Improved Reflexive Testing Algorithm for Hepatitis C Infection Using Signal-to-Cutoff Ratios of a Hepatitis C Virus Antibody Assay

• Published in: Clinical chemistry (Baltimore, Md.) Vol. 57; no. 7; pp. 1050 - 1056
• Main Authors: LAI, Keane K. Y, MING JIN, SHAN YUAN, LARSON, Meaghan F, DOMINITZ, Jason A, BANKSON, Daniel D
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for Clinical Chemistry 01.07.2011; Oxford University Press
• Subjects: Algorithms; Biological and medical sciences; Hepacivirus - genetics; Hepacivirus - immunology; Hepatitis; Hepatitis C; Hepatitis C - blood; Hepatitis C - diagnosis; Hepatitis C - immunology; Hepatitis C Antibodies - blood; Hepatitis C virus; Human viral diseases; Humans; Immunoassay - methods; Infectious diseases; Investigative techniques, diagnostic techniques (general aspects); Luminescent Measurements; Medical sciences; Ratios; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; ROC Curve; Viral diseases; Viral hepatitis; Viral infections; Viremia - blood; Viremia - diagnosis; Viremia - immunology; Human; Hepatic disease; Biochemistry; Enzyme immunoassay; Algorithm; Decision tree; Infection; Virus; Viral disease; Clinical biology; Immunoblotting assay; Digestive diseases; Ratio; Diagnosis; Flaviviridae; Molecular biology; Hepatitis C virus; Hepacivirus; Viral hepatitis C
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1373/clinchem.2010.158691

Chemiluminescence immunoassay (CIA) is used to detect hepatitis C virus (HCV) antibody status on the basis of signal-to-cutoff (S/Co) ratios. Positive results of antibody to HCV (anti-HCV) are followed by either recombinant immunoblot assay (RIBA) to confirm anti-HCV positivity or reverse transcription (RT)-PCR to detect viremia. We hypothesized that by analyzing S/Co ratios, we could determine a strategy to reduce unnecessary supplementary testing in our population. CIA was performed to screen for anti-HCV, and positive results were followed up with RT-PCR testing. Negative RT-PCR results were followed up with RIBA, whereas positive RT-PCR results were assumed to be RIBA positive. ROC curves were analyzed to determine the optimal S/Co ratios to predict HCV infection. We determined the S/Co ratios on 34 243 veteran patient samples. We found that with the CIA method 9.0% of patients had positive test results for anti-HCV. An S/Co ratio <3.0 ruled out active HCV infection and exposure with 100% negative predictive value. When the S/Co ratio was ≥20.0, positive predictive values were 98.5% compared with RIBA results, and 81.0% compared with RT-PCR results. RIBA is not necessary to confirm negative or positive CIA anti-HCV if the S/Co ratio is <3.0 or ≥20.0, respectively. To confirm HCV exposure, samples with an S/Co ratio between 3.0 and 19.9 should be followed up with RIBA unless PCR testing has been performed and the result is positive. Samples with an S/Co ratio ≥20.0 or positive RIBA results should be further tested by RT-PCR to determine HCV viremia status.