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Hall EW, Sandul AL, Kamili S, Cartwright EJ, Symum H, Wester C. Cost-Effectiveness Analysis of Testing Approaches for Diagnosis of Hepatitis C Among US Adults. Clin Infect Dis 2025:ciaf166. [PMID: 40396750 DOI: 10.1093/cid/ciaf166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Indexed: 05/22/2025] Open
Abstract
BACKGROUND Diagnosis of infection with hepatitis C virus (HCV) is the first step to accessing curative treatment, yet many infected adults in the United States are unaware of their infection. Viral-first HCV testing strategies may improve diagnosis. We assessed the cost-effectiveness of several hepatitis C testing strategies compared with the currently recommended testing algorithm. METHODS We used a decision tree framework with a Markov model of hepatitis C disease progression, to model a cohort representative of US adults at average risk. We modeled 4 strategies: anti-HCV test with automatic nucleic acid test (NAT) for HCV RNA when the anti-HCV result is reactive (comparator); anti-HCV test with automatic hepatitis C core antigen (HCVcAg) test when the anti-HCV result is reactive, followed by NAT for HCV RNA when the HCVcAg result is not reactive (intervention 1); concurrent anti-HCV and HCVcAg tests with automatic NAT for HCV RNA for discordant anti-HCV and HCVcAg results (intervention 2); and NAT for HCV RNA (intervention 3). We compared costs (in 2023 US dollars), quality-adjusted life-years (QALYs) and epidemiologic outcomes for the lifetime of the cohort. RESULTS Relative to the comparator, intervention 1 resulted in the same number of HCV diagnoses and subsequent health outcomes, with cost savings of $0.26 per person. Interventions 2 and 3 had increased costs per person ($8.60 2 and $21.48, respectively) and resulted in an increase in diagnosed infections, treated infections, and QALYs. CONCLUSIONS Compared with the current HCV testing approach, viral-first HCV testing approaches are potentially cost-effective strategies that resulted in gains in diagnoses and health outcomes.
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Affiliation(s)
- Eric W Hall
- OHSU-PSU School of Public Health, Oregon Health & Science University, Portland, Oregon, USA
| | - Amy L Sandul
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Saleem Kamili
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Emily J Cartwright
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
- Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA
- Infectious Diseases Section, Atlanta VA Health Care System, Decatur, Georgia, USA
| | - Hasan Symum
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Carolyn Wester
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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Treviño-Nakoura A, Sepúlveda-Crespo D, Bellon JM, Codina H, Quero-Delgado M, Ryan P, Martínez I, Resino S. Diagnostic performance of hepatitis C virus core antigen testing for detecting hepatitis C in people living with hepatitis B: a systematic review and meta-analysis. Infect Dis Poverty 2024; 13:89. [PMID: 39617947 PMCID: PMC11610273 DOI: 10.1186/s40249-024-01264-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 11/21/2024] [Indexed: 12/10/2024] Open
Abstract
BACKGROUND The current diagnostic strategy for hepatitis C virus (HCV) infection involves a two-step approach: antibody HCV screening followed by confirmatory nucleic acid testing. This study aimed to evaluate the diagnostic performance of the Abbott ARCHITECT HCV Ag assay in serum/plasma samples as a potential one-step alternative for diagnosing active HCV infection in people living with hepatitis B virus (PLWHB) through a systematic review and meta-analysis. METHODS A systematic review and meta-analysis were conducted following PRISMA-DTA guidelines. This protocol was registered on PROSPERO (CRD42023402093). A comprehensive search of electronic databases identified studies published up to 1 November 2024, comparing the ARCHITECT HCV Ag assay to an HCV-RNA reference standard. Sensitivity, specificity, and likelihood ratios were pooled using a random-effects model within the MIDAS module of Stata software. Study quality was assessed using QUADAS-2. Heterogeneity was evaluated using the Q statistic, quantified using the I², and further explored through meta-regression. RESULTS Ten studies (n = 494 participants) met inclusion criteria. The Abbott ARCHITECT HCV Ag assay demonstrated high sensitivity [91%, 95% confidence interval (CI): 76-97%] and specificity (99%, 95% CI: 99-100%). The positive likelihood ratio (PLR) was 81.20 (95% CI: 12.34-534.36), and the negative likelihood ratio (NLR) was 0.09 (95% CI: 0.03-0.27). The area under the summary receiver operating characteristic curve (AUC-SROC) was 99% (95% CI 98-100%). In regions with high HCV prevalence (≥ 10%), the test accurately confirmed active HCV infection in over 90% of cases. However, confirmatory testing remains necessary in low-prevalence settings (≤ 5%). The assay demonstrated an excellent ability to identify individuals without HCV infection, with a low false-negative rate (≤ 2%) regardless of HCV prevalence. Heterogeneity analysis revealed moderate to substantial variation in test performance (I² = 72.09% for sensitivity, 35.47% for PLR, and 78.33% for NLR). QUADAS-2 applicability concerns predicted heterogeneity, but differences were likely insignificant due to minimal variations and limited studies. CONCLUSIONS The Abbott ARCHITECT HCV Ag assay exhibited promising accuracy in detecting active HCV infection among PLWHB. This test might help diagnose active HCV infection in high-prevalence scenarios (≥ 10%) but needs further confirmation in low-prevalence settings (≤ 5%).
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Affiliation(s)
- Ana Treviño-Nakoura
- Servicio de Medicina Preventiva y Salud Pública, Hospital Universitario Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, Spain
- Instituto Mixto de Investigación Escuela Nacional de Sanidad-Universidad Nacional de Educación a Distancia (IMIENS-UNED), Madrid, Spain
| | - Daniel Sepúlveda-Crespo
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología - Instituto de Salud Carlos III, Km 2.2, 28220, Majadahonda (Madrid), Spain.
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
| | - José M Bellon
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Helena Codina
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología - Instituto de Salud Carlos III, Km 2.2, 28220, Majadahonda (Madrid), Spain
| | - Marta Quero-Delgado
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología - Instituto de Salud Carlos III, Km 2.2, 28220, Majadahonda (Madrid), Spain
| | - Pablo Ryan
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- Servicio de Medicina Interna, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - Isidoro Martínez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología - Instituto de Salud Carlos III, Km 2.2, 28220, Majadahonda (Madrid), Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología - Instituto de Salud Carlos III, Km 2.2, 28220, Majadahonda (Madrid), Spain.
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
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Naveed A, Khalid A, Janjua N, Cloherty GA, Akhter S. Performance of HCV core antigen and PCR testing in a predominantly genotype 3 population. J Viral Hepat 2024; 31:320-323. [PMID: 38483043 DOI: 10.1111/jvh.13937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 01/21/2024] [Accepted: 03/02/2024] [Indexed: 05/18/2024]
Abstract
Hepatitis C core antigen (HCVcAg) is becoming increasingly recognized as an alternative to molecular testing for the confirmation of chronic hepatitis C. However, there are limited data on the performance of this assay in a genotype 3 (GT3) predominant country like Pakistan. We conducted a study to evaluate the diagnostic performance of HCVcAg against the HCV polymerase chain reaction (PCR) molecular test. HCV antibody-positive patients requiring confirmatory testing were recruited from August to October 2018 at the Pakistan Kidney and Liver Institute and Research Center (PKLI&RC), Lahore, Pakistan. Patients with previously known diagnoses or treatment histories were excluded. The Abbott HCV Ag assay was used for HCVcAg testing. Results ≥3.00 fmol/L were considered positive for HCVcAg. The Abbott RealTime HCV assay was used for PCR testing with a lower detection limit of ≥12 IU/mL. We computed the sensitivity, specificity and correlation of HCVcAg against HCV PCR. A total of 394 patients were recruited. The median age of the patients was 42 years. Most participants were females (51.5%, n = 203), 30.7% (n = 121) had HTN, 10.4% DM (n = 41) and 5% had APRI ≥2. The overall sensitivity was 98.0% and the specificity was 98.6%. The lowest detection limit of cAg was an HCV RNA value of 4657 IU/mL. The levels of cAg were highly correlated with those of HCV RNA by Spearman's rank correlation test (r = 0.935, p < .001). HCVcAg represents a suitable alternative with high sensitivity and specificity compared with HCV PCR in the GT3-predominant population and can be incorporated into algorithms to improve linkage to care.
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Affiliation(s)
- Ammara Naveed
- Gastroenterology and Hepatology, Pakistan Kidney & Liver Institute & Research Center (PKLI&RC), Lahore, Pakistan
| | - Abdullah Khalid
- Gastroenterology and Hepatology, Pakistan Kidney & Liver Institute & Research Center (PKLI&RC), Lahore, Pakistan
| | - Naveed Janjua
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | | | - Saeed Akhter
- Gastroenterology and Hepatology, Pakistan Kidney & Liver Institute & Research Center (PKLI&RC), Lahore, Pakistan
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Handanagic S, Shadaker S, Drobeniuc J, Tsereteli M, Alkhazashvili M, Adesigbin C, Adamu I, Adabe R, Agwuocha C, Adisa O, Azania A, Boeke CE, Ngwije A, Serumondo J, Armstrong PA. Lessons Learned From Global Hepatitis C Elimination Programs. J Infect Dis 2024; 229:S334-S341. [PMID: 37739781 PMCID: PMC10985584 DOI: 10.1093/infdis/jiad198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/17/2023] [Accepted: 05/28/2023] [Indexed: 09/24/2023] Open
Abstract
In 2016, the World Health Organization introduced global targets for the care and management of hepatitis C virus (HCV) infection to eliminate hepatitis C as a public health threat by 2030. Despite significant improvements in testing and treatment, in 2020 only 23% of all persons infected with HCV globally were diagnosed. We explore examples from global hepatitis C programs in Georgia, Rwanda, and Nigeria that have used decentralized and integrated models to increase access to HCV testing. Georgia established the world's first national hepatitis C elimination program in 2015. In 2022, 2.6 million people (80% of the adults) have been screened for antibodies for HCV infection, and 80 000 persons with HCV RNA detected were treated. To achieve these results, Georgia implemented HCV core antigen testing, utilization of point-of-care (POC) HCV RNA testing, and simplification of HCV viremia detection by qualitative HCV RNA testing. Rwanda was the first country in sub-Saharan Africa to commit to HCV elimination in 2018, and as of 2022 it has achieved its screening target of 7 million people and initiated approximately 60 000 patients on hepatitis C treatment by rapid decentralization and integration of HCV services. In Nigeria, the integrated near-POC testing approach in Nasarawa State has been effective in expanding access to HCV viremia testing and enabling the possibility of same-day testing and treatment initiation. Examples of decentralization and integration of HCV testing and linkage to care in Georgia, Rwanda, and Nigeria could help inform effective strategies to reach 2030 hepatitis C elimination goals in other countries.
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Affiliation(s)
- Senad Handanagic
- Centers for Disease Control and Prevention, Division of Viral Hepatitis, Atlanta, Georgia, USA
| | - Shaun Shadaker
- Centers for Disease Control and Prevention, Division of Viral Hepatitis, Atlanta, Georgia, USA
| | - Jan Drobeniuc
- Centers for Disease Control and Prevention, Division of Viral Hepatitis, Atlanta, Georgia, USA
| | - Maia Tsereteli
- National Center for Disease Control and Public Health of Georgia, Tbilisi, Georgia
| | - Maia Alkhazashvili
- National Center for Disease Control and Public Health of Georgia, Tbilisi, Georgia
| | - Clement Adesigbin
- National AIDS/STIs Control Programme, Federal Ministry of Health, Abuja, Nigeria
| | - Ibrahim Adamu
- Nasarawa State Ministry of Health, Lafia, Nasarawa, Nigeria
| | - Ruth Adabe
- Nasarawa State Ministry of Health, Lafia, Nasarawa, Nigeria
| | | | | | - Amy Azania
- Clinton Health Access Initiative, Boston, Massachusetts, USA
| | | | - Alida Ngwije
- Clinton Health Access Initiative, Kigali, Rwanda
| | | | - Paige A Armstrong
- Centers for Disease Control and Prevention, Division of Viral Hepatitis, Atlanta, Georgia, USA
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Ivanov YD, Malsagova KA, Goldaeva KV, Pleshakova TO, Kozlov AF, Galiullin RA, Shumov ID, Popov VP, Abramova IK, Ziborov VS, Petrov OF, Dolgoborodov AY, Archakov AI. The Study of Performance of a Nanoribbon Biosensor, Sensitized with Aptamers and Antibodies, upon Detection of Core Antigen of Hepatitis C Virus. MICROMACHINES 2023; 14:1946. [PMID: 37893383 PMCID: PMC10609547 DOI: 10.3390/mi14101946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 10/09/2023] [Accepted: 10/11/2023] [Indexed: 10/29/2023]
Abstract
The development of highly sensitive diagnostic systems for the early revelation of diseases in humans is one of the most important tasks of modern biomedical research, and the detection of the core antigen of the hepatitis C virus (HCVcoreAg)-a protein marker of the hepatitis C virus-is just the case. Our study is aimed at testing the performance of the nanoribbon biosensor in the case of the use of two different types of molecular probes: the antibodies and the aptamers against HCVcoreAg. The nanoribbon sensor chips employed are based on "silicon-on-insulator structures" (SOI-NR). Two different HCVcoreAg preparations are tested: recombinant β-galactosidase-conjugated HCVcoreAg ("Virogen", Watertown, MA, USA) and recombinant HCVcoreAg ("Vector-Best", Novosibirsk, Russia). Upon the detection of either type of antigen preparation, the lowest concentration of the antigen detectable in buffer with pH 5.1 was found to be approximately equal, amounting to ~10-15 M. This value was similar upon the use of either type of molecular probes.
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Affiliation(s)
- Yuri D. Ivanov
- Institute of Biomedical Chemistry (IBMC), 119121 Moscow, Russia; (Y.D.I.); (K.A.M.); (T.O.P.); (A.F.K.); (R.A.G.); (I.D.S.); (I.K.A.); (V.S.Z.); (A.I.A.)
- Joint Institute for High Temperatures of Russian Academy of Sciences, 125412 Moscow, Russia; (O.F.P.); (A.Y.D.)
| | - Kristina A. Malsagova
- Institute of Biomedical Chemistry (IBMC), 119121 Moscow, Russia; (Y.D.I.); (K.A.M.); (T.O.P.); (A.F.K.); (R.A.G.); (I.D.S.); (I.K.A.); (V.S.Z.); (A.I.A.)
| | - Kristina V. Goldaeva
- Institute of Biomedical Chemistry (IBMC), 119121 Moscow, Russia; (Y.D.I.); (K.A.M.); (T.O.P.); (A.F.K.); (R.A.G.); (I.D.S.); (I.K.A.); (V.S.Z.); (A.I.A.)
| | - Tatyana O. Pleshakova
- Institute of Biomedical Chemistry (IBMC), 119121 Moscow, Russia; (Y.D.I.); (K.A.M.); (T.O.P.); (A.F.K.); (R.A.G.); (I.D.S.); (I.K.A.); (V.S.Z.); (A.I.A.)
| | - Andrey F. Kozlov
- Institute of Biomedical Chemistry (IBMC), 119121 Moscow, Russia; (Y.D.I.); (K.A.M.); (T.O.P.); (A.F.K.); (R.A.G.); (I.D.S.); (I.K.A.); (V.S.Z.); (A.I.A.)
| | - Rafael A. Galiullin
- Institute of Biomedical Chemistry (IBMC), 119121 Moscow, Russia; (Y.D.I.); (K.A.M.); (T.O.P.); (A.F.K.); (R.A.G.); (I.D.S.); (I.K.A.); (V.S.Z.); (A.I.A.)
| | - Ivan D. Shumov
- Institute of Biomedical Chemistry (IBMC), 119121 Moscow, Russia; (Y.D.I.); (K.A.M.); (T.O.P.); (A.F.K.); (R.A.G.); (I.D.S.); (I.K.A.); (V.S.Z.); (A.I.A.)
| | - Vladimir P. Popov
- Rzhanov Institute of Semiconductor Physics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia;
| | - Irina K. Abramova
- Institute of Biomedical Chemistry (IBMC), 119121 Moscow, Russia; (Y.D.I.); (K.A.M.); (T.O.P.); (A.F.K.); (R.A.G.); (I.D.S.); (I.K.A.); (V.S.Z.); (A.I.A.)
| | - Vadim S. Ziborov
- Institute of Biomedical Chemistry (IBMC), 119121 Moscow, Russia; (Y.D.I.); (K.A.M.); (T.O.P.); (A.F.K.); (R.A.G.); (I.D.S.); (I.K.A.); (V.S.Z.); (A.I.A.)
- Joint Institute for High Temperatures of Russian Academy of Sciences, 125412 Moscow, Russia; (O.F.P.); (A.Y.D.)
| | - Oleg F. Petrov
- Joint Institute for High Temperatures of Russian Academy of Sciences, 125412 Moscow, Russia; (O.F.P.); (A.Y.D.)
| | - Alexander Yu. Dolgoborodov
- Joint Institute for High Temperatures of Russian Academy of Sciences, 125412 Moscow, Russia; (O.F.P.); (A.Y.D.)
| | - Alexander I. Archakov
- Institute of Biomedical Chemistry (IBMC), 119121 Moscow, Russia; (Y.D.I.); (K.A.M.); (T.O.P.); (A.F.K.); (R.A.G.); (I.D.S.); (I.K.A.); (V.S.Z.); (A.I.A.)
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Toygar Deniz M, Akhan S, Sayan M, Sönmez Tamer G, Azak E. Evaluation of HCV-Core Antigen in Diagnosis of Chronic Hepatitis C Patients under Direct-Acting Antiviral Treatment. Egypt J Immunol 2022. [DOI: 10.4274/vhd.galenos.2022.2021-3-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Flores GL, Mota JC, da Silva Andrade LT, Lopes RS, Bastos FI, Villar LM. Performance of HCV Antigen Testing for the Diagnosis and Monitoring of Antiviral Treatment: A Systematic Review and Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2022; 2022:7348755. [PMID: 35028317 PMCID: PMC8752229 DOI: 10.1155/2022/7348755] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 11/21/2021] [Accepted: 12/01/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Active hepatitis C virus (HCV) infection is based on the detection of HCV RNA that it is effective but presents high cost and the need to hire trained personnel. This systematic review and meta-analysis is aimed at evaluating the diagnostic accuracy of HCV Ag testing to identify HCV cases and to monitor antiviral treatment including DAA treatment. METHODS The studies were identified through a search in PubMed, Lilacs, and Scopus from 1990 through March 31, 2020. Cohort, cross-sectional, and randomized controlled trials were included. Two independent reviewers extracted data and assessed quality using an adapted Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Our primary outcome was to determine the accuracy of HCV Ag detection for the diagnosis, which we estimated using random-effects meta-analysis. RESULTS Of 3,062 articles identified, 54 met our eligibility criteria. The studies described cohorts from 20 countries, including 14,286 individuals with chronic HCV individuals. Studies for ECLIA technology demonstrated highest quality compared to studies that used ELISA. The pooled sensitivity and specificity (95% CI) for HCV Ag detection of active HCV infection were 98.82% (95%CI = 98.04%; 99.30%) and 98.95% (95%CI = 97.84%; 99.49%), respectively. High concordance was found between HCV Ag testing and HCV RNA detection 89.7% and 95% to evaluate antiviral treatment. CONCLUSIONS According to our findings, HCV Ag testing could be useful to identify HCV active cases in low-resource areas. For antiviral treatment, HCV Ag testing will be useful at the end of treatment.
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Affiliation(s)
- Geane Lopes Flores
- Laboratory of Viral Hepatitis, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil
| | - Jurema Corrêa Mota
- Institute of Communication and Information on Science and Technology in Health, FIOCRUZ, Rio de Janeiro, Brazil
| | | | - Renata Serrano Lopes
- Laboratory of Viral Hepatitis, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil
| | - Francisco Inácio Bastos
- Institute of Communication and Information on Science and Technology in Health, FIOCRUZ, Rio de Janeiro, Brazil
| | - Livia Melo Villar
- Laboratory of Viral Hepatitis, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil
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Kallala O, Kacem S, Fodha I, Pozzetto B, Abdelhalim T. Role of hepatitis C virus core antigen assay in hepatitis C care in developing country. EGYPTIAN LIVER JOURNAL 2021; 11:77. [PMID: 34777874 PMCID: PMC8449518 DOI: 10.1186/s43066-021-00146-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Accepted: 09/07/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The World Health Organization (WHO) aims to achieve global hepatitis C elimination by 2030, defined as diagnosis of 90% of infected individuals and treating 80% of them. Current guidelines for the screening and diagnosis of hepatitis C infection denote using a relatively cheap screen with anti-hepatitis C virus (HCV) antibody immunoassay, followed by the much costlier molecular test for HCV RNA levels using polymerase chain reaction (PCR) assay to confirm active HCV infection. Simplification of the HCV evaluation algorithm to reduce the number of required tests could considerably expand the provision of HCV treatment especially in a developing country. This study investigates the performance of hepatitis C Core Antigen (HCV Ag) test by comparing HCV Ag results versus the results obtained with HCV ribonucleic acid (RNA) PCR which is considered the gold standard for the diagnosis of HCV infection. RESULTS Among the 109 anti-HCV positive sera, 96 were positive for both HCV Ag (> 3 fmol/L) and HCV RNA (> 15 IU/mL); 8 were negative for both tests, while the remaining 5 were positive for HCV RNA only. Considering the HCV RNA as gold standard; the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HCV Ag test were found to be 95.05%, 100%, 100%, and 61.54%, respectively. HCV genotype was performed for 59 patients. The most common HCV genotype was genotype 1 (72.9%). Genotype 2 (15.3%) and genotype 3 (11.9%) were detected in the others samples. A high level of correlation was seen between HCV RNA and HCV Ag (r = 0.958, p < 0.001). The correlation for the samples that were genotyped 1 was significant (r = 0.966, p < 0.001). CONCLUSION In our study, it was found that there was strong correlation between HCV RNA levels and HCV Ag levels. So, it can be used for a one-step HCV antigen test to diagnose active HCV infection.
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Affiliation(s)
- Ouafa Kallala
- Research Laboratory for “Epidemiology and Immunogenetics of Viral Infections” (LR14SP02), Sahloul University Hospital, University of Sousse, Sousse, Tunisia
- Faculty of Pharmacy, University of Monastir, Avicenne Street, Monastir, Tunisia
| | - Saoussen Kacem
- Research Laboratory for “Epidemiology and Immunogenetics of Viral Infections” (LR14SP02), Sahloul University Hospital, University of Sousse, Sousse, Tunisia
- Faculty of Pharmacy, University of Monastir, Avicenne Street, Monastir, Tunisia
| | - Imene Fodha
- Research Laboratory for “Epidemiology and Immunogenetics of Viral Infections” (LR14SP02), Sahloul University Hospital, University of Sousse, Sousse, Tunisia
- Faculty of Pharmacy, University of Monastir, Avicenne Street, Monastir, Tunisia
| | - Bruno Pozzetto
- GIMAP EA3064, Faculté de Médecine, Université de Saint-Etienne/Université de Lyon, Lyon, France
- Laboratoire des Agents infectieux et d’Hygiène, CHU de Saint-Etienne, Saint-Priest-en-Jarez, France
| | - Trabelsi Abdelhalim
- Research Laboratory for “Epidemiology and Immunogenetics of Viral Infections” (LR14SP02), Sahloul University Hospital, University of Sousse, Sousse, Tunisia
- Faculty of Pharmacy, University of Monastir, Avicenne Street, Monastir, Tunisia
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9
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Kumbhar N, Ramachandran K, Kumar G, Rao Pasupuleti SS, Sharma MK, Gupta E. Utility of hepatitis C virus core antigen testing for diagnosis and treatment monitoring in HCV infection: A study from India. Indian J Med Microbiol 2021; 39:462-466. [PMID: 34294505 DOI: 10.1016/j.ijmmb.2021.07.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Revised: 07/01/2021] [Accepted: 07/07/2021] [Indexed: 11/28/2022]
Abstract
PURPOSE The major bottleneck in most developing countries to attain the WHO goal of eliminating hepatitis C as a public health threat by 2030 is the limited access to molecular testing and loss of infected patients to follow up. Many of the hepatitis C virus (HCV) infected patients fail to get the confirmatory HCV RNA test done after initial screening for anti-HCV antibody. The hepatitis C core antigen (HCVcAg) chemiluminescence-based assay which is newly introduced in the Indian health setup could prove to be a potential marker in the single-point screening and confirmation of HCV infection. This study was done to evaluate the performance of the HCVcAg assay for diagnosis and treatment monitoring of patients with HCV infection. METHODS In this retrospective study 208 archived plasma samples from 184 patients were retrieved and all three markers for the laboratory diagnosis of HCV infection, anti-HCV, HCV RNA and HCVcAg were performed in a single freeze thaw cycle. For a subset of patients (n = 24), paired samples, baseline samples and samples collected at 12 weeks after completion of treatment (SVR12) were available. RESULTS The sensitivity and specificity of the HCVcAg assay were 91.58% and 99.12% respectively with HCV RNA as the gold standard for the detection of active infection. There was a strong correlation between HCVcAg and HCV RNA (R = 0.85, p < 0•0001). Among the paired samples, the concordance between the HCVcAg and HCV RNA at baseline and at SVR12 was 95.8%. CONCLUSION The HCVcAg assay showed a good correlation with the gold standard HCV RNA assay, especially in the case of treatment naïve patients. Thus, the use of HCVcAg assay as tool for testing and confirmation of HCV infection has the potential to increase the uptake of HCV testing.
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Affiliation(s)
- Nitin Kumbhar
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Krithiga Ramachandran
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Guresh Kumar
- Department of Research, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Manoj Kumar Sharma
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Ekta Gupta
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.
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Kannan A, Biswas L, Kumar A, Kurian J, S Nair A, Suresh P, Sadasivan S, Biswas R. Improving Diagnosis of Hepatitis C Virus Infection Using Hepatitis C Core Antigen Testing in a Resource-Poor Setting. Rev Soc Bras Med Trop 2021; 54:e02532020. [PMID: 33605377 PMCID: PMC7891558 DOI: 10.1590/0037-8682-0253-2020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 01/20/2021] [Indexed: 01/19/2023] Open
Abstract
INTRODUCTION: We compared the hepatitis C virus (HCV) core antigen test with the HCV RNA assay to confirm anti-HCV results to determine whether the HCV core antigen test could be used as an alternative confirmatory test to the HCV RNA test. METHODS: Sera from 156 patients were analyzed for anti-HCV and HCV core antigen using a chemiluminescent microparticle immunoassay (Architect i2000SR) and for HCV RNA using the artus HCV RG RT-PCR Kit (QIAGEN) in a Rotor-Gene Q instrument. RESULTS: The diagnostic sensitivity, specificity, and positive and negative predictive values of the HCV core antigen assay compared to the HCV RNA test were 77.35%, 100%, 100%, and 89.38%, respectively. HCV core antigen levels showed a good correlation with those from HCV RNA quantification (r =0.872). However, 13 samples with a viral load of less than 4000 IU/mL were negative in the HCV core antigen assay. All gray-zone reactive samples were also RNA positive and were positive on repeat testing. CONCLUSIONS: The Architect HCV core antigen assay is highly specific and has an excellent positive predictive value. At the present level of sensitivity (77%), the study is still relevant in a low-income setting in which most of the HCV-positive patients would go undiagnosed, since HCV RNA testing is not available and/or not affordable. HCV core antigen testing can also help determine the true burden of infection in a population, considering the fact that almost 50% of the anti-HCV positive cases are negative for HCV RNA.
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Affiliation(s)
- Ayswarya Kannan
- Amrita Vishwa Vidyapeetham, Amrita Institute of Medical Sciences, Department of Microbiology, Ponekara, Kochi, Kerala, India
| | - Lalitha Biswas
- Amrita Vishwa Vidyapeetham, Center for Nanoscience and Molecular Medicine, Ponekara, Kochi , Kerala, India
| | - Anil Kumar
- Amrita Vishwa Vidyapeetham, Amrita Institute of Medical Sciences, Department of Microbiology, Ponekara, Kochi, Kerala, India
| | - Jessy Kurian
- Amrita Vishwa Vidyapeetham, Amrita Institute of Medical Sciences, Molecular biology laboratory, Ponekara, Kochi , Kerala, India
| | - Anjaly S Nair
- Amrita Vishwa Vidyapeetham, Amrita Institute of Medical Sciences, Department of Biostatistics, Ponekara, Kochi, Kerala, India
| | - Parasmal Suresh
- Amrita Vishwa Vidyapeetham, Center for Nanoscience and Molecular Medicine, Ponekara, Kochi , Kerala, India
| | - Shine Sadasivan
- Amrita Vishwa Vidyapeetham, Amrita Institute of Medical Sciences, Department of Gastroenterology, Ponekara, Kochi, Kerala, India
| | - Raja Biswas
- Amrita Vishwa Vidyapeetham, Center for Nanoscience and Molecular Medicine, Ponekara, Kochi , Kerala, India
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11
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Bertisch B, Brezzi M, Negro F, Müllhaupt B, Ottiger C, Künzler-Heule P, Schmid P, Giudici F, Clerc O, Moriggia A, Roelens M, Marinucci F, Zehnder C, Moradpour D, Keiser O. Very Low Hepatitis C Viral Loads in Treatment-naive Persons: Do They Compromise Hepatitis C Virus Antigen Testing? Clin Infect Dis 2021; 70:653-659. [PMID: 30943286 DOI: 10.1093/cid/ciz270] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 03/28/2019] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) antigen testing is less expensive than quantitative reverse-transcription polymerase chain reaction but has lower sensitivity for very low viral load (VLVL; HCV RNA ≤3000 IU/mL). Currently the benefits of antigen testing for screening are discussed, but data on prevalence and outcomes of persons with VLVL are scarce. METHODS We assessed prevalence and predictors of VLVL by logistic regression in treatment-naive participants in the Swiss Hepatitis C Cohort Study. We analyzed if the last viral load after VLVL was low, compared cirrhosis and mortality in persons with and without VLVL, and evaluated the number of samples with VLVL that were reactive by antigen testing. RESULTS We included 2533 treatment-naive persons with available quantitative HCV RNA testing results. Overall, 133 persons (5.3%) had a VLVL. Age 18-40 years, female sex, and human immunodeficiency virus coinfection were associated with VLVL. Of 72 persons with a viral load available after VLVL, 14% had a VLVL and 17% had spontaneous viral clearance. The prevalence and incidence of cirrhosis and mortality were comparable in persons with and without VLVL; all 24 persons with VLVL and cirrhosis had excessive alcohol consumption or immunosuppression. Overall, 33% of samples with VLVL were reactive by antigen testing. CONCLUSIONS The frequency of VLVL was low. Among the persons who would probably be missed by antigen screening, some had a favorable disease course, but some had immunosuppression and liver cirrhosis. The benefit of HCV antigen testing for screening may be limited by the risk of missing patients with severe liver disease.
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Affiliation(s)
| | - Matteo Brezzi
- Institute of Global Health, University of Geneva, Zürich
| | - Francesco Negro
- Divisions of Gastroenterology and Hepatology and of Clinical Pathology, University Hospitals Geneva, Zürich
| | - Beat Müllhaupt
- Swiss Hepato-Pancreato-Biliary Center and Department of Gastroenterology and Hepatology, University Hospital, Zürich
| | | | | | - Patrick Schmid
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St Gallen
| | - Fabio Giudici
- Institute of Social and Preventive Medicine, University of Bern
| | - Olivier Clerc
- Department of Internal Medicine and Infectious Diseases, Pourtalès Hospital, Neuchâtel
| | | | | | | | | | - Darius Moradpour
- Division of Gastroenterology and Hepatology, University Hospital Lausanne, Switzerland
| | - Olivia Keiser
- Institute of Global Health, University of Geneva, Zürich
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12
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[Rapid diagnosis of sexually transmitted infections : Joint statement of DSTIG, RKI, and PEI, as well as the reference centers for HIV, HBV, and HCV and consulting laboratories for Chlamydia, gonococci, and Treponema pallidum]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020; 63:1271-1286. [PMID: 32930821 DOI: 10.1007/s00103-020-03218-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
In February 2019, the fourth expert meeting on rapid diagnostic tests (RDTs) for sexually transmitted infections (STI) was held at the Robert Koch Institute (RKI) in Berlin. Novel technical developments and new aspects of RDT applications were discussed by representatives from the German STI Society (DSTIG); RKI; the Paul Ehrlich Institute; national reference centers for HIV, HBV, and HCV; and reference laboratories for Chlamydia, gonococci, and Treponema pallidum.As a result of this meeting, we present a revision of the joint statement on STI diagnostics with RDTs from 2017. The Regulation (EU) 2017/746 of the European Parliament and of the Council on in vitro diagnostic medical devices became effective in May 2017 and includes more stringent regulatory requirements for RDTs, mainly concerning conformity of manufacturing processes and performance characteristics of class D in vitro diagnostics (detection of HIV, HBV, HCV, and T. pallidum). Some RDTs for HIV, HCV, and T. pallidum have been evaluated in clinical studies and/or were WHO prequalified and may be used in low-threshold services. Among them are some HIV RDTs available and approved for self-testing. In addition, some HBV RDTs based on detection of HBs antigen (HBsAg) received WHO prequalification. However, false negative results may occur in samples with low HBsAg levels, as for instance in HIV-coinfected patients receiving antiretroviral therapy. For Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), antigen-based RDTs still do not allow reliable detection of infection. Only PCR-based CT/NG RDTs possess sufficient diagnostic accuracy to be used as point-of-care tests. Rapid PCR tests for NG, however, do not provide any information about antimicrobial resistance.
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13
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Nanowire Aptamer-Sensitized Biosensor Chips with Gas Plasma-Treated Surface for the Detection of Hepatitis C Virus Core Antigen. COATINGS 2020. [DOI: 10.3390/coatings10080753] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Herein, we have demonstrated highly sensitive real-time biospecific detection of a protein marker of hepatitis C—the core antigen of hepatitis C virus (HCVcoreAg)—using a nanowire (NW) biosensor. The primary element of the NW-biosensor is a chip with p-type conductance, bearing silicon-on-insulator (SOI) nanowire structures on its surface. The nanowire structures are fabricated by gas-plasma treatment and electron beam lithography. The detection specificity was provided by sensitization of the sensor surface with aptamers against HCVcoreAg. The influence of buffer pH on the sensor response signal was studied. The effect of reverse polarity of the biosensor response signal with change from the acidic buffer pH to the neutral one was found. The lowest detectable HCVcoreAg concentration was determined to be 2.0 × 10−15 M in both acidic (pH 5.1) and neutral (pH 7.4) buffer solution. The proposed aptamer-sensitized sensor was also successfully applied to detect HCVcoreAg in serum samples of hepatitis C patients.
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14
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Patel J, Sharma P. Design of a novel rapid immunoassay for simultaneous detection of hepatitis C virus core antigen and antibodies. Arch Virol 2020; 165:627-641. [PMID: 31965313 DOI: 10.1007/s00705-019-04518-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 12/05/2019] [Indexed: 01/04/2023]
Abstract
HCV is a potential cause of viral hepatitis, which leads to blood-borne chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Anti-HCV antibody detection assays detect HCV infection after approximately 70 days. HCV core antigen can be detected much earlier than anti-HCV antibodies. However, it disappears soon after the appearance of anti-HCV antibodies. Thus, there is a need for a rapid assay for simultaneous detection of HCV core antigen and anti-HCV antibodies for early diagnosis of HCV infection. A rapid diagnostic assay (HCV Ag-Ab Combo) for simultaneous detection of HCV core antigen and anti-HCV antibodies for early diagnosis of HCV infection was developed. HCV Ag-Ab Combo was evaluated in order to determine its potential for detection of HCV infection earlier than anti-HCV antibody detection assays. We compared the sensitivity of the newly developed assay with anti-HCV antibody detection assays (ELISA [HCV Ab ELISA] and rapid test [HCV Ab Rapid]) and HCV core antigen/anti-HCV antibody detection ELISA (HCV Ag-Ab ELISA). This study included 11 samples that were found positive in HCV RNA detection and HCV Ag-Ab ELISA but negative in HCV antibody detection assays (HCV Ab ELISA and rapid), 10 samples that were found positive in HCV Ag-Ab ELISA and HCV Ab ELISA but negative in HCV Ab Rapid, 69 samples that were found positive in HCV Ag-Ab ELISA, HCV Ab ELISA, and HCV Ab Rapid, and 509 samples that were found negative in HCV Ag-Ab ELISA, HCV Ab ELISA, and HCV Ab Rapid. Three seroconversion panels, PHV 913, PHV 911 (M) and PHV904-00-1.0, and a HCV RNA genotype qualification panel (2400-0182) acquired from Seracare Life Sciences (USA) were also tested. HCV Ag-Ab Combo showed a combined sensitivity and specificity of 100% when tested with 90 samples that were positive for HCV by HCV Ag-Ab ELISA and 509 HCV-negative samples. Its positive predictive value (PPV) and negative predictive value (NPV) were found to be 100%. It detected HCV infection approximately 7 to 12 days earlier than the HCV Ab detection assays, and its performance was not affected when testing different genotypes of HCV. HCV Ag-Ab Combo did not detect HCV infection as early as HCV RNA or HCV Ag-Ab ELISA. HCV Ag-Ab Combo provided a significant improvement for the early detection of HCV infection during the preseroconversion phase when compared with anti-HCV antibody detection assays. It could be a useful screening assay, and an alternative to HCV RNA detection or HCV Ag-Ab ELISA when nucleic acid technologies cannot be implemented.
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Affiliation(s)
- Jayendrakumar Patel
- Department of Biotechnology, Veer Narmad South Gujarat University, Surat, Gujarat, 395007, India. .,Research and Development Department, ARKRAY Healthcare Pvt. Ltd. (Formerly Span Diagnostics Ltd.), Surat, Gujarat, India.
| | - Preeti Sharma
- Department of Biotechnology, Veer Narmad South Gujarat University, Surat, Gujarat, 395007, India
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15
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Pérez-García A, Aguinaga A, Navascués A, Castilla J, Ezpeleta C. Hepatitis C core antigen: Diagnosis and monitoring of patients infected with hepatitis C virus. Int J Infect Dis 2019; 89:131-136. [DOI: 10.1016/j.ijid.2019.09.022] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Revised: 09/21/2019] [Accepted: 09/25/2019] [Indexed: 02/06/2023] Open
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16
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Fourati S, Feld JJ, Chevaliez S, Luhmann N. Approaches for simplified HCV diagnostic algorithms. J Int AIDS Soc 2019; 21 Suppl 2:e25058. [PMID: 29633561 PMCID: PMC5978654 DOI: 10.1002/jia2.25058] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Accepted: 12/24/2017] [Indexed: 12/16/2022] Open
Abstract
Introduction In the light of the advances in HCV antiviral therapy, global control of HCV infection becomes feasible but depends on the capacity of countries to identify infected people and to offer them treatment. To achieve the WHO goal which targets a diagnosis rate of 90% by 2030, simplification of screening and diagnosis will be crucial. Methods Published literature, unpublished data and expert consensus were used to determine key parameters, including point‐of‐care, rapid diagnostic testing, screening, the use of HCV core Ag and dried blood spots; starting from 2008 until November 2017. In addition, a manual search was undertaken to detect relevant papers or websites related to specific data from countries which underwent or are planning a programme of HCV elimination. Results Several strategies have been developed and evaluated these last years to simplify and facilitate access to screening and diagnosis, the development of reliable HCV core antigen tests and new nucleic acid amplification technologies for use in decentralized settings. In high prevalence settings, a one‐step screening and diagnosis strategy could simplify diagnostic algorithms provided the cost is reduced. Finally, genotyping may no longer be required in the context of availability of pangenotypic antiviral therapy. Conclusions Despite relevant advances in HCV screening and diagnosis, the overall diagnosis package is still too expensive today and efforts must be made to allow generalized implementation of reliable tests in low and middle income countries. These efforts will be key factors to foster a real public health approach to HCV elimination.
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Affiliation(s)
- Slim Fourati
- Department of Virology, Henri Mondor Hospital, National Reference Center for Viral Hepatitis B, C and delta D, INSERMU955, Créteil, France
| | - Jordan J Feld
- Toronto Centre for Liver Disease, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Canada
| | - Stéphane Chevaliez
- Department of Virology, Henri Mondor Hospital, National Reference Center for Viral Hepatitis B, C and delta D, INSERMU955, Créteil, France
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17
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Łucejko M, Tomasiewicz K, Olczak A, Tudrujek-Zdunek M, Halota W, Jelski W, Donica H, Krintus M, Mroczko B, Flisiak R. Hepatitis C virus core antigen as a possible alternative for evaluation of treatment effectiveness after treatment with direct-acting antivirals. Br J Biomed Sci 2019; 76:190-194. [PMID: 31401936 DOI: 10.1080/09674845.2019.1654790] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Background: Chronic hepatitis C is a major public health problem around the world. In monitoring treatment efficacy, although costly and labour-intensive methods of molecular biology are often used, much cheaper and technically easier serological methods evaluating the concentration of HCV core antigen in serum are available. We evaluated HCVcAg quantification as a possible assessment of the treatment efficacy instead of HCV RNA quantification.Methods: We collected 514 serum samples from treated HCV infected patients. Quantitative evaluation of HCV RNA and HCVcAg was carried out before treatment, at the end of treatment, and at least 12 weeks following treatment termination. HCV RNA was determined by automated assay (Roche COBAS) and HCVcAg quantitation with ARCHITECT ci8200 analyser.Results: There was a significant correlation between HCVcAg and HCV RNA concentrations at baseline and follow-up visits, but not at the end of treatment. Among samples collected before the treatment, at the end of treatment and follow-up visit, concordance of HCV RNA and HCVcAg reached level of 98.1%, 98.9% and 98.7%, respectively. Diagnostic sensitivity, specificity, positive and negative predictive values of HCVcAg detection were >97%.Conclusions: HCVcAg measurement could be an alternative for determining HCV treatment efficacy after chemotherapy and could be an option in the diagnosis of HCV infection.
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Affiliation(s)
- M Łucejko
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
| | - K Tomasiewicz
- Department of Infectious Diseases and Hepatology, Division of Laboratory Diagnostics, Medical University of Lublin, Lublin, Poland
| | - A Olczak
- Department of Infectious Diseases and Hepatology, Nicolaus Copernicus University, Torun, Poland
| | - M Tudrujek-Zdunek
- Department of Infectious Diseases and Hepatology, Division of Laboratory Diagnostics, Medical University of Lublin, Lublin, Poland
| | - W Halota
- Department of Infectious Diseases and Hepatology, Nicolaus Copernicus University, Torun, Poland
| | - W Jelski
- Department of Biochemical Diagnostics, Medical University of Bialystok, Bialystok, Poland
| | - H Donica
- Department of Biochemical Diagnostics, Division of Laboratory Diagnostics, Medical University of Lublin, Lublin, Poland
| | - M Krintus
- Department of Laboratory Medicine, Nicolaus Copernicus University, Torun, Poland
| | - B Mroczko
- Department of Biochemical Diagnostics, Medical University of Bialystok, Bialystok, Poland
| | - R Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
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18
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Abstract
Many microbes, toxins, autoimmune diseases, and neoplastic diseases may cause liver inflammation; however, 5 viruses whose main pathogenesis is liver disease are referred to as hepatitis A, B, C, D, and E viruses. These viruses cause a significant burden of global illness. With the exception of hepatitis A virus, all may cause chronic infection potentially leading to cirrhosis and hepatocellular carcinoma. Excellent serologic and nucleic acid detection methods are available for determining the precise cause and, in some cases, the duration of infection. Diagnostics are critical for identifying individuals needing treatment and for monitoring the treatment success.
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Affiliation(s)
- Kunatum Prasidthrathsint
- Division of Infectious Diseases, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Division of Clinical Microbiology, Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, IA, USA; University of Iowa Hospitals and Clinics, SW54, GH, 200 Hawkins Drive, Iowa City, IA 52242, USA; Medicine and Research Services, Iowa City Veterans Administration Health Care Center, Iowa City, IA, USA
| | - Jack T Stapleton
- Division of Infectious Diseases, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, IA, USA; University of Iowa Hospitals and Clinics, SW54, GH, 200 Hawkins Drive, Iowa City, IA 52242, USA; Medicine and Research Services, Iowa City Veterans Administration Health Care Center, Iowa City, IA, USA.
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19
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Abstract
Introduction: The improvement of number of people diagnosed with hepatitis C virus (HCV) infection is crucial to reach the WHO objectives for eliminating viral hepatitis by 2030. Alternatives to classical HCV virological tests using serum or plasma taken from venous puncture including point-of-care (POC) tests and dried blood spot (DBS) are being considered for HCV screening, diagnosis, and monitoring. Reflex nucleic acid testing and HCV core antigen test have the potential to simplify diagnostic algorithm, increase diagnosis and facilitate linkage to care. Areas covered: This review examines strategies for the improvement of HCV testing and diagnosis including alternatives to classical HCV virological tests and approaches for simplified diagnostic algorithms. Expert opinion: Serological and molecular POC tests are now available for HCV antibody and HCV RNA detections in less than 20 and 60, respectively. DBS offers the main advantage to store desiccated blood that can be easily transported to reference centers where state-of-the-art molecular and serological diagnostic tests are used. Simplifications of diagnostic algorithms are urgently needed to enhance HCV testing, linkage to care and treatment.
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Affiliation(s)
- Stéphane Chevaliez
- a National Reference Center for Viral Hepatitis B, C and delta, Department of Virology, Hôpital Henri Mondor , Université Paris-Est , Créteil , France.,b INSERM U955 , Créteil , France
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20
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Galli C, Julicher P, Plebani M. HCV core antigen comes of age: a new opportunity for the diagnosis of hepatitis C virus infection. Clin Chem Lab Med 2019; 56:880-888. [PMID: 29702484 DOI: 10.1515/cclm-2017-0754] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Accepted: 12/08/2017] [Indexed: 12/13/2022]
Abstract
The diagnosis of hepatitis C virus (HCV) infection has been traditionally based on the detection of the host antibody response. Although antibody assays are available in different formats and are fairly accurate, they cannot distinguish between an ongoing infection with HCV replicative activity and a past infection where HCV has been cleared, spontaneously or after a successful therapy. As a chronic infection is mostly asymptomatic until the late clinical stages, there is a compelling need to detect active HCV infection by simple and reproducible methods. On this purpose, the clinical guidelines have suggested to search for the HCV ribonucleic acid (HCV-RNA) after anti-HCV has been detected, but this second step carries several limitations especially for population screening. The availability of fast and automated serological assays for the hepatitis C core antigen (HCVAg) has prompted an update of the guidelines that now encompass the use of HCVAg as a practical alternative to HCV-RNA, both for screening and monitoring purposes. In this paper, we summarize the features, benefits and limitations of HCVAg testing and provide an updated compendium of the evidences on its clinical utility and on the indications for use.
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Affiliation(s)
- Claudio Galli
- Associate Director, Medical Scientific Liaison Europe, Abbott Diagnostics, Viale Giorgio Ribotta 9, 00144 Rome, Italy
| | - Paul Julicher
- International Health Economics and Outcomes Research, Medical Affairs, Abbott Diagnostics, Wiesbaden, Germany
| | - Mario Plebani
- Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy
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21
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Pleshakova TO, Kaysheva AL, Shumov ID, Ziborov VS, Bayzyanova JM, Konev VA, Uchaikin VF, Archakov AI, Ivanov YD. Detection of Hepatitis C Virus Core Protein in Serum Using Aptamer-Functionalized AFM Chips. MICROMACHINES 2019; 10:E129. [PMID: 30781415 PMCID: PMC6413090 DOI: 10.3390/mi10020129] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Revised: 02/08/2019] [Accepted: 02/11/2019] [Indexed: 12/24/2022]
Abstract
In the present study, we demonstrate atomic force microscopy (AFM)-based detection of hepatitis C virus (HCV) particles in serum samples using a chip with aptamer-functionalized surface (apta-based AFM chip). The target particles, containing core antigen of HCV (HCVcoreAg protein), were biospecifically captured onto the chip surface from 1 mL of test solution containing 10 µL of serum collected from a hepatitis C patient. The registration of aptamer/antigen complexes on the chip surface was performed by AFM. The aptamers used in the present study were initially developed for therapeutic purposes; herein, these aptamers have been successfully utilized as probe molecules for HCVcoreAg detection in the presence of a complex protein matrix (human serum). The results obtained herein can be used for the development of detection systems that employ affine enrichment for protein detection.
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Affiliation(s)
| | | | - Ivan D Shumov
- Institute of Biomedical Chemistry, Moscow 119121, Russia.
| | - Vadim S Ziborov
- Institute of Biomedical Chemistry, Moscow 119121, Russia.
- Joint Institute for High Temperatures of Russian Academy of Sciences, Moscow 125412, Russia.
| | - Jana M Bayzyanova
- Pirogov Russian National Research Medical University (RNRMU), Moscow 117997, Russia.
| | - Vladimir A Konev
- Pirogov Russian National Research Medical University (RNRMU), Moscow 117997, Russia.
| | - Vasiliy F Uchaikin
- Pirogov Russian National Research Medical University (RNRMU), Moscow 117997, Russia.
| | | | - Yuri D Ivanov
- Institute of Biomedical Chemistry, Moscow 119121, Russia.
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22
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Lamoury FM, Hajarizadeh B, Soker A, Martinez D, Quek C, Cunningham P, Catlett B, Cloherty G, Marks P, Amin J, Grebely J, Dore GJ, Applegate TL. Evaluation of a Hepatitis C Virus Core Antigen Assay in Plasma and Dried Blood Spot Samples. J Mol Diagn 2018; 20:621-627. [DOI: 10.1016/j.jmoldx.2018.05.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Revised: 04/19/2018] [Accepted: 05/07/2018] [Indexed: 01/20/2023] Open
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23
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Xiang Y, Lai XF, Chen P, Yang Y. The correlation of HCV RNA and HCV core antigen in different genotypes of HCV. J Clin Lab Anal 2018; 33:e22632. [PMID: 30069909 PMCID: PMC6430366 DOI: 10.1002/jcla.22632] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 06/29/2018] [Accepted: 07/05/2018] [Indexed: 12/23/2022] Open
Abstract
Background To analyze the correlation of HCV RNA and HCV core antigen (HCV cAg) in different genotypes of HCV. Methods One hundred and six patients who were diagnosed with HCV infection by HCV RNA test were included in the study. HCV genotypes were detected by PCR fluorescent probe. Detected HCV cAg's expression in serum quantitatively and qualitatively with chemiluminescent micro‐particle immuno assay (CMIA) and enzyme‐linked immunosorbent assay (ELISA), respectively, and compared positive rates. Analyzed the correlation of HCV RNA and HCV cAg in different genotypes. Results Distribution of HCV genotypes in 106 HCV infected patients were as follows: 1b genotype 46 (43.4%); 2a genotype 7 (6.6%); 3a genotype 18 (17.0%); 3b genotype 3 (2.8%); 6a genotype 9 (8.5%); 1b/3b mixed type 13 (12.3%); and unidentified type 10 (9.4%). Positive rates of HCV cAg detected by CMIA and ELISA were 100% and 56%, respectively, with statistical significance (χ2 = 60.38, P = 0.000). HCV cAg in 1b genotype group was higher than that in 3b and 1b/3b genotype groups, with statistical significance (U = 3.0, P = 0.006, U = 165, P = 0.014). HCV RNA and HCV cAg in genotype 1b demonstrated a positive correlation (r = 0.894, P = 0.04). Conclusion Major genetic subtype of HCV genotype was 1b. Compared with ELISA, detection of HCV cAg by CMIA increased the positive rate and facilitated early diagnosis and treatment of HCV‐infected patients. With the increase in HCV RNA load and the expression of HCV cAg, HCV cAg could be an early indicator for the diagnosis of HCV infection in 1b genotype.
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Affiliation(s)
- Yu Xiang
- Department of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiao-Fei Lai
- Department of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Pu Chen
- Department of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yang Yang
- Department of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Benito R, Arribas J, Algarate S, Cebollada R, Gude MJ. Hepatitis C virus core antigen for screening organ donors and recipients. Diagn Microbiol Infect Dis 2018; 91:126-129. [PMID: 29477273 DOI: 10.1016/j.diagmicrobio.2018.01.021] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 01/25/2018] [Accepted: 01/28/2018] [Indexed: 02/07/2023]
Abstract
Organ donors and recipients are routinely screened for hepatitis C virus (HCV) infection, typically via anti-HCV detection. We analyze the utility of an alternative HCV core antigen (HCV-Ag) quantification system, the ARCHITECT HCV Ag Assay, in this setting. We simultaneously tested 315 samples from potential organ donors and recipients using two chemiluminescent microparticle immunoassays: ARCHITECT Anti-HCV and HCV Ag (Abbott, Germany). HCV-Ag was detected in 81 of the serum samples (25.71%) and anti-HCV in 87 (27.62%). Seventy-five of the HCV-Ag-positive samples were positive for anti-HCV (92.59%). Overall concordance between the two assays was 94.29%. Of the six HCV-Ag-positive/anti-HCV-negative patients, five had HCV-Ag values <32 fmol/L, and the sixth had a concentration of 477.50 fmol/L (viral load, 137,000 IU/mL). The HCV AG Assay detects HCV infections missed by the Anti-HCV Assay. Both markers should be used to screen for HCV infection in potential organ donors and recipients.
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Affiliation(s)
- Rafael Benito
- Department of Microbiology, University of Zaragoza, Pedro Cerbuna, 12, 50009, Zaragoza, Spain; Service of Microbiology, Hospital Clínico Universitario Lozano Blesa, Pedro Cerbuna, 12, 50009, Zaragoza, Spain.
| | - Jorge Arribas
- Service of Microbiology, Hospital Clínico Universitario Lozano Blesa, San Juan Bosco, 15, 50009, Zaragoza, Spain
| | - Sonia Algarate
- Department of Microbiology, University of Zaragoza, Pedro Cerbuna, 12, 50009, Zaragoza, Spain; Service of Microbiology, Hospital Clínico Universitario Lozano Blesa, Pedro Cerbuna, 12, 50009, Zaragoza, Spain
| | - Rocío Cebollada
- Service of Microbiology, Hospital Clínico Universitario Lozano Blesa, San Juan Bosco, 15, 50009, Zaragoza, Spain
| | - M José Gude
- Service of Microbiology, Hospital Clínico Universitario Lozano Blesa, San Juan Bosco, 15, 50009, Zaragoza, Spain
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Jülicher P, Galli C. Identifying cost-effective screening algorithms for active hepatitis C virus infections in a high prevalence setting. J Med Econ 2018; 21:1-10. [PMID: 28881157 DOI: 10.1080/13696998.2017.1369983] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVE To evaluate the cost-effectiveness of different screening patterns for active chronic hepatitis C virus (HCV) infections utilizing the hepatitis C core antigen test compared to standard care in the context of a general screening program in a high-prevalence country. METHODS This study developed a decision analytic model to estimate the cost-effectiveness of four screening algorithms for the detection of active HCV infections among asymptomatic individuals with an unknown HCV status in a context of high (>5%) HCV prevalence. Three algorithms started with a serological test for antibodies (AB) followed by a nucleic acid test for HCV-RNA (RNA), the HCVAg (AG) assay, or both. An additional single marker screening strategy with AG was added to the analysis. By the example of the Republic of Georgia, strategies were compared in terms of total costs for screening and diagnosis of an active infection from a health system perspective. RESULTS Replacing RNA with AG for confirmation of positive AB identified fewer active infections (-110 per 100,000 screened subjects) at significantly reduced total costs (-$2.74 per screened) and costs per diagnosed infection (-$44). Adding a subsequent RNA confirmatory test on AG negative results captured at least the same rate compared to the standard (AB followed by RNA) at still reduced costs (-$1.16 per subject screened, -$22 per case detected). Utilizing AG as the frontline test revealed the highest detection rate (97.9%) at the highest costs (+$3.80 per subject, +$323 per case detected vs standard). CONCLUSION A combined pattern of HCV AB screening followed by sequential confirmation with AG and RNA on AG negatives would provide equal or better diagnostic performance at lower cost over a broad range of scenarios. Potential long-term consequences of screening strategies to patients and society have to be considered, since the latency period for HCV to develop into severe liver disease is long.
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Affiliation(s)
- Paul Jülicher
- a International Health Economics and Outcomes Research, Medical Affairs, Abbott Diagnostics , Wiesbaden , Germany
| | - Claudio Galli
- b Medical Scientific Liaison Europe, Abbott Diagnostics , Roma , Italy
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HCV antigen instead of RNA testing to diagnose acute HCV in patients treated in the Dutch Acute HCV in HIV Study. J Int AIDS Soc 2017; 20:21621. [PMID: 28692208 PMCID: PMC5515013 DOI: 10.7448/ias.20.1.21621] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION Affordable and sensitive screening methods for acute hepatitis C (HCV) are necessary to successfully intervene in the current HCV epidemic among HIV-positive men having sex with men. HCV core antigen (Ag) testing has been proven effective in diagnosing chronic HCV-infected patients at low costs. We studied the characteristics of HCV Ag testing in acute HCV-infected HIV-positive patients. Methods Plasma samples were selected from acutely HCV genotype 1-infected patients treated with peginterferon, ribavirin and boceprevir in the Dutch Acute HCV in HIV Study. The control group consisted of HIV-positive patients with a newly raised alanine aminotransferase (ALT) (>41 U/L) in whom HCV RNA was undetectable and who were tested for HCV Ag. Spearman correlation coefficient between HCV RNA and HCV Ag was calculated together with the sensitivity and specificity of HCV Ag testing at acute HCV diagnosis. RESULTS AND DISCUSSION Upon acute HCV diagnosis, HCV Ag was identified in 39 out of 44 patients with detectable HCV RNA levels. In all 23 control patients without detectable HCV RNA in plasma, HCV Ag was undetectable as well. This resulted in a sensitivity and specificity of HCV Ag of respectively 89% (95% CI 75-96) and 100% (95% CI 82-100). The correlation between HCV Ag and HCV RNA was 0.97 (p < 0.001) upon diagnosis. CONCLUSION The data presented in this study suggest that HCV Ag testing is a sensitive and specific method that can be used in diagnosing AHCV in HIV-infected patients.
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Eng FJ, El-Shamy A, Doyle EH, Klepper A, Muerhoff AS, Branch AD. Newly discovered hepatitis C virus minicores circulate in human blood. Hepatol Commun 2017; 2:21-28. [PMID: 29404509 PMCID: PMC5776872 DOI: 10.1002/hep4.1125] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Revised: 10/03/2017] [Accepted: 10/05/2017] [Indexed: 12/18/2022] Open
Abstract
Hepatitis C virus (HCV) is one of the most prevalent causes of chronic blood‐borne infections worldwide. Despite developments of highly effective treatments, most infected individuals are unaware of their infection. Approximately 75% of infections are in low‐ and middle‐income countries; therefore, continuing research in HCV molecular virology and the development of vaccines and affordable diagnostics is required to reduce the global burden. Various intracellular forms of the HCV nucleocapsid (core) protein are produced in cell culture; these comprise the conventional p21 core and the newly discovered shorter isoforms (minicores). Minicores lack the N‐terminus of p21 core. This study was conducted to determine if minicores are secreted in cell culture and more importantly if they circulate in the blood of individuals infected with HCV. We also developed a new monoclonal antibody that detects minicores targeting a C‐terminal region common to p21 core and minicores. Direct evidence of minicores requires western blot analysis to distinguish the detection of p21 core from minicores. However, the sensitivity for western blot detection of HCV proteins from blood is nil without their prior purification/enrichment from blood. Therefore, we developed a purification method based on a heparin/Mn+2 precipitation of apolipoprotein B‐containing lipoproteins because HCV is thought to circulate as a hybrid lipoviral particle. Minicores are secreted in culture when cells are grown in the presence of human serum. The heparin/Mn+2 precipitate from HCV‐infected cell culture supernatants and from the blood of 4 patients with high‐titer genotype‐1 HCV contained minicores. Conclusion: Minicores are major newly discovered HCV proteins that are secreted and circulate in blood during natural infections. Minicore proteins have translational potential as targets in diagnostic assays and in vaccine development. (Hepatology Communications 2018;2:21–28)
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Affiliation(s)
- Francis J Eng
- Division of Liver Diseases, Department of Medicine Icahn School of Medicine at Mount Sinai New York NY
| | - Ahmed El-Shamy
- Division of Liver Diseases, Department of Medicine Icahn School of Medicine at Mount Sinai New York NY
| | - Erin H Doyle
- Division of Liver Diseases, Department of Medicine Icahn School of Medicine at Mount Sinai New York NY
| | - Arielle Klepper
- Division of Liver Diseases, Department of Medicine Icahn School of Medicine at Mount Sinai New York NY
| | - A Scott Muerhoff
- Abbott Diagnostics, Biologics Discovery and Design Abbott Laboratories Abbott Park IL
| | - Andrea D Branch
- Division of Liver Diseases, Department of Medicine Icahn School of Medicine at Mount Sinai New York NY
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Wasitthankasem R, Vichaiwattana P, Auphimai C, Siripon N, Klinfueng S, Tangkijvanich P, Vongpunsawad S, Poovorawan Y. HCV core antigen is an alternative marker to HCV RNA for evaluating active HCV infection: implications for improved diagnostic option in an era of affordable DAAs. PeerJ 2017; 5:e4008. [PMID: 29134150 PMCID: PMC5678506 DOI: 10.7717/peerj.4008] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Accepted: 10/18/2017] [Indexed: 12/18/2022] Open
Abstract
The core antigen of the hepatitis C virus (HCV Ag) presents an alternative marker to HCV RNA when screening patients for HCV viremia. This study sought to evaluate the utility of HCV Ag as a marker to assess active HCV infection in individuals residing in an HCV-endemic area. From 298 HCV-seropositive individuals evaluated for the presence of anti-HCV antibody, HCV Ag and HCV RNA, anti-HCV antibody was detected in 252 individuals (signal-to-cutoff ratios ≥5), HCV RNA was detected in 222 individuals (88%), and HCV Ag was reactive (≥3 fmol/L) in 220 individuals (87%). HCV genotype 1, 3, and 6 were identified. HCV Ag significantly correlated with HCV RNA irrespective of HCV genotype and/or HBV co-infection (log HCV RNA = 2.67 + 0.95 [log HCV Ag], R2 = 0.890, p < 0.001). To predict HCV viremia (HCV Ag ≥ 3 fmol/L), the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 99%, 99%, 100%, 100% and 97%, respectively. We concluded that HCV Ag was a good surrogate marker for HCV RNA and could be used to diagnose active HCV infection in a resource-limited setting. As a result, a cost-effective strategy for screening and identifying active HCV carriers using HCV Ag detection would enable more patients access to efficacious and increasingly affordable direct-acting antivirals (DAAs) for the treatment of HCV infection.
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Affiliation(s)
- Rujipat Wasitthankasem
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Preeyaporn Vichaiwattana
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Chompoonut Auphimai
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Nipaporn Siripon
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sirapa Klinfueng
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Pisit Tangkijvanich
- Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Thailand
| | - Sompong Vongpunsawad
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Pleshakova TO, Kaysheva AL, Bayzyanova JМ, Anashkina АS, Uchaikin VF, Ziborov VS, Konev VA, Archakov AI, Ivanov YD. The detection of hepatitis c virus core antigen using afm chips with immobolized aptamers. J Virol Methods 2017; 251:99-105. [PMID: 29042217 DOI: 10.1016/j.jviromet.2017.10.015] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Revised: 10/09/2017] [Accepted: 10/14/2017] [Indexed: 10/18/2022]
Abstract
In the present study, the possibility of hepatitis C virus core antigen (HCVcoreAg) detection in buffer solution, using atomic force microscope chip (AFM-chip) with immobilized aptamers, has been demonstrated. The target protein was detected in 1mL of solution at concentrations from 10-10М to 10-13М. The registration of aptamer/antigen complexes on the chip surface was carried out by atomic force microscopy (AFM). The further mass-spectrometric (MS) identification of AFM-registered objects on the chip surface allowed reliable identification of HCVcoreAg target protein in the complexes. Aptamers, which were designed for therapeutic purposes, have been shown to be effective in HCVcoreAg detection as probe molecules.
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Affiliation(s)
- T O Pleshakova
- Institute of Biomedical Chemistry, Pogodinskaya St. 10, Moscow, 119121, Russia
| | - A L Kaysheva
- Institute of Biomedical Chemistry, Pogodinskaya St. 10, Moscow, 119121, Russia.
| | - J М Bayzyanova
- Institute of Biomedical Chemistry, Pogodinskaya St. 10, Moscow, 119121, Russia
| | - А S Anashkina
- Institute of Biomedical Chemistry, Pogodinskaya St. 10, Moscow, 119121, Russia
| | - V F Uchaikin
- Institute of Biomedical Chemistry, Pogodinskaya St. 10, Moscow, 119121, Russia
| | - V S Ziborov
- Joint Institute for High Temperatures RAS, Izhorskaya St. 13/19, Moscow, 125412, Russia
| | - V A Konev
- Pirogov Russian National Research Medical University (RNRMU), Ostrovitianov str. 1, Moscow, 117997, Russia
| | - A I Archakov
- Institute of Biomedical Chemistry, Pogodinskaya St. 10, Moscow, 119121, Russia
| | - Y D Ivanov
- Institute of Biomedical Chemistry, Pogodinskaya St. 10, Moscow, 119121, Russia
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30
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Talal AH, Chen Y, Zeremski M, Zavala R, Sylvester C, Kuhns M, Brown LS, Markatou M, Cloherty GA. Hepatitis C virus core antigen: A potential alternative to HCV RNA testing among persons with substance use disorders. J Subst Abuse Treat 2017; 78:37-42. [PMID: 28554601 DOI: 10.1016/j.jsat.2017.04.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Revised: 04/12/2017] [Accepted: 04/17/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND The hepatitis C virus (HCV) core antigen (HCVcAg) may be an alternative diagnostic method to HCV RNA especially in populations such as substance users, the homeless or in resource-limited settings. AIMS To evaluate performance of HCVcAg test in patients with opioid use disorder (OUD) on methadone in order to document its performance characteristics in the target population and to ensure that its specificity remains consistent across different populations. METHODS HCVcAg levels from 109 methadone-maintained patients were compared to HCV RNA levels. RESULTS Mean age was 53.8±7.8years, 59.6% were male, 68.8% African American, and 44% HCV-infected. HCVcAg was detectable in 47 of 48 HCV-infected, and undetectable in all HCV RNA negative patients. The HCVcAg assay had sensitivity of 97.9% and specificity of 100%. Correlation with HCV RNA levels was excellent (r=0.88, 95% CI 0.76; 0.95, p<0.01). CONCLUSION HCVcAg has excellent performance for the diagnosis of HCV infection in patients with OUD on methadone.
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Affiliation(s)
- Andrew H Talal
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY, USA; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY, USA; START Treatment & Recovery Centers, Brooklyn, NY, USA.
| | - Yang Chen
- Department of Biostatistics, University at Buffalo, State University of New York, Buffalo, NY, USA
| | - Marija Zeremski
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY, USA.
| | | | | | - Mary Kuhns
- Abbott Diagnostics, Inc, Abbott Park, IL, USA
| | | | - Marianthi Markatou
- Department of Biostatistics, University at Buffalo, State University of New York, Buffalo, NY, USA
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31
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Khan H, Hill A, Main J, Brown A, Cooke G. Can Hepatitis C Virus Antigen Testing Replace Ribonucleic Acid Polymearse Chain Reaction Analysis for Detecting Hepatitis C Virus? A Systematic Review. Open Forum Infect Dis 2017; 4:ofw252. [PMID: 28567430 PMCID: PMC5445222 DOI: 10.1093/ofid/ofw252] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2016] [Accepted: 05/11/2017] [Indexed: 12/16/2022] Open
Abstract
The complexity and cost of current diagnostics for hepatitis C virus (HCV) may act as a prevention to the scale-up of treatment in the developing world. Currently, ribonucleic acid (RNA)-polymerase chain reaction tests are the gold standard. However, there is potential for the use of simpler and cheaper antigen tests to confirm HCV infection in different clinical settings. We evaluated the sensitivity and specificity of antigen assays. This was compared with the reference-standard RNA assays. A subanalysis also assessed Architect core antigen test, which is the only commercially available antigen test on the market. In 24 datasets, evaluating HCV-antigen assays in 8136 samples, the percentage of HCV-antigen positive, HCV-RNA negative was 0.57%. The percentage HCV-antigen negative, HCV-RNA positive was 3.52%. There is strong evidence that antigen detection performs as well as RNA-based assays for HCV management. The use of antigen tests could improve access to HCV care in underresourced healthcare settings.
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Affiliation(s)
- Harun Khan
- Faculty of Medicine, Imperial College London, United Kingdom
| | - Andrew Hill
- Department of Pharmacology and Therapeutics, Liverpool University, United Kingdom
| | - Janice Main
- Faculty of Medicine, Imperial College London, United Kingdom
| | - Ashley Brown
- Faculty of Medicine, Imperial College London, United Kingdom
| | - Graham Cooke
- Faculty of Medicine, Imperial College London, United Kingdom
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32
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Rockstroh JK, Feld JJ, Chevaliez S, Cheng K, Wedemeyer H, Sarrazin C, Maasoumy B, Herman C, Hackett J, Cohen DE, Dawson GJ, Cloherty G, Pawlotsky JM. HCV core antigen as an alternate test to HCV RNA for assessment of virologic responses to all-oral, interferon-free treatment in HCV genotype 1 infected patients. J Virol Methods 2017; 245:14-18. [PMID: 28359920 DOI: 10.1016/j.jviromet.2017.03.002] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Revised: 03/03/2017] [Accepted: 03/04/2017] [Indexed: 12/12/2022]
Abstract
In light of the advances in HCV therapy, simplification of diagnosis confirmation, pre- treatment diagnostic workup and treatment monitoring is required to ensure broad access to interferon-free therapies. HCV core antigen (HCV cAg) testing is rapid, giving results in approximately 60min, and less expensive than HCV RNA methods. While extensive data on the analytical performance of HCV cAg relative to RNA or comparisons in longitudinal studies of patients on interferon based (response guided) therapy there is very limited data on the relative performance of HCV cAg in diagnosis and monitoring patients receiving all-oral interferon free regimens. Furthermore, there is no data in the literature that describes the specificity of HCV cAg in patients with resolved HCV infection i.e. anti-HCV positive/HCV RNA negative. In this study a total of 1201 plasma samples from the 411 HCV genotype 1 subjects with a HCV RNA viral load >50,000IU/ml who enrolled in a clinical trial with ombitasvir, ritonavir-boosted paritaprevir and dasabuvir, with or without ribavirin were retrospectively tested in a blinded fashion with HCV cAg test and results were compared to HCV RNA levels. The specificity of the HCV cAg test was also evaluated in anti-HCV positive but HCV RNA negative samples. Overall concordance between HCV cAg and HCV RNA was 98.6% while concordance in pre-treatment samples was 99.5% (409/411; n=2 HCV RNA pos. with viral loads>3 Mill IU/ml but HCV cAg neg.) and 99.24% in post treatment week 12 samples (391/394; n=2 HCV RNA pos.<25IU/ml and n=1 HCV RNA pos. 2180IU/ml). Specificity in anti-HCV positive HCV RNA negative samples tested was 100%.
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Affiliation(s)
| | - Jordan J Feld
- Toronto Centre for Liver Disease McLaughlin-Rotman Centre for Global Health University of Toronto, Toronto, ON, Canada
| | - Stéphane Chevaliez
- National Reference Center for Viral Hepatitis B C and D Department of Virology Hôpital Henri Mondor Université Paris-Est and INSERM U955, Créteil, France
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie Hepatologie und Endokrinologie Medizinische Hochschule Hannover, Hannover, Germany
| | - Christoph Sarrazin
- Medizinische Klinik 1 Universitätsklinikum Frankfurt, Frankfurt am Main, Germany
| | - Benjamin Maasoumy
- Medizinische Klinik 1 Universitätsklinikum Frankfurt, Frankfurt am Main, Germany
| | | | | | | | | | | | - Jean-Michel Pawlotsky
- National Reference Center for Viral Hepatitis B C and D Department of Virology Hôpital Henri Mondor Université Paris-Est and INSERM U955, Créteil, France
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Çetiner S, Çetin Duran A, Kibar F, Yaman A. Performance comparison of new generation HCV core antigen test versus HCV RNA test in management of hepatitis C virus infection. Transfus Apher Sci 2017; 56:362-366. [PMID: 28342642 DOI: 10.1016/j.transci.2017.02.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2016] [Revised: 02/03/2017] [Accepted: 02/22/2017] [Indexed: 12/28/2022]
Abstract
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 103IU/mL. On the contrary, the correlation reached significance for the values higher than 103IU/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 103IU/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.
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Affiliation(s)
- Salih Çetiner
- Division of Basic Immunology, Balcali Hospital, Central Laboratory, Cukurova University, Adana, Turkey.
| | - Alev Çetin Duran
- Department of Medical Microbiology, Faculty of Medicine, Cukurova University, Adana, Turkey.
| | - Filiz Kibar
- Department of Medical Microbiology, Faculty of Medicine, Cukurova University, Adana, Turkey.
| | - Akgün Yaman
- Department of Medical Microbiology, Faculty of Medicine, Cukurova University, Adana, Turkey.
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Wang L, Chen W, Xi W, Feng J, Dang P, Ma Y, Yu Y. Utility of enzyme-linked immunosorbent assays to test core antigen in the diagnosis and antiviral therapy management of hepatitis C virus infections. J Med Virol 2017; 89:1235-1240. [PMID: 27958657 DOI: 10.1002/jmv.24754] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2016] [Revised: 12/02/2016] [Accepted: 12/05/2016] [Indexed: 12/21/2022]
Abstract
In this study, we evaluate the performance of the enzyme-linked immunosorbent assays (ELISAs) for HCV Ag detection in the diagnosis and antiviral therapy management of HCV infections. For the diagnosis of an active HCV infection, the limit of detection of HCV Ag corresponding to HCV RNA level was approximately 7300 IU/mL; the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of HCV-Ag were 88.96, 100, 100, and 91.33%, respectively. The Pearson's correlation coefficient between HCV Ag and HCV RNA was 0.891. All patients with negative HCV Ag at interferon-α2α/ribavirin therapy week 1 achieved a sustained viral response (SVR), and the PPV was 100%; whereas in patients with positive HCV Ag at therapy weeks 12, the NPV for achieving non-response (NR) was 100%. The results showed that ELISAs for HCV Ag detection could be cost effectively applied to diagnose and evaluate the response to antiviral therapy for HCV infections.
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Affiliation(s)
- Linchuan Wang
- Clinical Laboratory of the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | - Wei Chen
- Clinical Laboratory of the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | - Wen Xi
- Clinical Laboratory of the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | - Jin Feng
- Clinical Laboratory of the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | - Pei Dang
- Clinical Laboratory of the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | - Yanfen Ma
- Clinical Laboratory of the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | - Yan Yu
- Inspection Department of Hong-Hui Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
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35
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Alonso R, Pérez-García F, Ampuero D, Reigadas E, Bouza E. New direct-acting antivirals for patients with chronic HCV infection: can we monitor treatment using an HCV core antigen assay? Diagn Microbiol Infect Dis 2016; 87:243-246. [PMID: 27916546 DOI: 10.1016/j.diagmicrobio.2016.11.010] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2016] [Revised: 11/12/2016] [Accepted: 11/13/2016] [Indexed: 12/14/2022]
Abstract
We evaluated the diagnostic usefulness of an HCV core antigen (HCV-Ag) assay in HCV-infected patients undergoing treatment with direct-acting antivirals. We analyzed 103 samples from 28 patients. Compared with RT-PCR, sensitivity was 96.2% and specificity was 100%. The correlation between techniques was excellent (Pearson coefficient: 0.871). HCV-Ag proved to be useful in patients with sustained viral response and in patients who experienced treatment failures.
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Affiliation(s)
- R Alonso
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Department of Medicine, Universidad Complutense de Madrid, Spain
| | - F Pérez-García
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
| | - D Ampuero
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - E Reigadas
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Biomédica Gregorio Marañón, Madrid, Spain
| | - E Bouza
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Biomédica Gregorio Marañón, Madrid, Spain; Department of Medicine, Universidad Complutense de Madrid, Spain; CIBER Enfermedades Respiratorias (CB06/06/0058)
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Wang L, Lv H, Zhang G. Hepatitis C virus core antigen assay: an alternative method for hepatitis C diagnosis. Ann Clin Biochem 2016; 54:279-285. [PMID: 27614354 DOI: 10.1177/0004563216661218] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Background The study aimed to evaluate a fully automated chemiluminescent immunoassay and compared it with a quantitative RNA assay and anti-HCV assay to verify the utility of this automated Ag assay as an alternative method for hepatitis C diagnosis. Methods A total of 229 serum samples previously tested for anti-HCV concentrations by the Architect Anti-HCV assay, were selected for HCV RNA testing by real time RT-PCR kit (Shanghai ZJ Bio-Tec Co., Ltd) and 125 specimens were tested for HCV Ag by the Architect HCV core Antigen kit. Results The log10 HCVAg and HCV RNA concentrations were highly correlated [ r = 0.834); with HCV RNA as the comparator test, HCVAg had 100% specificity, 100% positive predictive value (PPV) and 94.8% sensitivity. We found 1 pg/mL of total HCV core Ag is equivalent to approximately 6607HCV RNA international units (IU)/mL. Receiver operator characteristic curve analysis showed that the area under the curve of HCV core Ag (0.989) was greater than HCV Ab (0.871). HCV Ag concentrations and RNA-to-Ag ratio of the groups for HCV RNA concentrations ≤105 and >105 IU/mL were both significantly different from each other ( P < 0.05). Conclusion The Architect HCV core Ag assay may be an alternative method for hepatitis C diagnosis, performed on the same analytical platform and sample as the anti-HCV assay, shortening the diagnostic window period, demonstrating good correlation with HCV RNA assay with high specificity and positive predictive value.
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Affiliation(s)
- Lijuan Wang
- Department of Clinical Laboratory, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Hong Lv
- Department of Clinical Laboratory, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Guojun Zhang
- Department of Clinical Laboratory, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
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Kim MN, Kim HS, Kim JK, Kim BK, Kim SU, Park JY, Kim DY, Ahn SH, Han KH. Clinical Utility of a New Automated Hepatitis C Virus Core Antigen Assay for Prediction of Treatment Response in Patients with Chronic Hepatitis C. J Korean Med Sci 2016; 31:1431-1437. [PMID: 27510387 PMCID: PMC4974185 DOI: 10.3346/jkms.2016.31.9.1431] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Accepted: 06/03/2016] [Indexed: 12/13/2022] Open
Abstract
Hepatitis C virus core antigen (HCV Ag) is a recently developed marker of hepatitis C virus (HCV) infection. We investigated the clinical utility of the new HCV Ag assay for prediction of treatment response in HCV infection. We analyzed serum from 92 patients with HCV infection who had been treated with pegylated interferon and ribavirin. HCV Ag levels were determined at baseline in all enrolled patients and at week 4 in 15 patients. Baseline HCV Ag levels showed good correlations with HCV RNA (r = 0.79, P < 0.001). Mean HCV Ag levels at baseline were significantly lower in patients with a sustained virologic response (SVR) than in those with a non SVR (relapse plus non responder) based on HCV RNA analysis (2.8 log₁₀fmol/L vs. 3.27 log₁₀fmol/L, P = 0.023). Monitoring of the viral kinetics by determination of HCV RNA and HCV Ag levels resulted in similarly shaped curves. Patients with undetectable HCV Ag levels at week 4 had a 92.3% probability of achieving SVR based on HCV RNA assay results. The HCV Ag assay may be used as a supplement for predicting treatment response in HCV infection, but not as an alternative to the HCV RNA assay.
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Affiliation(s)
- Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Hyon Suk Kim
- Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Ja Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Kwang Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
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Chevaliez S, Feld J, Cheng K, Wedemeyer H, Sarrazin C, Maasoumy B, Herman C, Hackett J, Cohen D, Dawson G, Pawlotsky JM, Cloherty G. Clinical utility of HCV core antigen detection and quantification in the diagnosis and management of patients with chronic hepatitis C receiving an all-oral, interferon-free regimen. Antivir Ther 2016; 23:211-217. [DOI: 10.3851/imp3042] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/04/2016] [Indexed: 10/21/2022]
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Garbuglia AR, Lionetti R, Lapa D, Taibi C, Visco-Comandini U, Montalbano M, D'Offizi G, Castiglione F, Capobianchi MR, Paci P. The clinical significance of HCV core antigen detection during Telaprevir/Peg-Interferon/Ribavirin therapy in patients with HCV 1 genotype infection. J Clin Virol 2015. [PMID: 26209382 DOI: 10.1016/j.jcv.2015.06.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Direct-acting antiviral drugs (DAA) regimen improve the SVR rate. However, adverse effects often lead to therapy interruption. This underlines the importance to find some predictive parameters of response in order to consider the possibility of a shorter time of antiviral treatment in the appearance of adverse effects without affecting the success of the therapy. OBJECTIVES We aimed to examine the HCVAg kinetics in the early phase of treatment and its predictive value of SVR in patients undergoing TPV/Peg-IFN/RBV treatment. STUDY DESIGN Twenty-three patients infected by HCV genotype 1 (1a n=11; 1b n=12) were included in this prospective study. RESULTS At baseline the median Log of HCVAg concentration in RVR and EVR patients were 3.15 fmol/L and 3.45 fmol/L, respectively with no significant differences. The baseline median HCV-RNA to HCVAg ratio was 233.77, this ratio was significantly lower when measured on day 1 (27.52) and on day 6 (24.84) (p<0.001). The two-tailed Fisher's exact test indicated that the SVR response is statistically significantly different in patients with detected HCVAg at week1 compared to patients with no detectable HCVAg (p=0.05). The sensitivity, specificity, and negative and positive predictive values (NPV, PPV) were 53.8, 87.5, 53.8 and 87.5%, respectively. The area under the ROC curve was 0.71 at day T6, the best cut-off of 3 fmol/L when evaluated with the HCVAg plasma concentration at day T6. CONCLUSION Undetectable HCVAg in the early phase of TPV/Peg-IFN/RBV treatment could represent an important parameter for predicting SVR.
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Affiliation(s)
- Anna Rosa Garbuglia
- Laboratory of Virology, "Lazzaro Spallanzani" National Institute for Infectious Diseases, Rome, Italy.
| | - Raffaella Lionetti
- Clinical Department, "Lazzaro Spallanzani" National Institute for Infectious Diseases, Rome, Italy
| | - Daniele Lapa
- Laboratory of Virology, "Lazzaro Spallanzani" National Institute for Infectious Diseases, Rome, Italy
| | - Chiara Taibi
- Clinical Department, "Lazzaro Spallanzani" National Institute for Infectious Diseases, Rome, Italy
| | - Ubaldo Visco-Comandini
- Clinical Department, "Lazzaro Spallanzani" National Institute for Infectious Diseases, Rome, Italy
| | - Marzia Montalbano
- Clinical Department, "Lazzaro Spallanzani" National Institute for Infectious Diseases, Rome, Italy
| | - Gianpiero D'Offizi
- Clinical Department, "Lazzaro Spallanzani" National Institute for Infectious Diseases, Rome, Italy
| | | | - Maria Rosaria Capobianchi
- Laboratory of Virology, "Lazzaro Spallanzani" National Institute for Infectious Diseases, Rome, Italy
| | - Paola Paci
- Istituto di Analisi dei Sistemi ed Informatica "Antonio Ruberti" (IASI) - CNR, Rome, Italy
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Laperche S, Nübling CM, Stramer SL, Brojer E, Grabarczyk P, Yoshizawa H, Kalibatas V, El Elkyabi M, Moftah F, Girault A, van Drimmelen H, Busch MP, Lelie N. Sensitivity of hepatitis C virus core antigen and antibody combination assays in a global panel of window period samples. Transfusion 2015; 55:2489-98. [PMID: 26013970 DOI: 10.1111/trf.13179] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2015] [Revised: 04/08/2015] [Accepted: 04/08/2015] [Indexed: 12/30/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) antigen and antibody combination assays have been launched as a cost-effective alternative to nucleic acid testing (NAT) for reducing the antibody-negative window period (WP). Later, a HCV antigen chemiluminescence immunoassay (CLIA) became available. STUDY DESIGN AND METHODS A panel composed of 337 HCV NAT-yield samples that were characterized for viral load (VL) and genotype was used to compare the sensitivity of two combination enzyme-linked immunosorbent assays (Monolisa, Bio-Rad; and Murex, formerly Abbott) and a HCV antigen CLIA (Abbott). Analytic sensitivity was compared with HCV RNA detection using Ultrio (Grifols) by testing serial dilutions of 10 genotype (gt)1 to gt4 samples. RESULTS HCV antigen CLIA detected 92.4% of samples, whereas Monolisa and Murex detected 38.3 and 47.5%, respectively. In the HCV RNA VL range of 10(5) to 10(7) IU/mL, Monolisa and Murex detected 38% to 56% of gt1, 85% to 78% of gt2, and 21% to 37% of gt3. The overall geometric mean 50% limit of detection (range) of Ultrio on gt1 to gt4 dilution series was 3.5 (1.2-7.7) copies/mL, compared to 3.3 × 10(6) (4.4 × 10(5) -2.7 × 10(7) ), 3.4 × 10(6) (2.2 × 10(5) -4.2 × 10(7) ), and 2728 (415-7243) copies/mL for Monolisa, Murex, and HCV antigen CLIA, respectively. CONCLUSION Analytical sensitivity of NAT was on average 1 million- and 780-fold higher than combination assays and HCV antigen CLIA, respectively. Relative sensitivities of combination assays differed for genotypes with Murex being more sensitive for gt1 and gt3 and Monolisa more sensitive for gt2. Although being less sensitive than NAT, combination assays could be considered in resource-limited settings since they detect 38% to 47% of seronegative WP donations.
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Affiliation(s)
- Syria Laperche
- Institut National de la Transfusion Sanguine (INTS), Département d'Études des Agents Transmissibles par le Sang, Centre National de Reference pour les Hepatites B et C en Transfusion, F-75015 Paris, France
| | - C Micha Nübling
- Section of Molecular Virology, Paul Ehrlich Institute, Langen, Germany
| | - Susan L Stramer
- Scientific Support Office, American Red Cross, Gaithersburg, Maryland
| | - Ewa Brojer
- Institute of Haematology and Transfusion Medicine, Warsaw, Poland
| | - Piotr Grabarczyk
- Institute of Haematology and Transfusion Medicine, Warsaw, Poland
| | - Hiroshi Yoshizawa
- Study Group of NAT Standardization under the Ministry of Health, Labor and Welfare of Japan (2001-2003), Tokyo, Japan
| | | | | | | | - Annie Girault
- Institut National de la Transfusion Sanguine (INTS), Département d'Études des Agents Transmissibles par le Sang, Centre National de Reference pour les Hepatites B et C en Transfusion, F-75015 Paris, France
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Hepatitis C Virus Core Mutations Associated with False-Negative Serological Results for Genotype 3a Core Antigen. J Clin Microbiol 2015; 53:2697-700. [PMID: 25994168 PMCID: PMC4508445 DOI: 10.1128/jcm.01062-15] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2015] [Accepted: 05/11/2015] [Indexed: 12/13/2022] Open
Abstract
Genetic characterization of the genotype 3a (GT3a) hepatitis C virus (HCV) core region from HCV core antigen (HCVcAg)-negative/RNA-positive cases and HCVcAg-positive/RNA-positive controls identified significant associations between the substitutions A48T and T49A/P and failure to detect HCVcAg (P < 0.05). Polymorphisms at residues 48 and 49 in the core protein are present across all major epidemic and endemic GTs. These findings have implications for HCV diagnosis, particularly in low-income regions in which GT3a HCV is endemic.
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Mixson-Hayden T, Dawson GJ, Teshale E, Le T, Cheng K, Drobeniuc J, Ward J, Kamili S. Performance of ARCHITECT HCV core antigen test with specimens from US plasma donors and injecting drug users. J Clin Virol 2015; 66:15-8. [DOI: 10.1016/j.jcv.2015.02.015] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Revised: 02/18/2015] [Accepted: 02/22/2015] [Indexed: 02/08/2023]
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Thong VD, Akkarathamrongsin S, Avihingsanon A, Theamboonlers A, Poovorawan Y, Tangkijvanich P. The correlation between hepatitis C core antigen and hepatitis C virus RNA levels with respect to human immunodeficiency virus status, hepatitis C virus genotype and interferon-lambda-4 polymorphism. Intervirology 2015; 58:73-79. [PMID: 25677196 DOI: 10.1159/000370070] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2014] [Accepted: 11/23/2014] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVES Serum hepatitis C virus (HCV) core antigen (HCVcAg) concentrations correlate with HCV RNA levels in HCV monoinfected patients. Data in HCV/HIV coinfected patients are still limited. We aim to compare the use of HCVcAg measurement with respect to HIV status, HCV genotypes, interferon-lambda-4 (IFNL4) polymorphism and clinical parameters. METHODS We analyzed an untreated cohort of 104 patients with HCV monoinfection and 85 patients with HCV/HIV coinfection. Serum HCVcAg was measured by a commercial chemiluminescent microparticle immunoassay. The presence of IFNL4 polymorphism ss469415590 was identified by real-time PCR. RESULTS log10 HCVcAg levels were significantly correlated with corresponding log10 HCV RNA levels (r = 0.889, p < 0.001), but not with ALT levels and liver stiffness. The correlation between HCV RNA and HCVcAg was particularly high in coinfected patients and those with high viremia. Mean log10 HCVcAg concentration was significantly higher in coinfected patients than in monoinfected patients. Patients harboring the TT/TT genotype of ss469415590 had significantly higher levels of log10 HCVcAg than those with the non-TT/TT genotype. HCVcAg levels were similar across HCV genotypes. CONCLUSIONS HCVcAg concentrations had an excellent correlation with HCV RNA levels, particularly in HCV/HIV-coinfected individuals and might be associated with IFNL4 polymorphism. HCVcAg testing could be used as an alternative to HCV RNA assays in resource-limited settings.
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Affiliation(s)
- Vo Duy Thong
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Firdaus R, Saha K, Biswas A, Sadhukhan PC. Current molecular methods for the detection of hepatitis C virus in high risk group population: A systematic review. World J Virol 2015; 4:25-32. [PMID: 25674515 PMCID: PMC4308525 DOI: 10.5501/wjv.v4.i1.25] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Revised: 11/20/2014] [Accepted: 12/31/2014] [Indexed: 02/05/2023] Open
Abstract
Hepatitis C virus (HCV) is an emerging infection worldwide and the numbers of persons infected are increasing every year. Poor blood transfusion methods along with unsafe injection practices are potential sources for the rapid spread of infection. Early detection of HCV is the need of the hour especially in high risk group population as these individuals are severely immunocompromised. Enzyme Immunoassays are the most common detection techniques but they provide no evidence of active viremia or identification of infected individuals in the antibody-negative phase and their efficacy is limited in individuals within high risk group population. Molecular virological techniques have an important role in detecting active infection with utmost specificity and sensitivity. Technologies for assessment of HCV antibody and RNA levels have improved remarkably, as well as our understanding of how to best use these tests in patient management. This review aims to give an overview of the different serological and molecular methods employed in detecting HCV infection used nowadays. Additionally, the review gives an insight in the new molecular techniques that are being developed to improve the detection techniques particularly in High Risk Group population who are severely immunocompromised.
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Evaluation of a hepatitis C virus (HCV) antigen assay for routine HCV screening among men who have sex with men infected with HIV. J Virol Methods 2014; 213:147-50. [PMID: 25528203 DOI: 10.1016/j.jviromet.2014.11.026] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2014] [Revised: 11/19/2014] [Accepted: 11/25/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND For detection of early HCV infection and reinfection, commercial HCV-RNA tests are available. However, these tests are relatively time-consuming and expensive. A commercially available test that may supplement current screening methods, targets the HCV core protein. METHODS During five waves of anonymous surveys at the Amsterdam STI clinic between 2009-2012, all HIV-infected MSM (N=439) were tested for HCV-antibodies (AxSYM HCV 3.0, Abbott), and HCV-RNA (TMA Versant, Siemens). To evaluate the potential value of the ARCHITECT HCV antigen (HCV-Ag) assay (Abbott), all HCV-RNA-positive sera (N=31) were tested with this assay, as well as two HIV-infected HCV-RNA-negative controls. In addition, all included samples were tested for alanine aminotransferase (ALT). RESULTS Among 439 HIV-infected MSM, 31 (7.1%) tested positive for HCV-RNA; the HCV-Ag assay showed concordant positive results for 31/31 (100%). A substantial number of MSM, i.e., 5/31 (16.1%), had detectable HCV-RNA but were HCV-seronegative at the time of screening and were presumed to have been recently infected. Concordant HCV-RNA-negative results were obtained in 57/60 control-samples. Specificity was 95.0% (95% CI: 86.1-99.0). The detection limit was between 3.0 and 3.7 Log10 IU/mL, irrespective of HCV genotype/subtype. ALT concentrations were elevated (i.e.,>40 U/L) in 9/31 (29.0%) HCV-RNA positive MSM, including 1/5 (20.0%) MSM with recent HCV-infection. CONCLUSIONS The HCV-Ag assay proved a valuable screening tool for detection of active HCV infection among HIV-infected MSM with and without anti-HCV. Adding ALT to current screening methods would improve case finding marginally. We therefore recommend implementation of routine HCV-Ag screening for populations at risk for HCV-(re)infection.
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Long L, Shen T, Gao J, Duan Z, Liang H, Lu F. Effectiveness of HCV core antigen and RNA quantification in HCV-infected and HCV/HIV-1-coinfected patients. BMC Infect Dis 2014; 14:577. [PMID: 25371245 PMCID: PMC4225041 DOI: 10.1186/s12879-014-0577-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Accepted: 10/22/2014] [Indexed: 12/15/2022] Open
Abstract
Background The measurement of hepatitis C virus core antigen (HCV-coreAg) has been shown to be an indicator of active HCV infection. The aim of the present study was 1) to investigate the stability and effectiveness of HCV-coreAg and HCV-RNA quantification in HCV infection with or without HIV-1 coinfection, 2) to explore the association between the HCV-coreAg/HCV-RNA (Ag/RNA) ratio and the immune status in chronic HCV/HIV-1-coinfected patients. Methods A longitudinal investigation comprised of 227 HCV-monoinfected (n = 129) and HCV/HIV-1-coinfected (n = 98) patients was initiated in August 2009, and 139 (73 with HCV monoinfection and 66 with HCV/HIV-1 coinfection) were followed up in August 2012. Both HCV core antigen and HCV RNA quantification were determined on this cryopreserved plasma. HCV core antigen and HCV RNA quantification were performed subsequently. In addition, an in vitro experiment investigating the possibility of degradation of HCV components (core antigen and RNA) were conducted. Results Significant and stable correlations (p < 0.001) were observed both in chronic HCV-monoinfected and HCV/HIV-1-coinfected patients over the 3-year observation. Coinfected patients with immunocompromised condition had a significantly higher (p < 0.05) Ag/RNA ratios than those patients with immunocompetent condition both at two time points (2009 and 2012). Moreover, the Ag/RNA ratios were negatively correlated with CD4+ T-cell counts (p < 0.001). An in vitro experiment investigated the possibility of the slower degradation of HCV particles under HIV-related immunocompromised condition was conducted and the data demonstrated that the Ag/RNA ratios were significantly higher in HIV-1-positive plasma than in healthy plasma (p = 0.005) in this study. Conclusions Our longitudinal study indicated that the HCV-coreAg presented comparable dynamics over time as HCV RNA in chronic HCV-infected patients. Meanwhile, the HCV-coreAg/HCV-RNA ratio was closely associated with immune status in HCV/HIV-1-coinfected patients. Electronic supplementary material The online version of this article (doi:10.1186/s12879-014-0577-1) contains supplementary material, which is available to authorized users.
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Heidrich B, Pischke S, Helfritz FA, Mederacke I, Kirschner J, Schneider J, Raupach R, Jäckel E, Barg-Hock H, Lehner F, Klempnauer J, von Hahn T, Cornberg M, Manns MP, Ciesek S, Wedemeyer H. Hepatitis C virus core antigen testing in liver and kidney transplant recipients. J Viral Hepat 2014; 21:769-79. [PMID: 24251818 DOI: 10.1111/jvh.12204] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2013] [Accepted: 09/24/2013] [Indexed: 02/07/2023]
Abstract
HCV RNA levels correlate with the long-term outcome of hepatitis C in liver transplant recipients. Nucleic acid testing (NAT) is usually used to confirm HCV reinfection and to examine viral loads after liver transplantation. HCV core antigen (HCVcoreAg) testing could be an alternative to NAT with some potential advantages including very low intra- and interassay variabilities and lower costs. The performance of HCVcoreAg testing in organ transplant recipients is unknown. We prospectively studied 1011 sera for HCV RNA and HCVcoreAg in a routine real-world setting including 222 samples obtained from patients after liver or kidney transplantation. HCV RNA and HCVcoreAg test results showed a consistency of 98% with a very good correlation in transplanted patients (r > 0.85). The correlation between HCV RNA and HCVcoreAg was higher in sera with high viral loads and in samples from patients with low biochemical disease. Patients treated with tacrolimus showed a better correlation between both parameters than individuals receiving cyclosporine A. HCV RNA/HCVcoreAg ratios did not differ between transplanted and nontransplanted patients, and HCV RNA and HCVcoreAg kinetics were almost identical during the first days after liver transplantation. HCVcoreAg testing can be used to monitor HCV viral loads in patients after organ transplantation. However, the assay is not recommended to monitor antiviral therapies.
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Affiliation(s)
- B Heidrich
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany
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Ansaldi F, Orsi A, Sticchi L, Bruzzone B, Icardi G. Hepatitis C virus in the new era: Perspectives in epidemiology, prevention, diagnostics and predictors of response to therapy. World J Gastroenterol 2014; 20:9633-9652. [PMID: 25110404 PMCID: PMC4123355 DOI: 10.3748/wjg.v20.i29.9633] [Citation(s) in RCA: 110] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Revised: 04/18/2014] [Accepted: 05/19/2014] [Indexed: 02/06/2023] Open
Abstract
Despite the great successes achieved in the fields of virology and diagnostics, several difficulties affect improvements in hepatitis C virus (HCV) infection control and eradication in the new era. New HCV infections still occur, especially in some of the poorest regions of the world, where HCV is endemic and long-term sequelae have a growing economic and health burden. An HCV vaccine is still no available, despite years of researches and discoveries about the natural history of infection and host-virus interactions: several HCV vaccine candidates have been developed in the last years, targeting different HCV antigens or using alternative delivery systems, but viral variability and adaption ability constitute major challenges for vaccine development. Many new antiviral drugs for HCV therapy are in preclinical or early clinical development, but different limitations affect treatment validity. Treatment predictors are important tools, as they provide some guidance for the management of therapy in patients with chronic HCV infection: in particular, the role of host genomics in HCV infection outcomes in the new era of direct-acting antivirals may evolve for new therapeutic targets, representing a chance for modulated and personalized treatment management, when also very potent therapies will be available. In the present review we discuss the most recent data about HCV epidemiology, the new perspectives for the prevention of HCV infection and the most recent evidence regarding HCV diagnosis, therapy and predictors of response to it.
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Tillmann HL. Hepatitis C virus core antigen testing: Role in diagnosis, disease monitoring and treatment. World J Gastroenterol 2014; 20:6701-6706. [PMID: 24944462 PMCID: PMC4051911 DOI: 10.3748/wjg.v20.i22.6701] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2013] [Accepted: 03/13/2014] [Indexed: 02/06/2023] Open
Abstract
While hepatitis B virus (HBV) screening relies on hepatitis B surface antigen to confirm HBV infection since the early days of hepatitis B disease management, hepatitis C virus (HCV) infection screening is based on anti-HCV testing which does not discriminate active from past infection. Thus to confirm infection HCV RNA testing has been required; recently a HCV core antigen assay became widely commercially available which could serve to confirm infection. That assay is less sensitive than current HCV RNA assays, but as more than 50% of anti-HCV positive persons will be HCV core antigen positive, HCV core antigen testing can be a cost effective and reflex test to confirm HCV infection in anti-HCV positive individuals and will be easier as it can be applied on the same platform. For treatment monitoring, more data need to be generated, but the early data available at present suggest that HCV core antigen may be an alternative to HCV RNA monitoring. With direct antivirals, HCV core antigen could even be superior to HCV RNA testing, as direct antivirals might already prevent virus formation when HCV core antigen is still produced and thereby correlates better with eventual viral clearance.
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Dichamp I, Abbas W, Kumar A, Di Martino V, Herbein G. Cellular activation and intracellular HCV load in peripheral blood monocytes isolated from HCV monoinfected and HIV-HCV coinfected patients. PLoS One 2014; 9:e96907. [PMID: 24809719 PMCID: PMC4014560 DOI: 10.1371/journal.pone.0096907] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Accepted: 04/13/2014] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND During HCV infection, the activation status of peripheral blood monocytes and its impact on HCV replication are poorly understood. We hypothesized that a modified activation of peripheral blood monocytes in HIV-HCV coinfected compared to HCV monoinfected patients may contribute to different monocytes reservoirs of HCV replication. METHODS We performed a case-control analysis involving HCV-infected patients with and without HIV coinfection. In peripheral blood mononuclear cells (PBMCs), peripheral blood lymphocytes (PBLs) and peripheral blood monocytes isolated from HCV monoinfected and HIV-HCV coinfected patients, intracellular HCV load and a marker of cellular activation, nuclear factor-kappaB (NF-κB) activation, were quantified using intracellular detection of HCV-core protein and electrophoretic mobility shift assay, respectively. RESULTS Intracellular HCV loads were higher in monocytes isolated from HIV-HCV coinfected patients than in those of monoinfected patients. Among PBMCs isolated from HIV-HCV coinfected patients, intracellular HCV loads were higher in monocytes compared to PBLs. Cellular activation as measured by NF-κB activation was higher in monocytes isolated from HIV-HCV coinfected patients than in those of monoinfected patients. CONCLUSIONS Our results reveal the peripheral blood monocytes as an important extrahepatic reservoir for HCV in HIV-HCV coinfected patients and indicate a potential association between the activation state of monocytes and the size of the HCV reservoir in HIV-HCV coinfected patients.
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Affiliation(s)
- Isabelle Dichamp
- Pathogens and Inflammation Department, UPRES EA4266, SFR FED 4234, University of Franche-Comté, Besancon, France
- Department of Virology, CHRU Besançon, Besançon, France
| | - Wasim Abbas
- Pathogens and Inflammation Department, UPRES EA4266, SFR FED 4234, University of Franche-Comté, Besancon, France
- Department of Virology, CHRU Besançon, Besançon, France
| | - Amit Kumar
- Pathogens and Inflammation Department, UPRES EA4266, SFR FED 4234, University of Franche-Comté, Besancon, France
- Department of Virology, CHRU Besançon, Besançon, France
| | - Vincent Di Martino
- Pathogens and Inflammation Department, UPRES EA4266, SFR FED 4234, University of Franche-Comté, Besancon, France
- Department of Hepatology, CHRU Besançon, Besançon, France
| | - Georges Herbein
- Pathogens and Inflammation Department, UPRES EA4266, SFR FED 4234, University of Franche-Comté, Besancon, France
- Department of Virology, CHRU Besançon, Besançon, France
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