Core Antigen Testing Research Articles

Hepatitis C virus core antigen testing in the monitoring of patients on dialysis

Hepatitis C virus core antigen testing in the monitoring of patients on dialysis

HCV core antigen testing in HIV- and HBV-coinfected patients, and in HCV-infected patients on hemodialysis

Background A quantitative HCV core antigen (HCVcoreAg) immunoassay has been developed for the confirmation of viremia in patients with hepatitis C. Objectives We evaluated the correlation of HCV RNA and HCVcoreAg in different patient populations without HCV-specific treatment: HIV/HCV-coinfection, HBV/HCV-coinfection, and patients with end-stage renal disease. Study design HCVcoreAg was quantified by a fully-automated immunoassay. Correlation of HCVcoreAg with HCV RNA was studied cross-sectionally in HIV/HCV- and HBV/HCV-coinfected patients, as well as before and after hemodialysis in patients with end-stage renal disease. Results A concordant positive or negative test result for both HCV RNA and HCVcoreAg was observed in 68 of 71 (96%), 55 of 57 (96%), and in 109 of 109 (100%) samples of patients with HIV- or HBV/HCV-coinfection, and patients undergoing hemodialysis, respectively. HCVcoreAg showed high correlation with HCV RNA in samples from HIV/HCV-coinfected patients and HCV-infected patients undergoing hemodialysis ( r = 0.97 and r = 0.94, p < 0.001). There was no overall correlation between HCVcoreAg and HCV RNA in HBV/HCV-coinfected individuals ( r = 0.04, p = 0.822). Excluding patients with HCV RNA to HCVcoreAg ratios below 100 and above 10,000 kIU/fmol led to improved correlation ( r = 0.53; p = 0.02), but remained worse than for the other cohorts. Overall, HCV RNA to HCVcoreAg ratios did not differ significantly between the different patient populations, though variation tended to be higher in HBV/HCV-coinfected patients. Patients with lower HCV RNA levels tend to have lower HCV RNA/HCVcoreAg ratios. Conclusions HCVcoreAg represents a reliable marker of viral replication showing a good correlation with HCV RNA in various patient populations, with some limitations in HBV/HCV-coinfection.

Comparison of a Newly Developed Automated and Quantitative Hepatitis C Virus (HCV) Core Antigen Test with the HCV RNA Assay for Clinical Usefulness in Confirming Anti-HCV Results

Hepatitis C virus (HCV) is a global health care problem. Diagnosis of HCV infection is mainly based on the detection of anti-HCV antibodies as a screening test with serum samples. Recombinant immunoblot assays are used as supplemental tests and for the final detection and quantification of HCV RNA in confirmatory tests. In this study, we aimed to compare the HCV core antigen test with the HCV RNA assay for confirming anti-HCV results to determine whether the HCV core antigen test may be used as an alternative confirmatory test to the HCV RNA test and to assess the diagnostic values of the total HCV core antigen test by determining the diagnostic specificity and sensitivity rates compared with the HCV RNA test. Sera from a total of 212 treatment-naive patients were analyzed for anti-HCV and HCV core antigen both with the Abbott Architect test and with the molecular HCV RNA assay consisting of a reverse transcription-PCR method as a confirmatory test. The diagnostic sensitivity, specificity, and positive and negative predictive values of the HCV core antigen assay compared to the HCV RNA test were 96.3%, 100%, 100%, and 89.7%, respectively. The levels of HCV core antigen showed a good correlation with those from the HCV RNA quantification (r = 0.907). In conclusion, the Architect HCV antigen assay is highly specific, sensitive, reliable, easy to perform, reproducible, cost-effective, and applicable as a screening, supplemental, and preconfirmatory test for anti-HCV assays used in laboratory procedures for the diagnosis of hepatitis C virus infection.

Efficacy of individual nucleic acid amplification testing in reducing the risk of transfusion‐transmitted hepatitis B virus infection in Switzerland, a low‐endemic region

The risk of transfusion-transmitted hepatitis B virus (HBV) in Switzerland by testing blood donors for hepatitis B surface antigen (HBsAg) alone has been historically estimated at 1:160,000 transfusions. The Swiss health authorities decided not to introduce mandatory antibody to hepatitis B core antigen (anti-HBc) testing but to evaluate the investigation of HBV nucleic acid testing (NAT). Between June 2007 and February 2009, a total of 306,000 donations were screened routinely for HBsAg and HBV DNA by triplex individual-donation (ID)-NAT (Ultrio assay on Tigris system, Gen-Probe/Novartis Diagnostics). ID-NAT repeatedly reactive donors were further characterized for HBV serologic markers and viral load by quantitative polymerase chain reaction. The relative sensitivity of screening for HBsAg, anti-HBc, and HBV DNA was assessed. The residual HBV transmission risk of NAT with or without anti-HBc and HBsAg was retrospectively estimated in a mathematical model. From the 306,000 blood donations, 31 were repeatedly Ultrio test reactive and confirmed HBV infected, of which 24 (77%) and 27 (87%) were HBsAg and anti-HBc positive, respectively. Seven HBV-NAT yields were identified (1:44,000), two pre-HBsAg window period (WP) donations (1:153,000) and five occult HBV infections (1:61,000). Introduction of ID-NAT reduced the risk of HBV WP transmission in repeat donors from 1:95,000 to 1:296,000. Triplex NAT screening reduced the HBV WP transmission risk approximately threefold. NAT alone was more efficacious than the combined use of HBsAg and anti-HBc. The data from this study led to the decision to introduce sensitive HBV-NAT screening in Switzerland. Our findings may be useful in designing more efficient and cost-effective HBV screening strategies in low-prevalence countries.

Prospective Analysis of Hepatitis B Virus Reactivation in Patients With Diffuse Large B-Cell Lymphoma After Rituximab Combination Chemotherapy

Recently, there have been reports of hepatitis B virus (HBV) reactivation after rituximab combination chemotherapy in hepatitis B surface antigen (HBsAg) -negative patients with B-cell lymphoma. In this prospective study, the frequency of and risk factors for HBV reactivation in patients who were receiving rituximab chemotherapy were examined. A total of 314 HBsAg-negative patients with diffuse large B-cell lymphoma were treated with rituximab chemotherapy. Antibody to hepatitis B surface antigen (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc) tests were performed in all patients. In patients who were positive for anti-HBs and/or anti-HBc, serum HBV-DNA was measured. Of the 314 patients, 51 (16.2%) were HBV carriers. HBV reactivation occurred during or after rituximab chemotherapy in six patients (12%). All six patients who developed HBV reactivation were anti-HBc positive, and three of them were also anti-HBs positive. In these six patients, the pretreatment anti-HBs titer was low. Entecavir administration was started when serum HBV DNA became positive, and serum HBV-DNA became negative within 1 to 3 weeks. Rituximab chemotherapy was then continued. Risk factors for HBV reactivation were being male and having a low anti-HBs titer. HBV reactivation occurred in some patients who had been anti-HBs negative or had a low anti-HBs level. In addition, HBV reactivation occurred at an early stage of rituximab chemotherapy, but rituximab chemotherapy could be continued after entecavir administration reduced the serum HBV-DNA level. Entecavir (BMS 200495) prophylaxis was not performed when rituximab chemotherapy was started, and it was thought that entecavir could be started when serum HBV-DNA increased.

Anti-hepatitis B core antigen testing with detection and characterization of occult hepatitis B virus by an in-house nucleic acid testing among blood donors in Behrampur, Ganjam, Orissa in southeastern India: implications for transfusion

BackgroundOccult hepatitis B virus (HBV) infection might transmit viremic units into the public blood supply if only hepatitis B surface antigen (HBsAg) testing is used for donor screening. Our aim was to evaluate the prevalence of occult HBV infection among the HBsAg negative/antiHBc positive donations from a highly HIV prevalent region of India.MethodsA total of 729 HBsAg negative donor units were included in this study. Surface gene and precore region were amplified by in house nucleic acid test (NAT) for detection of occult HBV infection and surface gene was analyzed after direct sequencing.ResultsA total of 220 (30.1%) HBsAg negative donors were antiHBc positive, of them 66 (30%) were HBV DNA positive by NAT. HBV DNA positivity among 164 antiHBc only group, was 27.1% and among 40 antiHBs positive group was 30.0%. HBV/D (93.3%) was predominant and prevalence of both HBV/C and HBV/A was 3.3%. Single or multiple amino acids substitutions were found in 95% samples.ConclusionThus, a considerable number of HBV infected donors remain undiagnosed, if only HBsAg is used for screening. Addition of antiHBc testing for donor screening, although will lead to rejection of a large number of donor units, will definitely eliminate HBV infected donations and help in reducing HBV transmission with its potential consequences, especially among the immunocompromised population. The HBV genetic diversity found in this donor population are in accordance with other parts of India.

Hepatitis C virus core antigen test in virological monitoring of patients on long-term dialysis.

Hepatitis C virus core antigen test in virological monitoring of patients on long-term dialysis.

Impact of a policy to permit the return of donors repeat‐reactive to the Abbott PRISM antibody to hepatitis B core antigen assay

The expected donor loss from recent implementation of antibody to hepatitis B core antigen (anti-HBc) testing in Canada was uncertain but potentially significant based on US experience. To reduce donor loss from false-reactive tests, repeat-reactive donors without other evidence of infection were eligible to return. The aim was to evaluate the impact of anti-HBc testing on donor loss and to evaluate the effectiveness of this policy. For each donor in the first year of implementation (April 9, 2005-April 8, 2006) repeat-reactive for the presence of anti-HBc only but eligible to return (screening test for hepatitis B surface antigen-negative, plus not reactive to antibody to hepatitis B surface antigen [anti-HBs] and hepatitis B virus [HBV] DNA supplemental tests), 10 matched donors not reactive to the anti-HBc assay were selected. Return rates over 2 years were compared using conditional logistic regression. Testing outcomes were tabulated. Over the first year of testing, 412,236 donors (951,423 donations) were tested for anti-HBc, and 4,489 donors were repeat-reactive (1.3% of first-time donors, 1.0% of repeat donors). Of these 85.6 percent were also reactive for the presence of anti-HBs and/or HBV DNA supplemental tests leaving less than 15 percent eligible to return, of whom 73 percent returned (vs. 90% of controls, p < 0.001). Of the 300 anti-HBc repeat-reactive returning donors, 74 percent were anti-HBc repeat-reactive again (thus permanently deferred), 19 percent were deferred for other reasons versus 14 percent of controls (p < 0.05), and 7 percent (21 donors) did not react and were eligible to continue donating. Most donors repeat-reactive for the presence of anti-HBc likely have past exposure to HBV. If eligible, most are willing to return, but likely to test anti-HBc repeat-reactive again.

Cost-Effectiveness of the National Screening Program for Hepatitis C Virus in the General Population and the High-Risk Groups

In Japan, the national screening for the hepatitis C virus (HCV) has been started for both the general population and the high-risk groups. Our cost-effectiveness analysis was based on the result of the screening program including 99,001 people among the general population and 42,538 people among the high risk group from 2003 to 2006. The screening was performed using the three steps of the semi-quantitative HCV antibody test, the HCV core antigen test and the HCV-PCR test. A Markov model for HCV infected patients was constructed to estimate the future clinical benefits and the lifetime cost and the cost-effectiveness analysis was performed considering the recent treatment with peginterferon plus ribavirin. In the cost-effectiveness analysis, the cohort, in which the screening was implemented (= screening strategy), was compared with the similar cohort without the screening (= no-screening strategy) in both the general population and the high-risk group, stratified by age. The infection rates of the general population and the high-risk group were 0.36% and 0.81%, respectively. The incremental cost-effectiveness ratio (ICER), a measure of cost-effectiveness, of the general population and the high-risk group was calculated to be from 848 to 4,825 and--749 to 2,297 $/life expectancy gained, respectively. The treatment effectiveness, transition probabilities and the infection rate varied in the one-way sensitivity analyses, but the superiority of the screening strategy regarding the cost-effectiveness was unchanged. In conclusion, the screening strategy in both the general population and the high-risk group therefore appears to be more cost-effective than a no-screening strategy.

Hepatitis B virus DNA–positive, hepatitis B surface antigen–negative blood donations intercepted by anti‐hepatitis B core antigen testing: the Canadian Blood Services experience

The benefit of introducing anti-hepatitis B core antigen (HBc) screening for intercepting potentially infectious donations missed by hepatitis B surface antigen (HBsAg) screening in Canada was studied. Anti-HBc testing of all donations was implemented in April 2005, along with antibody to hepatitis B surface antigen (anti-HBs) and hepatitis B virus (HBV) DNA supplemental testing of anti-HBc repeat-reactive, HBsAg-negative donations. The proportion of potentially infectious donations intercepted by anti-HBc over the initial 18 months of testing was calculated based on three assumptions relating infectivity of HBV DNA-positive units to anti-HBs levels. Lookback was conducted for all DNA-positive donations. Of 493,344 donors, 5,585 (1.13%) were repeat-reactive for the presence of anti-HBc, with 29 (0.52%) being HBV DNA-positive and HBsAg-negative. The proportion of potentially infectious donations intercepted by anti-HBc screening was 1 in 17,800 if all HBV DNA-positive donations were infectious, 1 in 26,900 if infectivity was limited to donations with an anti-HBs level of not more than 100 mIU per mL, and 1 in 69,300 if only donations with undetectable anti-HBs were infectious. For 279 components in the lookback study, no traced recipients were HBsAg-positive and 7 recipients were anti-HBc-reactive in association with 4 donors, 3 of whom had an anti-HBs level of more than 100 mIU per mL and 1 of whom had a level of 61 mIU per mL. Implementation of anti-HBc screening reduced the risk of transfusing potentially infectious units by at least as much as had been expected based on the literature. The lookback did not provide proof of transfusion transmission of HBV from HBV DNA-positive, anti-HBc-reactive, HBsAg-negative donors but it did not establish lack of transmission either.

HCV core antigen and combination (antigen/antibody) assays for the detection of early seroconversion

Detection of antibodies against hepatitis C virus (HCV) and/or detection of HCV RNA by nucleic acid testing (NAT) are the commonly utilized methods for detecting exposure to HCV in both blood screening and diagnostic laboratories. While several HCV core antigen tests have been developed over the last 10 years, these assays have not gained wide acceptance in routine laboratory practices, due in part to inadequate sensitivity. Over the last several years, improvements have been made in the formulation of the HCV core antigen assays that have resulted in significant sensitivity improvements. Recent studies indicate that between 85% and 98% of preseroconversion samples that are HCV RNA positive are detected with the improved HCV core antigen assays. These improved assays include stand-alone HCV core antigen tests and HCV antigen/antibody combination tests. As such, these assays could provide an alternative to HCV NAT in blood banks where such testing has not already been implemented, and may be utilized in diagnostic laboratories to identify early HCV infection. J. Med. Virol. 79:S54–S58, 2007. © 2007 Wiley-Liss, Inc.

HCV core antigen detection in seropositive samples

Detection of antibodies to HCV is typically the primary test utilized to identify HCV-infected individuals. Seropositive individuals may then be tested for HCV RNA by nucleic acid testing (NAT) to determine if the individual is actively infected with HCV. In addition, NAT assays that are based on quantitation of HCV RNA copies/ml, are utilized to determine the effectiveness of antiviral therapy. Over the last several years, HCV core antigen tests have been developed that have shown utility both for the identifying active HCV infection and for monitoring antiviral therapy. Although these assays are relatively simple and rapid, the HCV core antigen tests have not been widely accepted mostly due to their lack of sensitivity. Recently developed assays have shown improved sensitivity, and may represent an alternative or adjunct to HCV NAT both for identifying active HCV infection and for monitoring antiviral therapy. J. Med. Virol. 79:S52–S53, 2007. © 2007 Wiley-Liss, Inc.

Accuracy of hepatitis C virus core antigen testing in pools among seroconverters

Screening blood units for hepatitis C virus (HCV) with nucleic acid testing (NAT) reduces the risk associated with the long "window period" (8-9 weeks) after HCV infection. The feasibility of adding the HCV core antigen assay in pools to the existing anti-HCV individual screening was examined as an alternative of NAT, for early detection of HCV. Eighteen HCV seroconversion panels were tested for HCV antibodies, HCV antigen, and HCV RNA. Each sample was tested for HCV antigen individually and in pools of 3, 6, and 12. Statistical analyses included estimation of time until detection of the first positive HCV antigen bleed in each pool size, with a locally weighted regression (LOWESS) model. Sensitivity was calculated compared to NAT. Detection of HCV antigen in individual samples and in pools of 3 and 6 significantly preceded the detection of antibodies by 63, 53, and 46 days, respectively. Although the sensitivity of the HCV antigen test decreased with the increase in pool size, the estimated overall sensitivity of the "two-stage" antigen and antibody screening (where NAT of individual samples was the gold standard) was not significantly different between individual and the different pool sizes. Screening for HCV antigen in pools of 6 can be considered an efficient and easier-to-implement alternative to the costly NAT for identifying blood donors in the seroconversion period. It may offer a cost-effective approach in resource utilization in poor countries, that, after the implementation of HCV antibody testing, want to further improve blood safety.

Clinical usefulness of total hepatitis C virus core antigen quantification to monitor the response to treatment with peginterferon alpha‐2a plus ribavirin*

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.

De novo HCV infection among dialysis patients: a prospective study by HCV core antigen ELISA assay

Dialysis patients remain a high-risk group for hepatitis C virus infection. The current diagnosis of hepatitis C virus in dialysis patients includes serological measurement of anti-hepatitis C virus antibody; however, nucleic acid amplification technology for assessing hepatitis C virus viraemia is commonly used in other populations. An enzyme-linked immunosorbent assay test for detecting antibody to hepatitis C nucleocapsid core antigen (hepatitis C virus core antigen) in human serum has been recently developed (hepatitis C virus Core Antigen enzyme-linked immunosorbent assay test). It is conceived for screening of donor blood products to significantly reduce the 'serologic window' occurring before seroconversion during acute hepatitis C virus. A cohort (n = 72) of patients on maintenance haemodialysis in a single unit in the years 2000-2003 was included. Study patients were tested monthly by hepatitis C virus Core Antigen enzyme-linked immunosorbent assay in a prospective, clinical trial. Routine results obtained by hepatitis C virus Core Antigen enzyme-linked immunosorbent assay test were confirmed by assessing hepatitis C virus viraemia by branched-chain DNA (bDNA) signal amplification assay. De novo hepatitis C virus infection was identified in three patients during the study period; the hepatitis C virus incidence was 1.38% (95% confidence intervals, 1.31-4.09) per year. In each patient, hepatitis C virus core antigen testing allowed the serological identification of acute hepatitis C virus before anti-hepatitis C virus seroconversion. Hepatitis C virus RNA testing confirmed the results obtained by hepatitis C virus Core Antigen enzyme-linked immunosorbent assay in all cases. The time from initial hepatitis C virus detection by hepatitis C virus Core Antigen Assay and anti-hepatitis C virus seroconversion was not greater than four weeks. Two (67%) of three patients with de novo hepatitis C virus acquisition were HBsAg negative; both these patients underwent an initial phase of hepatitis C virus viraemia that was associated with an increase in alanine aminotransferase activity and preceded the seroconversion to anti-hepatitis C virus antibody. Nosocomial transmission of hepatitis C virus between haemodialysis patients was implicated in at least two (67%) of these three patients. Serological testing for hepatitis C virus core antigen can identify acute hepatitis C virus infection before anti-hepatitis C virus seroconversion. The time from initial hepatitis C virus detection by hepatitis C virus core antigen assay and anti-hepatitis C virus seroconversion was not >4 weeks. De novo acquisition of hepatitis C virus in haemodialysis was associated with a rise in alanine aminotransferase levels. Hepatitis C virus core antigen enzyme-linked immunosorbent assay test results can be obtained in routine laboratories without the need of special equipment or training. Hepatitis C virus core antigen testing among anti-hepatitis C virus negative patients on maintenance dialysis is suggested in order to early assess de novo hepatitis C virus within dialysis units.

Diagnostic Algorithm for Chronic Hepatitis C Virus Infection: Role of the New HCV-Core Antigen Assay

The diagnosis of chronic hepatitis C virus infection is based on nucleic acid testing (NAT) for HCV-RNA. We evaluated whether total HCV core antigen testing could be a substitute for NAT testing. Samples from 192 untreated chronic HCV positive patients previously tested for HCV-RNA by four different commercially available assays (SuperQuant, Amplicor HCV Monitor v 1.0 and v 2.0, Quantiplex) were tested for total HCV core antigen using the Ortho trak-C assay (Ortho Clinical Diagnostics, Raritan, NJ, USA). Furthermore, 52 HCV-RNA positive paired serum and plasma samples were analysed. Finally, inter-assay coefficients of variation for core antigen were determined by repeated testing of 59 samples. 172/192 (89.6 %) samples from untreated HCV patients showed positive results with the trak-C assay. Importantly, all but two trak-C positive samples were NAT positive. Only four of the twenty trak-C negative samples tested positive by two NAT assays with viral loads below 30,000 copies/mL. Moreover, HCV core antigen levels correlated significantly with HCV-RNA levels (r > 0.72; p > 0.001), gave consistent results in paired serum and plasma samples (r = 0.991), and showed a very low inter-assay variability (r = 0.943) independent of genotype. Based on the performance characteristics, easiness of use, and potential lower cost of the core Ag assay, we propose an alternative testing algorithm for establishing the diagnosis of chronic HCV infection in which the trak-C assay could substitute for NAT as the first choice for detection of HCV viraemia in anti-HCV positive individuals. NAT would only be necessary in rare cases with low viral load.

The role of core antigen detection in management of hepatitis C: a critical review

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.

The predictive value of core antigen testing for the management of hepatitis C patients receiving pegylated interferon/ribavirin treatment.

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.

Hepatitis C virus Core Antigen as a predictor of non-response in genotype 1 chronic hepatitis C patients treated with peginterferon α-2b plus ribavirin

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 α-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.

Relevance of total HCV core antigen testing for monitoring and predicting patients response

Relevance of total HCV core antigen testing for monitoring and predicting patients response