title: Lookback on donors who are repeatedly reactive on first-generation hepatitis C virus assays:justification and rational implementation.
abstract: BACKGROUND
  The purpose of this study was to explore strategies to minimize the number of unwarranted consignee notifications resulting from hepatitis C virus (HCV) first-generation (single-antigen) enzyme immunoassay (EIA 1.0) targeted lookback.
  
  
  METHODS
  The four blood centers participating in this study contributed data on 3753 HCV EIA 1.0-repeatably reactive (RR) donations. The analysis focused on 1) statistical evaluation of HCV EIA 1.0 signal-to-cutoff (S/CO) ratios versus HCV second-generation recombinant immunoblot assay (RIBA 2.0) interpretation from all participating blood centers and 2) RNA testing using transcription-mediated amplification on all HCV EIA 1.0 RR/RIBA 2. 0-positive or -indeterminate specimens and a subset of RIBA 2. 0-negative donations for which specimens were available.
  
  
  RESULTS
  Analysis of HCV EIA 1.0 S/CO ratios versus RIBA 2.0 indicated that 1180 (89%) of 1326 RIBA 2.0-positive specimens had an S/CO ratio >2. 5, while 146 (11%) had a ratio </=2.5. In contrast, of 2253 RIBA 2. 0-negative specimens, 299 (13%) had an S/CO ratio >2.5, while 1954 (87%) had a ratio </=2.5. Of 248 HCV EIA 1.0-RR/RIBA 2.0-positive samples with stored specimens available for additional testing, 198 (80%) were HCV RNA positive; 15 (7.5%) of these specimens had an S/CO ratio </=2.5, while 183 (92%) had a ratio >2.5. HCV RNA was detected in only 2 (1.5%) of 137 HCV EIA 1.0-RR/RIBA 2.0-negative specimens: 1 of these 2 specimens had an S/CO >2.5, while the other had an S/CO </=2.5.
  
  
  CONCLUSIONS
  A highly significant (<0.0001) correlation was found between the S/CO ratio on HCV EIA 1.0- and RIBA 2.0-positive or -negative results. An S/CO ratio >2.5 yielded an 89- percent sensitivity for RIBA 2.0-positive specimens, and donations with an S/CO ratio >2.5 had a 75-percent probability of being RIBA 2.0 positive. A policy recommendation to use the S/CO ratio to triage lookback would prevent unwarranted notification of 87 percent of recipients of blood from RIBA 2.0-negative donors and would result in a failure to notify only 5 to 10 percent of recipients potentially exposed to infectious units.
authors.affiliation: Blood Centers of the Pacific, Irwin Center, San Francisco, California 94118, USA. mpbusch@itsa.ucsf.edu
authors.forename: L H
authors.initials: LH
authors.lastname: Tobler
authors.forename: G
authors.initials: G
authors.lastname: Tegtmeier
authors.forename: S L
authors.initials: SL
authors.lastname: Stramer
authors.forename: S
authors.initials: S
authors.lastname: Quan
authors.forename: J
authors.initials: J
authors.lastname: Dockter
authors.forename: C
authors.initials: C
authors.lastname: Giachetti
authors.forename: M P
authors.initials: MP
authors.lastname: Busch
mesh_terms: D001782:Blood Donors; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood*; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D007124:Immunoenzyme Techniques; D008403:Mass Screening; D012313:RNA / Q000097:blood; D011994:Recombinant Proteins; D014218:Triage
chemical_list: D018937:Hepatitis C Antibodies; D011994:Recombinant Proteins; D012313:RNA