title: Sensitivity of hepatitis C virus core antigen and antibody combination assays in a global panel of window period samples.
abstract: BACKGROUND
  Hepatitis C virus (HCV) antigen and antibody combination assays have been launched as a cost-effective alternative to nucleic acid testing (NAT) for reducing the antibody-negative window period (WP). Later, a HCV antigen chemiluminescence immunoassay (CLIA) became available.
  
  
  METHODS
  A panel composed of 337 HCV NAT-yield samples that were characterized for viral load (VL) and genotype was used to compare the sensitivity of two combination enzyme-linked immunosorbent assays (Monolisa, Bio-Rad; and Murex, formerly Abbott) and a HCV antigen CLIA (Abbott). Analytic sensitivity was compared with HCV RNA detection using Ultrio (Grifols) by testing serial dilutions of 10 genotype (gt)1 to gt4 samples.
  
  
  RESULTS
  HCV antigen CLIA detected 92.4% of samples, whereas Monolisa and Murex detected 38.3 and 47.5%, respectively. In the HCV RNA VL range of 10(5) to 10(7) IU/mL, Monolisa and Murex detected 38% to 56% of gt1, 85% to 78% of gt2, and 21% to 37% of gt3. The overall geometric mean 50% limit of detection (range) of Ultrio on gt1 to gt4 dilution series was 3.5 (1.2-7.7) copies/mL, compared to 3.3 × 10(6) (4.4 × 10(5) -2.7 × 10(7) ), 3.4 × 10(6) (2.2 × 10(5) -4.2 × 10(7) ), and 2728 (415-7243) copies/mL for Monolisa, Murex, and HCV antigen CLIA, respectively.
  
  
  CONCLUSIONS
  Analytical sensitivity of NAT was on average 1 million- and 780-fold higher than combination assays and HCV antigen CLIA, respectively. Relative sensitivities of combination assays differed for genotypes with Murex being more sensitive for gt1 and gt3 and Monolisa more sensitive for gt2. Although being less sensitive than NAT, combination assays could be considered in resource-limited settings since they detect 38% to 47% of seronegative WP donations.
authors.affiliation: Institut National de la Transfusion Sanguine (INTS), Département d'Études des Agents Transmissibles par le Sang, Centre National de Reference pour les Hepatites B et C en Transfusion, F-75015 Paris, France.
authors.forename: Syria
authors.initials: S
authors.lastname: Laperche
authors.affiliation: Section of Molecular Virology, Paul Ehrlich Institute, Langen, Germany.
authors.forename: C Micha
authors.initials: CM
authors.lastname: Nübling
authors.affiliation: Scientific Support Office, American Red Cross, Gaithersburg, Maryland.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Stramer
authors.affiliation: Institute of Haematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Brojer
authors.affiliation: Institute of Haematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Grabarczyk
authors.affiliation: Study Group of NAT Standardization under the Ministry of Health, Labor and Welfare of Japan (2001-2003), Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshizawa
authors.affiliation: Nacionalinis Kraujo Centras, Vilnius, Lithuania.
authors.forename: Vytenis
authors.initials: V
authors.lastname: Kalibatas
authors.affiliation: Shabrawishi Hospital, Cairo, Egypt.
authors.forename: Magdy
authors.initials: M
authors.lastname: El Elkyabi
authors.affiliation: Shabrawishi Hospital, Cairo, Egypt.
authors.forename: Faten
authors.initials: F
authors.lastname: Moftah
authors.affiliation: Institut National de la Transfusion Sanguine (INTS), Département d'Études des Agents Transmissibles par le Sang, Centre National de Reference pour les Hepatites B et C en Transfusion, F-75015 Paris, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Girault
authors.affiliation: Biologicals Quality Control, Rijswijk, the Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: van Drimmelen
authors.affiliation: Blood Systems Research Institute, San Francisco, California.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.affiliation: Lelie Research, Paris, France.
authors.forename: Nico
authors.initials: N
authors.lastname: Lelie
mesh_terms: D005260:Female; D016174:Hepacivirus; D006526:Hepatitis C / Q000097:blood*; D018937:Hepatitis C Antibodies / Q000097:blood*; D018936:Hepatitis C Antigens / Q000097:blood*; D006801:Humans; D008163:Luminescent Measurements; D008297:Male; D021141:Nucleic Acid Amplification Techniques; D012367:RNA, Viral / Q000097:blood; D012680:Sensitivity and Specificity
chemical_list: D018937:Hepatitis C Antibodies; D018936:Hepatitis C Antigens; D012367:RNA, Viral