The significance of third‐generation HCV RIBA‐indeterminate, RNA‐negative results in voluntary blood donors screened with sequential third‐generation immunoassays

Kiely, Philip; Kay, Deborah; Parker, Susan; Piscitelli, Lisa

doi:10.1111/j.1537-2995.2003.00671.x

Cited by 32 publications

(39 citation statements)

References 47 publications

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“…The United Kingdom Health Protection Agency has recommended the use of a second anti-HCV antibody EIA for the confirmation of positive samples in the National Standard Method Minimum Testing Algorithm for the investigation of HCV infection (14). This algorithm is more cost effective and could reduce the number of samples in the problematic immunoblot-indeterminate group when following the CDC guidelines (17,26). Among the discordant samples, the number of cases in which only one of the four CLIAs gave a positive result was 10 (63%).…”

Section: Discussionmentioning

confidence: 95%

Clinical Performance Evaluation of Four Automated Chemiluminescence Immunoassays for Hepatitis C Virus Antibody Detection

Kim

Yoon

et al. 2008

J Clin Microbiol

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Various automated chemiluminescence immunoassay (CLIA) analyzers for the detection of antibodies to hepatitis C virus (HCV) are now commercially available in clinical laboratories and are replacing conventional enzyme immunoassays. We investigated the performance of four anti-HCV CLIAs (the Architect Anti-HCV assay on the Architect i2000 system, the Vitros Anti-HCV assay on the Vitros ECiQ Immunodiagnostic System, the Access HCV Ab PLUS assay on the UniCel DxI 800 analyzer, and the newly developed Elecsys Anti-HCV assay on the Cobas e 411 analyzer). The total percent coefficient of variation values of imprecision were 3.5 to 5.7% with positive control materials and 7.2 to 10.2% with negative control materials. The agreement between the results of the Elecsys, Architect, Vitros, and Access CLIAs ranged from 94.5 to 98.1%. The clinical sensitivity of all CLIAs was 100%. Each CLIA showed excellent reproducibility and clinical sensitivity. The Elecsys, Architect, Vitros, and Access CLIAs showed clinical specificities of 98.2, 98.8, 96.5, and 98.2%.Hepatitis C virus (HCV), first identified in 1989, is an enveloped positive-strand RNA virus classified in the Hepacivirus genus in the family Flaviviridae (6). The HCV genome is about 9.5 kb in length and encodes 3,011-to 3,033-amino-acid polypeptides in structural and nonstructural regions (20). The structural region contains the core protein and two envelope proteins (E1 and E2), and nonstructural proteins have been assigned protease (NS2, NS3, and NS4A), helicase (NS3), and RNA-dependent RNA polymerase (NS5B) (21) functions.The first commercially available anti-HCV enzyme immunoassay (EIA) used a single HCV recombinant antigen derived from the nonstructural NS4 protein designated c100-3 (19). The sensitivity of this first-generation EIA was low for a highprevalence population (approximately 80%) and showed a high false-positive rate (up to 70%) in a low-prevalence blood donor group (13). Therefore, a second-generation EIA was developed and approved for use by the Food and Drug Administration (FDA) in 1992 (3). The second-generation EIA, which contained additional HCV antigens from the core (c22-3) and NS3 (c33c) proteins, showed increased sensitivity and specificity and shortened the average seroconversion period from 16 to 10 weeks (1, 3, 13, 18). The third-generation EIA, which added a fourth antigen (NS5), showed significantly improved performance, particularly for high-risk patients (2, 8). However, a residual risk still exists due to the seroconversion period of approximately 56 days, and high false-positive rates were not resolved (12). The Centers for Disease Control and Prevention (CDC) recommended that an anti-HCV screening test positive result be verified by a more specific supplemental assay such as recombinant immunoblot or nucleic acid test (5). To facilitate the use of the supplemental assay, the revised guideline included an option for reflex supplemental testing based on signal-to-cutoff (s/co) ratios (4).Today, automated chemiluminescence immunoassay (...

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Section: Discussionmentioning

confidence: 95%

Clinical Performance Evaluation of Four Automated Chemiluminescence Immunoassays for Hepatitis C Virus Antibody Detection

Kim

Yoon

et al. 2008

J Clin Microbiol

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“…Some plausible causes are: 1) seroconversion phase, during which ELISA is already positive due to its higher sensitivity when compared to the IB test, which can still fail to meet the positivity criteria (19,20); 2) seroreversion in patients who spontaneously eliminate HCV. In these individuals, antibodies against some antigenic fractions have already turned negative for the IB test, but they are sufficient to yield ELISA-positive results (19,21); 3) individuals infected with genotype 3 or other uncommon genotypes that could have low reactivity to antigen fractions from genotype 1a used in most commercially available kits for anti-HCV. In this case, IB may be indeterminate but ELISA could be positive due to the reaction with better-preserved antigens such as core (22).…”

Section: Discussionmentioning

confidence: 99%

Cost-effective analysis of different algorithms for the diagnosis of hepatitis C virus infection

Barreto

Takei

Sabino

et al. 2008

Braz J Med Biol Res

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We compared the cost-benefit of two algorithms, recently proposed by the Centers for Disease Control and Prevention, USA, with the conventional one, the most appropriate for the diagnosis of hepatitis C virus (HCV) infection in the Brazilian population. Serum samples were obtained from 517 ELISA-positive or -inconclusive blood donors who had returned to Fundação Pró-Sangue/Hemocentro de São Paulo to confirm previous results. Algorithm A was based on signal-to-cut-off (s/co) ratio of ELISA anti-HCV samples that show s/co ratio ≥95% concordance with immunoblot (IB) positivity. For algorithm B, reflex nucleic acid amplification testing by PCR was required for ELISA-positive or -inconclusive samples and IB for PCR-negative samples. For algorithm C, all positive or inconclusive ELISA samples were submitted to IB. We observed a similar rate of positive results with the three algorithms: 287, 287, and 285 for A, B, and C, respectively, and 283 were concordant with one another. Indeterminate results from algorithms A and C were elucidated by PCR (expanded algorithm) which detected two more positive samples. The estimated cost of algorithms A and B was US$21,299.39 and US$32,397.40, respectively, which were 43.5 and 14.0% more economic than C (US$37,673.79). The cost can vary according to the technique used. We conclude that both algorithms A and B are suitable for diagnosing HCV infection in the Brazilian population. Furthermore, algorithm A is the more practical and economical one since it requires supplemental tests for only 54% of the samples. Algorithm B provides early information about the presence of viremia.

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“…The ODR was calculated by dividing the sample optical density (OD) by the cutoff value. Samples with an ODR Ն 2 were considered HP and samples with an ODR between 1 and 2 were considered LP (19,24).…”

Section: Methodsmentioning

confidence: 99%

“…Depending on previous reports' recommendation (19,24), the 192 anti-HCV positive samples were classified according to optical density ratio (ODR) of anti-HCV into (Group I) : comprises low positive (LP) cases with Methods.…”

Section: Methodsmentioning

confidence: 99%

Prevalence of Low Positive Anti‐HCV Antibodies in Blood Donors: Schistosoma mansoni Co‐Infection and Possible Role of Autoantibodies

Agha

El-Mashad

El-Malky

et al. 2006

Microbiology and Immunology

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Patients infected with schistosoma frequently show a high seroprevalence of anti‐hepatitis C virus (anti‐HCV) antibodies. The aim of this study was to find the underlying reason for this phenomenon, and to examine a possible involvement of autoantibodies. Out of 2,400 Egyptian blood donors, 192 (8%) were anti‐HCV positive by ELISA. They were 133 males and 59 females with age ranging from 27 to 48 years. According to optical density ratio (ODR) of anti‐HCV antibodies, 96 cases were low positive (LP) with ODR (1–2) designated as group I, and 96 were high positive (HP) with ODR (≥2) (group II). Both groups were examined for quantitative HCV core antigen (HCVcAg), liver function (Albumin, ALT, AST) and anti‐Schistosoma mansoni (anti‐Sm) IgG. Group I cases were HCVcAg negative with normal liver function tests, and 44 of them were anti‐Sm positive. Ninety cases (93.75%) of group II were HCVcAg positive with markedly affected liver function tests and 72 cases were anti‐Sm positive. All group I cases were examined for autoimmune markers (ANA, AMA, SMA and LKM). In group I, 33 (75%) of anti‐Sm positive cases were positive for one or more of the autoimmune markers examined, while none of anti‐Sm negative was positive for any marker with significant difference between the two groups (P<0.0001). Our results primarily on blood donors indicate that LP anti‐HCV frequently represents false‐positive reactivity with a possible role of Sm‐induced autoantibodies in this phenomenon.

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The significance of third‐generation HCV RIBA‐indeterminate, RNA‐negative results in voluntary blood donors screened with sequential third‐generation immunoassays

Cited by 32 publications

References 47 publications

Clinical Performance Evaluation of Four Automated Chemiluminescence Immunoassays for Hepatitis C Virus Antibody Detection

Clinical Performance Evaluation of Four Automated Chemiluminescence Immunoassays for Hepatitis C Virus Antibody Detection

Cost-effective analysis of different algorithms for the diagnosis of hepatitis C virus infection

Prevalence of Low Positive Anti‐HCV Antibodies in Blood Donors: Schistosoma mansoni Co‐Infection and Possible Role of Autoantibodies

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