title: Improved reflexive testing algorithm for hepatitis C infection using signal-to-cutoff ratios of a hepatitis C virus antibody assay.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Southern California Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis, Department of Pathology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Keane K Y
authors.initials: KK
authors.lastname: Lai
authors.forename: Ming
authors.initials: M
authors.lastname: Jin
authors.forename: Shan
authors.initials: S
authors.lastname: Yuan
authors.forename: Meaghan F
authors.initials: MF
authors.lastname: Larson
authors.forename: Jason A
authors.initials: JA
authors.lastname: Dominitz
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Bankson
mesh_terms: D000465:Algorithms; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000097:blood*; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008163:Luminescent Measurements; D012372:ROC Curve; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014766:Viremia / Q000097:blood / Q000175:diagnosis / Q000276:immunology
chemical_list: D018937:Hepatitis C Antibodies