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Hu KQ, Cui W, Rouster SD, Sherman KE. Hepatitis C virus antigens enzyme immunoassay for one-step diagnosis of hepatitis C virus coinfection in human immunodeficiency virus infected individuals. World J Hepatol 2019; 11:442-449. [PMID: 31183004 PMCID: PMC6547293 DOI: 10.4254/wjh.v11.i5.442] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 05/08/2019] [Accepted: 05/21/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Current diagnosis of hepatitis C virus (HCV) infection requires two sequential steps: testing for anti-HCV followed by HCV RNA PCR to confirm viremia. We have developed a highly sensitive and specific HCV-antigens enzyme immunoassay (HCV-Ags EIA) for one-step diagnosis of viremic HCV infection.
AIM To assess the clinical application of the HCV-Ags EIA in one-step diagnosis of viremic HCV infection in human immunodeficiency virus (HIV)-coinfected individuals.
METHODS The study blindly tested HCV-Ags EIA for its performance in one-step diagnosing viremic HCV infection in 147 sera: 10 without HCV or HIV infection; 54 with viremic HCV monoinfection; 38 with viremic HCV/HIV coinfection; and 45 with viremic HCV and non-viremic HIV coinfection.
RESULTS Upon decoding, it was 100% accordance of HCV-Ags EIA to HCV infection status by HCV RNA PCR test. In five sera with HCV infection, HCV RNA was as low as 50-59 IU/mL, and four out of five tested positive for HCV-Ags EIA. Likewise, it was also 100% accordance of HCV-Ags EIA to HCV infection status by HCV RNA PCR in 83 sera with HCV and HIV coinfection, regardless if HIV infection was active or not.
CONCLUSION The modified HCV-Ags EIA has a lower detection limit equivalent to serum HCV RNA levels of approximately 100 IU/mL. It is highly sensitive and specific in the setting of HIV coinfection, regardless of HIV infection status and CD4 count. These data support the clinical application of the HCV-Ags EIA in one-step diagnosis of HCV infection in HIV-infected individuals.
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Affiliation(s)
- Ke-Qin Hu
- Division of GI/Hepatology, University of California, Irvine, School of Medicine, Orange, CA 92868, United States
| | - Wei Cui
- Division of GI/Hepatology, University of California, Irvine, School of Medicine, Orange, CA 92868, United States
| | - Susan D Rouster
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States
| | - Kenneth E Sherman
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States
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Detection of Hepatitis C core antibody by dual-affinity yeast chimera and smartphone-based electrochemical sensing. Biosens Bioelectron 2016; 86:690-696. [DOI: 10.1016/j.bios.2016.07.023] [Citation(s) in RCA: 64] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Revised: 06/17/2016] [Accepted: 07/08/2016] [Indexed: 12/11/2022]
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Hu KQ, Cui W. A highly specific and sensitive hepatitis C virus antigen enzyme immunoassay for One-step diagnosis of viremic hepatitis C virus infection. Hepatology 2016; 64:415-24. [PMID: 27273268 DOI: 10.1002/hep.28663] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2015] [Revised: 04/23/2016] [Accepted: 04/25/2016] [Indexed: 12/20/2022]
Abstract
UNLABELLED The current standard in diagnosing hepatitis C virus (HCV) infection requires two sequential steps: anti-HCV test to screen, followed by HCV RNA reverse-transcription polymerase chain reaction to confirm viremic HCV (V-HCV) infection. HCV core antigen tests provided potential for possible one-step diagnosis. However, low sensitivity and specificity limit their clinical utility. The present study developed a novel HCV antigens enzyme immunoassay (HCV-Ags EIA) and assessed its sensitivity, specificity, and utility for one-step diagnosis of V-HCV infection using 365 serum specimens, including 176 without and 189 with V-HCV infection. First, we confirmed the presence of HCV nonstructural proteins 3, 4b, and 5a besides HCV core antigen during HCV infection and developed a novel HCV-Ags EIA through simultaneous detection of all four HCV proteins. For the first time, the present study demonstrated that serum sample denaturation decreases the test specificity due to release of HCV-Ags sequestered in HCV immune complexes and should not be used in any HCV-Ags, including all the current HCV core antigen assays. On the other hand, using sample nondenaturation, the HCV-Ags EIA results showed 98.9% specificity and 100% sensitivity compared to serum anti-HCV and HCV RNA reverse-transcription polymerase chain reaction results. Using serum sample dilution, and nondenaturation, the lowest limits of detection of the HCV-Ags EIA were equivalent to serum HCV RNA levels of approximate 150-250 IU/mL. CONCLUSIONS The highly specific and sensitive HCV-Ags EIA developed in the present study has the lowest limit of detection equivalent to serum HCV RNA levels of 150-250 IU/mL; using nondenaturation of serum samples, our HCV-Ags EIA reliably differentiated V-HCV infection from resolved HCV infection, accomplishing screening and diagnosis of V-HCV infection in one step. (Hepatology 2016;64:415-424).
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Affiliation(s)
- Ke-Qin Hu
- Division of GI/Hepatology, University of California, Irvine, School of Medicine, Orange, CA
| | - Wei Cui
- Division of GI/Hepatology, University of California, Irvine, School of Medicine, Orange, CA
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Villar LM, Cruz HM, Barbosa JR, Bezerra CS, Portilho MM, Scalioni LDP. Update on hepatitis B and C virus diagnosis. World J Virol 2015; 4:323-42. [PMID: 26568915 PMCID: PMC4641225 DOI: 10.5501/wjv.v4.i4.323] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Revised: 09/25/2015] [Accepted: 10/23/2015] [Indexed: 02/05/2023] Open
Abstract
Viral hepatitis B and C virus (HBV and HCV) are responsible for the most of chronic liver disease worldwide and are transmitted by parenteral route, sexual and vertical transmission. One important measure to reduce the burden of these infections is the diagnosis of acute and chronic cases of HBV and HCV. In order to provide an effective diagnosis and monitoring of antiviral treatment, it is important to choose sensitive, rapid, inexpensive, and robust analytical methods. Primary diagnosis of HBV and HCV infection is made by using serological tests for detecting antigens and antibodies against these viruses. In order to confirm primary diagnosis, to quantify viral load, to determine genotypes and resistance mutants for antiviral treatment, qualitative and quantitative molecular tests are used. In this manuscript, we review the current serological and molecular methods for the diagnosis of hepatitis B and C.
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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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Buket CA, Ayşe A, Selçuk K, Süleyman O, Emel SC. Comparison of HCV core antigen and anti-HCV with HCV RNA results. Afr Health Sci 2014; 14:816-20. [PMID: 25834488 DOI: 10.4314/ahs.v14i4.7] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND The measurement of anti-HCV antibodies using immunological methods and the confirmation of viral nuclear acid based on molecular methods is important in diagnosis and follow-up of the HCV infection. OBJECTIVES In this study, we aimed to analyse HCV core Antigen positivity among anti-HCV antibody positive sera to determine the significance of testing of HCV core Ag for the laboratory diagnosis of HCV infection, by considering the correlation between serum HCV core Ag and HCV RNA levels. METHODS 115 patients suspected of having hepatitis C and who were positive for anti-HCV antibody were investigated using chemiluminescent and molecular methods. Anti-HCV antibody, HCV core Ag and HCV RNA levels were detected by the Vitros ECiQ immunodiagnostic system, Architect i2000 system and RT-PCR, respectively. RESULTS The sensitivity, specificity, positive and negative predictive values and accuracy rate of HCV core Antigen assay were detected as 86.5%(83/96), 100%(19/19), 100%(83/83), 59.4%(19/32), 88.7%(102/115) respectively. CONCLUSION HCV core Ag assay could be used for diagnosis of HCV infection as it is easy to perform, cost-effective, has high specificity and positive predictive value. However, it should be kept in mind that it may have lack of sensitivity and negative predictive value.
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Uliana CV, Riccardi CS, Yamanaka H. Diagnostic tests for hepatitis C: Recent trends in electrochemical immunosensor and genosensor analysis. World J Gastroenterol 2014; 20:15476-15491. [PMID: 25400433 PMCID: PMC4229514 DOI: 10.3748/wjg.v20.i42.15476] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2013] [Revised: 02/19/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C is a liver disease that is transmitted through contact with the blood of an infected person. An estimated 150 million individuals worldwide have been chronically infected with the hepatitis C virus (HCV). Hepatitis C shows significant genetic variation in the global population, due to the high rate of viral RNA mutation. There are six variants of the virus (HCV genotypes 1, 2, 3, 4, 5, and 6), with 15 recorded subtypes that vary in prevalence across different regions of the world. A variety of devices are used to diagnose hepatitis C, including HCV antibody test, HCV viral load test, HCV genotype test and liver biopsy. Rapid, inexpensive, sensitive, and robust analytical devices are therefore essential for effective diagnosis and monitoring of disease treatment. This review provides an overview of current electrochemical immunosensor and genosensor technologies employed in HCV detection. There are a limited number of publications showing electrochemical biosensors being used for the detection of HCV. Due to their simplicity, specificity, and reliability, electrochemical biosensor devices have potential clinical applications in several viral infections.
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Garbuglia AR, Monachetti A, Galli C, Sabatini R, Ferreri ML, Capobianchi MR, Bagnarelli P. HCV core antigen and HCV-RNA in HIV/HCV co-infected patients with different HCV genotypes. BMC Infect Dis 2014; 14:222. [PMID: 24758157 PMCID: PMC4029812 DOI: 10.1186/1471-2334-14-222] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2013] [Accepted: 04/15/2014] [Indexed: 12/17/2022] Open
Abstract
Background A good correlation between HCV core antigen (HCVAg) and different HCV-RNA assays has been described, but little data are available in HCV/HIV co-infection. We aimed to evaluate HCVAg in comparison with HCV-RNA and to determine their kinetics during antiviral treatment in selected HCV/HIV co-infected patients. Methods 355 samples from 286 HCV/HIV co-infected subjects for whom HCV-RNA (Abbott RealTime) was requested were analysed also for HCVAg (Abbott ARCHITECT) in order to evaluate the correlation between the two parameters both in patients treated or untreated for chronic hepatitis C and according to different HCV genotypes. The differences between percentages were evaluated by chi square or Fisher’s exact test, while mean and median values were compared by Student’s t test or the Mann–Whitney test, respectively. All differences were considered significant for a p value <0.05. Results HCVAg was detectable on 288/315 sera (91.4%) positive for HCV-RNA and in 5 out of40 (12.5%) sera with undetectable HCV-RNA for a total concordance of 90.1%. The correlation was fair both in untreated (r = 0.742) and in treated (r = 0.881) patients and stronger for genotypes 1 and 4 than for genotype 3. Both HCV-RNA and HCVAg levels were significantly higher (p = 0.028 and p = 0.0098, respectively) in patients infected by genotype 1 than by genotype 3. The mean ratio of Log values between HCV-RNA (IU/mL) and HCVAg (fmol/liter) was 2.27 ± 1.09 in untreated and 2.20 ± 0.82 in treated patients (p = n.s.),consistent with a sensitivity of HCVAg corresponding to about 1,000 IU/mL of HCV-RNA, and ranged from 2.21 to 2.32 among HCV genotypes with no significant differences; five samples (1.4%; 2 genotype 1a or 1c, 3 genotype 3a) showed highly divergent values. The analysis of 18 monitoring profiles from patients treated with PEG-IFN and Ribavirin showed similar trends, except in one case in which relapse could be predicted by HCVAg and not by HCV-RNA. Conclusion These results suggest that HCVAg represents an adequate tool for determining an ongoing HCV infection also in HIV co-infected patients, with lower costs and faster turnaround time than HCV-RNA.
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Affiliation(s)
- Anna Rosa Garbuglia
- Virology, Laboratory of Virology, "L,Spallanzani" National Institute for Infectious Diseases, Via Portuense, 292, 00149 Rome, Italy.
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Comanor L, Hendricks D. Hepatitis C virus RNA tests: performance attributes and their impact on clinical utility. Expert Rev Mol Diagn 2014; 3:689-702. [PMID: 14628898 DOI: 10.1586/14737159.3.6.689] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The diagnostic market is driven by the burden of disease in the population and the ease or difficulty of disease diagnosis. The efficacy of available therapeutics determines the need for monitoring. Hepatitis C virus currently affects approximately 3% of the world's population, although the overall response rate to the best available therapies is 56%. Research regarding hepatitis C virus remains elusive due to lack of an efficient cell culture system. Diagnosis and monitoring of active hepatitis C virus infection therefore rely on sophisticated molecular tests. This review will focus on current molecular tests for hepatitis C virus RNA and the performance attributes that these tests require for accurate diagnosis and monitoring of infection.
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Ciotti M, D'Agostini C, Marrone A. Advances in the Diagnosis and Monitoring of Hepatitis C Virus Infection. Gastroenterology Res 2013; 6:161-170. [PMID: 27785248 PMCID: PMC5051090 DOI: 10.4021/gr576e] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/03/2013] [Indexed: 12/18/2022] Open
Abstract
Hepatitis C virus (HCV) infection represents a major health problem worldwide. Approximately 350,000 people die every year from hepatitis C related diseases. Antiviral therapy is given to prevent such complications. Advances in serological and molecular assays greatly improved the diagnosis of hepatitis C virus infection and the management of chronically infected patients. Sensitive real-time PCR methods are currently used to monitor the response to antiviral therapy, to guide treatment decisions, and to assess the sustained virological response 24 weeks after the end of therapy. HCV genotyping is part of the pretreatment evaluation. Determination of HCV genotype is important both for tailoring antiviral treatment and for determining treatment duration. It predicts also response to therapy. With the recent introduction of the serine protease inhibitors telaprevir and boceprevir, approved for the treatment of genotype 1 chronic hepatitis C in combination with INF-a and ribavirin, subtyping has become clinically relevant. Indeed, subtypes 1a and 1b may respond differently to current telaprevir-based or boceprevir-based triple therapy. This review summarizes the most recent advances in the diagnosis and monitoring of HCV chronic infection.
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Affiliation(s)
- Marco Ciotti
- Laboratory of Molecular Virology, Polyclinic Tor Vergata Foundation, Viale Oxford 81-00133, Rome, Italy
| | - Cartesio D'Agostini
- Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Rome, Italy; Laboratory of Clinical Microbiology and Virology, Polyclinic "Tor Vergata" Foundation, Viale Oxford 81, 00133, Rome, Italy
| | - Aldo Marrone
- Internal Medicine and Hepatology, School of Medicine of Naples, Second University of Naples, Via Pansini 5, Edificio 10, 80131, Napoli, Italy
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Label-free sandwich type of immunosensor for hepatitis C virus core antigen based on the use of gold nanoparticles on a nanostructured metal oxide surface. Mikrochim Acta 2012. [DOI: 10.1007/s00604-012-0842-1] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Gu S, Liu J, Zhang H, Gu B, Lai H, Zhou H, He C, Chen Y. Core antigen tests for hepatitis C virus: a meta-analysis. Mol Biol Rep 2012; 39:8197-208. [PMID: 22544611 DOI: 10.1007/s11033-012-1667-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2011] [Accepted: 04/18/2012] [Indexed: 12/12/2022]
Abstract
Diagnosis and monitoring of hepatitis C virus (HCV) infection relies mainly on the detection of HCV antibodies and HCV RNA. HCV antibody test has a longer window period and is not applicable in the immunosuppressed population. Although HCV RNA test reduces the window period, it is still not widely recommended because of its high cost and requirement of specific equipment. HCV core antigen is another direct virological marker which has been investigated in recent years. HCV core antigen assay is as simple as the HCV antibodies assay and can detect HCV infection only 1 day delay compared to the HCV RNA assay. In order to evaluate the application of HCV core antigen test in HCV diagnosis and management, we performed this meta-analysis. Twenty five articles were finally included in meta-analysis. All statistical analyses were performed with MetaDisc 1.4 and Stata 11.0. The pooled sensitivity of HCV core antigen assay was 0.84 (95 % CI, 0.83-0.85), and the pooled specificity was 0.98 (95 % CI, 0.97-0.98). HCV core antigen assays may not displace HCV RNA assays to be a definitive diagnosis of HCV infection until now. Considering the higher sensitivity (0.926) and specificity (0.991) of subgroup, HCV-cAg detection is a promising method as a confirmatory test for HCV antibody positive, therapy-naive individuals. Explored by meta-regression and subgroup analysis, possible sources of heterogeneity of specificity was found, while the heterogeneity of sensitivity was still significant.
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Affiliation(s)
- Shuijun Gu
- Department of Neurosurgery, Xiaoshan First Affiliated Hospital of Medical School of Hangzhou Normal University, Xiaoshan 311201, Zhejiang, China
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Is hepatitis C virus core antigen an adequate marker for community screening? J Clin Microbiol 2012; 50:1989-93. [PMID: 22461676 DOI: 10.1128/jcm.05175-11] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
A new hepatitis C virus (HCV) core antigen (HCV Ag) assay was thought to have a good correlation with HCV RNA. The aim was to elucidate the usefulness of this HCV Ag assay in community screening. In a township where HCV is endemic, 405 residents aged 58 years or older responded to a follow-up community screening. All subjects were tested for anti-HCV (AxSYM, version 3.0; Abbott Diagnostics) and HCV Ag (Architect HCV Ag test; Abbott Diagnostics). For subjects with anti-HCV signal-to-cutoff ratios (S/CO) > 10 and/or HCV Ag > 3 fmol/liter, HCV RNA data (Taqman HCV RNA; Roche Diagnostics) were further checked. A total of 115 (28.4%) subjects had their serum HCV RNA levels measured, and 93 were HCV RNA positive. The other 290 subjects were supposed to be HCV RNA negative. HCV Ag was significantly correlated with HCV RNA according to the following equation: (log HCV RNA) = 2.08 + 1.03 (log HCV Ag) (R(2) = 0.94; P < 0.001). As determined using a combination of the values for anti-HCV (S/CO > 40) and HCV Ag (>3 fmol/liter) as a cutoff to predict viremia, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 96.8%, 100%, 99.3%, 100%, and 99%, respectively. In conclusion, for a community study, HCV Ag showed good correlation with HCV RNA. In addition, anti-HCV or HCV Ag can predict HCV viremia well, while a combination of anti-HCV (>40 S/CO) and HCV Ag (>3 fmol/liter) can provide the best result validity.
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Hosseini-Moghaddam SM, Iran-Pour E, Rotstein C, Husain S, Lilly L, Renner E, Mazzulli T. Hepatitis C core Ag and its clinical applicability: Potential advantages and disadvantages for diagnosis and follow-up? Rev Med Virol 2011; 22:156-65. [PMID: 22121001 DOI: 10.1002/rmv.717] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2011] [Revised: 09/18/2011] [Accepted: 09/19/2011] [Indexed: 12/20/2022]
Affiliation(s)
- SM Hosseini-Moghaddam
- Division of Infectious Diseases; University of Toronto, University Health Network, Transplant Infectious Diseases, Toronto General Hospital; Toronto ON Canada
- Urology and Nephrology Research Center (UNRC); Shahid Beheshti University of Medical Sciences; Tehran IR Iran
| | - E. Iran-Pour
- Islamic Azad University; Tehran Medical Branch; Tehran IR Iran
| | - C. Rotstein
- Division of Infectious Diseases; University of Toronto, University Health Network, Transplant Infectious Diseases, Toronto General Hospital; Toronto ON Canada
| | - S. Husain
- Division of Infectious Diseases; University of Toronto, University Health Network, Transplant Infectious Diseases, Toronto General Hospital; Toronto ON Canada
| | - L. Lilly
- Hepatology; University of Toronto, University Health Network, Transplant Hepatology, Toronto General Hospital; Toronto ON Canada
| | - E. Renner
- Hepatology; University of Toronto, University Health Network, Transplant Hepatology, Toronto General Hospital; Toronto ON Canada
| | - T. Mazzulli
- Virology, Department of Microbiology; University of Toronto, University Health Network, Mount Sinai Hospital; Toronto ON Canada
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Ergünay K, Sener B, Alp A, Karakaya J, Hasçelik G. Utility of a commercial quantitative hepatitis C virus core antigen assay in a diagnostic laboratory setting. Diagn Microbiol Infect Dis 2011; 70:486-91. [PMID: 21767705 DOI: 10.1016/j.diagmicrobio.2011.04.011] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2011] [Revised: 04/14/2011] [Accepted: 04/23/2011] [Indexed: 12/12/2022]
Abstract
In this study, the utility and impact of hepatitis C virus (HCV) core antigen (Cag) detection via a commercial assay have been evaluated in diagnostic laboratory conditions. In a total of 272 samples from 226 individuals, HCV RNA was detected in 81.3% and anti-HCV antibody prevalence was 86.4%. HCV Cag reactivity was identified in 59.9% of the samples and in 75.8% with detectable RNA. The sensitivity and specificity of HCV Cag assay have been calculated as 75.8% and 95.1%, respectively, and agreement between HCV RNA and HCV Cag was moderate (κ = 0.554). HCV Cag and RNA levels were highly correlated (r = 0.915 and 0.937). A viral load threshold of 10(3) IU/mL has been recognized, above which the correlation with RNA became statistically significant and sensitivity increased to 90.9%. Detection and quantification of HCV core antigen have been observed as a strong alternative to nucleic acid testing for HCV monitorization.
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Affiliation(s)
- Koray Ergünay
- Department of Medical Microbiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
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Song D, Kang JE, Kim SY, Hwang SH, Kim HH, Lee EY, Son HC. [Evaluation of ARCHITECT HCV core antigen assay]. Korean J Lab Med 2011; 30:654-9. [PMID: 21157153 DOI: 10.3343/kjlm.2010.30.6.654] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) core antigen (Ag) levels are known to be well correlating with HCV RNA levels, and may be used as an alternative marker of HCV replication for monitoring the response to HCV treatment. However, the low sensitivity of HCV core Ag assay has been an obstacle for clinical use. In this study, recently developed ARCHITECT HCV Ag assay (Abbott Laboratories, USA) was evaluated for analytical performance and clinical usefulness. METHODS A total of 109 sera from HCV infected patients including various genotypes of HCV (1b, 2, 2a/2c, 2b, and 3a) and 20 sera from healthy donors were used for evaluating the sensitivity, precision, and linearity of the HCV core Ag assay. The cross reactivity with HIV, hepatitis B virus and myeloma proteins (N=5, each) and correlation with HCV RNA PCR assay were also evaluated. RESULTS The sensitivity of the HCV core Ag assay was 97.2% (106/109) and there were no false positive results and cross reactivity. The within-run, between-run and between-day CVs were 3.0%, 2.5% and 3.0%, respectively. The levels of HCV core antigen showed a good correlation with those of HCV RNA quantification (r=0.940). The HCV Ag assay showed an excellent linearity in the range from 0.63 to 17,114 fmol/L (r=0.999). CONCLUSIONS The ARCHITECT HCV Ag assay was good in sensitivity, precision, and linearity and its results well correlated with HCV RNA levels. This assay could be used as a good marker of viral replication for monitoring the therapy response in chronically HCV infected patients.
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Affiliation(s)
- Dual Song
- Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea
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Ross RS, Viazov S, Salloum S, Hilgard P, Gerken G, Roggendorf M. Analytical performance characteristics and clinical utility of a novel assay for total hepatitis C virus core antigen quantification. J Clin Microbiol 2010; 48:1161-8. [PMID: 20107102 PMCID: PMC2849592 DOI: 10.1128/jcm.01640-09] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2009] [Revised: 01/08/2010] [Accepted: 01/15/2010] [Indexed: 12/11/2022] Open
Abstract
The detection and quantification of hepatitis C virus (HCV) core antigen in serum or plasma by the use of different assay formats have previously been shown to represent useful markers of viral replication. In the present study, the intrinsic performance characteristics and the potential clinical utility of a novel assay for the quantification of total HCV core antigen were comprehensively assessed by using clinical serum samples and specimens contained in various evaluation panels. The Architect HCV Ag assay showed a specificity of 100%. The intra- and interassay coefficients of variation ranged from 3.6 to 8.0% and from 4.7 to 9.5%, respectively. Except for HCV genotype 2 isolates, the analytical sensitivity was always less than 10 fmol core antigen/liter, corresponding to approximately 500 to 3,000 IU of HCV RNA/ml. Linearity was guaranteed throughout the dynamic range (10 to 20,000 fmol/liter). When seroconversion panels were tested, the assay was not inferior to HCV RNA detection and reduced the preseroconversion period by 4 to 16 days. The results obtained by core antigen and HCV RNA quantification for 385 clinical specimens were correlated by regression analysis (r = 0.857), but the calculated conversion equation differed significantly from the line of identity. Monitoring of viral kinetics by use of either core antigen or RNA concentrations in 38 HCV-infected patients undergoing antiviral combination therapy resulted in very similarly shaped curves in all cases. Finally, the Architect HCV Ag assay was also shown to enable high-throughput screening of in vitro HCV RNA replication. With these results taken together, the Architect HCV Ag assay proved to be a specific, reproducible, highly sensitive, and clinically applicable test format which will find its future place in the context of virological HCV diagnostics.
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Affiliation(s)
- R S Ross
- Institute of Virology, National Reference Centre for Hepatitis C, Essen University Hospital, University of Duisburg-Essen, Essen, Germany.
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Miedouge M, Saune K, Kamar N, Rieu M, Rostaing L, Izopet J. Analytical evaluation of HCV core antigen and interest for HCV screening in haemodialysis patients. J Clin Virol 2010; 48:18-21. [PMID: 20233674 DOI: 10.1016/j.jcv.2010.02.012] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2009] [Revised: 02/15/2010] [Accepted: 02/18/2010] [Indexed: 12/18/2022]
Abstract
BACKGROUND It is important to diagnose a hepatitis C virus infection in the acute phase in order to reduce the incidence of this infection in high-risk populations like haemodialysis patients. But detection systems for serum HCV antibodies are insensitive in the acute phase because of the long serological window. Previous studies showed that the HCV core antigen (HCV Ag) may be an alternative to HCV RNA in this context. OBJECTIVES To evaluate the performances of the new Abbott ARCHITECT((R)) HCV Ag test and its usefulness in screening for HCV infections in haemodialysis patients. STUDY DESIGN The serum HCV Ag titre was compared to the HCV RNA viral load in 98 samples from HCV-infected patients to determine the correlation between the two markers and the influence of genotype. We screened 2752 patients from 37 French haemodialysis units who tested negative for HCV antibodies using the HCV Ag and RNA assays. RESULTS The HCV Ag titre was correlated with the HCV RNA (Spearman test coefficient 0.9041, p<0.0001) and all genotypes and subtypes were detected. The HCV Ag and HCV RNA results agreed well for haemodialysis patients. Diagnostic specificity of HCV Ag was high (99.2%) considering HCV RNA as the reference. The two seronegative patients (of 2752) who were HCV RNA positive were also HCV Ag positive. CONCLUSIONS The ARCHITECT HCV Ag test is a reliable, highly specific assay for screening acute HCV infections in haemodialysis units. It is a robust alternative to HCV RNA testing.
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Affiliation(s)
- Marcel Miedouge
- Laboratoire de Virologie, Institut Fédératif de Biologie de Purpan, 330 avenue de Grande Bretagne, TSA 40031, 31059 Toulouse Cédex 9, France.
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19
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A new sensitive and automated chemiluminescent microparticle immunoassay for quantitative determination of hepatitis C virus core antigen. J Virol Methods 2009; 157:8-14. [PMID: 19135481 DOI: 10.1016/j.jviromet.2008.12.009] [Citation(s) in RCA: 98] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2008] [Revised: 12/02/2008] [Accepted: 12/09/2008] [Indexed: 02/06/2023]
Abstract
A new sensitive and automated chemiluminescent assay was developed for the quantitative determination of hepatitis C virus (HCV) core antigen (Ag) in human sera or plasma: the Abbott ARCHITECT HCV Ag test. The assay sensitivity was determined by testing 10 commercial HCV seroconversion panels. Without exception, a positive result for HCV core Ag was observed before anti-HCV detection, resulting in an average reduction in the period between exposure and detection of 35.8 days. Both HCV core Ag and HCV RNA were detected in the panels at the same time, indicating equivalent sensitivity and detectability. A total of 197 HCV specimens comprising genotypes 1a, 1b, 2a, 2b, 3a, 3k, 4a, 5a and 6a were evaluated. Among these, 196 (99.5%), 191 (97%) and 193 (98%) were reactive using the HCV Ag, the immunoradiometric HCV Ag and the Amplicor HCV Monitor 2 assays, respectively. A comparison with the Amplicor HCV Monitor 2 showed a correlation coefficient (r) of 0.74. The specificity of the assay was established at 99.8% by testing 5403 specimens from US volunteer blood donors, hospitalized patients and individuals with medical conditions unrelated to HCV infection, in addition to specimens containing potentially interfering substances.
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20
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Kim SR, Imoto S, Fuki S, Kim KI, Taniguchi M, Nagano M, Hotta H, Shouji I, Kanbara Y, Maekawa Y, Kudo M, Hayashi Y. Pegylated interferon α-2b/ribavirin combination therapy for elderly patients with chronic hepatitis C with high viral load of HCV genotype 1b. KANZO 2008; 49:145-152. [DOI: 10.2957/kanzo.49.145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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21
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Clinical application and analysis of hepatitis C virus NS3 antigen detection by ELISA in human serum. Chin Med J (Engl) 2007. [DOI: 10.1097/00029330-200702020-00008] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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22
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Pham BN, Martinot-Peignoux M, Ripault MP, Boyer N, Levy V, Marcellin P. Quantitative measurement of hepatitis C virus core antigen is affected by the presence of cryoglobulins. Clin Exp Immunol 2007; 146:211-7. [PMID: 17034572 PMCID: PMC1942051 DOI: 10.1111/j.1365-2249.2006.03196.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
Mixed cryoglobulinaemia is associated strikingly with HCV infection. The aim of this study was to assess whether the adherence to proper methods of collecting samples for cryoglobulin detection was critical or not on virological parameters in hepatitis C virus (HCV) patients. We studied 56 consecutive patients. Blood samples were collected using a conventional method and a blood collection method at 37 degrees C adapted to cryoglobulin detection. HCV core antigen and HCV RNA were measured in sera and cryoglobulins issued from both blood collection methods. In cryoglobulin-positive patients, serum concentrations of HCV core antigen, but not that of HCV RNA, were significantly higher when a conventional method was used, compared to a blood collection method at 37 degrees C (P = 0.001). In the cryoprecipitates, concentration of HCV core antigen was optimum when the blood collection method at 37 degrees C, rather than the conventional method, was applied for cryoglobulin detection (P < 10(-4)). The recovery of HCV core antigen in the cryoprecipitate was improved when cryoglobulins were isolated using the blood collection method at 37 degrees C rather than the conventional method (P < 0.001). HCV parameter measurements and cryoglobulin study should not be performed on the same serum samples due to the potential impact of blood collection methods on results.
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Affiliation(s)
- B-N Pham
- Département d'Immunologie Microbiologie des Pathologies Infectieuses, Hôpital Beaujon, Clichy, France.
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23
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Kim KI, Kim SR, Sasase N, Taniguchi M, Harada S, Kinoshita K, Kim SH, Akimoto Y, Shikata M, Kimura N, Izawa S, Ohtani A, Nakao K, Motojima M, Kinoshita M, Hirai M, Ohzu M, Hirooka T, Nabeshima S, Ishii F, Tanaka K, Hotta H. 2'-,5'-Oligoadenylate synthetase response ratio predicting virological response to PEG-interferon-α2b plus ribavirin therapy in patients with chronic hepatitis C. J Clin Pharm Ther 2006; 31:441-6. [PMID: 16958821 DOI: 10.1111/j.1365-2710.2006.00761.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVE Although all the mechanisms of elimination of hepatitis C virus (HCV) by Interferon (IFN) have not been fully elucidated, the 2'-5'-oligoadenylate (2-5A) system is one of the mechanisms of the antiviral effect of IFN. Consequently, the measurement of 2'-5'-oligoadenylate synthetase (2-5AS) activity could be useful for the evaluation of IFN treatment. This retrospective study was aimed at assessing whether 2-5AS activity functions as a clinical marker of virological response to PEG-interferon-alpha2b (PEG-IFN) plus ribavirin therapy of chronic hepatitis C. METHODS The 32 patients included in this study had high viral loads of serum HCV-RNA of genotype 1b with chronic hepatitis C. All the patients received a regimen of PEG-IFN plus ribavirin for 48 weeks, and were then divided into two groups: one group (effective group) with undetectable serum HCV-RNA levels at 24 weeks (n = 22) of therapy, the other group (ineffective group) with persistent presence of HCV-RNA in serum at 24 weeks (n = 10). The 2-5AS activity in serum was measured 2, 8 and 12 weeks before initial administration. RESULTS The 2-5AS response ratio (measured value/measured value of baseline 2-5AS) at 2, 8 and 12 weeks after the administration in the effective group was significantly higher than that in the ineffective group. CONCLUSIONS These results suggest that the ratio of 2-5AS is closely related to the antiviral effect, and that the measurement of 2-5AS response ratio may be a useful clinical parameter of virological response to PEG-IFN plus ribavirin therapy of chronic hepatitis C.
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Affiliation(s)
- K-I Kim
- Department of Pharmacy, Kobe Asahi Hospital, Kobe, Japan
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24
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Pivert A, Payan C, Morand P, Fafi-Kremer S, Deshayes J, Carrat F, Pol S, Cacoub P, Perronne C, Lunel F. Comparison of serum hepatitis C virus (HCV) RNA and core antigen levels in patients coinfected with human immunodeficiency virus and HCV and treated with interferon plus ribavirin. J Clin Microbiol 2006; 44:417-22. [PMID: 16455894 PMCID: PMC1392678 DOI: 10.1128/jcm.44.2.417-422.2006] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Trak-C (Ortho-Clinical Diagnostics) is an enzyme-linked immunosorbent assay-based method capable of quantifying hepatitis C virus (HCV) core antigen (CA) in serum and could be an alternative to molecular detection and quantification of HCV RNA. We have evaluated the Trak-C assay in comparison with an HCV RNA quantitative assay (Versant HCV v3.0; Bayer Diagnostics) in the follow-up of 348 treated, human immunodeficiency virus (HIV)/HCV-coinfected patients included in the ANRS HC02 RIBAVIC trial. ANRS HC02 RIBAVIC is a therapeutic, multicenter, randomized protocol comparing the efficacy of alpha interferon 2b (IFN-alpha2b) (3 million units three times a week)-ribavirin (800 mg/day) to that of pegylated IFN-alpha2b (1.5 mug/kg of body weight/week)-ribavirin (800 mg/day) during 48 weeks of treatment of HIV/HCV-coinfected patients naïve to HCV treatment. Patients were assessed for virological analysis at day 0 and weeks 4, 12, 24, 48, and 72. Correlation of HCV RNA and HCV CA at the initiation of treatment was excellent (r = 0.92). HCV RNA and CA kinetics were similar during follow-up of HCV treatment from day 0 to week 72 whatever the group of response and genotype. The positive and negative predictive values of response to the treatment at week 4 were 59 and 94%, respectively, for HCV RNA load reduction of >2 log and 54 and 94%, respectively, for HCV CA below the threshold value (4.18 log(10) pg/ml . 10(4)). Trak-C, a new assay able to quantify CA in HIV/HCV-coinfected patients, correlates well with quantitative HCV RNA assays and is cheaper and easier to perform than molecular technology. HCV CA could be a valuable alternative test for therapeutic follow-up of coinfected patients treated with IFN plus ribavirin in developing countries.
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Affiliation(s)
- A Pivert
- Laboratoire de Bactériologie-Virologie-Hygiène Hospitalière, CHU Angers, 4 rue Larrey, 49933 ANGERS Cedex, France
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25
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Irshad M, Dhar I. Hepatitis C virus core protein: an update on its molecular biology, cellular functions and clinical implications. Med Princ Pract 2006; 15:405-16. [PMID: 17047346 DOI: 10.1159/000095485] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2005] [Accepted: 03/18/2006] [Indexed: 12/20/2022] Open
Abstract
The present review article is an update on various features of hepatitis C virus (HCV) core protein including its molecular biology, role in HCV replication, involvement in HCV pathogenesis, etiological role in hepatocellular carcinogenesis, significance in diagnosis and vaccination against HCV infection. Core protein is a structural protein of HCV virus and has only recently been characterized. It was found to play a major role in HCV-induced viral hepatitis. Although published information shows a lot about the clinical significance of HCV core protein, several studies are still needed to demonstrate its exact significance in viral biology and underlying HCV pathogenesis.
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Affiliation(s)
- M Irshad
- Clinical Biochemistry Division, Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India.
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26
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González V, Padilla E, Diago M, Giménez MD, Solà R, Matas L, Montoliu S, Morillas RM, Pérez C, Planas R. Clinical usefulness of total hepatitis C virus core antigen quantification to monitor the response to treatment with peginterferon alpha-2a plus ribavirin*. J Viral Hepat 2005; 12:481-7. [PMID: 16108762 DOI: 10.1111/j.1365-2893.2005.00628.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Early virological response may predict outcome following treatment with peginterferon alpha-2a and ribavirin in patients chronically infected with hepatitis C virus (HCV). As total HCV core antigen may constitute an alternative direct marker to HCV RNA for assessing the levels of viraemia in such patients, we evaluated the correlation between HCV core antigen and HCV RNA, and whether HCV core antigen at baseline, 4 and 12 weeks after treatment could predict sustained virological response (SVR) to combined therapy, in comparison with HCV RNA. A total of 290 serum samples from 58 previously treatment naïve chronic HCV patients were examined for HCV core antigen and HCV-RNA by means of quantitative HCV RNA when receiving combination therapy for the first time. SVR was significantly associated with basal HCV core antigen but not with HCV RNA. There was a good correlation between HCV core antigen and HCV RNA (r(2) = 0.781). The negative predictive value of HCV core antigen testing in predicting nonresponse at weeks 4 and 12 were 75 and 100%, and for undetectable or a 2-log drop in HCV RNA were 69.6 and 75% respectively. HCV core antigen detection is quick, and easy to perform alternative to HCV RNA, and could be used as a marker of HCV viraemia for monitoring the progress of therapy.
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Affiliation(s)
- V González
- Department of Microbiology, Hospital Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona, Barcelona, Spain.
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27
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Carabaich A, Ruvoletto M, Bernardinello E, Tono N, Cavalletto L, Chemello L, Gatta A, Pontisso P. Profiles of HCV core protein and viremia in chronic hepatitis C: possible protective role of core antigen in liver damage. J Med Virol 2005; 76:55-60. [PMID: 15778969 DOI: 10.1002/jmv.20322] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The relation between HCV core antigen and HCV RNA has been confirmed in patients with chronic hepatitis C and a parallel behavior of the two markers has been described in early kinetics analysis during antiviral therapy. Variations of the core antigen to HCV RNA ratio have been reported in individual patients and the existence of nucleocapsid particles, not always associated with viral genomes, have been described. To assess the characteristics of HCV core antigen reactivity in relation to viremia in patients with different clinical profiles, 233 patients with chronic hepatitis C were studied serially. Group A included 54 asymptomatic HCV carriers, group B included 8 viremic patients with biochemical long-term response after antiviral therapy, while group C was composed of 171 patients with chronic liver disease and 75 were treated with combination therapy. Core antigen levels were not significantly different in the three groups of patients and a wide range of antigenic reactivity was observed in individual patients. A close relationship was observed between core antigen and HCV RNA, although their ratio was significantly higher in biochemical long-term responders (group B), compared to the other groups (P < 0.05). Physicochemical characterization of core antigen reactivity by equilibrium CsCl density gradient identified two distinct peaks migrating at 1.08-1.12 g/ml CsCl density and at 1.18-1.31 CsCl density, respectively. The first one, corresponding to the lipid-associated fraction, contained higher amounts of core antigen reactivity and was associated with clinical remission of liver damage, while the second peak, corresponding to naked nucleocapsids, was observed mainly in sera with active disease. In conclusion, a close relationship between core and HCV RNA was documented both in treated and untreated patients. The finding of an excess of lipid-associated core particles in a subset of viremic patients without biochemical activity of liver disease suggests their protective effect in liver cell damage.
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Affiliation(s)
- Alessandro Carabaich
- Clinica Medica 5, Department of Clinical and Experimental Medicine, University of Padova, Italy
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28
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Seme K, Poljak M, Babic DZ, Mocilnik T, Vince A. The role of core antigen detection in management of hepatitis C: a critical review. J Clin Virol 2005; 32:92-101. [PMID: 15653411 DOI: 10.1016/j.jcv.2004.10.005] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2004] [Accepted: 10/12/2004] [Indexed: 02/07/2023]
Abstract
Several assays in research format and two commercial assays for the detection of hepatitis C virus (HCV) core protein or HCV core antigen have been developed in recent years. In order to elucidate the role and significance of HCV core antigen detection in the diagnosis and management of hepatitis C, we reviewed 56 studies published in peer-reviewed journals until September 2004. Evaluations in transfusion settings showed that the HCV core antigen assay detects HCV infection, similarly as nucleic acid techniques (NAT), between 40 and 50 days earlier than the current third generation HCV antibody screening assays. HCV core antigen levels closely track HCV RNA dynamics, and allow clinical monitoring of a patient's therapy, independently of HCV genotype, however, mainly in the samples with HCV RNA levels above 20,000 IU/ml. Considering the lower sensitivity of HCV core antigen detection in comparison to NAT, the HCV core antigen assay is not practical for the determination of the end of treatment response and sustained viral response, but could be useful for the determination of early viral response in the pegylated interferon-alpha and ribavirin treated patients infected with HCV genotype 1. The HCV core antigen detection is a viable tool for study of hepatitis C pathogenesis. The HCV core antigen can be used as a marker of HCV replication in anti-HCV positive individuals in the areas of the world that cannot afford NAT and/or in the settings that are not equipped or competent to perform HCV RNA testing. Because the manufacturer of HCV core antigen assays recently stopped an active marketing of these assays in several countries, it will, unfortunately and probably, never be possible to determine the actual potential and usefulness of HCV core antigen testing in the management of hepatitis C.
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Affiliation(s)
- Katja Seme
- Medical Faculty, Institute of Microbiology and Immunology, Zaloska 4, 1000 Ljubljana, Slovenia
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29
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Takahashi M, Saito H, Higashimoto M, Atsukawa K, Ishii H. Benefit of hepatitis C virus core antigen assay in prediction of therapeutic response to interferon and ribavirin combination therapy. J Clin Microbiol 2005; 43:186-91. [PMID: 15634970 PMCID: PMC540104 DOI: 10.1128/jcm.43.1.186-191.2005] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
A highly sensitive second-generation hepatitis C virus (HCV) core antigen assay has recently been developed. We compared viral disappearance and first-phase kinetics between commercially available core antigen (Ag) assays, Lumipulse Ortho HCV Ag (Lumipulse-Ag), and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor test, version 2 (Amplicor M), to estimate the predictive benefit of a sustained viral response (SVR) and non-SVR in 44 genotype 1b patients treated with interferon (IFN) and ribavirin. HCV core Ag negativity could predict SVR on day 1 (sensitivity = 100%, specificity = 85.0%, accuracy = 86.4%), whereas RNA negativity could predict SVR on day 7 (sensitivity = 100%, specificity = 87.2%, accuracy = 88.6%). None of the patients who had detectable serum core Ag or RNA on day 14 achieved SVR (specificity = 100%). The predictive accuracy on day 14 was higher by RNA negativity (93.2%) than that by core Ag negativity (75.0%). The combined predictive criterion of both viral load decline during the first 24 h and basal viral load was also predictive for SVR; the sensitivities of Lumipulse-Ag and Amplicor-M were 45.5 and 47.6%, respectively, and the specificity was 100%. Amplicor-M had better predictive accuracy than Lumipulse-Ag in 2-week disappearance tests because it had better sensitivity. On the other hand, estimates of kinetic parameters were similar regardless of the detection method. Although the correlations between Lumipulse-Ag and Amplicor-M were good both before and 24 h after IFN administration, HCV core Ag seemed to be relatively lower 24 h after IFN administration than before administration. Lumipulse-Ag seems to be useful for detecting the HCV concentration during IFN therapy; however, we still need to understand the characteristics of the assay.
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Affiliation(s)
- Masahiko Takahashi
- Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
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30
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Enomoto M, Nishiguchi S, Tamori A, Kohmoto M, Habu D, Sakaguchi H, Takeda T, Kawada N, Seki S, Shiomi S. Chemiluminescence enzyme immunoassay for monitoring hepatitis C virus core protein during interferon-α2b and ribavirin therapy in patients with genotype 1 and high viral loads. J Med Virol 2005; 77:77-82. [PMID: 16032731 DOI: 10.1002/jmv.20416] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
This study evaluated an updated chemiluminescence enzyme immunoassay (CLEIA) for hepatitis C virus (HCV) core protein for monitoring viral kinetics during treatment with interferon (IFN)-alpha and ribavirin. Using the CLEIA, serum levels of HCV core protein were measured in 17 patients with genotype 1 and high baseline viral loads during the first 4 weeks of combination therapy. HCV RNA was measured by the Amplicor Monitor test for comparison. At the start of therapy, the median HCV level (interquartile range) was 700 (540-940) kIU/ml of viral RNA and 11,310 (5,528-14,238) fmol/L of core protein. HCV RNA was above the upper limit of the linear range of the Amplicor Monitor test in 13 of the 17 patients, while the core protein level was within the linear range of the CLEIA in all patients. During therapy, the proportion of patients with HCV levels below the cutoff values at each time point was less with the Amplicor Monitor test than with CLEIA. Serum HCV core protein level decreased rapidly during the first 24 hr of therapy and more slowly thereafter, with median exponential decays of 1.08 and 0.046 log10/day, respectively. In the second phase, between day 1 and 28, the median decrease in HCV core protein level was higher in four patients with sustained virologic response (0.13 log10/day) than in 13 patients with no response (0.028 log10/day, P = 0.042). The wide linear range of the HCV core protein assay is appropriate for measuring viral loads during therapy with IFN-alpha and ribavirin.
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Affiliation(s)
- Masaru Enomoto
- Department of Hepatology, Osaka City University Medical School, Osaka, Japan
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31
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Valcavi P, Medici MC, Casula F, Arcangeletti MC, De Conto F, Pinardi F, Calderaro A, Chezzi C, Dettori G. Evaluation of a total hepatitis C virus (HCV) core antigen assay for the detection of antigenaemia in anti-HCV positive individuals. J Med Virol 2004; 73:397-403. [PMID: 15170635 DOI: 10.1002/jmv.20105] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
A new, sensitive enzyme immunoassay has been developed for detecting and quantifying total hepatitis C virus (HCV) core antigen in anti-HCV positive or negative sera ("trak-C", Ortho Clinical Diagnostics, Raritan, NJ). The purpose of this study was to evaluate the performance of trak-C as an additional laboratory diagnostic marker of viraemia. The performance was compared to HCV-RNA detection in the "screening" of sera from a large heterogeneous population of hospitalised patients and outpatients. Six hundred and eighteen anti-HCV negative sera, 405 anti-HCV positive/HCV-RNA negative sera, 604 anti-HCV positive/HCV-RNA positive sera and 67 anti-HCV negative sera containing antigens or antibodies potentially interfering with the performance of the assay were analysed. Supplemental HCV antibody testing was performed using a commercial strip immunoblot assay. HCV-RNA was investigated using a qualitative commercial assay. A quantitative commercial RT-PCR was used for the analysis of selected samples. Sensitivity and specificity values were 94.7 and 100%, respectively. The latter was also confirmed when anti-HCV negative samples containing potentially interfering antigens/antibodies were examined. Sensitivity below 100% was probably due to an antigenaemia below the detection limit of trak-C. Besides, because 65.6% of HCV-RNA positive/trak-C negative samples presented specific antibodies against all four RIBA antigens, the hypothesis was raised that, in some cases, the dissociation step efficiency could be sub-optimal. In conclusion, trak-C seems suitable for identifying HCV infection on large based populations. It is a rapid to perform, reliable and specific assay that can be adapted to any laboratory setting.
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Affiliation(s)
- Pierpaolo Valcavi
- Department of Pathology and Laboratory Medicine, Section of Microbiology, University of Parma, Parma, Italy.
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32
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Krajden M, Shivji R, Gunadasa K, Mak A, McNabb G, Friesenhahn M, Hendricks D, Comanor L. Evaluation of the core antigen assay as a second-line supplemental test for diagnosis of active hepatitis C virus infection. J Clin Microbiol 2004; 42:4054-9. [PMID: 15364989 PMCID: PMC516310 DOI: 10.1128/jcm.42.9.4054-4059.2004] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
The British Columbia Center for Disease Control laboratory performs approximately 95% of all hepatitis C virus (HCV) antibody tests for the province's 4 million inhabitants. In 2002, the laboratory tested 96,000 specimens for anti-HCV antibodies, of which 4,800 (5%) were seroreactive and required confirmation of active infection. Although HCV RNA assays with a sensitivity of 50 IU/ml or less are recommended for the confirmation of active HCV infection, given the large number of seroreactive specimens tested annually, we evaluated the Ortho trak-C assay (OTCA) as a second-line confirmatory test and determined its limit of detection (LoD). Of 502 specimens from treatment-naïve anti-HCV-positive individuals, 478 had sufficient volumes for evaluation by the OTCA and HCV RNA tests. Core antigen was not detected in 147 of 478 (30.8%) of these specimens, of which 37 of 147 (25.2%) were shown to be viremic by the VERSANT HCV (version 3.0) (branched-DNA) assay and/or the VERSANT HCV qualitative assay. Testing of 144 replicates of a World Health Organization standard dilution series indicated that the LoD of OTCA was approximately 27,000 IU/ml. This LoD is consistent with the inability of OTCA to detect core antigen in clinical specimens with low viral loads. We conclude that OTCA has limited value as a confirmatory test for the diagnosis of active HCV infection because 37 of 367 (10%) of viremic specimens had undetectable core antigen. Qualitative HCV RNA testing remains the present standard for the confirmation of active HCV infection in the diagnostic setting.
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Affiliation(s)
- Mel Krajden
- British Columbia Center for Disease Control, 655 W. 12th Ave., Vancouver, BC V5Z4R4, Canada.
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33
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Schüttler CG, Thomas C, Discher T, Friese G, Lohmeyer J, Schuster R, Schaefer S, Gerlich WH. Variable ratio of hepatitis C virus RNA to viral core antigen in patient sera. J Clin Microbiol 2004; 42:1977-81. [PMID: 15131157 PMCID: PMC404599 DOI: 10.1128/jcm.42.5.1977-1981.2004] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Quantification of hepatitis C virus (HCV) core antigen and RNA in serum samples leads to a highly variable ratio of both. It is not clear whether this is due to the inaccuracy of RNA quantification or whether both are independent parameters in a certain range. We established a real-time reverse transcription (RT)-PCR for HCV RNA that combines very high sensitivity with a large dynamic range and minimal standard deviations. The assay was calibrated with the first international standard, 96/790, and the international genotype panel for HCV from the National Institute of Biological Standardisation and Control. A linear readout was obtained between 200 and 5 x 10(7) IU/ml. The detection limit was 80 IU/ml, the reproducibility was <0.05 log, and the standard error within one run was <0.01. Comparison of the method with the Roche Monitor competitive RT-PCR revealed its high accuracy. The core protein concentration was determined within a range from 1.5 to 400 pg/ml by using the preliminary trak-C assay from Ortho Clinical Diagnostics. Correlating the HCV RNA levels with core antigen concentrations in 197 serum samples from 23 interferon-treated patients, a average ratio of 7,900 IU of HCV RNA per pg of core antigen was estimated, but the variability of this ratio exceeded largely the variability of the two assays, ranging from 50 to 20,000 IU/pg. Theoretically, HCV should contain ca. 43,000 IU of RNA/pg core. In conclusion, the core antigen assay seems to detect, in addition to complete virions, RNA-free core protein structures, which enhances its sensitivity (98% in this group). The variable ratio of RNA and core protein is not mainly due to standard deviations of quantification but could be an additional parameter for treatment follow-up and state of viral replication.
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34
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Soffredini R, Rumi MG, Parravicini ML, Ronchi G, Del Ninno E, Russo A, Colombo M. Serum levels of hepatitis C virus core antigen as a marker of infection and response to therapy. Am J Gastroenterol 2004; 99:1738-43. [PMID: 15330912 DOI: 10.1111/j.1572-0241.2004.30396.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Hepatitis C virus (HCV) core antigen is a recently developed marker of hepatitis C infection. We compared the predictive power of HCV core antigen with reverse transcription polymerase chain reaction (RT-PCR) and branched DNA assay for HCV-RNA as markers of infection and response to interferon therapy. METHODS Four hundred and forty-four sera from 111 patients (65 men, 52 yr) with chronic hepatitis C, receiving ribavirin together with standard interferon (n = 61) or pegylated interferon (n = 50) were retrospectively investigated. RESULTS Pretreatment, RT-PCR, branched DNA (median 621,887 IU/ml), and HCV core antigen (median 57 pg/ml) gave positive results in 100%, 99%, and 94% of the sera; the correlation between HCV core antigen and branched DNA was 0.75. The median HCV RNA level among the 7 of 111 (6%) patients that had a negative core Ag result was 15,016 IU/ml. Pretreatment levels of HCV core antigen were significantly lower in the 41 patients with a sustained virological response than in the 39 relapsers and 31 nonresponders (17 pg/ml, 114 pg/ml, 58 pg/ml; p-value 0.005). Independently of treatment schedule, wk 12 more than 2 log(10) reduction of viremia or a negative result for HCV core antigen had 100% negative predictive value (NPV) for a response to therapy compared to 94% for negative RT-PCR. The positive predictive value (PPV) of HCV core antigen and branched DNA was only 47% and 48%. CONCLUSIONS In conclusion, the HCV core antigen is a less sensitive test of HCV viremia than HCV-RNA assays and is competitive with the bDNA assay as an early predictor of a nonresponse.
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Affiliation(s)
- Roberta Soffredini
- A.M. Migliavacca Center for Liver Disease, Department of Gastroenterology and Endocrinology, IRCCS Maggiore Hospital and University of Milan, Via Pace 9, 20122 Milan, Italy
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35
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Netski DM, Wang XH, Mehta SH, Nelson K, Celentano D, Thongsawat S, Maneekarn N, Suriyanon V, Jittiwutikorn J, Thomas DL, Ticehurst JR. Hepatitis C virus (HCV) core antigen assay to detect ongoing HCV infection in thai injection drug users. J Clin Microbiol 2004; 42:1631-6. [PMID: 15071017 PMCID: PMC387596 DOI: 10.1128/jcm.42.4.1631-1636.2004] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
We evaluated a quantitative enzyme immunoassay (trak-C) for hepatitis C virus core antigen (HCV core Ag) by testing serum specimens from 820 injection drug users in Thailand with anti-HCV antibodies. The HCV genotypes in this population include genotypes 3 and 6, which have not been extensively tested with this assay. Among these specimens, 629 (76.7%) yielded positive results, with HCV core Ag concentrations predominantly spanning (35.7%) or above (58.2%) the measurable range of 1.5 to 100 pg/ml. To assess reproducibility, we retested 30 specimens representing six core Ag ranges; the mean coefficient of variation for each range was < or = 9.7% (highest for 1.5 to 25 pg/ml). We also tested 204 specimens of the 820-specimen set for HCV RNA: while 146 (71.6%) were core Ag positive, 168 (82.4%) had detectable HCV RNA, of which 96% were typeable as genotype 3 (39%), 1 (31%), or 6 (26%) by nested reverse transcription-PCR. Among RNA-positive specimens, 86.9% had core Ag; 94% of the RNA negatives were core Ag negative. While there was no apparent bias for detecting core Ag representing the tested genotypes, median quantified results were higher for types 1a and 6 than for genotype 3 (P = 0.01); similarly, the median core Ag concentration was higher in HCV-human immunodeficiency virus-coinfected subjects than in HCV-monoinfected subjects. Our results demonstrated a good correlation between core Ag and HCV RNA in this population with high frequencies of genotypes 3 and 6. Because most core Ag concentrations were greater than those in the measurable range, we recommend a 10-fold dilution of the specimen before quantification. Reproducibility, low technical requirements, and high throughput should make this assay useful for clinical or research monitoring of HCV levels during active infection.
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Affiliation(s)
- Dale M Netski
- Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland.
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36
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Cagnon L, Wagaman P, Bartenschlager R, Pietschmann T, Gao T, Kneteman NM, Tyrrell DLJ, Bahl C, Niven P, Lee S, Simmen KA. Application of the trak-C HCV core assay for monitoring antiviral activity in HCV replication systems. J Virol Methods 2004; 118:23-31. [PMID: 15158065 DOI: 10.1016/j.jviromet.2004.01.014] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2003] [Revised: 12/15/2003] [Accepted: 01/06/2004] [Indexed: 01/22/2023]
Abstract
The Ortho trak-C immunoassay has recently established detection of the HCV core antigen as a viable indirect marker of HCV replication in clinical samples. In this study, trak-C is used to monitor HCV replication in three pre-clinical models: the cellular HCV replicon system, transient transfection of HCV genomes, and the murine Alb-uPa/SCID HCV infection model. All of these systems utilize full-length HCV genomes that direct the expression of core, facilitating its detection with monoclonal antibodies. When performed with purified protein, the assay detects HCV core with a lower limit of detection at 1.5pg, and exhibits linear detection up to 100pg. When assaying extracts prepared from Huh-7 clone 21-5 cells harboring a full-length HCV replicon, core is detectable from as few as 63 cell equivalents. The assay was used to determine the sensitivity of Huh 21-5 cells to the antiviral effects of interferon (IFN). Inhibition by IFN-alpha using core detection was comparable to that observed using branched-DNA (bDNA 3.0) detection of HCV RNA. Replication of transfected full-length HCV 1a Con1 genomes in Huh-7 cells was also detectable using the trak-C assay. Finally, in the transgenic murine HCV infection model, the course of viral amplification was detected from serum using trak-C with kinetics similar to those observed with RNA detection. Given its ease of use and the lack of requirement for RNA purification, the trak-C assay has several advantages over RNA-based methods of viral monitoring.
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Affiliation(s)
- Laurence Cagnon
- Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA
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Mondelli MU. Monitoring response to antiviral treatment by serum hepatitis C virus core antigen: too early to take shortcuts? J Hepatol 2004; 40:536-8. [PMID: 15123372 DOI: 10.1016/j.jhep.2004.01.012] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
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38
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Buti M, Mendez C, Schaper M, Sauleda S, Valdes A, Rodriguez-Frias F, Jardi R, Esteban R. Hepatitis C virus Core Antigen as a predictor of non-response in genotype 1 chronic hepatitis C patients treated with peginterferon alpha-2b plus ribavirin. J Hepatol 2004; 40:527-32. [PMID: 15123370 DOI: 10.1016/j.jhep.2003.11.026] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2003] [Revised: 11/17/2003] [Accepted: 11/24/2003] [Indexed: 02/07/2023]
Abstract
BACKGROUND/AIMS Chronic hepatitis C patients infected by genotype 1 are the least responsive to combination therapy and therefore monitoring response is important in identifying non-responders quickly, permitting therapy discontinuation and avoiding side effects and costs. We examined the usefulness of measuring total HCV Core Ag in early treatment with peginterferon alpha-2b and ribavirin in genotype 1 patients in the prediction of response and compared the results with those from HCV RNA quantification. METHODS Two hundred and sixty-eight serum samples from 46 genotype 1 patients receiving combination therapy were examined for HCV Core Ag and quantitative HCV RNA. RESULTS At baseline, mean HCV RNA and HCV Core Ag concentrations were significantly lower in sustained virologic responders than in non-responders. The negative predictive value of HCV Core Ag testing in predicting non-response at week 12 is 100%, and for a 2 log drop in HCV RNA, using two quantitative tests, it is 88%. CONCLUSIONS HCV Core Ag determination allows the identification of non-responders with only one test at week 12 and permits stopping therapy in these patients. HCV Core Antigen testing is cheaper and easier to perform than HCV RNA quantification.
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Affiliation(s)
- Maria Buti
- Servicio de Hepatología, Hospital General Universitario Valle de Hebrón, Barcelona, Spain.
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39
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Agha S, Tanaka Y, Saudy N, Kurbanov F, Abo-Zeid M, El-Malky M, Khalaf M, Ohta N, Yoshizawa H, Mizokami M. Reliability of hepatitis C virus core antigen assay for detection of viremia in HCV genotypes 1, 2, 3, and 4 infected blood donors: A collaborative study between Japan, Egypt, and Uzbekistan. J Med Virol 2004; 73:216-22. [PMID: 15122795 DOI: 10.1002/jmv.20078] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Nucleic acid amplification-based methods are used for confirmation of viremia in antibody to hepatitis C virus (anti-HCV)-positive patients. However, this technology is labor intensive, time consuming, requires complex laboratory conditions, and expensive. The aim of this study was to evaluate the sensitivity and specificity of the HCV core antigen (HCVcAg) assay as an alternative approach for confirmation of viremia in HCV-infected subjects with HCV genotype 1-4. Two hundred forty-six asymptomatic HCV RNA- positive donors were enrolled in this study, consisting of 122 blood donors from Egypt (116 with genotype 4, 4 with genotype 1, and 2 with 1 + 4 genotypes), 109 from Japan (85 with genotype 1, and 24 with genotype 2), and 15 from Uzbekistan (all with genotype 3). A total of 234 (95.1%) of 246 RNA-positive specimens were detected by the HCVcAg assay; the sensitivity of HCVcAg assay consisted 93.4, 100, 100, and 94.8% for genotypes 1, 2, 3, and 4, respectively in comparison with RT-PCR assay. The specificity of the assay was confirmed in the absence of the false-positive results among 53 anti-HCV-negative, but anti-Schistosoma mansoni (anti-Sm) positive donors from Egypt. A positive correlation between HCVcAg and HCV RNA concentration levels (r = 0.671, P < 0.05) was observed among specimens with HCV genotype 4. The mean HCVcAg level was significantly lower in specimens with genotype 4 (2,935 fmol/L) comparing to genotypes 1, 2, and 3 (5,034, 4,962, and 4,740 fmol/L, respectively). No specific mutation was found in the core-encoding region of the studied specimens. In conclusion, HCVcAg is shown to be specific, sensitive, and informative qualitative index for HCV viremia in asymptomatic carriers.
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Affiliation(s)
- Salah Agha
- Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Pradat P, Maynard M, Buti M, Berthillon P, Picchio G, Tillmann HL, Wiegand J, Voirin N, Manns MP, Esteban JI, Martinot M, Marcellin P, Trepo C. The predictive value of core antigen testing for the management of hepatitis C patients receiving pegylated interferon/ribavirin treatment. J Med Virol 2004; 73:392-6. [PMID: 15170634 DOI: 10.1002/jmv.20104] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
A new quantitative marker of HCV viremia based on the detection of the core antigen of the virus has recently become commercially available in Europe. The usefulness of this test was examined for the management of patients treated with pegylated interferon/ribavirin. One hundred twenty-eight pegylated interferon/ribavirin treated patients were studied. Serum samples were available at baseline, week 4 and week 12 time-points, respectively. Core antigen was quantified using the trak-C assay (Ortho Clinical Diagnostics, Raritan, NJ). For all genotypes at week 4, the positive and negative predictive values of HCV core antigen were 81.4 and 92.9%, respectively, while at week 12 they were 67.9 and 100%, respectively. These predictive values varied substantially according to viral genotype. Among patients with a negative core antigen level (<1.5 pg/ml) at week 12, only 33% of those who were positive at week 4 achieved a sustained virological response whereas 85% of those who were already negative did (P < 0.001). The core antigen assay may be used at week 4 and week 12 to distinguish patients who will achieve a sustained virological response from those who will relapse/breakthrough. This assay is a new reliable alternative for early prediction of virological non-response in patients treated with pegylated interferon/ribavirin.
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