Hepatitis C Virus Ag Research Articles

Hepatitis C virus seroprevalence and prevalence of chronic infection in the adult population in Ireland: a study of residual sera, April 2014 to February 2016.

Robust data on hepatitis C virus (HCV) population prevalence are essential to inform national HCV services. In 2016, we undertook a survey to estimate HCV prevalence among the adult population in Ireland. We used anonymised residual sera available at the National Virus Reference Laboratory. We selected a random sample comprising persons ≥ 18 years with probability proportional to the general population age-sex distribution. Anti-HCV and HCV Ag were determined using the Architect anti-HCV and HCV Ag assays. Fifty-three of 3,795 specimens were seropositive (age-sex-area weighted seroprevalence 0.98% (95% confidence interval (CI): 0.73–1.3%)). Thirty-three specimens were HCV-antigen and antibody-positive (age-sex-area weighted prevalence of chronic infection 0.57% (95% CI: 0.40–0.81%)). The prevalence of chronic infection was higher in men (0.91%; 95% CI: 0.61–1.4%), in specimens from the east of the country (1.4%; 95%CI: 0.99–2.0%), and among persons aged 30–39 years and 40–49 years (1.1% (95% CI: 0.59–2.0%) and 1.1% (95% CI: 0.64–1.9%) respectively). Ireland ranks at the lower end of the spectrum of prevalence of chronic HCV infection internationally. Men born between 1965 and 1984 from the east of the country have the highest rate of chronic HCV infection.

Hepatitis C virus core antigen: A simplified treatment monitoring tool, including for post-treatment relapse

BackgroundSimple, affordable diagnostic tools are essential to facilitate global hepatitis C virus (HCV) elimination efforts. ObjectivesThis study evaluated the clinical performance of core antigen (HCVcAg) assay from plasma samples to monitor HCV treatment efficacy and HCV viral recurrence. Study designPlasma samples from a study of response-guided pegylated-interferon/ribavirin therapy for people who inject drugs with chronic HCV genotype 2/3 infection were assessed for HCV RNA (AmpliPrep/COBAS Taqman assay, Roche) and HCVcAg (ARCHITECT HCV Ag, Abbott Diagnostics) during and after therapy. The sensitivity and specificity of the HCVcAg assay was compared to the HCV RNA assay (gold standard). ResultsA total of 335 samples from 92 enrolled participants were assessed (mean 4 time-points per participant). At baseline, end of treatment response (ETR) and sustained virological response (SVR) visits, the sensitivity of the HCVcAg assay with quantifiable HCV RNA threshold was 94% (95% CI: 88%, 98%), 56% (21%, 86%) and 100%, respectively. The specificity was between 98 to 100% for all time-points assessed. HCVcAg accurately detected all six participants with viral recurrence, demonstrating 100% sensitivity and specificity. One participant with detectable (non-quantifiable) HCV RNA and non-reactive HCVcAg at SVR12 subsequently cleared HCV RNA at SVR24. ConclusionsHCVcAg demonstrated high sensitivity and specificity for detection of pre-treatment and post-treatment viraemia. This study indicates that confirmation of active HCV infection, including recurrent viraemia, by HCVcAg is possible. Reduced on-treatment sensitivity of HCVcAg may be a clinical advantage given the moves toward simplification of monitoring schedules.

INVESTIGATION OF THE SIGNIFICANCE OF DETECTION OF THE NUCLEOCAPSID ANTIGEN OF THE HEPATITIS C VIRUS IN CHILDREN WITH CHRONIC HEPATITIS C

The aim of this study was to investigate the clinical and diagnostic significance of the detection of core-antigen of hepatitis C virus (HCV) in children with chronic hepatitis C (CHC). Sera of 101 patients and 24 non-infected participants were analyzed. Core-antigen was determined by chemiluminescent method using «ARCHITECT HCV Ag» (Abbott, USA). HCV RNA was detected by highly sensitive OT-PCA. The presence of liver fibrosis was established by non-invasive methods. Antibody to core-antigen was detected by ELISA using commercial test-systems. A correlation was found between concentration of core-antigen and HCV RNA, viral subtypes, ALT level, and presence of liver fibrosis. High sensitivity and specificity of the chemiluminescent method for the detection of core antigen in children with CHC was shown. For the first time three ranges of core-antigen concentrations were proposed.

Hepatitis C Core Antigen Testing for Diagnosis of Hepatitis C Virus Infection: A Systematic Review and Meta-analysis.

Diagnosis of chronic hepatitis C virus (HCV) infection requires both a positive HCV antibody screen and confirmatory nucleic acid testing (NAT). Testing for hepatitis C virus core antigen (HCVcAg) is a potential alternative to NAT. To evaluate the accuracy of diagnosis of active HCV infection among adults and children for 5 HCVcAg tests compared with NAT. EMBASE, PubMed, Web of Science, Scopus, and Cochrane Database of Systematic Reviews from 1990 through 31 March 2016. Case-control, cross-sectional, cohort, or randomized trials that compared any of 5 HCVcAg tests with an NAT reference standard. 2 independent reviewers extracted data and assessed quality using an adapted QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool. 44 studies evaluated 5 index tests. Studies for the Abbott ARCHITECT HCV Ag assay had the highest quality, whereas those for the Ortho HCV Ag enzyme-linked immunosorbent assay (ELISA) had the lowest quality. From bivariate analyses, the sensitivity and specificity of the assays were as follows: Abbott ARCHITECT, 93.4% (95% CI, 90.1% to 96.4%) and 98.8% (CI, 97.4% to 99.5%); Ortho ELISA, 93.2% (CI, 81.6% to 97.7%) and 99.2% (CI, 87.9% to 100%); and Hunan Jynda Bioengineering Group HCV Ag ELISA, 59.5% (CI, 46.0% to 71.7%) and 82.9% (CI, 58.6% to 94.3%). Insufficient data were available for a meta-analysis about the Fujirebio Lumipulse Ortho HCV Ag and Eiken Lumispot HCV Ag assays. In 3 quantitative studies using Abbott ARCHITECT, HCVcAg correlated closely with HCV RNA levels greater than 3000 IU/mL. Insufficient data were available on covariates, such as HIV or hepatitis B virus status, for subgroup analyses. Few studies reported genotypes of isolates, and data for genotypes 4, 5, and 6 were scant. Most studies were conducted in high-resource settings and reference laboratories. The HCVcAg assays with signal amplification have high sensitivity, high specificity, and good correlation with HCV RNA levels greater than 3000 IU/mL and have the potential to replace NAT in settings with high HCV prevalence. National Institutes of Health.

Evolving strategy for HCV testing in an Italian tertiary care hospital

BackgroundDiagnostic tests for hepatitis C virus (HCV) infection should be adapted according to the clinical status of the patient. ObjectivesWe exploited the application of different HCV diagnostic algorithms in a tertiary care hospital practice. Study designThe laboratory clinical reports to the medical orders for HCV testing during three years were clustered by different combinations of assays for anti-HCV antibodies (HCV Ab) (screening and confirmatory), HCV nucleic acid (HCV-RNA), HCV core antigen (HCV Ag). The latter was the first-line assay in acute HCV infections requiring a rapid assessment of the infectious state. ResultsThe majority (91.9%) of the 2726 subjects whose samples were analyzed were inpatients. Most of the patients/subjects were tested for clinical suspicion of viral hepatitis (49.2%), or occupational accident to health care professionals (20.0%). On 66% of samples HCV Ag test alone was performed and resulted positive in 116 cases (6%), while it was detected in 50.3% of anti-HCV positive samples. The agreement between HCV Ag and HCV-RNA was very high (k=0.97); HCV Ag positivity rates increased according to the signal of the HCV Ab screening test. ConclusionsThe use of different testing strategies according to the patients’ history and clinical status allowed a significant reduction of the number of tests performed and the time needed to provide a diagnostic response useful for patients’ management without compromising the overall diagnostic accuracy for HCV infection.

Clinical Utility of a New Automated Hepatitis C Virus Core Antigen Assay for Prediction of Treatment Response in Patients with Chronic Hepatitis C.

Hepatitis C virus core antigen (HCV Ag) is a recently developed marker of hepatitis C virus (HCV) infection. We investigated the clinical utility of the new HCV Ag assay for prediction of treatment response in HCV infection. We analyzed serum from 92 patients with HCV infection who had been treated with pegylated interferon and ribavirin. HCV Ag levels were determined at baseline in all enrolled patients and at week 4 in 15 patients. Baseline HCV Ag levels showed good correlations with HCV RNA (r = 0.79, P < 0.001). Mean HCV Ag levels at baseline were significantly lower in patients with a sustained virologic response (SVR) than in those with a non SVR (relapse plus non responder) based on HCV RNA analysis (2.8 log10fmol/L vs. 3.27 log10fmol/L, P = 0.023). Monitoring of the viral kinetics by determination of HCV RNA and HCV Ag levels resulted in similarly shaped curves. Patients with undetectable HCV Ag levels at week 4 had a 92.3% probability of achieving SVR based on HCV RNA assay results. The HCV Ag assay may be used as a supplement for predicting treatment response in HCV infection, but not as an alternative to the HCV RNA assay.

Screening and confirmatory testing strategies for the major transfusion‐transmissible viral infections

BackgroundTesting donated blood for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human T‐cell lymphotropic virus (HTLV) is important as all are transfusion‐transmissible viral infections (TTVIs). A particular challenge in donor screening for TTVIs is that donor selection seeks to minimize the prevalence of TTVIs which in the context of testing substantially increases the likelihood that reactive test results represent ‘false’ rather than ‘true’ reactivity. To address this donor testing algorithms seek to combine strategies to optimize both sensitivity (optimal detection of the ‘target’ pathogen) and specificity (minimising ‘false’ reactivity)AimsFirst, review the fundamental principles underpinning TTVI screening and confirmatory algorithms and discuss key challenges. Second, using working examples illustrate how sound design can lead to optimal, cost‐effective solutions.Materials and MethodsScreening algorithms vary dependent on a number of factors including the epidemiology of the TTVI in the donor population and the available resources (e.g. funding, automation level, technical skill). TTVI screening tests include rapid tests (RT), immunoassays (IA) and nucleic acid tests (NAT). RTs and IAs target ‘serological’ markers of infection (anti‐HIV, HIV p24 antigen, anti‐HCV, HBsAg, anti‐HBc or anti‐HTLV) whereas NAT targets viral RNA (HCV and HIV) or DNA (HBV). NAT has the advantage of earlier detection because viral RNA/DNA appears in the bloodstream before serological markers. However NAT is comparatively expensive requiring higher levels of automation and more skilled staff. Confirmatory testing seeks to ‘confirm’ the presence of the pathogen of interest optimizing donor counselling and referral. The appropriate confirmatory strategy will be dependent primarily on the screening strategy and available resourcing.ResultsWhile optimal screening strategies for HIV, HCV and HBV generally include NAT for its superior ability to identify donors with early infection, there are alternative strategies which can provide almost equivalent safety. For example, the use of HIV and HCV ‘combo’ IAs which combine antibody with antigen (HIV p24Ag or HCV Ag) detection significantly improve sensitivity for early infection. In resource poor settings RT for HIV, HCV and to a lesser extent HBV can still provide a high level of safety particularly where carefully selected. Repeating samples reactive on a primary screening test on a second screening test (termed a ‘sequential immunoassay’ or SI algorithm) and assigning a final status based on concordant reactivity has been shown to improve effectiveness although is dependent on judicious test selection. For HIV, HCV and HTLV antibody based screening strategies immunoblots are often used to confirm the presence of antibody. However, immunoblots are relatively costly and can have poor specificity making it important to optimise the specificity of the screening algorithm. Immunoblotting subsequent to a sequential immunoassay approach has been shown to improve the efficiency and effectiveness of the strategy. Since NAT for HIV, HCV and HBV have demonstrated very high specificity, they now form an independent method of confirming infection for serology reactive samples. In some countries, samples concordantly reactive on serology and NAT screening tests are considered ‘confirmed’ without the need for immunoblotting.ConclusionsEven in resource constrained settings optimally designed screening and confirmatory strategies can significantly reduce the risk of transfusion‐transmissible viral infection.

Comparison of two diagnostic algorithms for the identification of patients with HCV viremia using a new HCV Antigen test

Background. Patients exposed to hepatitis C virus (HCV) may develop chronic infection with viremia. The diagnosis of this condition requires the use of several laboratory tests in algorithms tailored to the population and resources available for each laboratory.Aim. We compared the diagnostic efficacy of two diagnostic algorithms for the identification of viremic patients with HCV. One based on confirmation of reactive antibody results with molecular techniques (reverse transcription polymerase chain reaction, RT-PCR) and the other based on the use of a new HCV core antigen test (HCV Ag).Material and methods. We measured levels of anti-HCV, HCV Ag and viral load (trough RT-PCR) in parallel, in 211 samples (53 antibody positive, 158 antibody negative). Using the three results available for each sample we simulated the diagnostic performance of the two algorithms and compared them to the results of RT-PCR as gold standard.Results. Both algorithms showed a high degree of concordance for viremic patients. The percentage of correctly classified patients was 99.05% for the algorithm based on RT-PCR and 98.10% for the HCV Ag algorithm. The HCV core Ag test showed a clinical sensitivity of 0.917 and showed a good correlation to the results of molecular biology. Spearman rank correlation coefficient (ρ) of 0.97 (95% CI 0.95 to 0.99, p < 0.0001). Conclusion. An algorithm incorporating HCV Ag as confirmatory test for anti-HCV results is a feasible alternative to the use of molecular techniques in laboratories that do not have access to them or require faster turn around times.

Probable hepatitis C virus transmission from a seronegative blood donor via cellular blood products.

Probable hepatitis C virus transmission from a seronegative blood donor via cellular blood products.

Therapy‐induced clearance of HCV core antigen from plasma predicts an end of treatment viral response

During viral assembly, viral proteins are released into plasma and can be used to infer viral load. The Architect hepatitis C virus (HCV) core antigen (Ag) assay is a potential alternative to HCV RNA quantification for measuring response to therapy and predicting an end of treatment viral response (EOTR). The HCVp22Ag assay was used to infer viral load in 68 window RNA-containing samples and in 284 samples from baseline to week 14 of ribavirin/interferon treatment in 23 patients with EOTR including three who relapsed, 20 not achieving EOTR and 11 controls. HCV Ag and RNA correlated well (r = 0.86) with linear dose responses on dilution. In patients on therapy and control patients, plasma HCV antigen was detected in 51 of 54 with an interpolated LOD cut off between 10(3) and 10(4) RNA IU/mL. Plasma HCV antigenaemia and plasma RNA levels were significantly different in EOTR from non-EOTR patients at 3 days after treatment start and all times thereafter. Positive and negative EOTR predictive values for HCV RNA >2 log drop and HCV Ag loss at 12 weeks were 70% and 74%, 85% and 93% respectively. HCV Ag reactivity has a linear dose response independent of genotype and correlates well with HCV RNA. The failure to clear HCV Ag is as accurate as the failure to clear HCV RNA at twelve weeks into therapy in predicting the likelihood of failure to achieve EOTR. HCV Ag potentially offers a convenient alternative to RNA measurement for defining a futility flag in HCV therapy.

Clinical utility of the ARCHITECT HCV Ag assay for early treatment monitoring in patients with chronic hepatitis C genotype 1 infection

BackgroundVirologic response-monitoring is essential for determining therapy duration in patients with chronic hepatitis C virus (HCV) infection. This is usually performed using highly sensitive HCV-RNA assays. However, HCV-RNA assays are time-consuming, expensive and require highly trained personnel. Quantitative determination of HCV core-antigen (HCVAg) levels may be used to supplement treatment monitoring. ObjectivesThe clinical utility of the ARCHITECT HCV Ag assay (Abbott Diagnostics) for response-guided therapy was investigated. Study designWe analyzed serum from 160 patients with HCV genotype 1 infection who had been treated with peg-interferon alfa-2b/ribavirin. HCVAg levels were determined at baseline, weeks 1, 2, 4 and 12. HCVAg levels were compared to those obtained with HCV-RNA assays: VERSANT HCV Quantitative 3.0 (bDNA) and Qualitative (TMA, both Siemens Healthcare) assay and the Abbott RealTime HCV assay (ART; Abbott Diagnostics). ResultsBaseline HCVAg levels correlated well with HCV-RNA as assessed by bDNA (r=0.91; p<0.0001) and ART (r=0.92; p<0.0001), respectively. Patients with undetectable HCVAg levels at week 1 had a 90.9% probability (positive predictive value) to achieve a rapid virologic response (HCV-RNA undetectable at week 4) based on TMA and 86.4% based on ART, respectively. Patients with less than 1log10 reduction in HCVAg between baseline and week 12 had a 90% probability (negative predictive value) to achieve a nonresponse (<2log10 decline in HCV-RNA between baseline and week 12) based on bDNA and 100% based on ART, respectively. ConclusionsDetermination of HCVAg may be useful for antiviral response-monitoring in patients with HCV genotype 1 infection.

Is Hepatitis C Virus Core Antigen an Adequate Marker for Community Screening?

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.

Evaluation of ARCHITECT HCV Core Antigen Assay

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. 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. 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). 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.

Evaluation of a new quantitative test for HCV core Ag

Introduction.The quantitative determination of viral antigens is a diagnostic innovation. The availability of an automated test for detecting the “core” antigen of the hepatitis C virus (HCV) allowed to assess its characteristics and potential applications. Methods.The Abbott ARCHITECT HCV core Ag assay is a fully automated CMIA measuring HCV core antigen at concentrations between 3 and 180,000 fmol / L. The evaluation has been conducted on anti-HCV positive samples at various levels: on samples for which the quantitative (bDNA) and / or qualitative (TMA) HCV-RNA have been tested and on samples of hemodialysis patients. Results.A positivity for HCV Ag was detectable in 10/142 (7.0%) sera with single anti-core reactivity at additional RIBA 3 test while 58 samples reactive to NS3 or NS4 or NS5 were all HCV Ag negative.The frequency of Ag positivity was correlated with the anti-HCV signal (at anti-HCV ARCHITECT), ranging from 71% in samples with S / CO&gt; 5 to 6% in samples with S / CO &lt;5. The antigen was detectable at low concentrations (average 50±1.17 fmol / L) in 8 / 53 samples (15.1%) with viremia below 500 IU / mL. On samples with quantifiable HCV-RNA, the correlation between bDNA and HCV Ag was very good. Of the 65 examined hemodialysis patients, 46 were positive for both antibodies and antigen, 15 for only antibodies, 3 negative for both and one was highly positive for HCV Ag (and HCV-RNA), but anti-HCV negative. Conclusion. The sensitivity and the practicality of the new quantitative test for HCV Ag allow to envisage the use for the evaluation of active HCV infection in anti-HCV positive patients, monitoring patients at risk of infection and as a complement of quantitative viremia.

New Automated Hepatitis C Virus (HCV) Core Antigen Assay as an Alternative to Real-Time PCR for HCV RNA Quantification

An automated hepatitis C virus (HCV) antigen (Ag) assay was evaluated with clinical samples. Determination of HCV Ag and RNA levels in 282 subjects using Abbott HCV Ag and Roche Cobas TaqMan assays revealed that these two tests were highly correlated (r = 0.9464). Thus, the HCV Ag assay could be an alternative test to quantitative reverse transcription-PCR.

A new sensitive and automated chemiluminescent microparticle immunoassay for quantitative determination of hepatitis C virus core antigen

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.

Simultaneous Detection of Hepatitis C Virus (HCV) Core Antigen and Anti-HCV Antibodies Improves the Early Detection of HCV Infection

To evaluate whether a new enzyme immunoassay developed for the simultaneous detection of hepatitis C virus (HCV) core antigen (Ag) and anti-HCV antibodies (anti-HCV Ab) (Monolisa HCV Ag/Ab ULTRA; Bio-Rad) could improve the early detection of HCV infection, we compared its sensitivity to that of anti-HCV, HCV core Ag, and HCV RNA assays. The populations studied included 12 blood donor samples positive for HCV RNA and HCV core Ag but negative for anti-HCV antibodies and 23 hemodialysis patients who developed anti-HCV Ab (seroconversion) during the follow-up. From these 23 individuals, 83 samples sequentially collected prior to seroconversion and 108 samples collected after seroconversion were tested. Six of 12 blood donations were positive by the HCV Ag/Ab assay. In the hemodialysis cohort, the 24 HCV RNA-negative samples were negative by the HCV Ag/Ab assay and 23 of the 59 HCV RNA-positive samples (39%) were positive. The HCV Ag/Ab assay detected HCV infection on average 21.6 days before the most sensitive antibody assay. The HCV Ag/Ab assay did not detect HCV infection as early as the HCV RNA assay (mean delay, 30.3 days) or HCV Ag assay (mean delays, 27.9, and 16.3 days by the HCV core Ag quantification assay and the HCV Ag blood screening assay, respectively). This new assay provides a notable improvement for the early detection of HCV infection during the so-called window period compared with anti-HCV Ab assays and could be a useful alternative to HCV RNA detection or HCV core Ag assays for diagnosis or blood screening when nucleic acid technologies or HCV core Ag detection are not implemented.

Benefit of Hepatitis C Virus Core Antigen Assay in Prediction of Therapeutic Response to Interferon and Ribavirin Combination Therapy

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.

NAT: Perspectives for Cellular Components

The introduction of routine testing to detect viral genomes in donated blood was originally driven by requirements for plasma fractionation in relation to exclusion of hepatitis C virus (HCV) RNA. Nevertheless, it was obvious from the outset that a dual standard for fractionated products and individual blood components would be untenable. In many countries therefore, planning for introduction of nucleic acid testing (NAT) of blood incorporated progression to release of HCV RNA tested components. HCV was singled out because of its long seronegative ‘window period’, relatively high prevalence and incidence in blood donors, rapid burst time and high genome copy number during seroconversion. The latter properties made HCV particularly suitable for detection in pools of samples. If HCV RNA testing is required for release of labile components such as platelets, rapid provision of NAT results is vital because of short shelf life of platelets and the problems of delays when resolving the infectious unit in a reactive pool. For NAT release of labile components smaller sample pool sizes allow faster resolution of RNA positive units. Smaller pools involve high test throughput, the likely need for more testing laboratories and ensuing increased costs. Single sample testing is the ultimate extrapolation of reducing sample pool size. With reduced pool sizes or single sample testing, the option of testing for other viruses (e.g. HIV or HBV) singly or in multiplex also arises. The cost–benefit and incremental yield of such strategies in the light of ‘combo’ assays for HIV Ag/Ab and the recently described HCV Ag assay will require careful and objective assessment, together with re-appraisal of anti-HBc screening for detection of HBV infected donors at the “tail-end” of carriage.

Effect of immune globulin on the prevention of experimental hepatitis C virus infection.

The efficacy of postexposure prophylaxis for the prevention of hepatitis C virus (HCV) infection was studied in experimentally infected chimpanzees. Three chimpanzees were inoculated with HCV: Two were treated 1 h later with anti-HCV--negative intravenous immune globulin (IGIV) or hepatitis C immune globulin (HCIG), and a third animal was not treated. HCV infection was detected in all 3 animals within a few days of inoculation. Once passively transferred anti-HCV declined in the HCIG-treated animal, there was an increase of HCV antigen (Ag)--positive hepatocytes followed by reappearance of anti-HCV; HCV Ag disappeared concordant with the development of acute hepatitis. Acute hepatitis C developed in both the IGIV-treated and untreated chimpanzees, with peak liver enzyme activity on day 59, but was delayed in the HCIG-treated animal until day 146. Postexposure HCIG treatment markedly prolonged the incubation period of acute hepatitis C but did not prevent or delay HCV infection. IGIV had no effect on the course of HCV infection.