Performance of Determine Combo and other point-of-care HIV tests among Seattle MSM

Background and objectiveThe rapid test study was a real-time comparison of point-of-care (POC) HIV tests to determine their abilities to detect early HIV infection.Study designMen and transgender persons reporting sex with men in the prior year were recruited at the Public Health—Seattle & King County STD Clinic, Gay City Health Project, and University of Washington Primary Infection Clinic. Study tests included the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test performed on oral fluids and tests performed on fingerstick whole blood specimens including OraQuick, Uni-Gold Recombigen HIV test, Determine HIV-1/2 Ag/Ab Combo, and INSTI HIV-1 Rapid Antibody Test. Specimens from subjects with negative results were sent for EIA and nucleic acid amplification testing. McNemar's exact tests compared the numbers of HIV-infected subjects detected.ResultsBetween February 2010 and August 2014, there were 3438 study visits. Twenty-four subjects had discordant POC results with at least one reactive and one non-reactive test, including one subject with a reactive Determine p24 antigen. OraQuick performed on oral fluids identified fewer persons compared to all fingerstick tests. OraQuick performed on fingerstick whole blood detected fewer persons compared to the Determine Combo antibody component (p = .008) and Combo overall (p = .004), and there was a trend when compared to INSTI (p = .06). The Determine Combo specificity was 98.99%.ConclusionsAs reported by others, Determine Combo underperforms compared to laboratory-based testing, but it did detect one acute infection. If these results are validated, the specificity of Determine Combo may limit its usefulness in populations with lower HIV incidence.     

Evaluation of Oral Fluid Enzyme Immunoassay for Confirmation of a Positive Rapid Human Immunodeficiency Virus Test Result

The CDC recommends that a reactive rapid human immunodeficiency virus (HIV) test be confirmed with an approved supplemental test; the performance of an intermediate enzyme immunoassay (EIA) is optional. In support of this recommendation, it was found that of 1,431 reactive rapid HIV test results, 2 (0.1%) had false-negative oral fluid Western blot results and both had false-negative EIA results.Until 2002 in the United States, all tests for human immunodeficiency virus (HIV) infection were conducted in laboratories and the results were reported within several days to 2 weeks. Beginning in 2003, rapid HIV tests waived under the Clinical Laboratory Improvement Amendments of 1988 became available. The rapid tests can be performed with finger-stick whole-blood or oral fluid specimens in nonclinical settings, and the results (negative or preliminary positive) are available within an hour. Negative rapid test results may be reported without further testing. However, preliminary positive rapid test results must be confirmed in a laboratory with a supplemental test (e.g., a Western blot [WB] test) (2, 3). WB results from serum specimens are more accurate than WB results from oral fluid specimens, but because phlebotomy is not always feasible in nonclinical settings, some HIV testing programs use oral fluid for WB confirmation of rapid tests (4) (OraSure HIV type 1 [HIV-1] WB kit package insert; OraSure, Inc., Bethlehem, PA). Before 2007, the CDC recommended that a laboratory-based enzyme immunoassay (EIA) and a WB test be performed when oral fluid specimens were submitted for confirmation of positive rapid tests. In 2007, the CDC changed this recommendation because of the impending withdrawal of the only Food and Drug Administration (FDA)-approved oral fluid EIA and because postmarketing surveillance data identified several instances in which the oral fluid EIA was negative in persons whose rapid tests and oral fluid or serum WB were positive (1, 2). To evaluate the additional diagnostic usefulness of an oral fluid EIA to confirm preliminary positive rapid test results, the CDC examined the EIA and WB results for oral fluid specimens from persons confirmed to be HIV infected by serum WB.Study participants were persons with known HIV infection who had not taken antiretroviral treatment during the past 3 months. During the period from March 2006 to August 2007, 1,436 participants, all confirmed to be HIV infected by serum WB, were enrolled at clinics in six cities (Atlanta, GA; Baltimore, MD; Chicago, IL; Denver, CO; Louisville, KY; and Philadelphia, PA). Participants provided finger-stick whole-blood and oral fluid specimens, which were tested by the OraQuick Advance Rapid HIV-1/2 antibody test (OraSure, Inc., Bethlehem, PA) at the study site. Additional oral fluid specimens were collected using an OraSure HIV-1 oral specimen collection device and tested with the Vironostika HIV-1 Microelisa system EIA (bioMérieux, Marcy-l''Etoile, France) and the OraSure HIV-1 WB. The oral fluid EIA was not conducted for 429 specimens because of the unavailability of test kits due to a manufacturer shortage. Serum specimens were collected using standard BD Vacutainer tubes (Becton, Dickinson and Company, Franklin Lakes, NJ) and tested with the Genetic Systems HIV-1/HIV-2 Plus O EIA and HIV-1 WB (Bio-Rad, Redmond, WA).Specimens from 5 of the 1,436 participants were excluded from analysis: two specimens were suspected of having an error in identification labeling, and three oral fluid specimens had insufficient volume for confirmatory testing. All whole-blood (n = 1,431) and oral fluid (n = 1,429) specimens tested positive using the OraQuick rapid test. All serum specimens (n = 1,431) tested positive by serum WB. Of the 1,431 oral fluid specimens tested by oral fluid WB, 1,423 (99.4%) were positive, six (0.4%) were indeterminate, and two (0.1%) were negative. Oral fluid EIAs were performed on 994 of the 1,423 specimens that had positive oral fluid WB results, and all 994 oral fluid EIAs were reactive. Of the six oral fluid specimens with indeterminate WB results, five of six (83.3%) were positive by oral fluid EIA. Of the two oral fluid WB-negative specimens, neither was positive by oral fluid EIA.Data from this study indicate that oral fluid WB tests were positive in 99.4% of specimens from persons who were known to be HIV infected. However, specimens from approximately 0.1% of HIV-infected persons had false-negative oral fluid WB results, and both of these specimens also had false-negative oral fluid EIA results. Specimens from six (0.4%) HIV-infected persons had indeterminate oral fluid WB results, and one of these specimens had false-negative results for oral fluid EIA. Current guidelines require additional confirmatory testing using a blood specimen for any persons with a positive rapid test and a negative or indeterminate oral fluid WB (3). For these persons, even if there is a positive oral fluid EIA result, they will still need a follow-up WB.Postmarketing surveillance conducted in 2003 to monitor the performance of the OraQuick test indicated that some HIV-infected persons with preliminary positive rapid test results had false-negative oral fluid EIA results (2). In addition, the only FDA-approved oral fluid EIA was withdrawn from the market (1). The results of this study support current CDC recommendations that all preliminary positive rapid test results be confirmed with an additional approved supplemental test for HIV, such as WB or an immunofluorescence assay, and that performing an intermediate EIA is optional (2, 3). The CDC further recommends that if WB confirmatory testing of an oral fluid specimen produces a negative or an indeterminate result, confirmatory testing should be repeated with a blood specimen because of its greater sensitivity (2, 3).     

Hepatitis C virus antibodies among risk groups in a South African area endemic for hepatitis B virus

The prevalence of anti-HCV was studied in a South African area endemic for hepatitis B virus. A total of 35,685 volunteer blood donors (22,034 whites, 9,218 Asians, 3,077 Africans, 1,356 coloureds), 71 haemophiliacs, 84 chronic dialysis patients, 100 antenatal attenders, 212 nurses, and 20 HIV-positive male homosexuals were tested for anti-HCV. Repeat positive second generation Ortho HCV EIA was used to determine HCV status for the blood donors; Abbott-II HCV EIA combined with a neutralisation test was used for the other risk groups. Antibody to hepatitis B core antigen (anti-HBc) was also tested in the haemophiliacs, nurses, and chronic dialysis patients. Seroprevalence for the blood donor population was 0.16, 0.34, 0.75, and 0.22% for whites, Asians, Africans, and coloureds, respectively. Of the risk groups tested, 39.4% of haemophiliacs and 4.8% of chronic dialysis patients were positive; of the remainder tested none was positive. Fifty percent of nurses, 47.9% of haemophiliacs, and 22.6% of dialysis patients had serological evidence of past exposure to hepatitis B virus (anti-HBc positive). These findings indicate a low prevalence of anti-HCV in the blood donor population, thus probably resulting in a low prevalence in groups exposed to blood and blood derivatives. The overall difference in prevalence between the race groups was significant (P < 0.0001). The high prevalence of hepatitis B virus compared to the low prevalence of HCV suggests that the main modes of transmission of the two viruses are probably different. © 1993 Wiley-Liss, Inc.     

Performance of the OraQuick HCV Rapid Antibody Test for Screening Exposed Patients in a Hepatitis C Outbreak Investigation

During a nosocomial hepatitis C outbreak, emergency public clinics employed the OraQuick HCV rapid antibody test on site, and all results were verified by a standard enzyme immunoassay (EIA). Of 1,157 persons, 1,149 (99.3%) exhibited concordant results between the two tests (16 positive, 1,133 negative). The sensitivity, specificity, positive predictive value, and negative predictive value were 94.1%, 99.5%, 72.7%, and 99.9%, respectively. OraQuick performed well as a screening test during an outbreak investigation and could be integrated into future hepatitis C virus (HCV) outbreak testing algorithms.     

丙型肝炎病毒核心抗原检测用于献血者筛查价值的探讨

目的应用酶联免疫吸附技术筛查献血员中丙型肝炎病毒核心抗原（HCV—cAg）和抗体（HCV—Ab），了解丙型肝炎病毒核心抗原筛查献血员应用价值。方法对我站2004年8-12月间的3972份献血者血清标本进行抗-HCV初、复检和HCV—cAg ELISA检测，将ELISA法阳性的25份血清标本，再做RT-PCR检测证实。结果3972份血清标本检测中，有10份仅初检抗-HCV阳性样本，经HCVRNA检测阳性有l份，12份仅复检抗-HCV阳性样本，经HCVRNA检测阳性有1份，HCV—cAg检测阳性有3份，经HCVRNA检测阳性有2份。结论HCV—cAg ELISA检测技术的敏感性与HCVRNA技术类似，但成本明显降低，可与HCV抗体联合检测应用献血员筛查。     

Evaluation of a modified commercial assay in detecting antibody to hepatitis C virus in oral fluids and dried blood spots

Oral fluid testing is an effective alternative to serum antibody testing for surveillance of human immunodeficiency virus (HIV) and hepatitis B infections, and is being extended to hepatitis C infections. The objective of this study was to determine and compare the sensitivity and specificity of a modified commercial assay for the detection of antibody to hepatitis C virus (anti-HCV) in oral fluids collected by two different oral fluid collection devices (the Epitope OraSure trade mark and Sarstedt Salivette ) and in dried fingerprick blood spots. In this study, 253 anti-HCV seropositive patients and 394 blood donors (all anti-HCV negative) were recruited between August 2000 and January 2001. Each participant provided oral fluid specimens by OraSure and Salivette, and at least one dried blood spot. Serum specimens were collected from the patients whenever possible. For those injecting drug users who did not provide a serum specimen, HCV status was established on the basis of previous testing. All the nonserum samples were tested for the presence of anti-HCV, using a modified Ortho HCV 3.0 SAVe enzyme-linked immunosorbent assay (ELISA) protocol. The recommended preliminary cutoffs for the modified ELISA were suboptimal. Further, the sensitivity, specificity, and positive and negative predictive values could be improved by varying the cutoff and taking into account the likely prevalence of HCV in the population under investigation. For instance, given a population with a 50% prevalence of anti-HCV, the optimal sensitivities of the modified assay on OraSure, Salivette, and dried blood spots were 92%, 83%, and virtually 100%, respectively, in contrast to 83%, 59%, and 99% using the preliminary cutoffs. The respective optimal specificities were 99%, 93%, and 100%. In conclusion, oral fluids collected by the OraSure device provide an extremely useful method to conduct public health surveillance of not only HIV, but also hepatitis C, among injecting drug users. In addition, dried blood spot specimens may be useful for surveillance and could be employed as a first line diagnostic specimen.     

Seroprevalence of hepatitis C virus infection and its genotype in Lanzhou,Western China

The seroprevalence of hepatitis C virus (HCV) infection in Lanzhou, Western China was studied. HCV genotypes in 20 patients with HCV infection was determined by genotype-specific primer for polymerase chain reaction (PCR) based on HCV core region and compared with the genotype assigned by sequence comparison and molecular evolutionary analysis based on the same region. Antibody to HCV (anti-HCV) was present in 2.5% of volunteer blood donors and in 35.0% of paid blood donors (P < 0.01). HCV infection is uncommon in patients with liver disease who attended liver clinics in this locality; 4.0% with acute hepatitis and 4.0% with chronic hepatitis, 10.0% with liver cirrhosis, and none with hepatocellular carcinoma were seropositive for anti-HCV. Genotype 1b and 2a were both found to be prevalent. Together, they accounted for 19 of 20 (95%) patients with HCV infection. Sequencing of the HCV core region from two patients showed that the assignment of HCV genotype by genotype-specific primers for PCR matched well with the genotyping results based on sequence comparison and molecular evolutionary analysis. These data showed that HCV is present in Western China, HCV infection is more common in paid blood donors, and HCV genotypes 1b and 2a are both prevalent in Western China. © 1995 Wiley-Liss, Inc.     

Prevalence of anti-HCV and HCV viremia in hemodialysis patients in Taiwan.

Hepatitis C viral infection in 125 hemodialysis patients from Taiwan was studied using a second-generation anti-HCV immunoassay (EIA II) (Abbott HCV 2.0 EIA) and the polymerase chain reaction (PCR) to detect the HCV RNA in the serum. A total of 59 patients (47.2%) were positive by EIA II. In comparison, the conventional C100-3 anti-HCV assay was positive in 40 (32.0%). HCV RNA was found in 47 patients (37.6%). Patients with elevated serum transaminase level had a higher positive rate of anti-HCV and HCV RNA. The dialysis time was longer for those patients positive for anti-HCV than for those who were negative. A total of 57 of the 59 EIA II-positive cases had a history of blood transfusion. The HBsAg status did not influence the anti-HCV positivity. Among the 59 EIA II-positive patients, 66.1% were also positive for HCV RNA, and of the 47 HCV RNA-positive cases 83.0% were positive for EIA II. It is concluded that the high prevalence of specific HCV infection and HCV viremia was present in these patients. Prevention of cross-contamination during dialysis and blood screening before transfusion are important for the control of HCV infection in these patients.     

Development of a Simple and Highly Sensitive Enzyme Immunoassay for Hepatitis C Virus Core Antigen

A highly sensitive enzyme immunoassay (EIA) for the hepatitis C virus (HCV) core antigen (HCVcAg) was developed, and its performance was compared with that of the AMPLICOR HCV test (Roche Molecular Systems). The developed one-step pretreatment method, 30-min incubation of the specimen with a solution containing three different types of detergents (Triton X-100, 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate [CHAPS], and sodium dodecyl sulfate), does not require any special device. Because the interfering anti-core antibody in the sample was sufficiently inactivated by the pretreatment, HCVcAg in the sample could be detected. The immunoreactivity on gel filtration was shifted from void fractions to those corresponding to the molecular mass range from 20 to 25 kDa, which is equal to the estimated molecular mass of HCVcAg, after the pretreatment. By the recovery test with HCVcAg-positive serum, the recovery rate was 93.5 to 106. 5%. There was no interference with the EIA by anticoagulants or blood components in the serum. When the cutoff value was tentatively set at 0.5 mU/ml based on the distribution of healthy subjects' sera, the sera of all healthy subjects (n = 125) and patients with hepatitis B (n = 50) were negative. HCVcAg was detected in sera from 57 of 73 individuals (78.1%) with anti-HCV antibody. Similarly, HCV RNA was detected in sera from 59 individuals (80.8%) with the AMPLICOR HCV as the qualitative test (AMPLICOR HCV test) and in sera from 54 individuals (74.0%) by the AMPLICOR HCV Monitor as the quantitative test (AMPLICOR Monitor test). Concentrations of HCVcAg and HCV RNA (measured by the AMPLICOR Monitor test) correlated significantly (r = 0.8, P < 0.001). On seroconversion panels, HCVcAg was detected during the early stage of infection, when anti-HCV antibodies had not been produced. This assay for HCVcAg is simpler than assays for HCV RNA based on gene technology and shows specificity and sensitivity equivalent to those of the AMPLICOR HCV test.     

Prevalence of hepatitis C virus antibodies among patients infected with human immunodeficiency virus.

A study was undertaken to determine the prevalence and risk factors for serological evidence of hepatitis C virus (HCV) infection in patients infected with the human immunodeficiency virus (HIV). Tests for anti-HCV antibody were carried out by enzyme-linked immunoassay (EIA) on 101 HIV-infected patients from two university-based outpatient clinics. Anti-HCV antibody reactive samples were tested by using a recombinant immunoblot assay (RIBA) for HCV antibodies. Fourteen of 101 (13.9%) HIV-infected patients were anti-HCV reactive by EIA. Of these 14, only seven were reactive by RIBA: four were intravenous drug users as a sole risk factor for HIV infection; and the remaining three acquired HIV by blood transfusion, contaminated instrument exposure or IV drug use and sexual contact. Acquisition of HIV by sexual activity alone was not associated with HCV infection. It is concluded that HCV infection is found in approximately 7% of a university HIV clinic population. False-positive anti-HCV antibody serology may lead to overestimation of the prevalence of HCV infection. Female sex and intravenous drug use are significantly associated with HCV infection among HIV-infected individuals.     

Detection of antibodies to hepatitis C virus in U.S. blood donors.

An enzyme immunoassay (EIA) which utilizes a solid phase coated with a recombinant antigen (c100-3) derived from the hepatitis C virus (HCV) genome was evaluated for efficacy in the detection of antibodies to HCV (anti-HCV). The sensitivity of the antibody test was demonstrated by the detection of anti-HCV in a well-characterized panel of human specimens known to contain the infectious agent of non-A, non-B hepatitis. The specificity of the anti-HCV test was evaluated by testing 6,118 serum specimens from volunteer blood donors considered to be at low risk for exposure to HCV. The specificity of the anti-HCV EIA was demonstrated to be 99.56%, since 6,069 of 6,096 specimens from this low-risk group were nonreactive. A total of 49 (0.80%) of the 6,118 specimens were repeatedly reactive in the test, and 22 (46.81%) of the 47 specimens available for additional testing were confirmed as positive for antibodies to HCV c100-3. Among commercial plasma donors, 390 (10.49%) of 3,718 specimens were repeatedly reactive in the EIA. A total of 375 (97.40%) of the 385 specimens available for further testing were confirmed as positive. These limited data indicate that the prevalence of antibodies to HCV is 0.36% (22 confirmed positives among 6,118 specimens) among volunteer blood donors and 10.08% (375 confirmed positives among 3,718 specimens) among commercial plasma donors. The importance of confirmatory testing is discussed.     

Comparison of the performance of enzyme immunoassays for hepatitis B and C detection in dried blood spot

Dried blood spots (DBSs) could be an alternative to serum for hepatitis B virus (HBV) and hepatitis C virus (HCV) diagnosis. This study aims to evaluate two enzyme immunoassays (EIAs) for HBsAg and anti-HCV detection using DBS. Serum was tested using commercial EIA. DBS was tested using optimized EIA developed for serum and commercial EIA developed for DBS (Imunoscreen). Concordances between DBS and serum samples for both markers and EIAs were higher than 97%. Both EIAs demonstrated good performance for HBsAg and anti-HCV detection using DBS, and these methods could be used unchangeably increasing the access for HBV and HCV diagnosis.     

Prevalence of antibody to hepatitis C virus (HCV) in HIV-1-infected patients (nice seroco cohort)

The prevalence of antibody to hepatitis C virus (HCV) in a cohort of 272 HIV-infected patients was assessed by means of 4 anti-HCV assays: a 1st generation and a neutralization test, a 2nd generation test, and a confirmatory test, the dot-blot Matrix HCV? immunoassay. The cohort included, as a single risk factor, 35.7% intravenous drug users (IVDUs), 25% homosexual men, 30.1% heterosexual individuals, 5.9% transfused patients, 0.7% occupational infections, and 2.6% patients with unknown infection source, and was studied on entry and in samples collected for up to 36 months. Results showed that on entry (i) sera of 83 out of 272 members of the cohort were positive by the HCV 1st generation EIA (30.5%); 70 were confirmed by the neutralization test (84.3%); (ii) 115 of the cohort were reactive with the 2nd generation HCV EIA (41.3%); (iii) with the dot-blot immunoassay 99 (86.1%) of the cohort were confirmed and 16 remained indeterminate. The overall confirmed HCV antibody-positive rate in these 272 patients was 36.4%. Antibody to HCV was detected in 78.3% of IVDUs, 18.3% of heterosexual individuals, 31.2% of transfused patients, and only 2.9% of homosexual men. The 36-month follow-up of this cohort revealed that 4/145 patients became anti-HCV positive by second generation assay. Hepatitis B markers were frequently associated with HCV in IVDUs (71.1%) but infrequently in heterosexual (8.5%) or homosexual (1.5%) individuals. Our results suggest that HCV 2nd generation EIA used in combination with the semiautomated dot-blot assay as a confirmatory test improves the specificity and sensitivity for HCV antibody detection. Homosexual males are at low risk of HCV infection among HIV risk groups. © 1994 Wiiey-Liss, Inc.     

Low prevalence of hepatitis C virus infection among dentists in Taiwan

To evaluate whether hepatitis C virus (HCV) infection is an occupational hazard in the dental environment, serum samples collected in 1990–1991 from 461 dentists were tested for the antibody to HCV (anti-HCV) with first- and second-generation HCV enzyme-linked immunoassays (EIAs). Five of the 363 (1.38%) serum samples were reactive by the first-generation (C100–3) HCV EIA. Of the same 363 samples and the other 98 samples, 3 (0.65%) were reactive by the second-generation EIA. Those samples positive by the first- and/or second-generation HCV EIA were analyzed further by cDNA/polymerase chain reaction (PCR) to detect the presence of HCV RNA. Only 1 of the 5 first-generation EIA reactive samples were PCR positive. These results are comparable to the anti-HCV prevalence of healthy blood donors (0.95% by C100–3 assay) and pregnant women (0.63% by recombinant immunoblot assay). We conclude that the prevalence of HCV infection among dentists in Taiwan is low, and there is no increased risk of HCV infection through the practice of dentistry, at least in our area. © 1993 Wiley-Liss, Inc.     

Rapid HIV tests in acute care settings in an area of low HIV prevalence in Canada

Rapid HIV testing has the potential to improve medical care and reduce the transmission of infection. In this study, rapid HIV testing was performed on serum samples in acute care settings in five hospitals from urban and rural regions using the INSTI? HIV-1/HIV-2 Rapid Antibody Test (bioLytical Laboratories, Richmond, British Columbia). Parallel standard HIV antibody tests were performed at the provincial reference laboratory. Patient demographics, indication for testing and risk behaviours were collected. From April 30, 2007 and November 23, 2009, 1708 individuals were tested: 875 (50.3%) tests in pregnant women, 730 (42%) in source individuals in blood and body fluid exposures and 119 (5.8%) in acutely ill persons. Twenty-five (1.4%) samples were reactive by rapid HIV testing, of which 13 were reactive previously and 1 was a false reactive. Sensitivity of the rapid HIV test compared to standard HIV testing was 100%, specificity was 99.9%, the positive predictive value was 96% and the negative predictive value was 100%. The median time from specimen collection to availability of the rapid HIV result varied by site and ranged from 54 min to 1h 42 min. In this study, the INSTI? HIV-1 Rapid Antibody test identified reactive and non-reactive samples with similar accuracy to the conventional testing algorithm and provided a reliable way to perform rapid HIV testing in acute care settings.     

Commercial enzyme immunoassay adapted for the detection of antibodies to hepatitis C virus in dried blood spots.

BACKGROUND: Dried blood spots (DBS) provide a convenient method for blood sample collection in many settings where the prevalence of infection with hepatitis C virus (HCV) is increasing. Consequently, HCV assays are required that produce reliable results using samples derived from DBS. OBJECTIVES AND STUDY DESIGN: The optimum buffer for the elution of samples from DBS was selected and the performance of a commercial enzyme immunoassay (EIA) was evaluated using these DBS eluates and paired plasma samples. RESULTS: DBS with paired plasma samples were compared using this modified commercial EIA, which was found to have an estimated sensitivity and specificity of approximately 100% for detecting anti-HCV antibodies in DBS. CONCLUSION: A DBS-based assay for the detection of antibodies to HCV will prove valuable for collecting epidemiological data in the field or in under resourced settings.     

Surrogate markers are not useful for identification of HCV carriers in chronic hemodialysis patients.

Several diagnostic hepatitis C assays have been developed for the detection of antibodies to different antigens of the virus. This virus is the major cause of non-A, non-B hepatitis. Seventy-nine patients undergoing chronic hemodialysis and/or hemofiltration were tested for the presence of anti-HCV antibodies (anti-C-100-3 antibodies and anti-core antibodies), anti-hepatitis B core antibodies (anti-HBc), and aminotransferases (ALT). Seven patients were positive by one or more of the anti-HCV enzyme linked immunoassays (EIAs), while HCV-RNA was detectable in only four patients. These four patients had at least one, but not necessarily the same, positive anti-HCV EIA. HCV-RNA was not detected in patients who had no antibodies as determined by all six anti-HCV EIAs. All patients with a marker for HCV infection had persistent normal levels of transaminases. Three patients had elevated ALT values without a marker for HCV infection and suffered from hepatitis B virus infection. Anti-HBc was detected in 27/72 patients without any marker and in four patients with a marker of HCV infection. However, HCV-RNA was detectable in only one of these four anti-HBc positive patients. It is concluded that surrogate markers (anti-HBc and serum transaminases) are not useful for identification of HCV carriers in chronic hemodialysis patients.     

Usefulness of the hepatitis C virus core antigen assay for screening of a population undergoing routine medical checkup

We studied the usefulness of the recently designed Trak-C assay for the detection and quantification of the hepatitis C virus (HCV) core antigen (Ag) for the screening of HCV infection in 4,201 subjects selected from 74,150 consecutive volunteers undergoing routine medical checkups. Subjects were selected for screening because they had risk factors (group II, n = 321) and/or elevated alanine transaminase activity (group I, n = 3847). Initially, the anti-HCV antibody assay and the Trak-C assay were performed on each patient. Subsequently, the Trak-C assay was performed only when the anti-HCV enzyme immune assay (EIA) was positive. Positive samples were further evaluated for anti-HCV antibodies by a third-generation strip immunoblot assay and for HCV RNA. Four samples (1.2%) from group II and 113 (2.9%) from group I were anti-HCV EIA positive. We also tested 33 subjects who previously tested positive for anti-HCV in our medical center. Among the 150 anti-HCV EIA-positive samples, the HCV core Ag result was in accord with the HCV RNA result in 146 cases (97.3%). When the EIA result was positive, the HCV core Ag concentration and the HCV RNA load were correlated (r(2) = 0.78; P < 0.001). Four samples with low viral loads were Trak-C negative but HCV RNA positive. Among the 2,395 anti-HCV EIA-negative serum samples collected during the first part of the study, 17 (0.7%) were found to contain very low levels of HCV core Ag (<8.5 pg/ml, the cutoff value being 1.5 pg/ml). All these samples were HCV RNA negative and considered to be false positives. This was confirmed by HCV core Ag neutralization analysis. The HCV core Ag assay is a useful method in the screening strategy of HCV infection and provides a reliable means of distinguishing between current and cleared HCV infections that is well correlated with HCV RNA testing.