Hepatitis C Virus Core Antigen Research Articles

PREVALENCE AND GENOTYPING OF HEPATITIS C VIRUS IN HEMODIALYSIS PATIENTS AND EVALUATION OF HCV-CORE ANTIGEN TEST IN SCREENING PATIENTS FOR DIALYSIS IN SANA'A CITY, YEMEN

Hepatitis C virus infection is a constant worldwide public health concern. The prevalence of HCV infection is higher in patients on chronic haemodialysis (HD) than in the general population. Despite the control of blood products, hepatitis C virus transmission is still being observed among patients undergoing dialysis. Detection systems for serum HCV antibodies are insensitive in the acute phase because of the long serological window. Direct detection of HCV depends on PCR test but this test is not suitable for routine screening. The objective of this study was to determine prevalence of HCV, genotyping and if HCV core antigen test could be a better alternative to NAT techniques for the diagnosis of HCV infection during the window period and whether the sensitivity for antibody detection is preserved. We screened 159 patients on long-term dialysis by HVC antibodies test, PCR HCV-RNA and HCV core antigen test by commercial tests. The prevalence of HCV was 10.7% (17 patients) and genotype 4 was the most common one (64.7%). The sensitivity of HCV core antigen test was 94.1%, the specificity 100%, the positive predictive power 100%, and the negative predictive power 97.9%. In conclusions; patients on maintenance HD in Yemen have a high prevalence of HCV infection comparing with general population; and genotype 4 is predominant. The performance of serological detection of HCV core antigen was better than that of HCV antibodies test and may be an alternative to nucleic acid amplification technology (NAT) for routine monitoring of patients on chronic dialysis.

HCV core antigen is a useful predictor during pegylated-interferon/ribavirin therapy in patients with hepatitis C virus genotype 1b

Enzyme immunoassays for quantifying hepatitis C virus (HCV) core antigen (Ag) have been proposed as an alternative to HCV RNA detection. The present study aimed to investigate the early kinetics of serum HCVcAg and its usefulness in predicting virological responses.The clinical data of 135 patients with chronic hepatitis C treated with pegylated interferon alpha (PEG-IFN-α) and ribavirin was retrospectively collected. The patients were grouped according to their treatment outcomes as follows: sustained virological response (SVR), nonsustained virological response (N-SVR), and relapse.Higher HCVcAg and HCV RNA levels were observed in patients in the N-SVR group than in the other groups at baseline. HCVcAg better predicted rapid virological response (RVR) compared with HCV RNA and had a predictive value similar to that of HCV RNA for SVR and early virological response. In the relapse group, HCV RNA decreased to 0 after 48 weeks, whereas HCVcAg was still detectable, indicating that HCVcAg more sensitively predicted relapse in antiviral therapy than HCV RNA.For patients treated with PEG-INF-α and ribavirin, HCVcAg may more sensitively predict relapse than HCV RNA.

Evaluation of Dried Blood Spots as a Feasible Alternative to Plasma for the Detection and Quantification of Hepatitis C Virus in a Tropical Setting: A Pilot Study

AbstractIntroduction: Confirmatory diagnosis of hepatitis C virus (HCV) infection (HCV RNA detection) is essential before start of the therapy. HCV RNA detection is not available in many parts of India. Shipment of plasma from distant places to referral laboratories may affect HCV RNA titres. Dried blood spots (DBS) provide an easy alternative for transporting samples to centres where HCV RNA testing is done. Aim: Evaluation of DBS as a feasible alternative to plasma for HCV diagnosis. Methods: In this cross-sectional study, 40 consecutive patients’ blood samples were collected from patients referred from the Liver Clinic. Whole blood was spotted onto two Whatman 903TM cards. One card was incubated at ≥37°C and other at 4°C for 15 days, after drying. DBS was eluted and run in Abbott RealTime HCV assay. HCV was also quantified using the Abbott ARCHITECT HCV core antigen assay for 29 of the study patients. Results were compared with normal plasma values. Results: The median log HCV RNA value (in log10 IU/mL) of plasma was 5.74, with normalised DBS it was 4.92 (≥37°C) and 4.66 (4°C); difference in plasma and DBS median log values was 0.82 (≥37°C) and 1.08 (4°C) logs, respectively. Interclass correlation values were 0.943, P < 0.0001 (≥37°C) and 0.950, P < 0.0001 (4°C), showing high agreement. The median HCV core antigen value (in fmol/L) for plasma was 325.35, whereas it was 4.77 (≥37°C) and 4.64 (4°C) for DBS samples. Conclusions: DBS can be used for sampling patients from distant resource-limited settings as an alternative to plasma for HCV RNA estimation. Larger studies are required to evaluate the feasibility of DBS in the Indian subcontinent, especially for HCV core antigen estimation.

IgG1 and IgG4 antibodies against Core and NS3 antigens of hepatitis C virus.

IgG subclasses involved in the immune response to hepatitis C virus (HCV) antigens have been rarely studied. We investigated the immune response mediated by IgG1 and IgG4 antibodies against the recombinant core and NS3 antigens in patients with chronic hepatitis C. Sixty patients infected with HCV genotype 1 without antiviral treatment and 60 healthy subjects participated in the study. Serum levels of alanine aminotransferase, HCV viremia, and the presence of cryoglobulinemia and liver fibrosis were determined. We investigated the serum IgG1 and IgG4 antibodies against recombinant HCV core and NS3 non-structural protein antigens using amplified indirect ELISA. Anti-core and anti-NS3 IgG1 antibodies were detected in 33/60 (55%) and 46/60 (77%) patients, respectively, whereas only two healthy control samples reacted with an antigen (NS3). Anti-core IgG4 antibodies were not detected in either group, while 30/60 (50%) patients had anti-NS3 IgG4 antibodies. Even though there were higher levels of anti-NS3 IgG4 antibodies in patients with low viremia (< 8 × 105 IU/mL), IgG1 and IgG4 antibody levels did not correlate with ALT levels, the presence of cryoglobulinemia, or degree of hepatic fibrosis. High production of anti-core and anti-NS3 IgG1 antibodies was observed in chronic hepatitis C patients. In contrast, IgG4 antibodies seemed to only be produced against the NS3 non-structural antigen and appeared to be involved in viremia control. IgG1 antibodies against structural and non-structural antigens can be detected in chronic hepatitis C, while IgG4 antibodies seem to be selectively stimulated by non-structural HCV proteins, such as the NS3 antigen.

Confirmation of HCV viremia using HCV RNA and core antigen testing on dried blood spot in HIV infected peoples who inject drugs in Vietnam

BackgroundNucleic acid tests performed on blood samples collected on Dried Blood Spot (DBS) and detection of HCV core antigen (HCVcAg) are two approaches that may facilitate access to HCV diagnosis in low and middle incomes countries. In this study we evaluate HCV RNA and HCV antigen testing on DBS in HIV/HCV co-infected peoples who inject drugs in Vietnam.MethodOne hundred and four HIV/HCV seropositive patients managed in outpatient care at the Haiphong Viet Tiep hospital were included in this study from February to March, 2014 (ANRS 12262 study).ResultsEighty-six subjects were tested positive for HCV RNA in serum, median (IQR): 6.9 log10 IU/ml (5.6–7.4 log10 IU/ml). Genotypes consisted of 57 G1 (69%), 3 G3 (4%), and 22 G6 (27%). HCV RNA was detected on DBS specimens in 79 out 86 subjects with chronic hepatitis C (sensitivity 92.5%; 95% CI: 85.1–96.9%). HCV RNA level on DBS and serum was moderately correlated (r = 0.24; p = 0.05) suggesting a degradation of HCV RNA due to transportation and storage conditions. HCVcAg was detected in 75/86 dB specimens (sensitivity: 87.2%; 95% CI: 78.3–93.4%), with a strong positive relationship between DBS HCVcAg and serum HCV RNA levels (r = 0.80; P < 0.0001).ConclusionsQuantification of HCVcAg on DBS appears to benefit from substantial stability under prolonged storage conditions but with a lower analytical sensitivity compared to DBS HCV RNA testing. Detection of HCV RNA on DBS is an interesting approach for confirming viral replication in HCV seropositive persons but the impact of pre-analytical conditions on the integrity of HCV RNA needs to be controlled.

Vitamin D derivatives inhibit hepatitis C virus production through the suppression of apolipoprotein

Supplementation with vitamin D (VD) has been reported to improve the efficacy of interferon-based therapy for chronic hepatitis C. We found that 25-hydroxyvitamin D3 (25-(OH)D3), one of the metabolites of VD, has antiviral effects by inhibiting the infectious virus production of the hepatitis C virus (HCV). In this study, to clarify the underlying mechanisms of the anti-HCV effects, we searched VD derivatives that have anti-HCV effects and identified the common target molecule in the HCV life cycle by using an HCV cell culture system. After infection of Huh-7.5.1 cells with cell culture-generated HCV, VD derivatives were added to culture media, and the propagation of HCV was assessed by measuring the HCV core antigen levels in culture media and cell lysates. To determine the step in the HCV life cycle affected by these compounds, the single-cycle virus production assay was used with a CD81-negative cell line. Of the 14 structural derivatives of VD, an anti-HCV effect was detected in 9 compounds. Cell viability was not affected by these effective compounds. The 2 representative VD derivatives inhibited the infectious virus production in the single-cycle virus production assay. Treatment with these compounds and 25-(OH)D3 suppressed the expression of apolipoprotein A1 and C3, which are known to be involved in infectious virus production of HCV, and the knockdown of these apolipoproteins reduced infectious virus production. In conclusion, we identified several compounds with anti-HCV activity by screening VD derivatives. These compounds reduce the infectious virus production of HCV by suppressing the expression of apolipoproteins in host cells.

HCV core antigen as an alternative to HCV RNA testing in the era of direct-acting antivirals: retrospective screening and diagnostic cohort studies

Direct-acting antivirals for chronic hepatitis C (HCV) infection have reduced the need for on-treatment HCV RNA monitoring. We assessed the accuracy and cost implications of using HCV core antigen testing to replace HCV RNA testing for confirmation of diagnosis, on-treatment monitoring, and determination of sustained virological response (SVR). In a retrospective screening cohort study, de-identified residual serum from unselected samples were obtained from commercial laboratories in Ontario, Canada. Samples from each 5-year age-sex band from birth years 1945-74 collected from Aug 1, 2014, to Feb 28, 2015, were included. All samples that tested positive for HCV antibodies, and 10% of samples that tested negative for HCV antibodies, were tested for HCV core antigen and HCV RNA. A retrospective clinical cohort study was also done using blood samples from patients with confirmed HCV infection collected at four tertiary academic centres: one in Canada, two in Germany, and one in the USA. For assessment of SVR, we included samples from patients who started direct-acting antiviral-based treatment (excluding telaprevir and boceprevir) with or without peginterferon, ribavirin, or both, from Jan 1, 2014, to March 31, 2015. To ensure inclusion of adequate numbers for analysis, patients who relapsed after any treatment regimen were included. Serum samples included in the study were from baseline, week 4 on-treatment (only for patients treated with direct-acting antivirals), end of treatment, and week 12 or 24 of follow-up. The sensitivity and specificity of core antigen testing as a diagnostic tool was assessed in the screening cohort, using HCV RNA as a reference. The sensitivity and specificity of core antigen testing as well as its concordance with HCV RNA testing in the clinical cohort was assessed at baseline, week 4 on-treatment, and at weeks 12 or 24 after the end of treatment in patients undergoing therapy with direct-acting antivirals. The cost-effectiveness of core antigen testing with and without confirmatory HCV RNA testing for negative samples was also assessed. From 10 006 samples in the screening cohort, 75 of 80 viraemic (HCV RNA-positive) samples tested positive for HCV core antigen (sensitivity 94%, 95% CI 86-98), and none of the 993 HCV RNA-negative samples tested positive for HCV core antigen (specificity 100%, 95% CI 94-100). The five viraemic samples that tested negative for HCV core antigen had low corresponding HCV RNA concentrations. In the clinical cohort, two (1%) of 202 baseline samples tested negative for HCV core antigen; one had a low HCV RNA concentration (468 IU/mL), the other had a high HCV RNA concentration (>2 000 000 IU/mL). By week 4 of treatment, HCV core antigen concentrations decreased in all patients but were not predictive of SVR. Although there was good concordance between HCV RNA and HCV core antigen results at 12 weeks after the end of treatment (r=0·97; p<0·0001), three of the 148 patients who achieved SVR at 12 weeks tested HCV core antigen positive. 12 weeks after the end of treatment, HCV core antigen was undetectable in one (1%) of 71 samples from patients who were identified as having relapsed according to HCV RNA detection. On-treatment and end-of-treatment testing of core antigen or HCV RNA provided little clinical value. The use of HCV core antigen testing as a confirmatory diagnostic strategy was cost saving relative to HCV RNA testing, with a reduction of CAD$0·29-3·70 per patient screened depending on whether HCV RNA testing was used to confirm HCV core antigen-negative results. These data support the use of HCV core antigen testing to document HCV viraemia in a cost-saving diagnostic algorithm. In a treatment setting, HCV core antigen testing can be used instead of HCV RNA testing for diagnosis and documentation of treatment adherence, but it might not be adequate to determine SVR. This approach might improve access to care, particularly in low-income and middle-income countries. Abbott Diagnostics and Toronto Centre for Liver Disease.

HCV core antigen: toward elimination of nucleic acid testing?

Following the advent of highly effective direct-acting antivirals (DAAs), now available at generic prices in most countries, elimination of hepatitis C virus (HCV) has become a global health priority. 1 WHOGlobal health sector strategy on viral hepatitis 2016–2021: towards ending viral hepatitis. http://apps.who.int/iris/bitstream/10665/246177/1/WHO-HIV-2016.06-eng.pdfDate: June, 2016 Date accessed: September 10, 2018 Google Scholar However, the very small proportion of patients with HCV being tested and treated for hepatitis C globally overshadows the ambitious 2030 WHO elimination targets. Approximately 20% of patients with HCV are aware of their diagnosis, and less than 10% were treated for their infection in 2015; therefore, achieving the 80% treatment coverage goal recommended by WHO is still a long way off. 1 WHOGlobal health sector strategy on viral hepatitis 2016–2021: towards ending viral hepatitis. http://apps.who.int/iris/bitstream/10665/246177/1/WHO-HIV-2016.06-eng.pdfDate: June, 2016 Date accessed: September 10, 2018 Google Scholar HCV core antigen as an alternative to HCV RNA testing in the era of direct-acting antivirals: retrospective screening and diagnostic cohort studiesThese data support the use of HCV core antigen testing to document HCV viraemia in a cost-saving diagnostic algorithm. In a treatment setting, HCV core antigen testing can be used instead of HCV RNA testing for diagnosis and documentation of treatment adherence, but it might not be adequate to determine SVR. This approach might improve access to care, particularly in low-income and middle-income countries. Full-Text PDF

Screening haemodialysis patients for hepatitis C in Vietnam: The inconsistency between common hepatitis C virus serological and virological tests

Selecting the appropriate screening method and interval for the early detection of hepatitis C virus (HCV) infection in low-resourced haemodialysis settings is a challenge. The challenge occurs when patients are classified as HCV-RNA positive but negative to HCV-core antigen (HCV-coreAg), anti-HCV and genotyping tests. We aim to clarify the inconsistency between HCV-RNA, HCV-coreAg, anti-HCV and HCV genotyping tests in haemodialysis patients and determine the reliability of HCV-coreAg as a routine two-monthly screening strategy. Haemodialysis patients were tested every 2months between 2012 and 2014 at the largest district haemodialysis unit in Ho Chi Minh City, Vietnam, for aminotransferases, anti-HCV antibodies, HCV-coreAg, HCV-RNA and HCV genotype. HCV-coreAg and anti-HCV results were tested against HCV-RNA for sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV). All 201 patients participated in the study. The HCV-coreAg test performed better than the anti-HCV test for sensitivity (100% vs 31%), NPV (100% vs 90%) and accuracy (100% vs 90%). The HCV-coreAg and anti-HCV tests performed no differently for specificity (100% and 98%, respectively) or PPV (100% and 73%, respectively). Kappa values for HCV-coreAg and anti-HCV tests were 1 and 0.39, respectively. Early detection of HCV for the purpose of infection prevention requires a high level of sensitivity and HCV-coreAg performed better in our chronic haemodialysis population as a two-monthly screening method than routine anti-HCV testing. HCV-coreAg test is less labour-intensive with a higher level of accuracy in patients with low viral loads making it cost effective for low-resourced settings. Repeating genotyping may be required in HCV-coreAg positive patients with a low viral load.

Hepatitis C core antigen highly correlated to HCV RNA

Hepatitis C virus core antigen (HCV-Ag) immunoassay has been proposed as a more cost and time efficient one-step alternative to the current two-step screening and diagnostic process. This study investigates the correlation between the HCV-Ag immunoassay and the current gold standard of Hepatitis C Virus (HCV) ribonucleic acid (RNA) molecular assay. Stored sera of 221 consecutive treatment-naive patients tested anti-HCV positive were selected to undergo both HCV-Ag immunoassay and HCV RNA molecular assay. Active infection status and HCV genotype were determined using both assays, and correlation was calculated using a logarithmic scale. Among 221 anti-HCV-positive sera, 197 were positive for both HCV Ag (≥3 fmol/L) and HCV RNA (>15 IU/mL), 22 were negative for both tests, while 2 were positive to HCV RNA only. The sensitivity and specificity for HCV Ag in predicting HCV RNA were 99% and 100%, respectively. Out of 199 patients (90%) tested positive for HCV viremia, 107 (56%) were of genotype 1, 77 (38.7%) of genotype 2 and 15 of other genotypes. Analysis of 221 anti-HCV-positive patient sera found a strong positive correlation between HCV RNA and HCV-Ag (r = 0.960, p < 0.001). Genotype 1 (log [HCV RNA] = 0.988 x log [HCV-Ag] + 2.768), with correlation coefficient 0.945, exhibited a stronger correlation than genotype 2 (log [HCV RNA] = 0.859 x log [HCV-Ag] + 2.859; r = 0.862). Given the strong positive correlation between HCV-Ag immunoassay and HCV RNA molecular assay in genotyping affected individuals, we propose that HCV-Ag immunoassay is a more cost and time efficient alternative to the current two-step diagnostic process.

The correlation of HCV RNA and HCV core antigen in different genotypes of HCV

BackgroundTo analyze the correlation of HCV RNA and HCV core antigen (HCV cAg) in different genotypes of HCV.MethodsOne hundred and six patients who were diagnosed with HCV infection by HCV RNA test were included in the study. HCV genotypes were detected by PCR fluorescent probe. Detected HCV cAg's expression in serum quantitatively and qualitatively with chemiluminescent micro‐particle immuno assay (CMIA) and enzyme‐linked immunosorbent assay (ELISA), respectively, and compared positive rates. Analyzed the correlation of HCV RNA and HCV cAg in different genotypes.ResultsDistribution of HCV genotypes in 106 HCV infected patients were as follows: 1b genotype 46 (43.4%); 2a genotype 7 (6.6%); 3a genotype 18 (17.0%); 3b genotype 3 (2.8%); 6a genotype 9 (8.5%); 1b/3b mixed type 13 (12.3%); and unidentified type 10 (9.4%). Positive rates of HCV cAg detected by CMIA and ELISA were 100% and 56%, respectively, with statistical significance (χ 2 = 60.38, P = 0.000). HCV cAg in 1b genotype group was higher than that in 3b and 1b/3b genotype groups, with statistical significance (U = 3.0, P = 0.006, U = 165, P = 0.014). HCV RNA and HCV cAg in genotype 1b demonstrated a positive correlation (r = 0.894, P = 0.04).ConclusionMajor genetic subtype of HCV genotype was 1b. Compared with ELISA, detection of HCV cAg by CMIA increased the positive rate and facilitated early diagnosis and treatment of HCV‐infected patients. With the increase in HCV RNA load and the expression of HCV cAg, HCV cAg could be an early indicator for the diagnosis of HCV infection in 1b genotype.

Performance evaluation of the mindray anti-HCV assay for the detection of hepatitis C virus infection.

Anti-hepatitis C virus (anti-HCV) antibody assays are recommended for HCV infection screening. The Mindray anti-HCV assay, based on a third-generation immunoassay, was recently launched in China. We aimed to evaluate its diagnostic performance compared with that of two other widely used assays. Six HCV infection seroconversion panels were used to evaluate the sensitivity of the assay for early detection. A total of 1952 clinical samples were tested by the Mindray anti-HCV, Elecsys anti-HCV II, and Architect anti-HCV assays. Samples with reactive results using at least one anti-HCV assay were further tested with the recombinant immunoblot assay (RIBA). Inconsistent results were investigated by the HCV RNA assay and HCV core antigen assay. HCV infection diagnosis was made according to the results of laboratory tests and medical records. The Mindray anti-HCV assay and Elecsys anti-HCV II assay detected seroconversion in an average of 12.5days and 10.5days, respectively, and this difference was not significant (P=.818). Of the 1952 cases, 90 were categorized as "HCV infection" and 1862 were categorized as "no HCV infection." The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) of each assay were as follows: the Mindray anti-HCV assay, 95.6%, 99.2%, 85.1%, 99.8%, 118.6 and 0.045, respectively; the Architect anti-HCV assay, 98.9%, 95.2%, 50.0%, 99.9%, 20.69 and 0.012, respectively; and the Elecsys anti-HCV II assay, 96.7%, 99.9%, 98.9%, 99.8%, 1799.9 and 0.033, respectively. There were significant differences in the specificity, PPV and LR+ among the three assays (P<.001). There were no significant differences in the sensitivity, NPV or LR- among the three assays (P>.05). The Mindray anti-HCV assay displays a similar sensitivity to the Elecsys anti-HCV II assay with respect to the early detection of HCV infection. The Mindray anti-HCV assay shows excellent diagnostic performance and is suitable for the screening of HCV infection.

Evaluation of a Hepatitis C Virus Core Antigen Assay in Plasma and Dried Blood Spot Samples

Simplified, affordable tools to diagnose active hepatitis C virus (HCV) infection are needed to scale up treatment. This study evaluated the analytical performance of HCV core antigen (HCVcAg) detection in samples of plasma and dried venous blood spots (DBSs). Paired plasma and DBS samples were prepared from remnant diagnostic samples, and plasma HCV RNA and HCVcAg were quantified. Sensitivity and specificity for HCVcAg (>3 fmol/L) at two HCV RNA thresholds (≥15 and ≥3000 IU/mL) were calculated. Of 120 paired samples tested, 25 had nonquantifiable HCV RNA and 95 had quantifiable HCV RNA. The median HCV RNA level in plasma was 5.6 log10 IU/mL (interquartile range: 5.2 to 6.2). The median HCVcAg levels in plasma and DBS samples were 2.3 log10 fmol/L (interquartile range: 0.1 to 3.1) and 1.1log10 fmol/L (interquartile range: 0.0 to 1.9), respectively. For diagnosing HCV RNA ≥3000 IU/mL, the sensitivity and specificity of HCVcAg in plasma were 97.7% (95% CI, 91%-100%) and 100% (95% CI, 87%-100%), respectively. The sensitivity and specificity of HCVcAg in DBS were 88.6% (95% CI, 80%-94%) and 97% (95% CI, 82%-100%), respectively. The data from this study demonstrate good sensitivity and specificity of HCVcAg inplasma at an HCV RNA threshold of ≥3000 IU/mL. The level of HCVcAg quantified in plasma was higher than that in DBS.

Evaluation of in vitro screening and diagnostic kits for hepatitis C virus infection

BackgroundTo detect infection by hepatitis C virus (HCV), a reliable kit with high sensitivity and specificity is indispensable. Detection kits for anti-HCV antibodies (anti-HCV) are used for screening, and quantification kits for HCV RNA and core antigen are used for definite diagnosis of HCV infection. ObjectivesWe evaluated the performance of these kits using International Standards and a regional reference panel with HCV negative and positive specimens. Study designIn vitro diagnostic kits (10 anti-HCV, two HCV RNA, and three HCV core antigen) were included. ResultsNearly all specimens in the regional reference panel were correctly identified by all anti-HCV detection kits (one false-positive was observed in one kit). Both HCV RNA quantification kits also correctly identified and quantified HCV RNA titers, without genotype-specific differences. Among the HCV core antigen kits, International Standard values were inconsistent. The sensitivities of these kits were insufficient to detect HCV in positive specimens in the regional reference panel. ConclusionsIn vitro diagnostic kits assessing anti-HCV and HCV RNA have sufficient sensitivities and specificities to screen and detect HCV infection. However, HCV core antigen quantification kits have some limitations in their sensitivities and consistencies for diagnosis of HCV infection. Quality control with International Standards and a regional reference panel is important to maintain the performances of diagnostic kits for HCV infection and to verify the clinical reliability of these kits.

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

The diagnosis of hepatitis C virus (HCV) infection has been traditionally based on the detection of the host antibody response. Although antibody assays are available in different formats and are fairly accurate, they cannot distinguish between an ongoing infection with HCV replicative activity and a past infection where HCV has been cleared, spontaneously or after a successful therapy. As a chronic infection is mostly asymptomatic until the late clinical stages, there is a compelling need to detect active HCV infection by simple and reproducible methods. On this purpose, the clinical guidelines have suggested to search for the HCV ribonucleic acid (HCV-RNA) after anti-HCV has been detected, but this second step carries several limitations especially for population screening. The availability of fast and automated serological assays for the hepatitis C core antigen (HCVAg) has prompted an update of the guidelines that now encompass the use of HCVAg as a practical alternative to HCV-RNA, both for screening and monitoring purposes. In this paper, we summarize the features, benefits and limitations of HCVAg testing and provide an updated compendium of the evidences on its clinical utility and on the indications for use.

Approaches for simplified HCV diagnostic algorithms.

IntroductionIn the light of the advances in HCV antiviral therapy, global control of HCV infection becomes feasible but depends on the capacity of countries to identify infected people and to offer them treatment. To achieve the WHO goal which targets a diagnosis rate of 90% by 2030, simplification of screening and diagnosis will be crucial.MethodsPublished literature, unpublished data and expert consensus were used to determine key parameters, including point‐of‐care, rapid diagnostic testing, screening, the use of HCV core Ag and dried blood spots; starting from 2008 until November 2017. In addition, a manual search was undertaken to detect relevant papers or websites related to specific data from countries which underwent or are planning a programme of HCV elimination.ResultsSeveral strategies have been developed and evaluated these last years to simplify and facilitate access to screening and diagnosis, the development of reliable HCV core antigen tests and new nucleic acid amplification technologies for use in decentralized settings. In high prevalence settings, a one‐step screening and diagnosis strategy could simplify diagnostic algorithms provided the cost is reduced. Finally, genotyping may no longer be required in the context of availability of pangenotypic antiviral therapy.ConclusionsDespite relevant advances in HCV screening and diagnosis, the overall diagnosis package is still too expensive today and efforts must be made to allow generalized implementation of reliable tests in low and middle income countries. These efforts will be key factors to foster a real public health approach to HCV elimination.

DIAGNOSIS MOLEKUL DAN APLIKASI DALAM PENGOBATAN HEPATITIS B &amp; C

In the whole world, up to now hepatitis B and C virus are still the main causes of chronic hepatitis, cirrhosis until hepatocellularcarcinoma. Most diagnosis is based on a serological examination such as the determination of antigen and antibody, for exampleHbsAg, HbeAg and anti HCV. Recently, for hepatitis C examination, HCV core antigen is used for the detection of HCV infection duringthe window period, chronic C hepatitis and for treatment monitoring. At present, serological assays are not sufficient to confirm thediagnosis of hepatitis B and C due to mutations of false negative HbsAg or HbeAg results. Occult hepatitis B can occur with a negativeresult of HbsAg, which cause difficulties in confirming the diagnosis and treatment as well. The success of treatment can be influencedof both hepatitis B and hepatitis C that have genotypes. By using molecular examination, such as determination of HBV-DNA and HCVRNA,it is expected that the problem of serological determination can be overcome. Molecular examination is not only useful for just thediagnosis confirmation, such as for active phase and replicative determination. This sequence is also very useful as a data base prior tothe treatment of hepatitis B and hepatitis C as well as for their following success result.

Role of Hepatitis C Virus Core Antigen Assay in Blood Donors Screening at Zagazig University Hospitals

Background and study aim: Hepatitis C virus (HCV) infection is a major public health problem worldwide. Blood donations screening achieved mainly by serological identification of HCV-Antibody (Ab), has largely reduced HCV transmission. HCV Core Antigen (CAg) tests have been introduced to supplement anti-HCV tests and HCV PCR analyses. CAg may be a useful screening test for identifying window phase of HCV infected patients whom are candidate for blood donations. The study aimed to evaluate diagnostic performance of HCV core antigen in comparison to HCV-RNA quantification and anti-HCV-Ab analyses in attendances of blood bank of Zagazig University hospitals. Patients and Methods: The study was performed on 92 participants attending the blood banks of Zagazig University Hospitals for blood donation between May 2015 to November 2017. The participants were classified into two groups; group A, which included 46 donors (32 males and 14 females) with negative HCV antibody and group B, which Included 46 patients (30 males and 16 females) with positive HCV antibody. Clinical assessment, HCV AB detection by ELISA, Prototype ELISA for HCV core antigen for presence of HCV core antigen and HCV RNA Quantitative were done for all participants. Results: No significant differences between both studied regarding sex and age. A high significant relation between HCV AB positivity and negativity as regard HCV PCR was found in both groups. A high significant relation between HCV core antigen positivity and negativity as regard HCV PCR. There was high significant relation between HCV core antigen positivity and HCV PCR in group A patients. There was a high significant relation between HCV core antigen positivity and HCV PCR in positive HCV antibody patients and statistically a high significant relation between HCV core antigen negativity and HCV PCR in group B patients. Conclusion: HCV core Ag can be identified by serological ELISA. This assay is cheap, easily performed, and compatible with HCV PCR. Its application may prevent the vast majority of HCV transmissions caused by the transfusion of window phase donations.

HCV core-antigen assay as an alternative to HCV RNA quantification: A correlation study for the assessment of HCV viremia

IntroductionDetection of hepatitis C virus (HCV) RNA and the HCV core antigen assay (HCV-Ag) are reliable techniques for the diagnosis of active and chronic HCV infection. Our aim was to evaluate the HCV-Ag assay as an alternative to quantification of HVC RNA. MethodsA comparison was made of the sensitivity and specificity of an HCV-Ag assay (204 serum samples) with those of a PCR assay, and the correlation between the two techniques was determined. ResultsThe sensitivity and specificity of HCV-Ag was 76.6% and 100%, respectively. Both assays were extremely well correlated (Pearson coefficient=0.951). The formula (LogCV=1.15*LogAg+2.26) was obtained to calculate the viral load by PCR from HCV-Ag values. HCV-Ag was unable to detect viral loads below 5000IU/mL. ConclusionAlthough the HCV-Ag assay was less sensitive than the PCR assay, the correlation between both assays was excellent. HCV-Ag can be useful as a first step in the diagnosis of acute or chronic HCV infection and in emergency situations.

Hepatitis C virus core antigen for screening organ donors and recipients

Organ donors and recipients are routinely screened for hepatitis C virus (HCV) infection, typically via anti-HCV detection. We analyze the utility of an alternative HCV core antigen (HCV-Ag) quantification system, the ARCHITECT HCV Ag Assay, in this setting. We simultaneously tested 315 samples from potential organ donors and recipients using two chemiluminescent microparticle immunoassays: ARCHITECT Anti-HCV and HCV Ag (Abbott, Germany). HCV-Ag was detected in 81 of the serum samples (25.71%) and anti-HCV in 87 (27.62%). Seventy-five of the HCV-Ag–positive samples were positive for anti-HCV (92.59%). Overall concordance between the two assays was 94.29%. Of the six HCV-Ag–positive/anti-HCV–negative patients, five had HCV-Ag values <32 fmol/L, and the sixth had a concentration of 477.50 fmol/L (viral load, 137,000 IU/mL). The HCV AG Assay detects HCV infections missed by the Anti-HCV Assay. Both markers should be used to screen for HCV infection in potential organ donors and recipients.