Role of hepatitis C virus core antigen assay in hepatitis C care in developing country

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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Hepatitis C Virus Core Antigen as an Alternative to RNA in the Assessment of Response to Treatment with Direct-acting Oral Antivirals

Hepatitis Monthly ◽

10.5812/hepatmon.118579 ◽

2021 ◽

Vol 21 (9) ◽

Author(s):

Antonio Mancebo Martínez ◽

Paula Núñez Serrano ◽

José Carlos Fernández de Cañete Camacho ◽

José María Moreno Planas

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Strong Correlation ◽

Predictive Value ◽

Core Antigen ◽

Hcv Rna ◽

Molecular Testing ◽

The Mean ◽

Direct Acting ◽

Rna Levels

Background: Affordable and effective diagnostic and treatment monitoring algorithms are urgently needed to achieve the global elimination of hepatitis C virus (HCV) infection. Methods: A total of 274 patients were treated with direct-acting antivirals (DAAs) in the Spanish Hospital of Albacete between 2004 and 2020. This study compared the enzyme-immunoassay technique for HCV core antigen (HCVcAg) with the determination of RNA of HCV (HCV RNA) by polymerase chain reaction (PCR) in monitoring treatment with DAA, setting the lower limit of detection of HCVcAg < 3 fmol/L and RNA < 10 IU/mL. In all cases, the P value of differences associated with the contrast test was less than or equal to 0.05. Results: We evaluated the viral loads of our patients before treatment, during their treatment, and after its completion. The HCV RNA quantification at diagnosis was 2309327 IU/mL. The mean HCVcAg load was 5972 fmol/L. There was a strong correlation between HCVcAg levels and RNA levels with a Spearman rho of 0.832 (P < 0.01). The HCVcAg sensitivity at diagnosis was 99%, but the specificity could not be calculated because there were no true negatives or false positives at this point. Twelve weeks after treatment, in patients with treatment failure, we obtained a mean of 19084 IU/mL for RNA, while for HCVcAg, the mean was 103 fmol/L. At this time point, we also found a strong correlation between HCVcAg levels and HCV RNA levels with a Spearman rho of 0.775 (P < 0.01). Finally, the virological cure was achieved in 99% of our patients. The results for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 100%, 99.87%, 86.33%, and 100%, respectively. Conclusions: HCVcAg determination is an excellent alternative to HCV RNA in the assessment of treatment response. This is particularly relevant in lower- and middle-income countries and resource-limited settings where the high cost of labor, equipment, and reagents can prohibit molecular testing.

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Serologic, Virologic, and Histologic Characteristics of Chronic Phase Hepatitis C Virus Disease in Children Infected by Transfusion

PEDIATRICS ◽

10.1542/peds.94.6.919 ◽

1994 ◽

Vol 94 (6) ◽

pp. 919-922

Author(s):

Suguru Matsuoka ◽

Katsuyoshi Tatara ◽

Yasunobu Hayabuchi ◽

Yoshiyuki Taguchi ◽

Kazuhiro Mori ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Acute Infection ◽

Chronic Phase ◽

Hcv Infection ◽

Core Antigen ◽

Hcv Rna ◽

Histologic Evidence ◽

Group A ◽

Group B

Objective. We studied the time course of hepatic dysfunction, seropositivity to hepatitis C virus (HCV) antibodies, viremia, and histologic evidence of hepatic injury to evaluate the course of HCV infection in children infected by blood transfusion. Patients and methods. Twenty-nine patients (ages 4 to 18 years) who underwent open-heart surgeries for congenital heart disease were grouped into three categories based on alterations in serum alanine aminotransferase (ALT) levels: Group A, acute infection; Group B, subacute infection; and Group C, chronic infection. Results. In Group C, all 13 patients had detectable HCV RNA in serum. In contrast, all patients in Group A had no detectable HCV RNA. In Group B, one of nine patients had detectable HCV RNA and two of four patients examined had persistent chronic hepatitis by histologic criteria. Antibodies directed against C100-3 antigen or core-antigen were more useful than second-generation HCV antibody assays in determining the relationship between viremia and immunologic response. Infection with HCV genotype II and the presence of higher HCV RNA copy numbers were associated with histologic evidence of hepatic damage. Conclusion. An abnormal ALT value is frequently associated with viremia, and biochemically resolved acute infection reflects clearance of HCV. However, a normal ALT does not always reflect an absence of hepatocyte damage and HCV replication in patients with subacute disease. The measures outlined in this study are useful indicators of disease activity during the chronic phase of post-transfusion HCV infection.

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Age and Prediction of Sustained Virological Response to Hepatitis C Virus (HCV) Infection Treatment Based on 28‐Day Decrease in HCV RNA Levels

The Journal of Infectious Diseases ◽

10.1086/644507 ◽

2009 ◽

Vol 200 (9) ◽

pp. 1484-1485 ◽

Cited By ~ 6

Author(s):

Giorgio Antonucci ◽

Claudio Angeletti ◽

Francesco Vairo ◽

Maria Antonella Longo ◽

Enrico Girardi

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Sustained Virological Response ◽

Virological Response ◽

Hcv Infection ◽

Hcv Rna ◽

Infection Treatment ◽

Rna Levels

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Hepatitis C Core Antigen Testing to Diagnose Active Hepatitis C Infection Among Haemodialysis Patients

10.21203/rs.3.rs-33936/v2 ◽

2020 ◽

Author(s):

XZ Wong ◽

CC Gan ◽

R M ◽

R Y ◽

S G ◽

...

Keyword(s):

Hepatitis C ◽

Predictive Value ◽

Hcv Infection ◽

Core Antigen ◽

Hcv Rna ◽

Hepatitis C Infection ◽

Hcv Treatment ◽

Serological Screening ◽

Cross Sectional ◽

Spearman Test

Abstract BACKGROUNDHepatitis C virus (HCV) infects more than 71 million people worldwide and chronic HCV infection increases the risk of liver cirrhosis and failure. Haemodialysis (HD) is one of the renal replacement therapies with risk of HCV transmission. Anti-HCV antibodies are the serological screening test for HCV infection that does not detect active phase of infection. Majority HCV infected HD patients in Malaysia do not have further HCV RNA performed due to high cost and thus HCV treatment is less frequently offered. HCV Core Antigen (HCV Ag) can potentially be used to diagnose active HCV infection in HD population in comparison to HCV RNA, at lower cost. METHODS We conducted a cross-sectional study to assess the correlation between HCV Ag and HCV RNA and to identify the prevalence of active HCV infection among HCV seropositive HD patients from dialysis centres across West Malaysia from July 2019 to May 2020. Pre-dialysis blood was taken and tested for both HCV Ag and HCV RNA tests. HCV Ag was tested with Abbott ARCHITECT HCV Ag test.RESULTS We recruited 112 seropositive HD patients from 17 centres with mean age of 54.04±11.62 years, HD vintage of 14.1±9.7 years, and male constitute 59.8% (67) of the study population. HCV Ag correlates well with HCV RNA (Spearman test coefficient 0.833, p<0.001). The sensitivity was 90.7%, specificity 100%, positive predictive value (PPV) 100%, negative predictive value (NPV) 76.5%, and accuracy 92.9%. For HCV RNA level >3000 IU/mL, HCV Ag had a higher sensitivity of 95.1% and greater correlation (Spearman test coefficient 0.897, p<0.001). The prevalence of active HCV infection was 76.8% among HCV seropositive HD patients. CONCLUSIONS Although HCV Ag is less sensitive, it shows an excellent correlation with HCV RNA and has 100% PPV. HCV Ag can be considered as an alternative diagnostic tool for chronic active HCV infection among HD cohort, who can then be considered for HCV treatment. For seropositive HD patient with negative HCV Ag, we recommend to follow-up with HCV RNA test.

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Evaluation of Hepatitis C Virus Core Antigen Assay in a Resource-Limited Setting in Pakistan

Diagnostics ◽

10.3390/diagnostics11081354 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1354

Author(s):

Adeel Abid ◽

Murad Uddin ◽

Taj Muhammad ◽

Safia Awan ◽

Tanya Applegate ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Sensitivity And Specificity ◽

Resource Limited Setting ◽

Hcv Infection ◽

Confirmatory Test ◽

Core Antigen ◽

Hcv Rna ◽

Resource Limited ◽

Limited Setting

The diagnosis of Hepatitis C virus (HCV) infection can be challenging due to its cost and a lack of access to centralized testing. There is an urgent need to develop simplified HCV testing algorithms. The aim of this study was to evaluate the performance characteristics of a Hepatitis C core antigen (HCVcAg) assay in a decentralized, resource-limited setting. This is a descriptive cross-sectional study from a highly endemic area of Karachi, Pakistan. Between October 2019 and July 2020, subjects aged 12 years and above who screened positive for HCV antibodies were simultaneously tested for HCV RNA (Xpert HCV Viral Load, GeneXpert® IV, Cepheid, France) and HCVcAg (ARCHITECT HCV Ag assay, Abbott® Diagnostics) to confirm active HCV infection. An Abbott ARCHITECT® i1000SR Immunoassay Analyser was installed at a local district hospital as a point-of-care (POC) facility for HCVcAg testing, while samples for HCV RNA were tested in a central lab. Two hundred individuals (mean age 46.4 ± 14.5 years, 71.5% females), who screened positive for HCV antibody, were included in the study. HCV RNA was detected in 128 (64.0%) while HCVcAg was reactive in 119 (59.5%) cases. Performance of the Immunoassay Analyser was excellent with a higher throughput and quicker readout value compared to the GeneXpert System. The sensitivity and specificity of HCVcAg (≥10 fmol/L) at HCV RNA thresholds of ≥12 was 99.1% (95% CI: 95–100%) and 87.6% (95%CI: 78.4–94%). A strong agreement was observed between the HCVcAg assay and HCV RNA. The ARCHITECT HCV Ag assay showed high sensitivity and specificity compared to HCV RNA in a decentralized, resource-limited setting. It can therefore be used as a confirmatory test in HCV elimination programs, particularly for low-income countries such as Pakistan.

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Hepatitis C Virus Core Mutations Reduce the Sensitivity of a Fluorescence Enzyme Immunoassay

Journal of Clinical Microbiology ◽

10.1128/jcm.38.9.3450-3452.2000 ◽

2000 ◽

Vol 38 (9) ◽

pp. 3450-3452 ◽

Cited By ~ 12

Author(s):

Hajime Tokita ◽

Gilbert R. Kaufmann ◽

Mamoru Matsubayashi ◽

Isao Okuda ◽

Tsukasa Tanaka ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Enzyme Immunoassay ◽

Core Region ◽

Core Antigen ◽

Nucleotide Sequencing ◽

Hcv Rna ◽

Virus Core ◽

Hcv Core Antigen ◽

Rna Levels

Four of 107 samples obtained from hepatitis C virus (HCV) carriers showed lower HCV core antigen levels in a fluorescence enzyme immunoassay (FEIA) than expected from corresponding HCV RNA levels. Nucleotide sequencing revealed a mutation in the HCV core region (Thr49Pro) that appears to have reduced the FEIA sensitivity.

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HCV core antigen comes of age: a new opportunity for the diagnosis of hepatitis C virus infection

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-0754 ◽

2018 ◽

Vol 56 (6) ◽

pp. 880-888 ◽

Cited By ~ 5

Author(s):

Claudio Galli ◽

Paul Julicher ◽

Mario Plebani

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hcv Infection ◽

Second Step ◽

Core Antigen ◽

Hcv Rna ◽

Hepatitis C Virus Infection ◽

Past Infection ◽

Antibody Assays ◽

Ongoing Infection

AbstractThe 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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Hepatitis C Virus (HCV) diagnosis, epidemiology and access to treatment in a UK cohort

10.1101/216937 ◽

2017 ◽

Author(s):

Emily Adland ◽

Gerald Jesuthasan ◽

Louise Downs ◽

Victoria Wharton ◽

Gemma Wilde ◽

...

Keyword(s):

Hepatitis C Virus ◽

Viral Load ◽

Hepatitis C ◽

Positive Predictive Value ◽

Predictive Value ◽

Clinical Care ◽

Virologic Response ◽

Hcv Infection ◽

Hcv Rna ◽

Direct Acting Antiviral

ABSTRACTBackgroundAs direct acting antiviral (DAA) therapy is progressively rolled out for patients with hepatitis C virus (HCV) infection, careful scrutiny of HCV epidemiology, diagnostic testing, and access to care is crucial to underpin improvements in delivery of treatment.MethodsWe performed a retrospective study of HCV infection in a UK teaching hospital to evaluate the performance of different diagnostic laboratory tests, to describe the population with active HCV infection, and to determine the proportion of these individuals who access clinical care.ResultsOver a total time period of 33 months between 2013 and 2016, we tested 38,510 individuals for HCV infection and confirmed a new diagnosis of active HCV infection (HCV-Ag+ and/or HCV RNA+) in 359 (positive rate 0.9%). Our in-house HCV-Ab test had a positive predictive value of 87% when compared to repeat HCV-Ab testing in a regional reference laboratory, highlighting the potential for false positives to arise based on a single round of antibody-based screening. Of those confirmed Ab-positive, 70% were HCV RNA positive. HCV-Ag screening performed well, with 100% positive predictive value compared to detection of HCV RNA. There was a strong correlation between quantitative HCV-Ag and HCV RNA viral load (p<0.0001). Among the 359 cases of infection, the median age was 37 years, 85% were male, and 36% were in prison. Among 250 infections for which genotype was available, HCV genotype-1 (n=110) and genotype-3 (n=111) accounted for the majority. 117/359 (33%) attended a clinic appointment and 48 (13%) had curative treatment defined as sustained virologic response at 12 weeks (SVR12).ConclusionsHCV-Ab tests should be interpreted with caution as an indicator of population prevalence of HCV infection, both as a result of the detection of individuals who have cleared infection and due to false positive test results. We demonstrate that active HCV infection is over-represented among men and in the prison population. A minority of patients with a diagnosis of HCV infection access clinical care and therapy; enhanced efforts are required to target diagnosis and providing linkage to clinical care within high risk populations.ABBREVIATIONSDAADirect Acting AntiviralELISAEnzyme linked immunosorbent assayHCVHepatitis C VirusHCV-AbIgG antibody to Hepatitis C virusHCV-AgHepatitis C virus core antigenHCV RNAHepatitis C ribonucleic acid (viral load)MSMmen who have sex with menNATnucleic acid testingPCRpolymerase chain reaction (test for viral load)PPVpositive predictive valuePWIDpeople who inject drugsSDGSustainable Development GoalsSVRsustained virologic responseWHOWorld Health Organisation

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Ultracentrifugation of Serum Samples Allows Detection of Hepatitis C Virus RNA in Patients with Occult Hepatitis C

Journal of Virology ◽

10.1128/jvi.02750-06 ◽

2007 ◽

Vol 81 (14) ◽

pp. 7710-7715 ◽

Cited By ~ 62

Author(s):

Javier Bartolomé ◽

Juan Manuel López-Alcorocho ◽

Inmaculada Castillo ◽

Elena Rodríguez-Iñigo ◽

Juan Antonio Quiroga ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hcv Infection ◽

Hcv Rna ◽

Serum Samples ◽

Occult Hepatitis ◽

Viral Particles ◽

Occult Hepatitis C ◽

Detectable Serum ◽

Rna Levels

ABSTRACT Occult hepatitis C virus (HCV) infection of patients with abnormal liver function tests of unknown origin who are anti-HCV and serum HCV RNA negative but who have HCV RNA in the liver has been described. As HCV replicates in the liver cells of these patients, it could be that the amount of circulating viral particles is under the detection limit of the most sensitive techniques. To prove this hypothesis, serum samples from 106 patients with occult HCV infection were analyzed. Two milliliters of serum was ultracentrifuged over a 10% sucrose cushion for 17 h at 100,000 × g av, where av means average, and HCV RNA detection was performed by strand-specific real-time PCR. Out of the 106 patients, 62 (58.5%) had detectable serum HCV RNA levels after ultracentrifugation, with a median load of 70.5 copies/ml (range, 18 to 192). Iodixanol density gradient studies revealed that HCV RNA was positive at densities of 1.03 to 1.04 and from 1.08 to 1.19 g/ml, which were very similar to those found in the sera of patients with classical chronic HCV infection. Antigenomic HCV RNA was found in the livers of 56 of 62 (90.3%) patients with detectable serum HCV RNA levels after ultracentrifugation, compared to 27 of 44 (61.4%) negative patients (P < 0.001). No differences in the median loads of antigenomic HCV RNA between patients with an those without serum HCV RNA (4.5 × 104 [range, 7.9 × 102 to 1.0 × 106] versus 2.3 × 104 [range, 4.0 × 102 to 2.2 × 105]) were found. Alanine aminotransferase and gamma-glutamyl transpeptidase levels, liver necroinflammatory activity, and fibrosis did not differ between both groups. In conclusion, HCV RNA can be detected in the sera of patients with occult HCV infection after circulating viral particles are concentrated by ultracentrifugation.

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