30; early discontinuation at week 2, n = 1; per protocol 100%, 29/29). No relapse or reinfection was observed. In conclusion, paritaprevir/ritonavir/ombitasvir and dasabuvir (with ribavirin) for eight weeks were highly effective among HIV-positive and HIV-negative individuals with recent HCV infection. These data support the use of this shortened duration direct-acting antiviral regimen in this population. © 2018 John Wiley & Sons Ltd.

Clinical relevance of total HCV core antigen testing for hepatitis C monitoring and for predicting patients' response to therapy.

PubMed

Maynard, M; Pradat, P; Berthillon, P; Picchio, G; Voirin, N; Martinot, M; Marcellin, P; Trepo, C

2003-07-01

To study the correlation between total Hepatitis C virus (HCV) Core antigen (Ag) and HCV-RNA, and to assess the proficiency of HCV Core Ag testing in monitoring and predicting virologic response during and after pegylated interferon (PEG-IFN) and ribavirin combination therapy. A total of 307 samples from treated and untreated patients were used to assess the correlation between the total HCV Core Ag test and quantitative HCV-RNA assays (Superquant, and Quantiplex branched DNA 2.0 assay). Twenty-four patients received combination therapy for 48 weeks. Blood samples were collected at day 0, and week 2, 4, 12, 24, 48 and 72 for virologic evaluation. A linear relation exists between total HCV Core Ag and HCV-RNA levels. At 3 months the positive predictive value (PPV) of response to therapy was 100% with either HCV Core Ag or HCV-RNA. For HCV Core Ag the negative predictive value (NPV) was 100% whereas for HCV-RNA the NPV was 80% (P > 0.05). At month 1, the PPV was 95% and 100% when determined by HCV Core Ag and HCV-RNA, respectively. The NPV value was 100% for HCV Core Ag and 33% for HCV-RNA (P = 0.005). HCV Core Ag quantification could be useful in clinical practice to predict a sustained virological response early during therapy (4 weeks), reaching an optimal performance at month 3. The determination of total HCV Core Ag levels in serum, constitutes an accurate and reliable alternative to HCV-RNA for monitoring and predicting treatment outcome in patients receiving PEG-IFN/Ribavirin combination therapy.

HCV prevalence can predict HIV epidemic potential among people who inject drugs: mathematical modeling analysis.

PubMed

Akbarzadeh, Vajiheh; Mumtaz, Ghina R; Awad, Susanne F; Weiss, Helen A; Abu-Raddad, Laith J

2016-12-03

Hepatitis C virus (HCV) and HIV are both transmitted through percutaneous exposures among people who inject drugs (PWID). Ecological analyses on global epidemiological data have identified a positive association between HCV and HIV prevalence among PWID. Our objective was to demonstrate how HCV prevalence can be used to predict HIV epidemic potential among PWID. Two population-level models were constructed to simulate the evolution of HCV and HIV epidemics among PWID. The models described HCV and HIV parenteral transmission, and were solved both deterministically and stochastically. The modeling results provided a good fit to the epidemiological data describing the ecological HCV and HIV association among PWID. HCV was estimated to be eight times more transmissible per shared injection than HIV. A threshold HCV prevalence of 29.0% (95% uncertainty interval (UI): 20.7-39.8) and 46.5% (95% UI: 37.6-56.6) were identified for a sustainable HIV epidemic (HIV prevalence >1%) and concentrated HIV epidemic (HIV prevalence >5%), respectively. The association between HCV and HIV was further described with six dynamical regimes depicting the overlapping epidemiology of the two infections, and was quantified using defined and estimated measures of association. Modeling predictions across a wide range of HCV prevalence indicated overall acceptable precision in predicting HIV prevalence at endemic equilibrium. Modeling predictions were found to be robust with respect to stochasticity and behavioral and biological parameter uncertainty. In an illustrative application of the methodology, the modeling predictions of endemic HIV prevalence in Iran agreed with the scale and time course of the HIV epidemic in this country. Our results show that HCV prevalence can be used as a proxy biomarker of HIV epidemic potential among PWID, and that the scale and evolution of HIV epidemic expansion can be predicted with sufficient precision to inform HIV policy, programming, and resource

Randomized, Placebo-Controlled, Single-Ascending-Dose Study of BMS-791325, a Hepatitis C Virus (HCV) NS5B Polymerase Inhibitor, in HCV Genotype 1 Infection

PubMed Central

Lemm, Julie; Eley, Timothy; Liu, Menping; Berglind, Anna; Sherman, Diane; Lawitz, Eric; Vutikullird, Apinya B.; Tebas, Pablo; Gao, Min; Pasquinelli, Claudio; Grasela, Dennis M.

2014-01-01

BMS-791325 is a nonnucleoside inhibitor of hepatitis C virus (HCV) NS5B polymerase with low-nanomolar potency against genotypes 1a (50% effective concentration [EC50], 3 nM) and 1b (EC50, 7 nM) in vitro. BMS-791325 safety, pharmacokinetics, and antiviral activity were evaluated in a double-blind, placebo-controlled, single-ascending-dose study in 24 patients (interferon naive and experienced) with chronic HCV genotype 1 infection, randomized (5:1) to receive a single dose of BMS-791325 (100, 300, 600, or 900 mg) or placebo. The prevalence and phenotype of HCV variants at baseline and specific posttreatment time points were assessed. Antiviral activity was observed in all cohorts, with a mean HCV RNA decline of ≈2.5 log10 copies/ml observed 24 h after a single 300-mg dose. Mean plasma half-life among cohorts was 7 to 9 h; individual 24-hour levels exceeded the protein-adjusted EC90 for genotype 1 at all doses. BMS-791325 was generally well tolerated, with no serious adverse events or discontinuations. Enrichment for resistance variants was not observed at 100 to 600 mg. At 900 mg, variants (P495L/S) associated with BMS-791325 resistance in vitro were transiently observed in one patient, concurrent with an observed HCV RNA decline of 3.4 log10 IU/ml, but were replaced with wild type by 48 h. Single doses of BMS-791325 were well tolerated; demonstrated rapid, substantial, and exposure-related antiviral activity; displayed dose-related increases in exposure; and showed viral kinetic and pharmacokinetic profiles supportive of once- or twice-daily dosing. These results support its further development in combination with other direct-acting antivirals for HCV genotype 1 infection. (This trial has been registered at ClinicalTrials.gov under registration no. NCT00664625.) PMID:24733462

Performance evaluation of the QIAGEN EZ1 DSP Virus Kit with Abbott RealTime HIV-1, HBV and HCV assays.

PubMed

Schneider, George J; Kuper, Kevin G; Abravaya, Klara; Mullen, Carolyn R; Schmidt, Marion; Bunse-Grassmann, Astrid; Sprenger-Haussels, Markus

2009-04-01

Automated sample preparation systems must meet the demands of routine diagnostics laboratories with regard to performance characteristics and compatibility with downstream assays. In this study, the performance of QIAGEN EZ1 DSP Virus Kit on the BioRobot EZ1 DSP was evaluated in combination with the Abbott RealTime HIV-1, HCV, and HBV assays, followed by thermalcycling and detection on the Abbott m2000rt platform. The following performance characteristics were evaluated: linear range and precision, sensitivity, cross-contamination, effects of interfering substances and correlation. Linearity was observed within the tested ranges (for HIV-1: 2.0-6.0 log copies/ml, HCV: 1.3-6.9 log IU/ml, HBV: 1.6-7.6 log copies/ml). Excellent precision was obtained (inter-assay standard deviation for HIV-1: 0.06-0.17 log copies/ml (>2.17 log copies/ml), HCV: 0.05-0.11 log IU/ml (>2.09 log IU/ml), HBV: 0.03-0.07 log copies/ml (>2.55 log copies/ml)), with good sensitivity (95% hit rates for HIV-1: 50 copies/ml, HCV: 12.5 IU/ml, HBV: 10 IU/ml). No cross-contamination was observed, as well as no negative impact of elevated levels of various interfering substances. In addition, HCV and HBV viral load measurements after BioRobot EZ1 DSP extraction correlated well with those obtained after Abbott m2000sp extraction. This evaluation demonstrates that the QIAGEN EZ1 DSP Virus Kit provides an attractive solution for fully automated, low throughput sample preparation for use with the Abbott RealTime HIV-1, HCV, and HBV assays.

Costs and absence of HCV-infected employees by disease stage.

PubMed

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

HCV kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir, simeprevir or ledipasvir

PubMed Central

Dahari, Harel; Canini, Laetitia; Graw, Frederik; Uprichard, Susan L.; Araújo, Evaldo S.A.; Penaranda, Guillaume; Coquet, Emilie; Riso, Aurelie; Renou, Christophe; Bourliere, Marc; Cotler, Scott J.; Halfon, Philippe

2016-01-01

Background&Aims Recent clinical trials of direct-acting-antiviral agents (DAAs) against hepatitis C virus (HCV) achieved >90% sustained-virological response (SVR) rates, suggesting that cure often took place before the end of treatment (EOT). We sought to evaluate retrospectively whether early response kinetics can provide the basis to individualize therapy to achieve optimal results while reducing duration and cost. Methods 58 chronic-HCV patients were treated with 12-week sofosbuvir+simeprevir(n=19), sofosbuvir+daclatasvir(n=19), or sofosbuvir+ledipasvir in three French referral centers. HCV was measured at baseline, day 2, every other week, EOT and 12 weeks post EOT. Mathematical modeling was used to predict the time to cure,i.e,<1 virus copy in the entire extracellular-body fluid. Results All but one patient who relapsed achieved SVR. Mean age was 60±11 years, 53% were male, 86% HCV genotype-1, 9% HIV coinfected, 43% advanced fibrosis (F3), and 57% had cirrhosis. At weeks 2, 4 and 6, 48%, 88% and 100% of patients had HCV<15 IU/ml, with 27%, 74% and 91% of observations having target-not-detected, respectively. Modeling results predicted that 32(43%), 16(23%), 7(13%), 5(9%) and 3(5%) subjects were predicted to reach cure within 6, 8, 10, 12 and 13 weeks of therapy, respectively. The modeling suggested that the patient who relapsed would have benefitted from an additional week of sofosbuvir+ledipasvir. Adjusting duration of treatment according to the modeling predicts reduced medication costs of 43%-45% and 17%-30% in subjects who had HCV<15 IU/ml at weeks 2 and 4, respectively. Conclusions The use of early viral-kinetic analysis has the potential to individualize duration of DAA therapy with a projected average cost-saving of 16%-20% per 100-treated persons. PMID:26907973

HCV kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir, simeprevir or ledipasvir

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dahari, Harel; Canini, Laetitia; Graw, Frederik

Recent clinical trials of direct-acting-antiviral agents (DAAs) against hepatitis C virus (HCV) achieved >90% sustained virological response (SVR) rates, suggesting that cure often took place before the end of treatment (EOT). We sought to evaluate retrospectively whether early response kinetics can provide the basis to individualize therapy to achieve optimal results while reducing duration and cost. 58 chronic HCV patients were treated with 12-week sofosbuvir + simeprevir (n = 19), sofosbuvir + daclatasvir (n = 19), or sofosbuvir + ledipasvir in three French referral centers. HCV was measured at baseline, day 2, every other week, EOT and 12 weeks postmore » EOT. Furthermore, mathematical modeling was used to predict the time to cure, i.e., <1 virus copy in the entire extracellular body fluid. All but one patient who relapsed achieved SVR. Mean age was 60 ± 11 years, 53% were male, 86% HCV genotype-1, 9% HIV coinfected, 43% advanced fibrosis (F3), and 57% had cirrhosis. At weeks 2, 4 and 6, 48%, 88% and 100% of patients had HCV <15 IU/ml, with 27%, 74% and 91% of observations having target not detected, respectively. Modeling results predicted that 23 (43%), 16 (30%), 7 (13%), 5 (9%) and 3 (5%) subjects were predicted to reach cure within 6, 8, 10, 12 and 13 weeks of therapy, respectively. The modeling suggested that the patient who relapsed would have benefitted from an additional week of sofosbuvir + ledipasvir. Adjusting duration of treatment according to the modeling predicts reduced medication costs of 43–45% and 17–30% in subjects who had HCV <15 IU/ml at weeks 2 and 4, respectively. Finally, the use of early viral kinetic analysis has the potential to individualize duration of DAA therapy with a projected average cost saving of 16–20% per 100-treated persons.« less

HCV kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir, simeprevir or ledipasvir

DOE PAGES

Dahari, Harel; Canini, Laetitia; Graw, Frederik; ...

2016-06-01

Recent clinical trials of direct-acting-antiviral agents (DAAs) against hepatitis C virus (HCV) achieved >90% sustained virological response (SVR) rates, suggesting that cure often took place before the end of treatment (EOT). We sought to evaluate retrospectively whether early response kinetics can provide the basis to individualize therapy to achieve optimal results while reducing duration and cost. 58 chronic HCV patients were treated with 12-week sofosbuvir + simeprevir (n = 19), sofosbuvir + daclatasvir (n = 19), or sofosbuvir + ledipasvir in three French referral centers. HCV was measured at baseline, day 2, every other week, EOT and 12 weeks postmore » EOT. Furthermore, mathematical modeling was used to predict the time to cure, i.e., <1 virus copy in the entire extracellular body fluid. All but one patient who relapsed achieved SVR. Mean age was 60 ± 11 years, 53% were male, 86% HCV genotype-1, 9% HIV coinfected, 43% advanced fibrosis (F3), and 57% had cirrhosis. At weeks 2, 4 and 6, 48%, 88% and 100% of patients had HCV <15 IU/ml, with 27%, 74% and 91% of observations having target not detected, respectively. Modeling results predicted that 23 (43%), 16 (30%), 7 (13%), 5 (9%) and 3 (5%) subjects were predicted to reach cure within 6, 8, 10, 12 and 13 weeks of therapy, respectively. The modeling suggested that the patient who relapsed would have benefitted from an additional week of sofosbuvir + ledipasvir. Adjusting duration of treatment according to the modeling predicts reduced medication costs of 43–45% and 17–30% in subjects who had HCV <15 IU/ml at weeks 2 and 4, respectively. Finally, the use of early viral kinetic analysis has the potential to individualize duration of DAA therapy with a projected average cost saving of 16–20% per 100-treated persons.« less

Cyclophilin B stimulates RNA synthesis by the HCV RNA dependent RNA polymerase

PubMed Central

Heck, Julie A.; Meng, Xiao; Frick, David N.

2009-01-01

Cyclophilins are cellular peptidyl isomerases that have been implicated in regulating hepatitis C virus (HCV) replication. Cyclophilin B (CypB) is a target of cyclosporin A (CsA), an immunosuppressive drug recently shown to suppress HCV replication in cell culture. Watashi et al. recently demonstrated that CypB is important for efficient HCV replication, and proposed that it mediates the anti-HCV effects of CsA through an interaction with NS5B (Mol. Cell 19:111). We examined the effects of purified CypB proteins on the enzymatic activity of NS5B. Recombinant CypB purified from insect cells directly stimulated NS5B-catalyzed RNA synthesis. CypB increased RNA synthesis by NS5B derived from genotype 1a, 1b, and 2a HCV strains. Stimulation appears to arise from an increase in productive RNA binding. NS5B residue Pro540, a previously proposed target of CypB peptidyl-prolyl isomerase activity, is not required for stimulation of RNA synthesis. PMID:19174155

Bystander hyperactivation of preimmune CD8+ T cells in chronic HCV patients

PubMed Central

Alanio, Cécile; Nicoli, Francesco; Sultanik, Philippe; Flecken, Tobias; Perot, Brieuc; Duffy, Darragh; Bianchi, Elisabetta; Lim, Annick; Clave, Emmanuel; van Buuren, Marit M; Schnuriger, Aurélie; Johnsson, Kerstin; Boussier, Jeremy; Garbarg-Chenon, Antoine; Bousquet, Laurence; Mottez, Estelle; Schumacher, Ton N; Toubert, Antoine; Appay, Victor; Heshmati, Farhad; Thimme, Robert; Pol, Stanislas; Mallet, Vincent; Albert, Matthew L

2015-01-01

Chronic infection perturbs immune homeostasis. While prior studies have reported dysregulation of effector and memory cells, little is known about the effects on naïve T cell populations. We performed a cross-sectional study of chronic hepatitis C (cHCV) patients using tetramer-associated magnetic enrichment to study antigen-specific inexperienced CD8+ T cells (i.e., tumor or unrelated virus-specific populations in tumor-free and sero-negative individuals). cHCV showed normal precursor frequencies, but increased proportions of memory-phenotype inexperienced cells, as compared to healthy donors or cured HCV patients. These observations could be explained by low surface expression of CD5, a negative regulator of TCR signaling. Accordingly, we demonstrated TCR hyperactivation and generation of potent CD8+ T cell responses from the altered T cell repertoire of cHCV patients. In sum, we provide the first evidence that naïve CD8+ T cells are dysregulated during cHCV infection, and establish a new mechanism of immune perturbation secondary to chronic infection. DOI: http://dx.doi.org/10.7554/eLife.07916.001 PMID:26568315

[Chronic HCV hepatopathy and cryoglobulinemia. The associated clinical spectrum].

PubMed

Pellicano, R; Leone, N; Maiocco, I A; Modena, V; Arena, V; Marietti, G; Puiatti, P; Palmas, F; Rizzetto, M; Ponzetto, A

1999-01-01

The hepatitis C infection (HCV) has numerous extrahepatic manifestations owing to the systemic nature of the infection itself. HCV infects the cells that carry a CD 81 receptor and show a marked tropism for hepatocytes, bone marrow staminal cells and circulating lymphomonocytes. One consequence of this tropism is the activation of B lymphocyte clones with the consequent production of autoantibodies and cryoglobulins. The secondary event is the formation of circulating immune complexes which, having precipitated at an intravascular level, may cause part of the extrahepatic manifestations associated with these infections. This retrospective study evaluated the manifestations correlated and/or associated with HCV hepatitis and mixed cryoglobulinaemia. This analysis showed that 75% of consecutively studied patients reveal clinically important extrahepatic manifestations. This underlines the "broad spectrum" action played by the hepatitis C virus in the host organism.

Biological properties of purified recombinant HCV particles with an epitope-tagged envelope

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takahashi, Hitoshi; Akazawa, Daisuke; Toray Industries, Inc., Kanagawa

2010-05-14

To establish a simple system for purification of recombinant infectious hepatitis C virus (HCV) particles, we designed a chimeric J6/JFH-1 virus with a FLAG (FL)-epitope-tagged sequence at the N-terminal region of the E2 hypervariable region-1 (HVR1) gene (J6/JFH-1/1FL). We found that introduction of an adaptive mutation at the potential N-glycosylation site (E2N151K) leads to efficient production of the chimeric virus. This finding suggests the involvement of glycosylation at Asn within the envelope protein(s) in HCV morphogenesis. To further analyze the biological properties of the purified recombinant HCV particles, we developed a strategy for large-scale production and purification of recombinant J6/JFH-1/1FL/E2N151K.more » Infectious particles were purified from the culture medium of J6/JFH-1/1FL/E2N151K-infected Huh-7 cells using anti-FLAG affinity chromatography in combination with ultrafiltration. Electron microscopy of the purified particles using negative staining showed spherical particle structures with a diameter of 40-60 nm and spike-like projections. Purified HCV particle-immunization induced both an anti-E2 and an anti-FLAG antibody response in immunized mice. This strategy may contribute to future detailed analysis of HCV particle structure and to HCV vaccine development.« less

Is response guided therapy dead? Low cure rates in patients with detectable hepatitis C virus at week 4 of treatment.

PubMed

Thornton, Karla; Deming, Paulina; Manch, Richard A; Moore, Ann; Kohli, Anita; Gish, Robert; Sussman, Norman L; Khaderi, Saira; Scott, John; Mera, Jorge; Box, Terry; Qualls, Clifford; Sedillo, Miranda; Arora, Sanjeev

2016-07-01

Historically, chronic hepatitis C virus (HCV) treatment was response-guided. Clinical trials with sofosbuvir indicated on-treatment virologic response was not predictive of sustained virologic response (SVR) and hence response-guided therapy (RGT) was abandoned. The purpose of this study is to examine the association between on-treatment 4-week HCV RNA and SVR in patients treated in real-world practice. The study is a retrospective analysis of consecutive patients started on treatment with a sofosbuvir-containing regimen, January 1, 2014 through August 20, 2014, for HCV genotype 1-6 infection. Patients were treated by HCV specialists at 6 centers in the Project ECHO (Extension for Community Healthcare Outcomes) HCV Collaborative or in the community by primary care clinicians mentored by HCV specialists through Project ECHO. Patients were included if they were over 18 years, had evidence of chronic HCV, and were started on a sofosbuvir-containing regimen. The aspartate aminotransferase:platelet ratio index (APRI) was used to estimate fibrosis. The main outcome measures were 4-week HCV RNA and SVR. Overall SVR was 82.5 %. At week 4, HCV RNA was detected in 27.4 % of patients. Stepwise multivariable logistic-regression analyses identified APRI > 1.0, male sex, genotype 3, and detectable on treatment 4-week HCV RNA as independent predictors of failure to achieve SVR. In a real-world setting, a significant proportion of sofosbuvir treated patients have detectable on-treatment 4-week HCV RNA. Detectable on-treatment 4-week HCV RNA is associated with virologic failure. More data are needed to formulate guidance for RGT with newly available HCV therapies.

Distinctive gene expression profiles characterize donor biopsies from HCV-positive kidney donors.

PubMed

Mas, Valeria R; Archer, Kellie J; Suh, Lacey; Scian, Mariano; Posner, Marc P; Maluf, Daniel G

2010-12-15

Because of the shortage of organs for transplantation, procurement of kidneys from extended criteria donors is inevitable. Frequently, donors infected with hepatitis C virus (HCV) are used. To elucidate an initial compromise of molecular pathways in HCV graft, gene expression profiles were evaluated. Twenty-four donor allograft biopsies (n=12 HCV positive (+) and n=12 HCV negative (-)) were collected at preimplantation time and profiled using microarrays. Donors were age, race, gender, and cold and warm ischemia time matched between groups. Probe level data were read into the R programming environment using the affy Bioconductor package, and the robust multiarray average method was used to obtain probe set expression summaries. To identify probe sets exhibiting differential expression, a two sample t test was performed. Molecular and biologic functions were analyzed using Interaction Networks and Functional Analysis. Fifty-eight probe sets were differentially expressed between HCV (+) versus HCV (-) donors (P<0.001). The molecular functions associated with the two top scored networks from the analysis of the differentially expressed genes were connective tissue development and function and tissue morphology (score 34), cell death, cell signaling, cellular assembly, and organization (score 32). Among the differentially affected top canonical pathways, we found the role of RIG1-like receptors in antiviral innate immunity (P<0.001), natural killer cell signaling (P=0.007), interleukin-8 signaling (P=0.048), interferon signaling (P=0.0 11; INFA21, INFGR1, and MED14), ILK signaling (P=0.001), and apoptosis signaling. A unique gene expression pattern was identified in HCV (+) kidney grafts. Innate immune system and inflammatory pathways were the most affected.

Clinical evaluation of the COBAS Ampliprep/COBAS TaqMan for HCV RNA quantitation in comparison with the branched-DNA assay.

PubMed

Pittaluga, Fabrizia; Allice, Tiziano; Abate, Maria Lorena; Ciancio, Alessia; Cerutti, Francesco; Varetto, Silvia; Colucci, Giuseppe; Smedile, Antonina; Ghisetti, Valeria

2008-02-01

Diagnosis and monitoring of HCV infection relies on sensitive and accurate HCV RNA detection and quantitation. The performance of the COBAS AmpliPrep/COBAS TaqMan 48 (CAP/CTM) (Roche, Branchburg, NJ), a fully automated, real-time PCR HCV RNA quantitative test was assessed and compared with the branched-DNA (bDNA) assay. Clinical evaluation on 576 specimens obtained from patients with chronic hepatitis C showed a good correlation (r = 0.893) between the two test, but the CAP/CTM scored higher HCV RNA titers than the bDNA across all viral genotypes. The mean bDNA versus CAP/CTM log10 IU/ml differences were -0.49, -0.4, -0.54, -0.26 for genotype 1a, 1b, 2a/2c, 3a, and 4, respectively. These differences reached statistical significance for genotypes 1b, 2a/c, and 3a. The ability of the CAP/CTM to monitor patients undergoing antiviral therapy and correctly identify the weeks 4 and 12 rapid and early virological responses was confirmed. The broader dynamic range of the CAP/CTM compared with the bDNA allowed for a better definition of viral kinetics. In conclusion, the CAP/CTM appears as a reliable and user-friendly assay to monitor HCV viremia during treatment of patients with chronic hepatitis. Its high sensitivity and wide dynamic range may help a better definition of viral load changes during antiviral therapy. (Copyright) 2007 Wiley-Liss, Inc.

Chimeric antigen receptor (CAR)-engineered T cells redirected against hepatitis C virus (HCV) E2 glycoprotein

PubMed Central

Sautto, Giuseppe A; Wisskirchen, Karin; Clementi, Nicola; Castelli, Matteo; Diotti, Roberta A; Graf, Julia; Clementi, Massimo; Burioni, Roberto; Protzer, Ulrike; Mancini, Nicasio

2016-01-01

Objective The recent availability of novel antiviral drugs has raised new hope for a more effective treatment of hepatitis C virus (HCV) infection and its severe sequelae. However, in the case of non-responding or relapsing patients, alternative strategies are needed. To this end we have used chimeric antigen receptors (CARs), a very promising approach recently used in several clinical trials to redirect primary human T cells against different tumours. In particular, we designed the first CARs against HCV targeting the HCV/E2 glycoprotein (HCV/E2). Design Anti-HCV/E2 CARs were composed of single-chain variable fragments (scFvs) obtained from a broadly cross-reactive and cross-neutralising human monoclonal antibody (mAb), e137, fused to the intracellular signalling motif of the costimulatory CD28 molecule and the CD3ζ domain. Activity of CAR-grafted T cells was evaluated in vitro against HCV/E2-transfected cells as well as hepatocytes infected with cell culture-derived HCV (HCVcc). Results In this proof-of-concept study, retrovirus-transduced human T cells expressing anti-HCV/E2 CARs were endowed with specific antigen recognition accompanied by degranulation and secretion of proinflammatory and antiviral cytokines, such as interferon γ, interleukin 2 and tumour necrosis factor α. Moreover, CAR-grafted T cells were capable of lysing target cells of both hepatic and non-hepatic origin expressing on their surface the HCV/E2 glycoproteins of the most clinically relevant genotypes, including 1a, 1b, 2a, 3a, 4 and 5. Finally, and more importantly, they were capable of lysing HCVcc-infected hepatocytes. Conclusions Clearance of HCV-infected cells is a major therapeutic goal in chronic HCV infection, and adoptive transfer of anti-HCV/E2 CARs-grafted T cells represents a promising new therapeutic tool. PMID:25661083

Preserved MHC-II antigen processing and presentation function in chronic HCV infection

PubMed Central

DH, Canaday; CJ, Burant; L, Jones; H, Aung; L, Woc-Colburn; DD, Anthony

2010-01-01

Individuals with chronic HCV infection have impaired response to vaccine, though the etiology remains to be elucidated. Dendritic cells (DC) and monocytes (MN) provide antigen uptake, processing, presentation, and costimulatory functions necessary to achieve optimal immune responses. The integrity of antigen processing and presentation function within these antigen presenting cells (APC) in the setting of HCV infection has been unclear. We used a novel T cell hybridoma system that specifically measures MHC-II antigen processing and presentation function of human APC. Results demonstrate MHC-II antigen processing and presentation function is preserved in both myeloid DC (mDC) and MN in the peripheral blood of chronically HCV-infected individuals, and indicates that an alteration in this function does not likely underlie the defective HCV-infected host response to vaccination. PMID:21055734

Anti-HCV effect of Lentinula edodes mycelia solid culture extracts and low-molecular-weight lignin.

PubMed

Matsuhisa, Koji; Yamane, Seiji; Okamoto, Toru; Watari, Akihiro; Kondoh, Masuo; Matsuura, Yoshiharu; Yagi, Kiyohito

2015-06-19

Lentinula edodes mycelia solid culture extract (MSCE) contains several bioactive molecules, including some polyphenolic compounds, which exert immunomodulatory, antitumor, and hepatoprotective effects. In this study, we examined the anti-hepatitis C virus (HCV) activity of MSCE and low-molecular-weight lignin (LM-lignin), which is the active component responsible for the hepatoprotective effect of MSCE. Both MSCE and LM-lignin inhibited the entry of two HCV pseudovirus (HCVpv) types into Huh7.5.1 cells. LM-lignin inhibited HCVpv entry at a lower concentration than MSCE and inhibited the entry of HCV particles in cell culture (HCVcc). MSCE also inhibited HCV subgenome replication. LM-lignin had no effect on HCV replication, suggesting that MSCE contains additional active substances. We demonstrate here for the first time the anti-HCV effects of plant-derived LM-lignin and MSCE. The hepatoprotective effect of LM-lignin suggests that lignin derivatives, which can be produced in abundance from existing plant resources, may be effective in the treatment of HCV-related diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Hepatitis C virus (HCV) RNA level determined by second-generation branched-DNA probe assay as predictor of response to interferon treatment in patients with chronic HCV viremia.

PubMed

Furusyo, Norihiro; Hayashi, Jun; Kashiwagi, Kenichiro; Nakashima, Hisashi; Nabeshima, Shigeki; Sawayama, Yasunori; Kinukawa, Naoko; Kashiwagi, Seizaburo

2002-03-01

Using first- and second-generation branched-DNA probe assays (1st- and 2nd-bDNA), we investigated the predictors of favorable clinical response to interferon (IFN) treatment in patients with chronic HCV viremia. A total of 122 patients (85 genotype lb and 37 genotype 2a) with chronic HCV viremia received 24-week IFN-alpha treatment. Patients with sustained clearance of serum HCV RNA by polymerase chain reaction at six months after IFN treatment were defined as having a sustained response (SR). HCV RNA level was determined by 1st- and 2nd-bDNA assays prior to treatment. Mean HCV RNA level by 1st-bDNA was significantly higher in genotype lb patients [5.4 x 10(6) HCV genome equivalent (Meq)/ ml] than in genotype 2a patients (0.9 Meq/ml) (P < 0.05). There was no significant difference between patients with these genotypes in the level by 2nd-bDNA (1b: 5.2 Meq/ml and 2a: 3.1 Meq/ml). SR was achieved by 43 (35.2%) of 122 patients. Mean HCV RNA levels by both the 1st- and 2nd-bDNA of SR patients (1.0 and 1.9 Meq/ml) were significantly lower than those of non-SR patients (5.3 and 6.0 Meq/ml) (both P < 0.05). The SR rate in genotype 2a patients (59.5%) was significant higher than in genotype lb patients (24.7%) (P < 0.05). Stepwise logistic regression analysis showed that HCV RNA level < or = 1.0 Meq/ml by 2nd-bDNA (odds ratio = 7.6, compared to level > 1.0 Meq/ml, P < 0.05) was a significant predictive cutoff for SR. Using 2nd-bDNA, a significantly higher rate of SR was found in genotype lb patients with level < or = 1.0 Meq/ml (57.6%) than in those with level > 1.0 Meq/ml (3.8%) (P < 0.05). The SR rate of genotype 2a patients with level >1.0 Meq/ml (68.6%) was somewhat higher than for those with level < or = 1.0 Meq/ml (52.4%). These findings suggested that, using 2nd-bDNA, a low HCV RNA level of < or = 1.0 Meq/ml was the most favorable marker of successful IFN treatment and that patients with genotype 2a, even those with level >1.0 Meq/ml, had a high rate of SR to IFN

Seroprevalence of HIV, HBV, HCV, and HTLV among Pregnant Women in Southwestern Nigeria.

PubMed

Opaleye, Oluyinka Oladele; Igboama, Magdalene C; Ojo, Johnson Adeyemi; Odewale, Gbolabo

2016-01-01

Sexually transmitted infections (STIs) are major public health challenge especially in developing countries. This study was designed to determine the prevalence of Hepatitis B virus (HBV), Hepatitis C Virus (HCV), Human immunodeficiency virus (HIV), and Human T-cell lymphotropic Virus type I (HTLV-I) among pregnant women attending antenatal clinic, in Ladoke Akintola University Teaching Hospital, Osogbo, and South-Western Nigeria. One hundred and eighty two randomly selected pregnant women were screened for HBsAg, anti-HCV, anti-HIV and HTLV-1 IgM antibodies using commercially available ELISA kit. Of the 182 blood samples of pregnant women screened whose age ranged from 15-49 years, 13 (7.1%), 5 (2.7%), 9 (4.9%), and 44 (24.2%) were positive for HBsAg, anti-HCV, anti-HIV, and HTLV-1 IgM antibodies, respectively. The co-infection rate of 0.5% was obtained for HBV/HCV, HBV/HIV, HIV/HTLV-1, and HCV/HTLV-1 while 1.1% and 0% was recorded for HBV/HTLV-1 and HCV/HIV co-infections, respectively. Expected risk factors such as history of surgery, circumcision, tattooing and incision showed no significant association with any of the viral STIs (P > 0.05). This study shows that there is the need for a comprehensive screening of all pregnant women for HBsAg, anti-HCV, anti-HIV and HTLV-1 to prevent mother to child transmission of these viral infections and its attending consequences.

Prediction of Post-operative Mortality in Patients with HCV-related Cirrhosis Undergoing Non-Hepatic Surgeries

PubMed Central

Hemida, Khalid; Shabana, Sherif Sadek; Said, Hani; Ali-Eldin, Fatma

2016-01-01

Introduction Patients with chronic liver diseases are at great risk for both morbidity and mortality during the post-operative period due to the stress of surgery and the effects of general anaesthesia. Aim The main aim of this study was to evaluate the value of Model for End-stage Liver Disease (MELD) score, as compared to Child-Turcotte-Pugh (CTP) score, for prediction of 30- day post-operative mortality in Egyptian patients with liver cirrhosis undergoing non-hepatic surgery under general anaesthesia. Materials and Methods A total of 60 patients with Hepatitis C Virus (HCV) - related liver cirrhosis were included in this study. Sensitivity and specificity of MELD and CTP scores were evaluated for the prediction of post-operative mortality. A total of 20 patients who had no clinical, biochemical or radiological evidence of liver disease were included to serve as a control group. Results The highest sensitivity and specificity for detection of post-operative mortality was detected at a MELD score of 13.5. CTP score had a sensitivity of 75%, a specificity of 96.4%, and an overall accuracy of 95% for prediction of post-operative mortality. On the other side and at a cut-off value of 13.5, MELD score had a sensitivity of 100%, a specificity of 64.0%, and an overall accuracy of 66.6% for prediction of post-operative mortality in patients with HCV- related liver cirrhosis. Conclusion MELD score proved to be more sensitive but less specific than CTP score for prediction of post-operative mortality. CTP and MELD scores may be complementary rather than competitive in predicting post-operative mortality in patients with HCV- related liver cirrhosis. PMID:27891371

gC1qR expression in chimpanzees with resolved and chronic infection: Potential role of HCV core/gC1qR-mediated T cell suppression in the outcome of HCV infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yao Zhiqang; Shata, Mohamed Tarek; Tricoche, Nancy

2006-03-15

Chimpanzee is a unique animal model for HCV infection, in which about 50% of infections resolve spontaneously. It has been reported that the magnitude of T cell responses to HCV core in recovered chimpanzees is greater than that in chronically infected ones. However, the mechanism(s) by which the chimpanzees with resolved infection overcome core-mediated immunosuppression remains unknown. In this study, we examined the effect of HCV core on T cell responsiveness in chimpanzees with resolved and chronic HCV infection. We found that core protein strongly inhibited T cell activation and proliferation in chimpanzees with chronic infection, while this inhibition wasmore » limited in chimpanzees with resolved infection. Notably, the level of gC1qR, as well as the binding of core protein, on the surface of T cells was lower in recovered chimpanzees when compared to chimpanzees with chronic HCV infection. Intriguingly, the observed differences in gC1qR expression levels and susceptibility to core-induced suppression amongst HCV-chronically infected and recovered chimpanzees were observed prior to HCV challenge, suggesting a possible genetic determination of the outcome of infection. These findings suggest that gC1qR expression on the surface of T cells is crucial for HCV core-mediated T cell suppression and viral clearance, and that represents a novel mechanism by which a virus usurps host machinery for persistence.« less

Dual-Routine HCV/HIV Testing: Seroprevalence and Linkage to Care in Four Community Health Centers in Philadelphia, Pennsylvania.

PubMed

Coyle, Catelyn; Kwakwa, Helena

2016-01-01

Despite common risk factors, screening for hepatitis C virus (HCV) and HIV at the same time as part of routine medical care (dual-routine HCV/HIV testing) is not commonly implemented in the United States. This study examined improvements in feasibility of implementation, screening increase, and linkage to care when a dual-routine HCV/HIV testing model was integrated into routine primary care. National Nursing Centers Consortium implemented a dual-routine HCV/HIV testing model at four community health centers in Philadelphia, Pennsylvania, on September 1, 2013. Routine HCV and opt-out HIV testing replaced the routine HCV and opt-in HIV testing model through medical assistant-led, laboratory-based testing and electronic medical record modification to prompt, track, report, and facilitate reimbursement for tests performed on uninsured individuals. This study examined testing, seropositivity, and linkage-to-care comparison data for the nine months before (December 1, 2012-August 31, 2013) and after (September 1, 2013-May 31, 2014) implementation of the dual-routine HCV/HIV testing model. A total of 1,526 HCV and 1,731 HIV tests were performed before, and 1,888 HCV and 3,890 HIV tests were performed after dual-routine testing implementation, resulting in a 23.7% increase in HCV tests and a 124.7% increase in HIV tests. A total of 70 currently HCV-infected and four new HIV-seropositive patients vs. 101 HCV-infected and 13 new HIV-seropositive patients were identified during these two periods, representing increases of 44.3% for HCV antibody-positive and RNA-positive tests and 225.0% for HIV-positive tests. Linkage to care increased from 27 currently infected HCV--positive and one HIV-positive patient pre-dual-routine testing to 39 HCV--positive and nine HIV-positive patients post-dual-routine testing. The dual-routine HCV/HIV testing model shows that integrating dual-routine testing in a primary care setting is possible and leads to increased HCV and HIV screening

Dual-Routine HCV/HIV Testing: Seroprevalence and Linkage to Care in Four Community Health Centers in Philadelphia, Pennsylvania

PubMed Central

Kwakwa, Helena

2016-01-01

Objective Despite common risk factors, screening for hepatitis C virus (HCV) and HIV at the same time as part of routine medical care (dual-routine HCV/HIV testing) is not commonly implemented in the United States. This study examined improvements in feasibility of implementation, screening increase, and linkage to care when a dual-routine HCV/HIV testing model was integrated into routine primary care. Methods National Nursing Centers Consortium implemented a dual-routine HCV/HIV testing model at four community health centers in Philadelphia, Pennsylvania, on September 1, 2013. Routine HCV and opt-out HIV testing replaced the routine HCV and opt-in HIV testing model through medical assistant-led, laboratory-based testing and electronic medical record modification to prompt, track, report, and facilitate reimbursement for tests performed on uninsured individuals. This study examined testing, seropositivity, and linkage-to-care comparison data for the nine months before (December 1, 2012–August 31, 2013) and after (September 1, 2013–May 31, 2014) implementation of the dual-routine HCV/HIV testing model. Results A total of 1,526 HCV and 1,731 HIV tests were performed before, and 1,888 HCV and 3,890 HIV tests were performed after dual-routine testing implementation, resulting in a 23.7% increase in HCV tests and a 124.7% increase in HIV tests. A total of 70 currently HCV-infected and four new HIV-seropositive patients vs. 101 HCV-infected and 13 new HIV-seropositive patients were identified during these two periods, representing increases of 44.3% for HCV antibody-positive and RNA-positive tests and 225.0% for HIV-positive tests. Linkage to care increased from 27 currently infected HCV--positive and one HIV-positive patient pre-dual-routine testing to 39 HCV--positive and nine HIV-positive patients post-dual-routine testing. Conclusion The dual-routine HCV/HIV testing model shows that integrating dual-routine testing in a primary care setting is possible and leads

HIV, HBV and HCV Coinfection Prevalence in Iran--A Systematic Review and Meta-Analysis.

PubMed

Bagheri Amiri, Fahimeh; Mostafavi, Ehsan; Mirzazadeh, Ali

2016-01-01

worldwide, hepatitis C and B virus infections (HCV and HCV), are the two most common coinfections with human immunodeficiency virus (HIV) and has become a major threat to the survival of HIV-infected persons. The review aimed to estimate the prevalence of HIV, HBV, HCV, HIV/HCV and HIV/HBV and triple coinfections in different subpopulations in Iran. Following PRISMA guidelines, we conducted a systematic review and meta-analysis of reports on prevalence of HIV, HBV, HCV and HIV coinfections in different subpopulations in Iran. We systematically reviewed the literature to identify eligible studies from January 1996 to March 2012 in English or Persian/Farsi databases. We extracted the prevalence of HIV antibodies (diagnosed by Elisa confirmed with Western Blot test), HCV antibodies and HBsAg (with confirmatory laboratory test) as the main primary outcome. We reported the prevalence of the three infections and coinfections as point and 95% confidence intervals. HIV prevalence varied from %0.00 (95% CI: 0.00-0.003) in the general population to %17.25 (95% CI: 2.94-31.57) in people who inject drugs (PWID). HBV prevalence ranged from % 0.00 (95% CI: 0.00-7.87) in health care workers to % 30.9 (95% CI: 27.88-33.92) in PWID. HCV prevalence ranged from %0.19 (95% CI: 0.00-0.66) in health care workers to %51.46 (95% CI: 34.30-68.62) in PWID. The coinfection of HIV/HBV and also HIV/HCV in the general population and in health care workers was zero, while the most common coinfections were HIV/HCV (10.95%), HIV/HBV (1.88%) and triple infections (1.25%) in PWID. We found that PWID are severely and disproportionately affected by HIV and the other two infections, HCV and HBV. Screenings of such coinfections need to be reinforced to prevent new infections and also reduce further transmission in their community and to others.

HIV, HBV and HCV Coinfection Prevalence in Iran - A Systematic Review and Meta-Analysis

PubMed Central

Bagheri Amiri, Fahimeh; Mostafavi, Ehsan; Mirzazadeh, Ali

2016-01-01

Background worldwide, hepatitis C and B virus infections (HCV and HCV), are the two most common coinfections with human immunodeficiency virus (HIV) and has become a major threat to the survival of HIV-infected persons. The review aimed to estimate the prevalence of HIV, HBV, HCV, HIV/HCV and HIV/HBV and triple coinfections in different subpopulations in Iran. Method Following PRISMA guidelines, we conducted a systematic review and meta-analysis of reports on prevalence of HIV, HBV, HCV and HIV coinfections in different subpopulations in Iran. We systematically reviewed the literature to identify eligible studies from January 1996 to March 2012 in English or Persian/Farsi databases. We extracted the prevalence of HIV antibodies (diagnosed by Elisa confirmed with Western Blot test), HCV antibodies and HBsAg (with confirmatory laboratory test) as the main primary outcome. We reported the prevalence of the three infections and coinfections as point and 95% confidence intervals. Findings HIV prevalence varied from %0.00 (95% CI: 0.00–0.003) in the general population to %17.25 (95% CI: 2.94–31.57) in people who inject drugs (PWID). HBV prevalence ranged from % 0.00 (95% CI: 0.00–7.87) in health care workers to % 30.9 (95% CI: 27.88–33.92) in PWID. HCV prevalence ranged from %0.19 (95% CI: 0.00–0.66) in health care workers to %51.46 (95% CI: 34.30–68.62) in PWID. The coinfection of HIV/HBV and also HIV/HCV in the general population and in health care workers was zero, while the most common coinfections were HIV/HCV (10.95%), HIV/HBV (1.88%) and triple infections (1.25%) in PWID. Conclusions We found that PWID are severely and disproportionately affected by HIV and the other two infections, HCV and HBV. Screenings of such coinfections need to be reinforced to prevent new infections and also reduce further transmission in their community and to others. PMID:27031352

Modeling combination HCV prevention among HIV-infected men who have sex with men and people who inject drugs

PubMed Central

Martin, Natasha K.; Skaathun, Britt; Vickerman, Peter; Stuart, David

2017-01-01

Background People who inject drugs (PWID) and HIV-infected men who have sex with men (MSM) are key risk groups for hepatitis C virus (HCV) transmission. Mathematical modeling studies can help elucidate what level and combination of prevention intervention scale-up is required to control or eliminate epidemics among these key populations. Methods We discuss the evidence surrounding HCV prevention interventions and provide an overview of the mathematical modeling literature projecting the impact of scaled-up HCV prevention among PWID and HIV-infected MSM. Results Harm reduction interventions such as opiate substitution therapy and needle and syringe programs are effective in reducing HCV incidence among PWID. Modeling and limited empirical data indicate HCV treatment could additionally be used for prevention. No studies have evaluated the effectiveness of behavior change interventions to reduce HCV incidence among MSM, but existing interventions to reduce HIV risk could be effective. Mathematical modeling and empirical data indicates that scale-up of harm reduction could reduce HCV transmission, but in isolation is unlikely to eliminate HCV among PWID. By contrast, elimination is possibly achievable through combination scale-up of harm reduction and HCV treatment. Similarly, among HIV-infected MSM, eliminating the emerging epidemics will likely require HCV treatment scale-up in combination with additional interventions to reduce HCV-related risk behaviors. Conclusions Elimination of HCV will likely require combination prevention efforts among both PWID and HIV-infected MSM populations. Further empirical research is required to validate HCV treatment as prevention among these populations, and to identify effective behavioral interventions to reduce HCV incidence among MSM. PMID:28534885

Rituximab-based treatment, HCV replication, and hepatic flares.

PubMed

Sagnelli, Evangelista; Pisaturo, Mariantonietta; Sagnelli, Caterina; Coppola, Nicola

2012-01-01

Rituximab, a chimeric mouse-human monoclonal antibody directed to the CD20 antigen expressed on pre-B lymphocytes and mature lymphocytes, causes a profound B-cell depletion. Due to its peculiar characteristics, this drug has been used to treat oncohaematological diseases, B cell-related autoimmune diseases, rheumatoid arthritis, and, more recently, HCV-associated mixed cryoglobulinaemic vasculitis. Rituximab-based treatment, however, may induce an increased replication of several viruses such as hepatitis B virus, cytomegalovirus, varicella-zoster virus, echovirus, and parvovirus B19. Recent data suggest that rituximab-based chemotherapy induces an increase in HCV expression in hepatic cells, which may become a target for a cell-mediated immune reaction after the withdrawal of treatment and the restoration of the immune control. Only a few small studies have investigated the occurrence of HCV reactivation and an associated hepatic flare in patients with oncohaematological diseases receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). These studies suggest that the hepatic flares are frequently asymptomatic, but life-threatening liver failure occurs in nearly 10% of cases.

Differential predictors of ART adherence among HIV-monoinfected versus HIV/HCV-coinfected individuals.

PubMed

Shuper, Paul A; Joharchi, Narges; Irving, Hyacinth; Fletcher, David; Kovacs, Colin; Loutfy, Mona; Walmsley, Sharon L; Wong, David K H; Rehm, Jürgen

2016-08-01

Although adherence is an important key to the efficacy of antiretroviral therapy (ART), many people living with HIV (PLWH) fail to maintain optimal levels of ART adherence over time. PLWH with the added burden of Hepatitis C virus (HCV) coinfection possess unique challenges that potentially impact their motivation and ability to adhere to ART. The present investigation sought to (1) compare ART adherence levels among a sample of HIV/HCV-coinfected versus HIV-monoinfected patients, and (2) identify whether ART-related clinical and psychosocial correlates differ by HCV status. PLWH receiving ART (N = 215: 105 HIV/HCV-coinfected, 110 HIV-monoinfected) completed a comprehensive survey assessing ART adherence and its potential correlates. Medical chart extraction identified clinical factors, including liver enzymes. Results demonstrated that ART adherence did not differ by HCV status, with 83.7% of coinfected patients and 82.4% of monoinfected patients reporting optimal (i.e., ≥95%) adherence during a four-day recall period (p = .809). Multivariable logistic regression demonstrated that regardless of HCV status, optimal ART adherence was associated with experiencing fewer adherence-related behavioral skills barriers (AOR = 0.56; 95%CI = 0.43-0.73), lower likelihood of problematic drinking (AOR = 0.15; 95%CI = 0.04-0.67), and lower likelihood of methamphetamine use (AOR = 0.14; 95%CI = 0.03-0.69). However, among HIV/HCV-coinfected patients, optimal adherence was additionally associated with experiencing fewer ART adherence-related motivational barriers (AOR = 0.23; 95%CI = 0.08-0.62) and lower likelihood of depression (AOR = 0.06; 95%CI = 0.00-0.84). Findings suggest that although HIV/HCV-coinfected patients may face additional, distinct barriers to ART adherence, levels of adherence commensurate with those demonstrated by HIV-monoinfected patients might be achievable if these barriers are addressed.

Hepatitis B (HBV), Hepatitis C (HCV) and Hepatitis Delta (HDV) Viruses in the Colombian Population—How Is the Epidemiological Situation?

PubMed Central

Alvarado-Mora, Mónica Viviana; Gutierrez Fernandez, María Fernanda; Gomes-Gouvêa, Michele Soares; de Azevedo Neto, Raymundo Soares; Carrilho, Flair José; Pinho, João Renato Rebello

2011-01-01

Background Viral hepatitis B, C and delta still remain a serious problem worldwide. In Colombia, data from 1980s described that HBV and HDV infection are important causes of hepatitis, but little is known about HCV infection. The aim of this study was to determine the currently frequency of HBV, HCV and HDV in four different Colombian regions. Methodology/Principal Findings This study was conducted in 697 habitants from 4 Colombian departments: Amazonas, Chocó, Magdalena and San Andres Islands. Epidemiological data were obtained from an interview applied to each individual aiming to evaluate risk factors related to HBV, HCV or HDV infections. All samples were tested for HBsAg, anti-HBc, anti-HBs and anti-HCV markers. Samples that were positive to HBsAg and/or anti-HBc were tested to anti-HDV. Concerning the geographical origin of the samples, the three HBV markers showed a statistically significant difference: HBsAg (p = 0.033) and anti-HBc (p<0.001) were more frequent in Amazonas and Magdalena departments. Isolated anti-HBs (a marker of previous vaccination) frequencies were: Chocó (53.26%), Amazonas (32.88%), Magdalena (17.0%) and San Andrés (15.33%) - p<0.001. Prevalence of anti-HBc increased with age; HBsAg varied from 1.97 to 8.39% (p = 0.033). Amazonas department showed the highest frequency for anti-HCV marker (5.68%), while the lowest frequency was found in San Andrés Island (0.66%). Anti-HDV was found in 9 (5.20%) out of 173 anti-HBc and/or HBsAg positive samples, 8 of them from the Amazonas region and 1 from them Magdalena department. Conclusions/Significance In conclusion, HBV, HCV and HDV infections are detected throughout Colombia in frequency levels that would place some areas as hyperendemic for HBV, especially those found in Amazonas and Magdalena departments. Novel strategies to increase HBV immunization in the rural population and to strengthen HCV surveillance are reinforced by these results. PMID:21559488

Drug Abuse, HIV, and HCV in Asian Countries.

PubMed

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.

Characterization of SPP inhibitors suppressing propagation of HCV and protozoa

PubMed Central

Hirano, Junki; Okamoto, Toru; Sugiyama, Yukari; Suzuki, Tatsuya; Kusakabe, Shinji; Tokunaga, Makoto; Fukuhara, Takasuke; Sasai, Miwa; Tougan, Takahiro; Matsunaga, Yasue; Yamashita, Kazuo; Sakai, Yusuke; Yamamoto, Masahiro; Horii, Toshihiro; Standley, Daron M.; Moriishi, Kohji; Moriya, Kyoji; Koike, Kazuhiko; Matsuura, Yoshiharu

2017-01-01

Signal peptide peptidase (SPP) is an intramembrane aspartic protease involved in the maturation of the core protein of hepatitis C virus (HCV). The processing of HCV core protein by SPP has been reported to be critical for the propagation and pathogenesis of HCV. Here we examined the inhibitory activity of inhibitors for γ-secretase, another intramembrane cleaving protease, against SPP, and our findings revealed that the dibenzoazepine-type structure in the γ-secretase inhibitors is critical for the inhibition of SPP. The spatial distribution showed that the γ-secretase inhibitor compound YO-01027 with the dibenzoazepine structure exhibits potent inhibiting activity against SPP in vitro and in vivo through the interaction of Val223 in SPP. Treatment with this SPP inhibitor suppressed the maturation of core proteins of all HCV genotypes without the emergence of drug-resistant viruses, in contrast to the treatment with direct-acting antivirals. YO-01027 also efficiently inhibited the propagation of protozoa such as Plasmodium falciparum and Toxoplasma gondii. These data suggest that SPP is an ideal target for the development of therapeutics not only against chronic hepatitis C but also against protozoiasis. PMID:29187532

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

PubMed

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.

Cyclophilin B stimulates RNA synthesis by the HCV RNA dependent RNA polymerase.

PubMed

Heck, Julie A; Meng, Xiao; Frick, David N

2009-04-01

Cyclophilins are cellular peptidyl isomerases that have been implicated in regulating hepatitis C virus (HCV) replication. Cyclophilin B (CypB) is a target of cyclosporin A (CsA), an immunosuppressive drug recently shown to suppress HCV replication in cell culture. Watashi et al. recently demonstrated that CypB is important for efficient HCV replication, and proposed that it mediates the anti-HCV effects of CsA through an interaction with NS5B [Watashi K, Ishii N, Hijikata M, Inoue D, Murata T, Miyanari Y, et al. Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase. Mol Cell 2005;19:111-22]. We examined the effects of purified CypB proteins on the enzymatic activity of NS5B. Recombinant CypB purified from insect cells directly stimulated NS5B-catalyzed RNA synthesis. CypB increased RNA synthesis by NS5B derived from genotype 1a, 1b, and 2a HCV strains. Stimulation appears to arise from an increase in productive RNA binding. NS5B residue Pro540, a previously proposed target of CypB peptidyl-prolyl isomerase activity, is not required for stimulation of RNA synthesis.

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

PubMed

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.

Isolation and Characterization of Highly Replicable Hepatitis C Virus Genotype 1a Strain HCV-RMT

PubMed Central

Arai, Masaaki; Tokunaga, Yuko; Takagi, Asako; Tobita, Yoshimi; Hirata, Yuichi; Ishida, Yuji; Tateno, Chise; Kohara, Michinori

2013-01-01

Multiple genotype 1a clones have been reported, including the very first hepatitis C virus (HCV) clone called H77. The replication ability of some of these clones has been confirmed in vitro and in vivo, although this ability is somehow compromised. We now report a newly isolated genotype 1a clone, designated HCV-RMT, which has the ability to replicate efficiently in patients, chimeric mice with humanized liver, and cultured cells. An authentic subgenomic replicon cell line was established from the HCV-RMT sequence with spontaneous introduction of three adaptive mutations, which were later confirmed to be responsible for efficient replication in HuH-7 cells as both subgenomic replicon RNA and viral genome RNA. Following transfection, the HCV-RMT RNA genome with three adaptive mutations was maintained for more than 2 months in HuH-7 cells. One clone selected from the transfected cells had a high copy number, and its supernatant could infect naïve HuH-7 cells. Direct injection of wild-type HCV-RMT RNA into the liver of chimeric mice with humanized liver resulted in vigorous replication, similar to inoculation with the parental patient’s serum. A study of virus replication using HCV-RMT derivatives with various combinations of adaptive mutations revealed a clear inversely proportional relationship between in vitro and in vivo replication abilities. Thus, we suggest that HCV-RMT and its derivatives are important tools for HCV genotype 1a research and for determining the mechanism of HCV replication in vitro and in vivo. PMID:24358200

Isolation and characterization of highly replicable hepatitis C virus genotype 1a strain HCV-RMT.

PubMed

Arai, Masaaki; Tokunaga, Yuko; Takagi, Asako; Tobita, Yoshimi; Hirata, Yuichi; Ishida, Yuji; Tateno, Chise; Kohara, Michinori

2013-01-01

Multiple genotype 1a clones have been reported, including the very first hepatitis C virus (HCV) clone called H77. The replication ability of some of these clones has been confirmed in vitro and in vivo, although this ability is somehow compromised. We now report a newly isolated genotype 1a clone, designated HCV-RMT, which has the ability to replicate efficiently in patients, chimeric mice with humanized liver, and cultured cells. An authentic subgenomic replicon cell line was established from the HCV-RMT sequence with spontaneous introduction of three adaptive mutations, which were later confirmed to be responsible for efficient replication in HuH-7 cells as both subgenomic replicon RNA and viral genome RNA. Following transfection, the HCV-RMT RNA genome with three adaptive mutations was maintained for more than 2 months in HuH-7 cells. One clone selected from the transfected cells had a high copy number, and its supernatant could infect naïve HuH-7 cells. Direct injection of wild-type HCV-RMT RNA into the liver of chimeric mice with humanized liver resulted in vigorous replication, similar to inoculation with the parental patient's serum. A study of virus replication using HCV-RMT derivatives with various combinations of adaptive mutations revealed a clear inversely proportional relationship between in vitro and in vivo replication abilities. Thus, we suggest that HCV-RMT and its derivatives are important tools for HCV genotype 1a research and for determining the mechanism of HCV replication in vitro and in vivo.

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

PubMed

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 log 10 (range: 0-6.98log 10 ) 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.

Prevalence of HCV, HBV, and HIV Seropositivity among Cadavers Referred to Autopsy Hall of Legal Medicine Bureau of Tehran, Iran

PubMed Central

Gharehdaghi, Jaber; Abedi Khorasgani, Mohammad Hassan; Ghadiani, Mohammad Hassan; Solhi, Hassan; Solhi, Sadra

2017-01-01

A large number of dead bodies are referred to forensic autopsy halls for medicolegal examination. They can be a source of transmission of infectious diseases through direct contact or autopsy tools. The main aim of this study was to estimate the virus infection rates in the dead bodies. One thousand consecutive dead bodies that had been referred to autopsy hall of Legal Medicine Bureau of Tehran, Iran, during 2016, were included. The blood samples were analyzed in the laboratory for detection of HBs Ag, HBs Ab, HIV Ab, and HCV Ab, after providing informed consent from legal next of kin of the dead bodies. The general characteristics of the dead bodies were also collected by a checklist. Forty-seven cases of HIV seropositivity, 80 cases of HBs Ag seropositivity, and 97 cases for HCV Ab seropositivity were found. Among them, 27 cases of HIV, 40 cases of anti-HBC positive, and 94 cases of RIBA testing positive for HCV were proved through confirmatory tests. In other words, 2.6% of the dead bodies were infected with HIV, 3.8% with HBV, and 9% with HCV. The total infection rate was 15.5%. This is a worrying risk for pathologist and autopsy technicians. PMID:29318049

Prevalence of HCV, HBV, and HIV Seropositivity among Cadavers Referred to Autopsy Hall of Legal Medicine Bureau of Tehran, Iran.

PubMed

Gharehdaghi, Jaber; Abedi Khorasgani, Mohammad Hassan; Ghadiani, Mohammad Hassan; Kazemifar, Amir Mohammad; Solhi, Hassan; Solhi, Sadra

2017-01-01

A large number of dead bodies are referred to forensic autopsy halls for medicolegal examination. They can be a source of transmission of infectious diseases through direct contact or autopsy tools. The main aim of this study was to estimate the virus infection rates in the dead bodies. One thousand consecutive dead bodies that had been referred to autopsy hall of Legal Medicine Bureau of Tehran, Iran, during 2016, were included. The blood samples were analyzed in the laboratory for detection of HBs Ag, HBs Ab, HIV Ab, and HCV Ab, after providing informed consent from legal next of kin of the dead bodies. The general characteristics of the dead bodies were also collected by a checklist. Forty-seven cases of HIV seropositivity, 80 cases of HBs Ag seropositivity, and 97 cases for HCV Ab seropositivity were found. Among them, 27 cases of HIV, 40 cases of anti-HBC positive, and 94 cases of RIBA testing positive for HCV were proved through confirmatory tests. In other words, 2.6% of the dead bodies were infected with HIV, 3.8% with HBV, and 9% with HCV. The total infection rate was 15.5%. This is a worrying risk for pathologist and autopsy technicians.

Connecting rules from paired miRNA and mRNA expression data sets of HCV patients to detect both inverse and positive regulatory relationships

PubMed Central

2015-01-01

Background Intensive research based on the inverse expression relationship has been undertaken to discover the miRNA-mRNA regulatory modules involved in the infection of Hepatitis C virus (HCV), the leading cause of chronic liver diseases. However, biological studies in other fields have found that inverse expression relationship is not the only regulatory relationship between miRNAs and their targets, and some miRNAs can positively regulate a mRNA by binding at the 5' UTR of the mRNA. Results This work focuses on the detection of both inverse and positive regulatory relationships from a paired miRNA and mRNA expression data set of HCV patients through a 'change-to-change' method which can derive connected discriminatory rules. Our study uncovered many novel miRNA-mRNA regulatory modules. In particular, it was revealed that GFRA2 is positively regulated by miR-557, miR-765 and miR-17-3p that probably bind at different locations of the 5' UTR of this mRNA. The expression relationship between GFRA2 and any of these three miRNAs has not been studied before, although separate research for this gene and these miRNAs have all drawn conclusions linked to hepatocellular carcinoma. This suggests that the binding of mRNA GFRA2 with miR-557, miR-765, or miR-17-3p, or their combinations, is worthy of further investigation by experimentation. We also report another mRNA QKI which has a strong inverse expression relationship with miR-129 and miR-493-3p which may bind at the 3' UTR of QKI with a perfect sequence match. Furthermore, the interaction between hsa-miR-129-5p (previous ID: hsa-miR-129) and QKI is supported with CLIP-Seq data from starBase. Our method can be easily extended for the expression data analysis of other diseases. Conclusion Our rule discovery method is useful for integrating binding information and expression profile for identifying HCV miRNA-mRNA regulatory modules and can be applied to the study of the expression profiles of other complex human diseases

Detection of Hepatitis B and C Viruses in Almost All Hepatocytes by Modified PCR-Based In Situ Hybridization▿

PubMed Central

Nuriya, Hideko; Inoue, Kazuaki; Tanaka, Takeshi; Hayashi, Yukiko; Hishima, Tsunekazu; Funata, Nobuaki; Kaji, Kyosuke; Hayashi, Seishu; Kaneko, Shuichi; Kohara, Michinori

2010-01-01

Although PCR-based in situ hybridization (PCR-ISH) can be used to determine the distribution and localization of pathogens in tissues, this approach is hampered by its low specificity. Therefore, we used a highly specific and sensitive PCR-ISH method to reveal the lobular distribution and intracellular localization of hepatitis B virus (HBV) and HCV in chronic liver disease and to clarify the state of persistent HBV and HCV infection in the liver. HBV genomic DNA was detected in almost all hepatocytes, whereas HBV RNA or protein was differentially distributed only in a subset of the HBV DNA-positive region. Further, HCV genomic RNA was detected in almost all hepatocytes and was localized to the cytoplasm. HCV RNA was also detected in the epithelium of the large bile duct but not in endothelial cells, portal tracts, or sinusoidal lymphocytes. In patients with HBV and HCV coinfection, HCV RNA was localized to the noncancerous tissue, whereas HBV DNA was found only in the cancerous tissue. Using this novel PCR-ISH method, we could visualize the staining pattern of HBV and HCV in liver sections, and we obtained results consistent with those of real-time detection (RTD)-PCR analysis. In conclusion, almost all hepatocytes are infected with HBV or HCV in chronic liver disease; this finding implies that the viruses spreads throughout the liver in the chronic stage. PMID:20739486

Distinct features in natural history and outcomes of acute hepatitis C.

PubMed

Bunchorntavakul, Chalermrat; Jones, Lisa M; Kikuchi, Masahiro; Valiga, Mary E; Kaplan, David E; Nunes, Frederick A; Aytaman, Ayse; Reddy, K Rajender; Chang, Kyong-Mi

2015-04-01

Acute hepatitis C (AHCV) provides a diagnostic challenge with diverse clinical presentations. This study was aimed to examine the clinical and demographic features as well as outcomes in AHCV patients identified from inpatient and outpatient hospital settings. Patients with suspected AHCV were recruited from Philadelphia VA Medical Center, Hospital of University of Pennsylvania and Brooklyn VA Medical Center between 2000 and 2010. AHCV was diagnosed by acute serum alanine aminotransferase elevation with anti-hepatitis C virus (HCV) seroconversion, HCV-RNA fluctuations above 1 log, and/or recent high-risk exposure without prior HCV infection, excluding those with human immunodeficiency virus infection. Clinical and therapeutic outcomes were monitored for at least 6 months. A total of 40 AHCV patients were enrolled with a median follow-up of 129 weeks. They were mostly men (68%) and whites (73%) with median age of 43 years, diverse risk factors (33% injection drugs, 20% health care-associated, 3% sexual, and 45% unknown), and wide variations in peak alanine aminotransferase (143 to 3435 U/L) and total bilirubin levels (0.4 to 19.3 mg/dL). Viremia resolved spontaneously in 23% and persisted without therapy in 27%, whereas 50% received interferon α-based therapy with 90% cure (18/20). Distinct clinical scenarios included: (1) wide viremic fluctuations >1 log (65%) and intermittent HCV-RNA negativity; (2) autoantibodies (25% antinuclear antibodies, 69% antismooth muscle antibodies) or autoimmune features; (3) delayed spontaneous viral clearance in 2 patients; (4) rapid cirrhosis progression in 2 patients. AHCV is a heterogenous disease that requires careful monitoring. The lack of apparent risk factor in high proportion of patients and its diverse presentations warrant diagnostic vigilance.

The undiagnosed chronically-infected HCV population in France. Implications for expanded testing recommendations in 2014.

PubMed

Brouard, Cécile; Le Strat, Yann; Larsen, Christine; Jauffret-Roustide, Marie; Lot, Florence; Pillonel, Josiane

2015-01-01

Recent HCV therapeutic advances make effective screening crucial for potential HCV eradication. To identify the target population for a possible population-based screening strategy to complement current risk-based testing in France, we aimed to estimate the number of adults with undiagnosed chronic HCV infection and age and gender distribution at two time points: 2004 and 2014. A model taking into account mortality, HCV incidence and diagnosis rates was applied to the 2004 national seroprevalence survey. In 2014, an estimated 74,102 individuals aged 18 to 80 were undiagnosed for chronic HCV infection (plausible interval: 64,920-83,283) compared with 100,868 [95%CI: 58,534-143,202] in 2004. Men aged 18-59 represented approximately half of the undiagnosed population in 2014. The proportion of undiagnosed individuals in 2004 (43%) varied from 21.9% to 74.1% in the 1945-1965 and 1924-1944 birth cohorts. Consequently, age and gender distributions between the chronically-infected (diagnosed and undiagnosed) and undiagnosed HCV populations were different, the 1945-1965 birth cohort representing 48.9% and 24.7%, respectively. Many individuals were still undiagnosed in 2014 despite a marked reduction with respect to 2004. The present work contributed to the 2014 recommendation of a new French complementary screening strategy, consisting in one-time simultaneous HCV, HBV and HIV testing in men aged 18-60. Further studies are needed to assess the cost-effectiveness and feasibility of such a strategy. We also demonstrated that data on the undiagnosed HCV population are crucial to help adapt testing strategies, as the features of the chronically-infected HCV population are very distinct.

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

PubMed

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 < 0.0001) than those not lost to follow-up. Medical comorbidities and substance abuse predicted HCV 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.

Seroprevalence of HBV, HCV & HIV Co-Infection and Risk Factors Analysis in Tripoli-Libya

PubMed Central

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

2014-01-01

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. PMID:24936655

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].

PubMed

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.

Prevalence of HCV Infection in Adults with Congenital Heart Disease and Treatment with Direct Antiviral Agents.

PubMed

Gade, Ajay Reddy; Patel, Manisha; West, Donna R; Abrams, Gary A

2018-03-01

Hepatitis C virus (HCV) infection affects >3% of the US population, which over time can lead to cirrhosis and hepatocellular carcinoma. The lack of a reliable screening method for HCV before 1992 resulted in a higher prevalence of the virus in adults with congenital heart disease who underwent corrective surgery that required blood transfusions. Direct-acting antiviral agents such as sofosbuvir/ledipasvir have significantly increased the efficacy of HCV therapy, although use of these medications in adults with congenital heart disease has not been described. Ours was a retrospective study of 188 adults with congenital heart conditions who had cardiac surgery before 1992. These patients were screened for HCV using HCV antibody followed by HCV RNA if the screening test was positive. Of the 188 adults, 116 (43% male patients, 24-70 years) were screened for the HCV antibody, demonstrating that 104 individuals were negative and 12 subjects were positive for the virus. Subsequently, further testing for the presence of HCV demonstrated 11 of 12 were infected, with an overall prevalence of 9.5%. Five individuals chose to be treated with sofosbuvir/ledipasvir and 5 of 5 have successfully cleared the virus and are considered cured. Adults with congenital heart disease who underwent cardiac surgery before 1992 warrant being screened for HCV, and, if testing positive, may be considered for therapy using direct-acting antiviral agents with close monitoring for cardiac complications.

Mental disorders in HIV/HCV coinfected patients under antiviral treatment for hepatitis C.

PubMed

Martin-Subero, Marta; Diez-Quevedo, Crisanto

2016-12-30

This paper aims to review the epidemiology and management of mental disorders in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients, the need for antiviral therapy in this specific population, and current treatment strategies for HIV/HCV patients with psychiatric and/or substance use disorders. This is a narrative review. Data was sourced from electronic databases and was not limited by language or date of publication. HIV infection has become a survivable chronic illness. Prevalence of HCV infection among HIV-infected patients is high ranging from 50% to 90%. Patients with psychiatric diseases have also an increased risk for HIV/HCV coinfection. The most effective strategy to decrease HCV-related morbidity and mortality in coinfection is to achieve viral eradication. Although psychiatric symptoms often appear during antiviral treatment and may be associated with the use of interferon-alpha (IFN-α), recent evidence suggests that many patients with comorbid mental and substance use disorders can be treated safely. Recent data indicate that IFNα-induced psychiatric side effects have a similar prevalence in HIV/HCV coinfected patients than in monoinfected patients and they can be managed and even prevented successfully with psychopharmacological strategies in the frame of a multidisciplinary team. New antivirals offer INF-free therapies for this specific population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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.

Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1.

PubMed

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

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

PubMed

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

2013-01-01

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

Symptoms of anxiety and depression are frequent in patients with acute hepatitis C and are not associated with disease severity.

PubMed

Deterding, Katja; Grüner, Norbert; Buggisch, Peter; Galle, Peter R; Spengler, Ulrich; Hinrichsen, Holger; Berg, Thomas; Potthoff, Andrej; Grohennig, Anika; Koch, Armin; Diepolder, Helmut; Lüth, Stefan; Feyerabend, Sandra; Jung, Maria C; Rogalska-Taranta, Magdalena; Schlaphoff, Verena; Cornberg, Markus; Manns, Michael P; Wedemeyer, Heiner; Wiegand, Johannes

2016-02-01

Neuropsychiatric symptoms of hepatitis C virus (HCV) infection and during peginterferon α therapy have been investigated in the chronic stage of the infection, but have not been described during the acute phase of the disease so far. We therefore evaluated anxiety and depression in patients with acute hepatitis C by the Hospital Anxiety and Depression Scale (HADS) within a clinical trial. Data were analysed from the German Hep-Net Acute HCV-III study. Anxiety and depression were characterized by an anxiety (HADS-A) and a depression subscale (HADS-D). More than eight points in each subscale were considered clinically relevant. Data were prospectively collected at baseline, end of treatment and at the end of the study. At baseline, a HADS-A above eight points was observed significantly more frequently than a HADS-D above eight points [n=23/103 (22%) vs. n=12/103 (12%); P=0.041].A pathological HADS-A or HADS-D score did not correlate with age, sex, IL28B genotype, the probable mode of infection, HCV genotype or severity of disease as investigated by alanine aminotransferase and bilirubin levels.Antiviral therapy did not influence anxiety as 12/50 (24%) of patients had HADS-A above 8 at the end of therapy. The proportion of patients with HADS-D above eight points increased from 12% at baseline to 24% (n=12/50) at the end of therapy (P=0.06). HADS results were not associated with lost to follow-up or sustained virological response rates. HADS data in acute HCV infection indicate that anxiety and depression do not correlate with severity of the disease, mode of acquisition, lost to follow-up and sustained virological response rates.

Detection of hepatitis C virus RNA in saliva of patients with active infection not associated with periodontal or liver disease severity

PubMed Central

2014-01-01

Background Hepatitis C virus (HCV) is mainly transmitted by parenteral route, being blood transfusion and intravenous drug use the most frequent risk factors. However, it has been suggested that there are other routes of transmission. There are several studies where HCV RNA has been detected in saliva of patients infected with HCV, and epidemiological studies have proposed the dental treatments as possible risk factors for HCV transmission. The purpose of this study was to detect the presence of HCV RNA in saliva of patients with active infection and associating with periodontal or liver disease. Methods Patients with quantifiable HCV-RNA in serum were enrolled in the study. Periodontal disease was assessed using the modified gingival index (MGI). Presence of dental plaque was assessed with the use of disclosing tablets. Patients were clinically and laboratory evaluated to identify the stage of liver disease, the HCV RNA was determinate in saliva by nested RT-PCR. To determine associations between different parameters univariate and multivariate analysis were used. Results A total of 45 patients were included. Of these patients, 21 (46.6%) had hepatitis, 23 (51.1%) had cirrhosis and one patient (2.4%) presented hepatocellular carcinoma (HCC). Viral loads in serum ranged from 2.31–6.68 log IU/ml with a mean of 5.46 log IU/ml (95% CI 5.23–5.70). HCV RNA was positive in saliva of 29 patients (64.4%) and was not detected in 16 (35.6%). For univariate analysis three independent variables were associated with the detection of HCV-RNA in saliva: gender, viral load and dental plaque and multivariate analysis only one independent variable viral load >5.17 log IU/mL remained significantly associated with the detection of HCV in saliva (p = 0.0002). A statistical difference was observed when viral load was analyzed, log 5.85 IU/mL (95% CI 5.67–6.02) for patients with HCV in saliva vs. log 4.77 IU/mL (95% CI 4.35–5.19) for patients without HCV in saliva (p�

HCV Treatment Initiation in Patients with Chronic Kidney Disease: Results from ERCHIVES

PubMed Central

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

Liver disease in adult transfusion-dependent beta-thalassaemic patients: investigating the role of iron overload and chronic HCV infection.

PubMed

Kountouras, Dimitrios; Tsagarakis, Nikolaos J; Fatourou, Evangelia; Dalagiorgos, Efthimios; Chrysanthos, Nikolaos; Berdoussi, Helen; Vgontza, Niki; Karagiorga, Markissia; Lagiandreou, Athanasios; Kaligeros, Konstantinos; Voskaridou, Ersi; Roussou, Paraskevi; Diamanti-Kandarakis, Evanthia; Koskinas, John

2013-03-01

Iron overload and hepatitis-C virus (HCV) infection, have been implicated in the evolution of liver disease, in patients with transfusion-dependent beta-thalassaemia major (BTM). However, the impact of these factors in late stages of liver disease in adults with BTM, has not been extensively studied. To investigate serum indices of iron overload, HCV infection and liver disease, in a cohort of 211 adult Greek patients with BTM, in relation with the findings from liver biopsies. In this cross-sectional study, 211 patients with BTM were enrolled and studied, in relation with HCV infection, ferritin, transaminases, chelation treatment and antiviral treatment. Based on 109 patients biopsied, we correlated liver fibrosis, haemosiderosis and inflammation, with serum indices and HCV status Among all patients, 74.4% were anti-HCV positive (HCV+). Ferritin was positively correlated with transaminases and negatively correlated with age, while it was not significantly different among HCV+ and HCV- patients. Among the HCV+ patients, 55.4% reported antiviral treatment, while genotype 1 predominated. In a subfraction of 109 patients, in which liver biopsy was performed, 89% were HCV+ and 11% HCV-. Fibrosis was significantly correlated with age (P = 0.046), AST (P = 0.004), ALT (P = 0.044) and inflammation (P < 0.001). Advanced fibrosis was present with even minimal haemosiderosis, independently of ferritin values or HCV history. These data suggest that in the late stages of liver disease in BTM patients, iron overload may be the critical determinant, since fibrosis is related to the minimal haemosiderosis, independently of HCV history. © 2012 John Wiley & Sons A/S.

Abacavir coadministration does not interfere with the suppressive activity of ribavirin in an HCV replicon system.

PubMed

Van den Eynde, Eva; Quer, Josep; Cubero, María; Curran, Adriá; Homs, María; Garcia-Cehic, Damir; Falco, Vicenç; Ribera, Esteban; Esteban, Juan I; Pahissa, Albert; Crespo, Manuel

2011-01-01

HCV is a major cause of morbidity and mortality in HIV-coinfected patients. Several observational studies have suggested that HCV response to pegylated interferon and ribavirin is lower in HIV-coinfected patients treated with abacavir. It has been postulated that abacavir could compete with ribavirin to be phosphorylated, leading to a reduction in the active form of the drug (triphosphorylated ribavirin). Here, we studied the effect of abacavir, tenofovir or lamivudine addition on the suppressive activity of ribavirin in an HCV RNA replicon system. We used the human hepatoma HuH-7 cell clone 9B containing the HCV genotype 1b replicon I389/NS3-3'. Cells were treated for 24 h with ribavirin (0, 10 and 50 μM) plus abacavir, tenofovir or lamivudine at doses of 0, 10 and 50 μM and HCV RNA production was quantified by real-time PCR in triplicate assays. Results were expressed as mean±SD of the HCV RNA produced per cell (log(10) IU/cell). Means were compared using the Student's t-test. Ribavirin treatment produced a dose-dependent suppression of HCV RNA production by the replicon system. Combination of ribavirin and interferon resulted in an additive antiviral activity. The addition of abacavir did not modify the suppressive activity of ribavirin on the replicon HCV RNA expression. Similar results were obtained when ribavirin was used in combination with tenofovir or lamivudine. In a subgenomic HCV RNA replicon system, the antiviral effect of ribavirin was not modified by the addition of abacavir, tenofovir or lamivudine. © 2011 International Medical Press

Candidiasis and other oral mucosal lesions during and after interferon therapy for HCV-related chronic liver diseases.

PubMed

Nagao, Yumiko; Hashimoto, Kouji; Sata, Michio

2012-11-02

Oral lichen planus (OLP) is seen frequently in patients with hepatitis C virus (HCV) infection. The aim of this study was to evaluate the occurrence of oral candidiasis, other mucosal lesions, and xerostomia during interferon (IFN) therapy for HCV infection. Of 124 patients with HCV-infected liver diseases treated with IFN therapy in our hospital, 14 (mean age 56.00 ± 12.94 years) who attended to receive administration of IFN once a week were identified and examined for Candida infection and other oral lesions and for the measurement of salivary flow. Serological assays also were carried out. Cultures of Candida from the tongue surfaces were positive in 7 (50.0%) of the 14 patients with HCV infection at least once during IFN therapy. C. albicans was the most common species isolated. The incidence of Candida during treatment with IFN did not increase above that before treatment. Additional oral mucosal lesions were observed in 50.0% (7/14) of patients: OLP in three (21.4%), angular cheilitis in three (21.4%) and recurrent aphthous stomatitis in one (7.1%). OLP occurred in one patient before treatment with IFN, in one during treatment and in one at the end of treatment. 85.7% of the oral lesions were treated with topical steroids. We compared the characteristics of the 7 patients in whom Candida was detected at least once during IFN therapy (group 1) and the 7 patients in whom Candida was not detected during IFN therapy (group 2). The prevalence of oral mucosal lesions (P=0.0075) and incidence of external use of steroids (P=0.0308) in group 1 were significantly higher than in group 2. The average body weight of group 1 decreased significantly compared to group 2 (P=0.0088). Salivary flow decreased in all subjects throughout the course of IFN treatment and returned at 6th months after the end of treatment. In group 1, the level of albumin at the beginning of the 6th month of IFN administration was lower than in group 2 (P=0.0550). According to multivariate analysis

A succinct method to generate multi-type HCV beams with a spatial spiral varying retardation-plate

NASA Astrophysics Data System (ADS)

Qi, Junli; Zhang, Hui; Pan, Baoguo; Deng, Haifei; Yang, Jinhong; Shi, Bo; Wang, Hui; Du, Ang; Wang, Weihua; Li, Xiujian

2018-03-01

A simple novel and practical scheme is presented to generate high-power cylindrical vector (HCV) beams with a 36-segment spiral varying retardation-plate sandwiched between two quarter-wave plates (QWPs). Four kinds of HCV beams, such as radially polarized beam and azimuthally polarized beam, are formed by simply rotating two QWPs. A segmented spiral varying phase-plate with isotropy is used to modulate spatial phase distribution to generate in-phase HCV beams. The intensity distributions and polarizing properties of HCV beams are investigated and analyzed in detail. It is demonstrated experimentally that the system can effectively generate multi-type HCV beams with high purity up to 99%, and it can be manufactured as cylindrical vector beam converter commercially.

A Novel Structurally Stable Multiepitope Protein for Detection of HCV

PubMed Central

Galdino, Alexsandro S.; Santos, José C.; Souza, Marilen Q.; Nóbrega, Yanna K. M.; Xavier, Mary-Ann E.; Felipe, Maria S. S.; Freitas, Sonia M.; Torres, Fernando A. G.

2016-01-01

Hepatitis C virus (HCV) has emerged as the major pathogen of liver diseases in recent years leading to worldwide blood-transmitted chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Accurate diagnosis for differentiation of hepatitis C from other viruses is thus of pivotal importance for proper treatment. In this work we developed a recombinant multiepitope protein (rMEHCV) for hepatitis C diagnostic purposes based on conserved and immunodominant epitopes from core, NS3, NS4A, NS4B, and NS5 regions of the virus polyprotein of genotypes 1a, 1b, and 3a, the most prevalent genotypes in South America (especially in Brazil). A synthetic gene was designed to encode eight epitopes in tandem separated by a flexible linker and bearing a his-tag at the C-terminal end. The recombinant protein was produced in Escherichia coli and purified in a single affinity chromatographic step with >95% purity. Purified rMEHCV was used to perform an ELISA which showed that the recombinant protein was recognized by IgG and IgM from human serum samples. The structural data obtained by circular dichroism (CD) spectroscopy showed that rMEHCV is a highly thermal stable protein at neutral and alkaline conditions. Together, these results show that rMEHCV should be considered an alternative antigen for hepatitis C diagnosis. PMID:26942007

Ribavirin and abacavir drug interaction in HIV-HCV coinfected patients: fact or fiction?

PubMed

Solas, Caroline; Pambrun, Elodie; Winnock, Maria; Salmon, Dominique; Poizot-Martin, Isabelle; Dominguez, Stéphanie; Bani-Sadr, Firouzé; Izopet, Jacques; Garraffo, Rodolphe; Peytavin, Gilles

2012-11-13

To examine the impact of ribavirin and abacavir coadministration on hepatitis C virus (HCV) virological response and trough ribavirin plasma concentration (Cmin) in HIV-HCV coinfected patients. Pharmacokinetic substudy on patients from the ANRS CO-13 HEPAVIH cohort. Patients receiving ribavirin-pegylated interferon for whom a ribavirin steady state Cmin was prospectively determined were included. Rapid virological response (RVR), early virological response (EVR) and sustained virological response (SVR) as well as HCV-RNA decline were evaluated. Overall, 124 HIV-HCV coinfected patients (95% on antiretroviral therapy) were enrolled. Of these patients, 22% received abacavir. The overall median (interquartile range) ribavirin Cmin was 1.6 mg/l (1.2-2.2) with no statistical difference between abacavir users and nonusers [1.5 mg/l (0.99-2.1) and 1.7 (1.2-2.3), P = 0.15]. RVR and EVR were 52 and 72%, respectively. There was no difference observed in the proportion of abacavir users vs. nonusers achieving RVR (respectively 59 vs. 50%, P = 0.40) or EVR (72 vs. 73%, P = 0.94), or in the HCV-RNA decline at week 4 [-2.24 log(10) IU/ml, (-3.58; -0.81) and -1.27 (-2.8; -0.47) P = 0.28] or at week 12 [-1.76 log(10) IU/ml (-3.67; -0.35) and -1.85 (-3.13; -1.13) (P = 0.58)]. The SVR rate was 45% for abacavir users and 24% for abacavir nonusers, but the difference was not statistically significant (P = 0.059). In our study, there was no evidence that abacavir affected HCV treatment outcomes and the ribavirin Cmin was similar in abacavir users and nonusers, confirming the absence of pharmacokinetic interaction between abacavir and ribavirin. An abacavir-containing regimen is, therefore, a well tolerated treatment alternative for coinfected patients starting HCV treatment.

Non-invasive detection of infection in acute pancreatic and acute necrotic collections with diffusion-weighted magnetic resonance imaging: preliminary findings.

PubMed

Islim, Filiz; Salik, Aysun Erbahceci; Bayramoglu, Sibel; Guven, Koray; Alis, Halil; Turhan, Ahmet Nuray

2014-06-01

The purpose of this study was to evaluate the contribution of diffusion-weighted magnetic resonance imaging (DW-MRI) to the detection of infection in acute pancreatitis-related collections. A total of 21 DW-MRI, and computed tomography (CT) were performed on 20 patients diagnosed as acute pancreatitis with acute peri-pancreatic fluid or necrotic collections. Collections were classified as infected or sterile according to the culture and follow-up results. Collections with gas bubbles on CT images were considered to be infected. Collections with peripheral bright signals on DW-MRI images were considered to be positive, whereas those without signals were considered to be negative. Apparent diffusion coefficient (ADC) values of the peripheral and central parts of the collections were measured. Student's t test was used to compare the means of ADC values of independent groups. Apart from one false positive result, the presence of infection was detected by DW-MRI with 95.2% accuracy. The sensitivity and accuracy of DW-MRI were higher than CT for the detection of infection. The ADC values in the central parts of the collections were significantly different between the infected and sterile groups. DW-MRI can be used as a non-invasive technique for the detection of infection in acute pancreatitis-associated collections.

HIV and HCV coinfection: prevalence, associated factors and genotype characterization in the Midwest Region of Brazil.

PubMed

Freitas, Solange Zacalusni; Teles, Sheila Araújo; Lorenzo, Paulo Cesar; Puga, Marco Antonio Moreira; Tanaka, Tayana Serpa Ortiz; Thomaz, Danilo Yamamoto; Martins, Regina Maria Bringel; Druzian, Angelita Fernandes; Lindenberg, Andréa Siqueira Campos; Torres, Marina Sawada; Pereira, Sérgio A; Villar, Livia Melo; Lampe, Elisabete; Motta-Castro, Ana Rita Coimbra

2014-01-01

A cross-sectional study on prevalence, associated factors and genotype distribution of HCV infection was conducted among 848 HIV-infected patients recruited at reference centers in the Midwest Region of Brazil. The prevalence rate of HIV-HCV coinfection was 6.9% (95% CI: 5.2 to 8.6). In multivariable analysis, increasing age, use of illicit drugs (injection and non-injection), a history of blood transfusion before 1994, and the absence of a steady partnership were significant independent associated factors for HIV-HCV coinfection. The phylogenetic analysis based on the NS5B region revealed the presence of two major circulating genotypes of HCV: genotypes 1 (58.3%) and 3 (41.7%). The prevalence of HIV-HCV coinfection was lower than those reported in studies conducted with HIV-infected patients in different regions of Brazil, due to the fact that illicit drug use is not a frequent mode of HIV transmission in this region of Brazil. Serologic screening of HIV-patients for HCV before initiating antiretroviral treatment, a comprehensive identification of associated factors, and the implementation of effective harm reduction programs are highly recommended to provide useful information for treatment and to prevent HCV coinfection in these patients.

Human Liver Transplantation As A Model To Study HCV Pathogenesis

PubMed Central

Hughes, Michael G.; Rosen, Hugo R.

2010-01-01

Hepatitis C is a leading etiology of liver cancer and cause for liver transplantation. Although new therapies have improved the rates of sustained response, a large proportion of patients (~50%) fail to respond to antiviral treatment, thus remaining at risk for disease progression. While chimpanzees have been used to study HCV biology and treatments, their cost is quite high and their use is strictly regulated; indeed, the NIH no longer supports the breeding of chimpanzees for study. The development of HCV therapies has been hindered by the relative paucity of small animal models to study HCV pathogenesis. This review presents the strengths of the human liver transplant, highlighting the advances derived from this model, including insights into viral kinetics and quasispecies, viral receptor binding and entry, innate and adaptive immunity. Moreover, consideration is made of current and emerging antiviral therapeutic approaches based on translational research results. PMID:19877210

Sofosbuvir, a Significant Paradigm Change in HCV Treatment

PubMed Central

McQuaid, Thomas; Savini, Carolyn; Seyedkazemi, Star

2015-01-01

Nucleotide compounds like sofosbuvir, acyclovir, and tenofovir have proven to be amongst the most potent orally available antiviral treatments. These drugs exhibit high efficacy and a wide therapeutic index, with demonstrated utility in a number of chronic viral infections. The approval of Sovaldi™, brand name for sofosbuvir, by the U.S. Food and Drug Administration heralded improvements in chronic hepatitis C virus (HCV) treatment. Sofosbuvir was originally discovered by Pharmasset Corporation and named PSI-7977. It was subsequently acquired and advanced through phase 3 development by Gilead Sciences, Inc. In Sofosbuvir both a unique pharmacology and a high specificity for the HCV ribonucleic acid polymerase are present in a molecule that is well tolerated and highly efficacious. Phase 2 and 3 clinical trials have consistently demonstrated durable and high rates of sustained virologic response (SVR), curing patients in excess of 80% in all genotypes and >90% in treatment-naïve subjects being administered combination therapy with other agents. Harvoni® is the combination of sofosbuvir and the NS5A inhibitor ledipasvir in a fixed-dose oral tablet, and it has demonstrated high SVR rates in patients infected with HCV genotype 1, without the need for exogenous interferon and/or ribavirin. Here, we discuss the discovery, development, pharmacologic characterization, and results from the phase 3 trials of sofosbuvir. Hepatitis C is a chronic disease, for which most patients have been undiagnosed, are unwilling to start treatment, or are ineligible for treatment because of the high toxicity and low efficacy of interferon and ribavirin-based therapy. Clinical studies with sofosbuvir have demonstrated significant improvement over the prior standard of care, thus ushering in a new paradigm of HCV treatment and an update of treatment guidelines. PMID:26357632

Estimating the number of injecting drug users in Scotland's HCV-diagnosed population using capture-recapture methods.

PubMed

McDonald, S A; Hutchinson, S J; Schnier, C; McLeod, A; Goldberg, D J

2014-01-01

In countries maintaining national hepatitis C virus (HCV) surveillance systems, a substantial proportion of individuals report no risk factors for infection. Our goal was to estimate the proportion of diagnosed HCV antibody-positive persons in Scotland (1991-2010) who probably acquired infection through injecting drug use (IDU), by combining data on IDU risk from four linked data sources using log-linear capture-recapture methods. Of 25,521 HCV-diagnosed individuals, 14,836 (58%) reported IDU risk with their HCV diagnosis. Log-linear modelling estimated a further 2484 HCV-diagnosed individuals with IDU risk, giving an estimated prevalence of 83. Stratified analyses indicated variation across birth cohort, with estimated prevalence as low as 49% in persons born before 1960 and greater than 90% for those born since 1960. These findings provide public-health professionals with a more complete profile of Scotland's HCV-infected population in terms of transmission route, which is essential for targeting educational, prevention and treatment interventions.

EFFECT OF HIV PREVENTION AND TREATMENT PROGRAM ON HIV AND HCV TRANSMISSION AND HIV MORTALITY AT AN INDONESIAN NARCOTIC PRISON.

PubMed

Nelwan, Erni J; Indrati, Agnes K; Isa, Ahmad; Triani, Nurlita; Alam, Nisaa Nur; Herlan, Maria S; Husen, Wahid; Pohan, Herdiman T; Alisjahbana, Bachti; Meheus, Andre; Van Crevel, Reinout; van der Ven, Andre Jam

2015-09-01

Validated data regarding HIV-transmission in prisons in developing countries is scarce. We examined sexual and injecting drug use behavior and HIV and HCV transmission in an Indonesian narcotic prison during the implementation of an HIV prevention and treatment program during 2004-2007 when the Banceuy Narcotic Prison in Indonesia conducted an HIV transmission prevention program to provide 1) HIV education, 2) voluntary HIV testing and counseling, 3) condom supply, 4) prevention of rape and sexual violence, 5) antiretroviral treatment for HIV-positive prisoners and 6) methadone maintenance treatment. During a first survey that was conducted between 2007 and 2009, new prisoners entered Banceuy Narcotics Prison were voluntary tested for HIV and HCV-infection after written informed consent was obtained. Information regarding sexual and injecting risk behavior and physical status were also recorded at admission to the prison. Participants who tested negative for both HIV and HCV during the first survey were included in a second survey conducted during 2008-2011. During both surveys, data on mortality among HIV-seropositive patients were also recorded. All HIV-seropositive participants receive treatment for HIV. HIV/ AIDS-related deaths decreased: 43% in 2006, 18% in 2007, 9% in 2008 and 0% in 2009. No HIV and HCV seroconversion inside Banceuy Narcotic Prison were found after a median of 23 months imprisonment (maximum follow-up: 38 months). Total of 484.8 person-years observation was done. Participants reported HIV transmission risk-behavior in Banceuy Prison during the second survey was low. After implementation of HIV prevention and treatment program, no new HIV or HCV cases were detected and HIV-related mortality decreased.

HCV Health Policy Developments in Response to the National Viral Hepatitis Action Plan: A Brief Update.

PubMed

Guo, Yuqi; Sims, Omar T

2017-02-17

Hepatitis C virus (HCV) kills 366,000 people worldwide and 17,000 people in the United States each year. In 2011, the U.S. Department of Health and Human Services (HHS) published a national viral hepatitis action plan to control and combat HCV in the United States. This article provides a brief update of HCV health policy developments that have emerged since publication of HHS's national viral hepatitis action plan and concludes with a discussion of the public health impact of these recent HCV health policy developments.

[HCV and HBV seropositivity in university students of the State of Nuevo Leòn, Mexico].

PubMed

Flores-Castañeda, M S; García-Méndez, B L; Tijerina-Menchaca, R

1996-01-01

Viral hepatitis is a contagious disease. Patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV), may be either chronically symptomatic or asymptomatic, and suffer cirrhosis and high risk of hepatic carcinoma. Asymptomatic carriers of HBV surface antigen (HBs-Ag) or with anti-HCV antibodies are potentially infectious, and therefore a risk to public health. This work seeks to establish the frequency of seropositivity for HBs-Ag and anti-HCV antibodies in a population of 774 newly accepted students of the Medical School of the Autonomous University of Nuevo Leon, whose average age was 18 years. Second generation ELISA test were used to screen for HBs-Ag and anti-HCV antibodies. HBs-Ag was confirmed by a neutralization test and anti-HCV antibodies were confirmed by a RIBA test. Three sera were positive for HBs-Ag by ELISA and only one serum (0.13% of analyzed samples) was confirmed by the neutralization technique. On the other hand 12 sera were positive for anti-HCV antibodies by ELISA, and eight of these were confirmed by RIBA (1.03% of the analyzed samples). Intensive reactivity bands were found in two sera, and weak reactivity bands were found in six sera. ELISA screening for anti-HCV antibodies showed 0.5% of false positives. This study shows that the frequency of anti-HCV antibodies is 7.95% times higher than that found for HBs-Ag. All seropositive patients were asymptomatic and potentially infective. This demonstrates the need to routinely screen for HBs-Ag and anti-HCV antibodies to establish the prevalence of these diseases in our area.

Identification of drug resistance and immune-driven variations in hepatitis C virus (HCV) NS3/4A, NS5A and NS5B regions reveals a new approach toward personalized medicine.

PubMed

Ikram, Aqsa; Obaid, Ayesha; Awan, Faryal Mehwish; Hanif, Rumeza; Naz, Anam; Paracha, Rehan Zafar; Ali, Amjad; Janjua, Hussnain Ahmed

2017-01-01

Cellular immune responses (T cell responses) during hepatitis C virus (HCV) infection are significant factors for determining the outcome of infection. HCV adapts to host immune responses by inducing mutations in its genome at specific sites that are important for HLA processing/presentation. Moreover, HCV also adapts to resist potential drugs that are used to restrict its replication, such as direct-acting antivirals (DAAs). Although DAAs have significantly reduced disease burden, resistance to these drugs is still a challenge for the treatment of HCV infection. Recently, drug resistance mutations (DRMs) observed in HCV proteins (NS3/4A, NS5A and NS5B) have heightened concern that the emergence of drug resistance may compromise the effectiveness of DAAs. Therefore, the NS3/4A, NS5A and NS5B drug resistance variations were investigated in this study, and their prevalence was examined in a large number of protein sequences from all HCV genotypes. Furthermore, potential CD4 + and CD8 + T cell epitopes were predicted and their overlap with genetic variations was explored. The findings revealed that many reported DRMs within NS3/4A, NS5A and NS5B are not drug-induced; rather, they are already present in HCV strains, as they were also detected in HCV-naïve patients. This study highlights several hot spots in which HLA and drug selective pressure overlap. Interestingly, these overlapping mutations were frequently observed among many HCV genotypes. This study implicates that knowledge of the host HLA type and HCV subtype/genotype can provide important information in defining personalized therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Ghrelin gene polymorphism as a genetic biomarker for prediction of therapy induced clearance in Egyptian chronic HCV patients.

PubMed

Hamdy, Marwa; Kassim, Samar Kamal; Khairy, Eman; Maher, Mohsen; Mansour, Khaled Amr; Albreedy, Ashraf M

2018-04-05

Ghrelin (GHRL) has important implications for liver disease. It has anti-inflammatory effects, regulates cell proliferation, modulates the fibrogenic response and protects liver tissue. Genetic variations in the GHRL gene may play a crucial role in the development of chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Therefore, we examined the association of GHRL gene polymorphisms (rs26312 and rs27647), and its serum level to virologic responses to combined sofosbuvir and Simeprevir therapy for a course of 12 successive weeks in Egyptian chronic hepatitis C (CHC) patients. Human genomic and clinical data were collected from 100 Egyptian participants in this study, 90 HCV patients who received sofosbuvir and Simeprevir and 10 non-HCV healthy subjects. Genotyping of GHRL rs26312 and rs27647, were determined with the TaqMan qRT-PCR allele detection assay. The serum GHRL concentrations were determined using enzyme-linked immunosorbent assay (ELISA). GHRL polymorphisms (rs26312 and rs27647) genotype distributions and allele frequencies did not differ between HCV patients and normal healthy subjects or between patient groups when compared according to the therapeutic response. In addition, we found significant lower serum GHRL levels in CHC patients compared with the healthy controls. However, there was no significant association of the GHRL rs26312 and rs27647 polymorphisms with GHRL levels in CHC patients. We conclude that GHRL SNPs (rs26312 and rs27647) do not affect response to combined sofosbuvir and Simeprevir treatment in chronic Egyptian HCV patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Vitamin D deficiency is associated with severity of liver disease in HIV/HCV coinfected patients.

PubMed

Guzmán-Fulgencio, María; García-Álvarez, Mónica; Berenguer, Juan; Jiménez-Sousa, M Ángeles; Cosín, Jaime; Pineda-Tenor, Daniel; Carrero, Ana; Aldámiz, Teresa; Alvarez, Emilio; López, Juan Carlos; Resino, Salvador

2014-02-01

To study the association of plasma 25-hydroxy vitamin D (25(OH)D) levels in HIV/HCV coinfected patients with severity of liver disease and virological response to hepatitis C virus (HCV) therapy with pegylated-interferon-alpha plus ribavirin (pegIFNα/RBV). A cross-sectional study in 174 HIV/HCV coinfected patients that underwent a liver biopsy previously to start HCV therapy and a retrospective study of 125 of them. Plasma 25(OH)D levels were quantified by enzyme immunoassay. Liver biopsies were evaluated by METAVIR score. A sustained virological response (SVR) was defined as an undetectable serum HCV viral load (<10 IU/mL) up through 24 weeks after the end of HCV treatment. The median of plasma 25(OH)D level was 48 nmol/L (p25th: 32.5; p75th: 56.1) and 27 (15.5%) had 25(OH)D deficiency (<25 nmol/L). The percentage of 25(OH)D deficiency was higher in patients with significant fibrosis (F ≥ 2) (92.6% vs. 57.1%; p = 0.010) and moderate necroinflammatory activity grade (A ≥ 2) (85.2% vs. 60%; p = 0.043). However, adjusted logistic regression analyses showed that 25(OH)D deficiency was only associated with severity of liver disease [F ≥ 2 (OR = 8.47 (95% of confidence interval (CI) = 1.88; 38.3); p = 0.005) and A ≥ 2 (OR = 3.25 (95%CI = 1.06; 10.1); p = 0.040)]. Moreover, any significant relationship was found between 25(OH)D deficiency and SVR after HCV therapy. Plasma 25(OH)D deficiency was associated with liver disease severity in HIV/HCV coinfected patients, but it was not associated with HCV treatment failure. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

HIV AND HCV COINFECTION: PREVALENCE, ASSOCIATED FACTORS AND GENOTYPE CHARACTERIZATION IN THE MIDWEST REGION OF BRAZIL

PubMed Central

Freitas, Solange Zacalusni; Teles, Sheila Araújo; Lorenzo, Paulo Cesar; Puga, Marco Antonio Moreira; Tanaka, Tayana Serpa Ortiz; Thomaz, Danilo Yamamoto; Martins, Regina Maria Bringel; Druzian, Angelita Fernandes; Lindenberg, Andréa Siqueira Campos; Torres, Marina Sawada; Pereira, Sérgio A.; Villar, Livia Melo; Lampe, Elisabete; Motta-Castro, Ana Rita Coimbra

2014-01-01

A cross-sectional study on prevalence, associated factors and genotype distribution of HCV infection was conducted among 848 HIV-infected patients recruited at reference centers in the Midwest Region of Brazil. The prevalence rate of HIV-HCV coinfection was 6.9% (95% CI: 5.2 to 8.6). In multivariable analysis, increasing age, use of illicit drugs (injection and non-injection), a history of blood transfusion before 1994, and the absence of a steady partnership were significant independent associated factors for HIV-HCV coinfection. The phylogenetic analysis based on the NS5B region revealed the presence of two major circulating genotypes of HCV: genotypes 1 (58.3%) and 3 (41.7%). The prevalence of HIV-HCV coinfection was lower than those reported in studies conducted with HIV-infected patients in different regions of Brazil, due to the fact that illicit drug use is not a frequent mode of HIV transmission in this region of Brazil. Serologic screening of HIV-patients for HCV before initiating antiretroviral treatment, a comprehensive identification of associated factors, and the implementation of effective harm reduction programs are highly recommended to provide useful information for treatment and to prevent HCV coinfection in these patients. PMID:25351547

Evaluation of Mir-224, Mir-215 and Mir-143 as Serum Biomarkers for HCV Associated Hepatocellular Carcinoma

PubMed

Mamdouh, Samah; Khorshed, Fatma; Aboushousha, Tarek; Hamdy, Hussam; Diab, Ayman; Seleem, Mohamed; Saber, Mohamed

2017-11-26

HCV induced hepatitis and hepatocellular carcinoma as its sequel are major health problems world-wide and especially in Egypt. For diagnosis and during treatment of liver diseases, liver functions are monitored through determination of serum levels of liver enzymes and α-fetoprotein although the obtained information is generally not sufficient for either early detection of hepatic insult or effective follow up of therapeutic effects. More sensitive biomarkers may help to achieve these goals. MiRNAs are small non-coding RNAs that have an important role in gene expression and regulation. Many, such as miR-224, miR-215, miR-143 are correlated with tumor appearance and with the degree of fibrosis in lung, breast and colon cancer. This study was performed to estimate the level of these miRNAs in serum of patients with HCV-associated hepatitis and HCC in relation to grade of hepatitis, stage of fibrosis and differentiation of tumor tissue. In addition, correlations between serological and tissue levels were assessed. A total of 80 patients were examined, out of which 50 were included in the study. Blood samples and tissue specimens from malignant tumor and corresponding non-tumor tissue of HCV hepatitis patients were collected. Blood samples from 20 healthy volunteers were also obtained as controls. It was found that miRNAs profiles differed in HCC patients compared to controls and HCV-associated hepatitis cases. Distinction of tumor grade and fibrosis stage of patients as well as between different grades of tumor differentiation proved possible, making miRNAs promising biomarkers for diagnosis and assessment of treatment response of HCC patients. Creative Commons Attribution License

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

PubMed

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

2014-01-01

The incidence of recent hepatitis C virus infection (HCV) infection has been noted to be increasing among men who have sex with men (MSM), especially those with HIV infection, in several resource-rich settings. In Taiwan, the incidence of recent HCV infection increased from 0 in 1994-2000, 2.29 in 2001-2005 to 10.13 per 1000 person-years of follow-up (PYFU) in 2006-2010. In this study, we aimed to estimate the incidence rate of recent HCV infection among those individuals who sought voluntary counselling and testing (VCT) service at a University Hospital. Between May 2006 and December 2013, 18,246 tests for HIV antibody were performed among 12,143 individuals at the VCT services. A total of 2157 clients without HIV or HCV infection at baseline were included for estimation of incidence rate of recent HCV infection. Antibodies to HCV were determined with a third-generation enzyme immunoassay. A nested case-control study with four matched controls without HCV seroconversion for one HCV seroconverter was conducted to investigate the factors associated with recent HCV infection. Phylogenetic analysis was performed among the HCV strains obtained from VCT clients and patients coinfected with HIV and HCV between 2006 and 2013. During the study period, 2157 clients received a total of 8260 tests. The HCV seroprevalence at baseline was 0.3%. Of the 2150 HCV-negative clients who contributed 5074.99 PYFU, 17 developed HCV seroconversion (incidence rate, 3.35 per 1000 PYFU; 95% CI, 1.76-4.94); the rate increased from 2.28 per 1000 PYFU (95% CI, 0.05-4.51) in 2006-2009, to 3.33 per 1000 PYFU (95% CI, 0.86-5.80) in 2010-2011, to 4.94 per 1000 PYFU (95% CI, 0.99-8.99) in 2012-2013. In case-control study, HCV seroconverters were more likely to have HIV-infected partners, recent syphilis and a Rapid Plasma Reagin (RPR) titre of 4 or greater. In multivariate analysis, having HIV-infected partners remained as the only independent associated factors with HCV seroconversion (AOR, 6

The frequency of hypothyroidism and its relationship with HCV positivity in patients with thalassemia major in southern Iran.

PubMed

Haghpanah, Sezaneh; Jelodari, Shohreh; Karamifar, Hammdollah; Saki, Forough; Rahimi, Rahil; De Sanctis, Vincenzo; Dehbozorgian, Javad; Karimi, Mehran

2018-03-27

Hypothyroidism is one the most complication due to iron overload in patients with β-thalassemia major (TM). On the other hand these patients are prone to Hepatitis C virus (HCV) infection that can cause  thyroid dysfunction by itself or as the side effect of treatment with interferon (INF) or IFN plus ribavirin. The aim of this study is to evaluate the association of hypothyroidism with HCV positivity and serum ferritin levels in patients with TM. In this cross-sectional study, 201 randomly selected patients with TM who were registered at the Thalassemia Clinic of a tertiary hospital in Shiraz, southern Iran were investigated. Thyroid function tests and serologic screening assays for HCV seropositivity (HCV Ab and HCV-RNA) were conducted for all patients. Frequency of hypothyroidism was 22.9% including 19.9% subclinical hypothyroidism, 2% primary overt hypothyroidism and 1% central hypothyroidism. Eighty six patients (42.8%) were HCV Ab positive and 60 patients (29.9%) were HCV RNA positive. No significant relationship was found between hypothyroidism and HCV positivity or receiving IFN-α (P>0.05). Hypothyroidism showed a borderline significant association with high serum ferritin levels in TM patients (P=0.055). Our results showed no significant association between hypothyroidism and HCV infection in TM patients. It seems that the main mechanism of hypothyroidism in our patients is iron overload; however, for better evaluation a larger multicenter study is recommended.  Also due to the importance of consequences of HCV infection, more careful pre-transfusional screening of blood should be considered in TM patients.

Temporal changes in HCV genotype distribution in three different high risk populations in San Francisco, California

PubMed Central

2011-01-01

Background Hepatitis C virus (HCV) genotype (GT) has become an important measure in the diagnosis and monitoring of HCV infection treatment. In the United States (U.S.) HCV GT 1 is reported as the most common infecting GT among chronically infected patients. In Europe, however, recent studies have suggested that the epidemiology of HCV GTs is changing. Methods We assessed HCV GT distribution in 460 patients from three HCV-infected high risk populations in San Francisco, and examined patterns by birth cohort to assess temporal trends. Multiple logistic regression was used to assess factors independently associated with GT 1 infection compared to other GTs (2, 3, and 4). Results Overall, GT 1 was predominant (72.4%), however younger injection drug users (IDU) had a lower proportion of GT 1 infections (54.7%) compared to older IDU and HIV-infected patients (80.5% and 76.6%, respectively). Analysis by birth cohort showed increasing proportions of non-GT 1 infections associated with year of birth: birth before 1970 was independently associated with higher adjusted odds of GT 1: AOR 2.03 (95% CI: 1.23, 3.34). African-Americans as compared to whites also had higher adjusted odds of GT 1 infection (AOR: 3.37; 95% CI: 1.89, 5.99). Conclusions Although, HCV GT 1 remains the most prevalent GT, especially among older groups, changes in GT distribution could have significant implications for how HCV might be controlled on a population level and treated on an individual level. PMID:21810243

Enhanced liver fibrosis test using ELISA assay accurately discriminates advanced stage of liver fibrosis as determined by transient elastography fibroscan in treatment naïve chronic HCV patients.

PubMed

Omran, Dalia; Yosry, Ayman; Darweesh, Samar K; Nabeel, Mohammed M; El-Beshlawey, Mohammed; Saif, Sameh; Fared, Azza; Hassany, Mohamed; Zayed, Rania A

2018-02-01

Evaluation of liver fibrosis stage is crucial in the assessment of chronic HCV patients, regarding decision to start treatment and during follow-up. Our aim was to assess the validity of the enhanced liver fibrosis (ELF) score in discrimination of advanced stage of liver fibrosis in naïve chronic HCV patients. We prospectively evaluated liver fibrosis stage in one hundred eighty-one naïve chronic HCV Egyptian patients by transient elastography (TE)-FibroScan. Patients were categorized into mild to moderate fibrosis (≤F2) group and advanced fibrosis (≥F3) group. The ELF score components, hyaluronic acid (HA), amino-terminal propeptide of type-III-procollagen (PIIINP) and tissue inhibitor of metalloproteinase type-1 (TIMP-1), were done using ELISA test. The mean values of ELF and its individual components significantly correlated with the hepatic fibrosis stage as measured by TE-FibroScan (P value 0.001). ELF cutoff value of 9.8 generated a sensitivity of 77.8%, specificity of 67.1%, area under the receiver operator characteristic curve (AUROC) of 0.76 with 95% confidence interval [CI] (0.68-0.83) for detecting advanced fibrosis (F ≥ 3). ELF panel is a good, reliable noninvasive test and showed comparable results to TE-FibroScan in detecting liver fibrosis stage in treatment naïve chronic HCV patients.

Transitions from injecting to non-injecting drug use: potential protection against HCV infection

PubMed Central

Des Jarlais, Don C.; McKnight, Courtney; Arasteh, Kamyar; Feelemyer, Jonathan; Perlman, David C.; Hagan, Holly; Cooper, Hannah L. F.

2013-01-01

Transitions from injecting to non-injecting drug use have been reported from many different areas, particularly in areas with large human immunodeficiency virus (HIV) epidemics. The extent to which such transitions actually protect against HIV and HCV has not been determined. A cross-sectional survey with HIV and hepatitis C (HCV) testing was conducted with 322 former injectors (persons who had injected illicit drugs but permanently transitioned to non-injecting use) and 801 current injectors recruited in New York City between 2007 and 2012. There were no differences in HIV prevalence, while HCV prevalence was significantly lower among former injectors compared to current injectors. Years injecting functioned as a mediating variable linking former injector status to lower HCV prevalence. Transitions have continued well beyond the reduction in the threat of AIDS to injectors in the city. New interventions to support transitions to non-injecting drug use should be developed and supported by both drug treatment and syringe exchange programs. PMID:24161262

Real-World Experiences with the Combination Treatment of Ledipasvir plus Sofosbuvir for 12 Weeks in HCV Genotype 1-Infected Japanese Patients: Achievement of a Sustained Virological Response in Previous Users of Peginterferon plus Ribavirin with HCV NS3/4A Inhibitors.

PubMed

Kanda, Tatsuo; Yasui, Shin; Nakamura, Masato; Suzuki, Eiichiro; Arai, Makoto; Ooka, Yoshihiko; Ogasawara, Sadahisa; Chiba, Tetsuhiro; Saito, Tomoko; Haga, Yuki; Takahashi, Koji; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Tawada, Akinobu; Maruyama, Hitoshi; Imazeki, Fumio; Kato, Naoya; Yokosuka, Osamu

2017-04-25

The aim of this study was to characterize the treatment response and serious adverse events of ledipasvir plus sofosbuvir therapies in Japanese patients infected with hepatitis C virus (HCV) genotype 1 (GT1). This retrospective study analyzed 240 Japanese HCV GT1 patients treated for 12 weeks with 90 mg of ledipasvir plus 400 mg of sofosbuvir daily. Sustained virological response at 12 weeks post-treatment (SVR12) was achieved in 236 of 240 (98.3%) patients. Among treatment-naïve patients, SVR12 was achieved in 136 of 138 (98.6%) patients, and among treatment-experienced patients, SVR12 was achieved in 100 of 102 (98.0%) patients. In patients previously treated with peginterferon plus ribavirin with various HCV NS3/4A inhibitors, 100% SVR rates (25/25) were achieved. Two relapsers had HCV NS5A resistance-associated variants (RAVs), but no HCV NS5B-S282 was observed after they relapsed. We experienced two patients with cardiac events during treatment. In conclusion, combination of ledipasvir plus sofosbuvir for 12 weeks is a potential therapy for HCV GT1 patients. Caution is needed for HCV NS5A RAVs, which were selected by HCV NS5A inhibitors and cardiac adverse events.

Detection of hepatitis E virus RNA in saliva for diagnosis of acute infection.

PubMed

Rivero-Juarez, A; Frias, M; Lopez-Lopez, P; Martinez-Peinado, A; Risalde, M Á; Brieva, T; Machuca, I; Camacho, Á; García-Bocanegra, I; Gomez-Villamandos, J C; Rivero, A

2018-04-16

Diagnosis of acute hepatitis E virus (HEV) infection is established by detection of anti-HEV IgM antibodies by ELISA or by amplification of serum viral RNA. Here, we evaluate the diagnostic value of testing HEV RNA in saliva to identify patients with acute HEV infection. Prospective proof-of-concept study including patients with acute hepatitis. Whole blood and neat saliva samples were obtained from all patients. Saliva samples were processed and analysed for HEV RNA by RT-PCR within 2 hr after collection. A total of 34 patients with acute hepatitis and 12 healthy donors were included in the study. HEV RNA in serum was confirmed by RT-PCR in eight of these patients (23.5%; 95% CI: 12.2%-40.2%). HEV was isolated in the saliva of eight of 34 patients (23.5%; 95% CI: 12.2%-40.2%). All patients with HEV RNA amplified in saliva had detectable HEV RNA in serum. HEV was isolated neither in the saliva of any of the 26 patients without detectable HEV RNA in serum nor in healthy donors. Our study suggests that acute HEV infection could be diagnosed by assessing viral load in saliva. © 2018 Blackwell Verlag GmbH.

Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection.

PubMed

Feld, Jordan J; Jacobson, Ira M; Hézode, Christophe; Asselah, Tarik; Ruane, Peter J; Gruener, Norbert; Abergel, Armand; Mangia, Alessandra; Lai, Ching-Lung; Chan, Henry L Y; Mazzotta, Francesco; Moreno, Christophe; Yoshida, Eric; Shafran, Stephen D; Towner, William J; Tran, Tram T; McNally, John; Osinusi, Anu; Svarovskaia, Evguenia; Zhu, Yanni; Brainard, Diana M; McHutchison, John G; Agarwal, Kosh; Zeuzem, Stefan

2015-12-31

A simple treatment regimen that is effective in a broad range of patients who are chronically infected with the hepatitis C virus (HCV) remains an unmet medical need. We conducted a phase 3, double-blind, placebo-controlled study involving untreated and previously treated patients with chronic HCV genotype 1, 2, 4, 5, or 6 infection, including those with compensated cirrhosis. Patients with HCV genotype 1, 2, 4, or 6 were randomly assigned in a 5:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir in a once-daily, fixed-dose combination tablet or matching placebo for 12 weeks. Because of the low prevalence of genotype 5 in the study regions, patients with genotype 5 did not undergo randomization but were assigned to the sofosbuvir-velpatasvir group. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. Of the 624 patients who received treatment with sofosbuvir-velpatasvir, 34% had HCV genotype 1a, 19% genotype 1b, 17% genotype 2, 19% genotype 4, 6% genotype 5, and 7% genotype 6. A total of 8% of patients were black, 19% had cirrhosis, and 32% had been previously treated for HCV. The rate of sustained virologic response among patients receiving sofosbuvir-velpatasvir was 99% (95% confidence interval, 98 to >99). Two patients receiving sofosbuvir-velpatasvir, both with HCV genotype 1, had a virologic relapse. None of the 116 patients receiving placebo had a sustained virologic response. Serious adverse events were reported in 15 patients (2%) in the sofosbuvir-velpatasvir group and none in the placebo group. Once-daily sofosbuvir-velpatasvir for 12 weeks provided high rates of sustained virologic response among both previously treated and untreated patients infected with HCV genotype 1, 2, 4, 5, or 6, including those with compensated cirrhosis. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT02201940.).

HIV/HCV Co-infection, Liver Disease Progression, and Age-Related IGF-1 Decline.

PubMed

Quinn, Jeffrey; Astemborski, Jacquie; Mehta, Shruti H; Kirk, Gregory D; Thomas, David L; Balagopal, Ashwin

2017-01-01

We have previously reported that persons co-infected with HIV and hepatitis C virus (HCV) had liver disease stages similar to HIV-uninfected individuals who were approximately 10 years older. Insulin-like growth factor 1(IGF-1) levels have long been known to decline with advancing age in humans and non-humans alike. We examined whether HIV infection affects the expected decline in IGF-1 in persons with chronic hepatitis C virus (HCV) infection and if that alteration in IGF-1 decline contributes to the link between HIV, aging, and liver disease progression. A total of 553 individuals with HCV infection were studied from the AIDS Linked to the Intravenous Experience (ALIVE) cohort for whom more than 10 years of follow-up was available. Serum IGF-1 levels were determined by ELISA and evaluated according to baseline characteristics and over time by HIV status and liver disease progression. Linear regression with generalized estimating equations was used to determine whether IGF-1 decline over time was independently associated with liver disease progression. Baseline IGF-1 levels were strongly associated with age ( P < 0.0001) but not with gender or HIV infection. Levels of IGF-1 declined at a rate of -1.75 ng/mL each year in HCV mono-infected individuals and at a rate of -1.23 ng/mL each year in HIV/HCV co-infected individuals ( P < 0.05). In a multivariable linear regression model, progression of liver fibrosis was associated with HIV infection and age, as well as with a slower rate of IGF-1 decline ( P = 0.001); however, the rate of IGF-1 decline did not alter the strength of the associations between HIV, liver disease, and age. The normal decline in IGF-1 levels with age was attenuated in HIV/HCV co-infected individuals compared to those with HCV mono-infection, and slower IGF-1 decline was independently associated with liver disease progression.

Rapid and large-scale implementation of HCV treatment advances in France, 2007-2015.

PubMed

Brouard, Cécile; Boussac-Zarebska, Marjorie; Silvain, Christine; Durand, Julien; de Lédinghen, Victor; Pillonel, Josiane; Delarocque-Astagneau, Elisabeth

2017-12-20

The last decade was marked by major advances in HCV treatment with the introduction of first wave protease inhibitors (1st-wave PIs, telaprevir or boceprevir) in 2011 and second direct-acting antivirals (2nd-wave DAAs) in 2014, that followed low effective pegylated interferon α / ribavirin bitherapy. We estimated the number of patients initiating HCV treatment in France between 2007 and 2015 according to the type of therapy, described their demographical characteristics, and estimated how many were cured with 2nd-wave DAAs in 2014-2015. Individual data from the national health insurance information system were analysed. HCV treatment initiation was defined as a drug reimbursement in the absence of any reimbursement for the same drug in the previous six weeks. Between 2007 and 2015, 72,277 patients initiated at least one HCV treatment. The annual number of patients initiating treatment decreased from 2007 (~13,300) to 2010 (~10,000). It then increased with the introduction of 1st-wave PIs (~12,500 in 2012), before decreasing again in 2013 (~8400). A marked increase followed upon the approval of 2nd-wave DAAs in 2014 (~11,600). Approximately, 8700 and 14,700 patients initiated 2nd-wave DAAs in 2014 and 2015, respectively, corresponding to an estimated 20,300 cured patients in 2014-2015. Patients initiating HCV treatment were mostly male (~65% throughout the 9-year period). Women were older than men (mean age: 55.0 vs. 48.9). Increasing age was associated with more advanced treatment. Among patients initiating 2nd-wave DAAs, the proportions of those under 40 and over 79 years old increased between 2014 and 2015, whereas the proportion of those previously treated for HCV 2007 onwards declined. Successive advances in HCV treatment have been rapidly and widely implemented in France. With the announcement of universal access to DAAs in mid-2016 and price reductions, access to 2nd-wave DAAs is expected to expand even more.

Renal function is impaired in normotensive chronic HCV patients: role of insulin resistance.

PubMed

Sciacqua, Angela; Perticone, Maria; Tassone, Eliezer J; Cimellaro, Antonio; Caroleo, Benedetto; Miceli, Sofia; Andreucci, Michele; Licata, Anna; Sesti, Giorgio; Perticone, Francesco

2016-06-01

Renal dysfunction is an independent predictor for cardiovascular morbidity and mortality. We investigated whether chronic hepatitis C virus (HCV) infection and the related insulin resistance/hyperinsulinemia influence renal function in comparison with a group of healthy subjects and with another group with metabolic syndrome. We enrolled 130 newly diagnosed HCV outpatients matched for age and gender with 130 patients with metabolic syndrome and 130 healthy subjects. Renal function was evaluated by calculation of glomerular filtration rate (e-GFR, mL/min/1.73 m(2)) using the CKD-EPI equation. The following laboratory parameters were measured: fasting plasma glucose and insulin, total, LDL- and HDL-cholesterol, triglyceride, creatinine, and HOMA to evaluate insulin sensitivity. HCV patients with respect to both healthy subjects and metabolic syndrome patients have a decreased e-GFR: 86.6 ± 16.1 vs 120.2 ± 23.1 mL/min/1.73 m(2) (P < 0.0001) and 94.9 ± 22.6 mL/min/1.73 m(2) (P = 0.003), respectively. Regarding biochemical variables, HCV patients, in comparison with healthy subjects, have a higher triglyceride level, creatinine, fasting insulin and HOMA (3.4 ± 1.4 vs 2.6 ± 1.3; P < 0.0001). At linear regression analysis, the correlation between e-GFR and HOMA is similar in the metabolic syndrome (r = -0.555, P < 0.0001) and HCV (r = -0.527, P < 0.0001) groups. At multiple regression analysis, HOMA is the major determinant of e-GFR in both groups, accounting for, respectively, 30.8 and 27.8 % of its variation in the metabolic syndrome and HCV. In conclusion, we demonstrate that HCV patients have a significant reduction of e-GFR and that insulin resistance is the major predictor of renal dysfunction.

HCV NS5A Up-Regulates COX-2 Expression via IL-8-Mediated Activation of the ERK/JNK MAPK Pathway

PubMed Central

Chen, Wei-Chun; Tseng, Chin-Kai; Chen, Yen-Hsu; Lin, Chun-Kuang; Hsu, Shih-hsien; Wang, Shen-Nien; Lee, Jin-Ching

2015-01-01

Chronic hepatitis C virus (HCV) infection leads to intrahepatic inflammation and liver cell injury, which are considered a risk factor for virus-associated hepatitis, cirrhosis, and hepatocellular carcinoma worldwide. Inflammatory cytokines are critical components of the immune system and influence cellular signaling, and genetic imbalances. In this study, we found that cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) were significantly induced by HCV infection and HCV NS5A expression, and induction of COX-2 correlated with HCV-induced IL-8 production. We also found that the ERK and JNK signaling pathways were involved in the regulation of IL-8-mediated COX-2 induction in response to HCV infection. Using a promoter-linked reporter assay, we identified that the C/EBP regulatory element within the COX-2 promoter was the dominant factor responsible for the induction of COX-2 by HCV. Silencing C/EBP attenuated HCV-induced COX-2 expression. Our results revealed that HCV-induced inflammation promotes viral replication, providing new insights into the involvement of IL-8-mediated COX-2 induction in HCV replication. PMID:26231035

Sofosbuvir/Velpatasvir for 12 Weeks in Genotype 1-4 HCV-Infected Liver Transplant Recipients.

PubMed

Agarwal, Kosh; Castells, Lluís; Müllhaupt, Beat; Rosenberg, William M C; McNabb, Brian; Arterburn, Sarah; Camus, Gregory; McNally, John; Stamm, Luisa M; Brainard, Diana M; Subramanian, G Mani; Mariño, Zoe; Dufour, Jean-François; Forns, Xavier

2018-06-07

Sofosbuvir, an NS5B inhibitor, combined with velpatasvir, an NS5A inhibitor (SOF/VEL), produces high sustained virologic response rates 12 weeks after treatment (SVR12) in patients with genotype 1-6 HCV infection, and has no anticipated clinically relevant drug-drug interactions with immunosuppressants. This study evaluated the safety and efficacy of SOF/VEL in adults with recurrent chronic genotype 1-4 HCV infection after liver transplant. Patients received SOF/VEL 400/100 mg daily for 12 weeks. Patients could be treatment experienced or treatment naïve with no cirrhosis or with compensated cirrhosis. The primary endpoints were SVR12 and discontinuations due to adverse events. The study enrolled and treated 79 patients (37 [47%] had genotype 1, 3 [4%] genotype 2, 35 [44%] genotype 3, and 4 [5%] genotype 4 HCV). Of these, 81% were male, 82% were white, 18% had compensated cirrhosis, and 59% were treatment experienced. The most commonly used immunosuppressants were tacrolimus (71%), mycophenolic acid (24%), cyclosporine (14%), and azathioprine (11%). Median (range) time from liver transplantation was 7.5 (0.3, 24) years. The SVR12 rate was 96%. By genotype, SVR12 rates were 95% (genotype 1), 100% (genotype 2), 97% (genotype 3), and 100% (genotype 4). Two patients experienced virologic relapse: one with genotype 1a infection was non-cirrhotic and treatment naïve, and one with genotype 3 infection was non-cirrhotic and treatment experienced. One patient discontinued SOF/VEL due to hyperglycemia. No serious or severe adverse events were deemed SOF/VEL-related by the investigator, and no liver transplant rejection episodes or deaths occurred during the study period. Treatment with SOF/VEL for 12 weeks was highly effective and well tolerated in genotype 1-4 HCV-infected liver transplant recipients with and without cirrhosis. Sofosbuvir/velpatasvir is a combination of two drugs in one tablet that is approved for the treatment of patients with chronic hepatitis C virus

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

PubMed

Pacheco, Suzy Danielly Barbosa; Silva-Oliveira, Gláucia Caroline; Maradei-Pereira, Luciana Maria Cunha; Crescente, José Ângelo Barletta; Lemos, José Alexandre Rodrigues de; Oliveira-Filho, Aldemir Branco de

2014-01-01

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. 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. 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. Strategies for preventing and controlling HCV transmission should be implemented among DUs.

Inferring Viral Dynamics in Chronically HCV Infected Patients from the Spatial Distribution of Infected Hepatocytes

DOE PAGES

Graw, Frederik; Balagopal, Ashwin; Kandathil, Abraham J.; ...

2014-11-13

Chronic liver infection by hepatitis C virus (HCV) is a major public health concern. Despite partly successful treatment options, several aspects of intrahepatic HCV infection dynamics are still poorly understood, including the preferred mode of viral propagation, as well as the proportion of infected hepatocytes. Answers to these questions have important implications for the development of therapeutic interventions. In this study, we present methods to analyze the spatial distribution of infected hepatocytes obtained by single cell laser capture microdissection from liver biopsy samples of patients chronically infected with HCV. By characterizing the internal structure of clusters of infected cells, wemore » are able to evaluate hypotheses about intrahepatic infection dynamics. We found that individual clusters on biopsy samples range in size from 4-50 infected cells. In addition, the HCV RNA content in a cluster declines from the cell that presumably founded the cluster to cells at the maximal cluster extension. These observations support the idea that HCV infection in the liver is seeded randomly (e.g. from the blood) and then spreads locally. Assuming that the amount of intracellular HCV RNA is a proxy for how long a cell has been infected, we estimate based on models of intracellular HCV RNA replication and accumulation that cells in clusters have been infected on average for less than a week. Further, we do not find a relationship between the cluster size and the estimated cluster expansion time. Lastly, our method represents a novel approach to make inferences about infection dynamics in solid tissues from static spatial data.« less

Inferring Viral Dynamics in Chronically HCV Infected Patients from the Spatial Distribution of Infected Hepatocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graw, Frederik; Balagopal, Ashwin; Kandathil, Abraham J.

Chronic liver infection by hepatitis C virus (HCV) is a major public health concern. Despite partly successful treatment options, several aspects of intrahepatic HCV infection dynamics are still poorly understood, including the preferred mode of viral propagation, as well as the proportion of infected hepatocytes. Answers to these questions have important implications for the development of therapeutic interventions. In this study, we present methods to analyze the spatial distribution of infected hepatocytes obtained by single cell laser capture microdissection from liver biopsy samples of patients chronically infected with HCV. By characterizing the internal structure of clusters of infected cells, wemore » are able to evaluate hypotheses about intrahepatic infection dynamics. We found that individual clusters on biopsy samples range in size from 4-50 infected cells. In addition, the HCV RNA content in a cluster declines from the cell that presumably founded the cluster to cells at the maximal cluster extension. These observations support the idea that HCV infection in the liver is seeded randomly (e.g. from the blood) and then spreads locally. Assuming that the amount of intracellular HCV RNA is a proxy for how long a cell has been infected, we estimate based on models of intracellular HCV RNA replication and accumulation that cells in clusters have been infected on average for less than a week. Further, we do not find a relationship between the cluster size and the estimated cluster expansion time. Lastly, our method represents a novel approach to make inferences about infection dynamics in solid tissues from static spatial data.« less

Therapeutic vaccines in HBV: lessons from HCV.

PubMed

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.

Evaluation of the VERSANT HCV RNA 3.0 assay for quantification of hepatitis C virus RNA in serum.

PubMed

Trimoulet, Pascale; Halfon, Philippe; Pohier, Eric; Khiri, Hacène; Chêne, Geneviève; Fleury, Hervé

2002-06-01

We assessed the performance of a new assay (VERSANT HCV RNA 3.0 [bDNA 3.0] assay [Bayer Diagnostics]) to quantitate HCV RNA levels and compared the results of the bDNA 3.0 assay to results of the Quantiplex HCV RNA 2.0 (bDNA 2.0) assay. Samples used in this study included 211 serum specimens from hepatitis C virus (HCV)-infected persons from two sites (Bordeaux and Marseille, France) with different genotypes; 383 serum specimens from HCV antibody-negative, HCV RNA-negative persons; and serial dilutions of World Health Organization (WHO) HCV RNA standard at a titer of 100,000 IU/ml. The specificity of the bDNA 3.0 assay was 98.2%. A high correlation was observed between expected and observed values in all dilutions of WHO standard (r = 0.9982), in serial dilutions of pooled samples (r = 0.9996), and in diluted sera from different HCV genotypes (r = 0.9930 to 0.9995). The standard deviations (SD) for the within-run and between-run reproducibility of the bDNA 3.0 assay were HCV RNA quantification.

Evaluation of the VERSANT HCV RNA 3.0 Assay for Quantification of Hepatitis C Virus RNA in Serum

PubMed Central

Trimoulet, Pascale; Halfon, Philippe; Pohier, Eric; Khiri, Hacène; Chêne, Geneviève; Fleury, Hervé

2002-01-01

We assessed the performance of a new assay (VERSANT HCV RNA 3.0 [bDNA 3.0] assay [Bayer Diagnostics]) to quantitate HCV RNA levels and compared the results of the bDNA 3.0 assay to results of the Quantiplex HCV RNA 2.0 (bDNA 2.0) assay. Samples used in this study included 211 serum specimens from hepatitis C virus (HCV)-infected persons from two sites (Bordeaux and Marseille, France) with different genotypes; 383 serum specimens from HCV antibody-negative, HCV RNA-negative persons; and serial dilutions of World Health Organization (WHO) HCV RNA standard at a titer of 100,000 IU/ml. The specificity of the bDNA 3.0 assay was 98.2%. A high correlation was observed between expected and observed values in all dilutions of WHO standard (r = 0.9982), in serial dilutions of pooled samples (r = 0.9996), and in diluted sera from different HCV genotypes (r = 0.9930 to 0.9995). The standard deviations (SD) for the within-run and between-run reproducibility of the bDNA 3.0 assay were ≤0.2 and ≤0.14, respectively. The intersite SD ranged from 0.03 to 0.14. The bDNA 3.0 assay results were positively correlated with the bDNA 2.0 assay results (r = 0.9533). Taking in account the overall performance, this assay could be used as a routine tool for the HCV RNA quantification. PMID:12037059

Impact of Race/Ethnicity and Gender on HCV Screening and Prevalence Among US Veterans in Department of Veterans Affairs Care

PubMed Central

Belperio, Pamela S.; Loomis, Timothy P.; Mole, Larry A.

2014-01-01

Objectives. We assessed HCV screening and prevalence among veterans and estimated the potential impact of complete birth cohort screening, accounting for the disparate HCV disease burden by race/ethnicity and gender. Methods. We used the Department of Veterans Affairs (VA) Corporate Data Warehouse to identify birth dates, gender, race/ethnicity, and laboratory tests for veterans with at least 1 VA outpatient visit in 2012. We calculated HCV screening rates, prevalence, and HCV infection incident diagnosis. Results. Among 5 499 743 veterans, 54.7% had HCV screening through the VA. In more than 2.9 million veterans screened, HCV prevalence was 6.1% overall and highest among Blacks (11.8%), particularly Black men born in 1945 to 1965 (17.7%). HCV infection incident diagnosis in 2012 was 5.9% for men and 2.3% for women. An estimated additional 48 928 male veterans, including 12 291 Black men, and 1484 female veterans would potentially be identified as HCV infected with full birth cohort screening. Conclusions. HCV prevalence was markedly elevated among veterans born in 1945 to 1965, with substantial variation by race/ethnicity and gender. Full adoption of birth cohort screening may reveal substantial numbers of veterans with previously unknown HCV infection. PMID:25100421